News and upcoming events
Small Media - what is in the bars and how to get more information about it:
Need Help?
Need Help? (5th edition, striped cover) is an update of our pocket-sized guide to
everything that's gay in London. It's a complete listing of virtually all the help lines,
websites, and support organisations across the capital. It includes contact details for
gay youth groups in several different boroughs. There is a large section on sexual health
clinics, divided up by location (so you can find the one nearest you), clinics that offer
gay-specific services and ones that offer 1-hour HIV testing. You will also find
contact details of support groups for HIV-positive men, victims of homophobic violence,
men who sell sex, and services for black and Asian men, as well as where to go for
counselling services and how to sign up for self-help workshops.
Camden & Islington Gay Men's Team small media resources
What do you do when you're Wasted? This is a new, mini version of Camden &
Islington's booklet about drugs, alcohol and how they affect the decisions gay
men make regarding their sexual health. A Little Bit Wasted looks at the
reasons why gay men use drugs and alcohol in the first place - and
gives practical advice on how to use them more safely or cut down. There is
information about which drugs don't mix together and why - and a section about
which HIV medications have negative interactions with recreational drugs. Wasted
includes advice for recreational drug and alcohol users on how to have safer sex
when high.
'Reasons To Be Tested' is a new mini booklet that explains why it's a good idea to
take a test and know your HIV status. It explains how, if you are HIV-positive,
your best chance of living a long and healthy life lies in knowing your status.
Once diagnosed, you will be able to get the medical, practical and emotional
help that you need.
Upcoming Courses & Workshops for gay men:
Workshops and courses in May and June are:
GMFA Courses
If you want to stop smoking then our seven session Stop Smoking course for gay men can help. Evidence shows that the support you get from a Stop Smoking course, combined with the relief from withdrawal symptoms that Nicotine Replacement Therapy gives you, makes your attempt to quit ten times more likely to succeed than if you use willpower alone.
- The next course begins 7pm Tuesday 17th June for 7 weeks
- The following course begins 7pm Thursday 7th August for 7 weeks
To book a place or for more information, click on the link above or call 020 7738 3712.
PACE Workshops
TwentySomething - is a relaxed and friendly monthly social and support group for gay and bi men in their 20s enabling them to meet others, talk about issues that matter to them and have fun. Monthly events will include discussions and workshops on all aspects of gay life including sex, relationships, coming-out, self esteem and assertiveness.
Mondays: 9 June. 6.30 till 9.30pm.
The Black Connection - is a monthly group for black men who have sex with men, to meet, talk & socialise as well as explore themes that will help celebrate the diverse community, relationships and lifestyles of Black men who love men.
Sundays: 18 May, 15 June. 6 till 9pm
Positive Hub - is a monthly space for positive men to talk and engage in a new kind of positive community. This isn't a space for invited speakers and dead end conversations, but for connection, honesty, laughter and exploration.
Sundays: 25 May, 29 June. 6 till 9pm
Sex Programme - is an opportunity to explore your own sexuality with other gay men in a safe and challenging environment over an eight-week period. Using individual and group exercises, homework assignments and discussion in the group, we will first explore how you relate to yourself sexually, and then move on to consider your sexual relations with other people.
Thursdays: 15 May to 10th July. 6pm. Plus Saturday 17 May and Sunday 6 July.
Getting Intimate - is a weekend workshop exploring the art of intimacy and relationship skills. All gay/bi men welcome, whether or not in a relationship.
Begins 6.30pm Friday 23 May. Continues Saturday 24 and Sunday 25 May.
Super Sexy - is a weekend workshop to explore how you can enhance your own sexiness.
Begins 6.30pm Friday 30 May. Continues Saturday 31 May and Sunday 1 June.
Sexual Healing - is a safe, confidential and fun weekend workshop for men who want to enjoy sex more.
Begins 6.30pm Friday 27 June. Continues Saturday 28 and Sunday 29 June.
To book a place or for more information call 020 7700 1323.
Other courses
Recently Diagnosed Course - held four times a year, this is a structured course open to anyone newly diagnosed in London who would like to be better informed.
To access this course, call Simon Johnson on 020 7812 1777 during office hours from Monday to Friday.
Living with HIV in Tower Hamlets - this course is for you if you want to know more about sex, intimacy and status disclosure, dealing with medication, coping with frustration, fatigue and isolation, and moving forward with your life.
Whether you are recently diagnosed or have been living with HIV/AIDS for some time you will find this course helpful and fun!
For more information on the next available course, please call Simon on 020 8694 9988 ext 208 or email epp@thepositiveplace.org.uk
Support Groups
The Midweek Group
Thanks to sponsorship from The Eddie Surman Trust (020 7738 6893) and the hospitality of South Central pub in Vauxhall, 'The Midweek Group', formerly supported by the UKC, continues to meet, socialise and have speakers on a regular basis (Tuesdays 6 - 9pm). Anyone interested in joining the group can come along on a Tuesday to enquire about membership.
Support groups for gay men from THT
Newly Diagnosed Gay Men's Group which meets twice a month at a Soho location, a support group for gay men diagnosed within the last year in London.
Gay Men's HIV Support Group which meets each Monday evening at a Soho location, for longer term diagnosed gay men in London.
Negative Partners Group which meets the last Thursday of the month at THT on Gray's Inn Road, open to the negative partner in a serodiscordant relationship.
In the autumn THT will be starting a Sex Addiction Support Group facilitated by their new addictions counsellor.
To access any of the above support groups, please call Simon Johnson on 020 7812 1777 during office hours from Monday to Friday.
Helplines
London Lesbian & Gay Switchboard
LLGS normal opening helpline hours are 10am to 11pm daily.
Broken Rainbow
The Broken Rainbow LGBT Domestic Violence Helpline is now open during the hours outlined below. The Helpline has recently partnered with London Lesbian & Gay Switchboard to provide an improved service to the Lesbian Gay Bisexual and Transgender community specifically. The helpline is staffed by LGBT people and offers a confidential service, across the UK, and supports LGBT individuals, family, and friends experiencing domestic violence. They also take calls from agencies seeking information and advice.
The Broken Rainbow LGBT Domestic Violence Helpline is open on: Mondays and Thursdays from 2pm to 8pm; Wednesdays 10am till 1pm. The Helpline number is 08452 60 44 60.
Further information is also available via their website: www.broken-rainbow.org.uk.
FS magazine
The spring 2008 issue of FS is now available online and in bars and clubs across
London. You can download the pdf of the current issue by clicking on the image on the
right. Download pdf's of previous issues of FS from the
website.
Issue magazine
The latest edition of 'Issue', the magazine of HIV and sexual health sector development,
has been published. Copies can be obtained by emailing Andie Dyer at
andie.dyer@tht.org.uk.
U+ magazine
Terrence Higgins Trust have launched a new magazine for gay men with HIV. U+ presents
health information in an easy to read magazine format, with a mix of articles, interviews
and quizzes, as well as a problem page.
Each issue focuses on a particular theme. Issue one (out now) is about sex for gay men with HIV – dealing with hepatitis C, other sexually transmitted infections, sexual addiction and relationships. Click on the image to download a copy from this website.
If you distribute health promotion resources to gay venues in your area, we would particularly encourage you to help us make U+ available on the commercial gay scene.
To order free copies for your organisation, please contact healthpromotion@tht.org.ukMass Media - what is in the press and how to get more information about it:
GMFA's HIV Detector Campaign:
This mass media campaign is designed to encourage men to think about the ways they establish someone's HIV status and to use condoms to avoid sexual risks. The ads, featuring a makeshift HIV detector, highlight the uncertainty of knowing a guy's status for sure.
Gay men are more likely to have unprotected anal intercourse with partners they know have the same HIV status as themselves. However, studies have shown that around 40% of HIV negative men who say they know their partner's HIV status are in fact guessing. And with around a third of gay men with HIV not knowing that they are infected, trusting that someone will be able to tell you their HIV status can be risky.
For more information contact rob.dawson@gmfa.org.uk
THT's Biology of Transmission Pt 2:
On the 17th December THT launches the new CHAPS national campaign
'Biology of Transmission Pt 2' which aims to alert gay men to the added risk of
using nitrite inhalents (commonly known as 'poppers') when being the receptive
partner during UAI.
The programme of work will be lead by a mass media campaign in gay publications from 19/12 until mid-February and will be supported by a website www.chapsonline.org.uk/biology; a new booklet 'Ready for action' which details how HIV is passed and how to reduce the risk; Exposed! 11, and a CHAPS Poppers Sector Summary Report.
For more information on the campaign and materials contact campbell.parker@tht.org.uk
Counselling waiting times & information:
New Counselling Service from GMIP
The new GMI partnership counselling Service offers talking therapies which are designed to assist men who have sex with men:
- identify their risk factors for unsafe sex
- reflect on the issues and challenges in practising safer sex
- set goals and plan and implement strategies for reducing or eliminating risk.
This service is open to all men who have sex with men regardless of HIV status who have concerns with adopting or maintaining safer sex and HIV risk reduction behaviour. All men entering the Service will be offered a confidential assessment, and through a process of discussion will be able to identify the most appropriate talking therapy for them. These include:
- cognitive behaviour therapy
- peer mentoring
- sexual health counselling
For further information or to book an appointment please call 020 8305 5000 or email info@gmipartnership.org.uk.
Healthy Gay Living Counselling @ THT
THT now have a dedicated substance misuse and addictions counsellor within the well-being team offering a One-2-One service to gay and bisexual men. It may well be that you do not want to talk to friends or family about your concerns so if you are worried or anxious about the drugs you take, then this counselling resource may be able to help. So if your relationship with drugs is having a negative impact on other areas of your life, feels out of control or you are using drugs in combination and don't know what the consequences might be, feel free to call us with your concerns. You can arrange an assessment by calling the Wellbeing Service on 0207 812 1777 and speak with either Simon or Jason.
Also appointed is a specialist young person's counsellor working with young men living, working or studying in the borough of Southwark. To access this service you need to be male, aged between 16 and 24 and either gay, bisexual or questioning your sexuality. There is currently no waiting time for this service.
Languages we can provided counselling in are: English, French, German, Portuguese, Spanish, Italian, Yoruba, Luganda, Shona. Counselling is available for couples and individuals at sites across London, with appointments available in the evenings or on Saturdays, as well as during the day.
To book an appointment call Simon Johnson on 7812 1777 - Office hours are 9.30am to 5.30pm
Volunteers needed
The Gay Men's Interactions Partnership has exciting new opportunities for
volunteer peer mentors, counsellors and health trainers. For more information
click on the image to view the full advert, call 020 8583 2404 or email
info@gmipartnership.org.uk
Sector Information
University Certificate in Gay Men’s Health
Admission for 2007 is now closed. Check the University of East London website (www.uel.ac.uk) in February 2008 for information about applying in 2008.
This innovative programme is for people who want to develop their skills and competency in the area of gay men’s health promotion. Involving the study of health within a particular vocational focus, the programme is offered as career development within the specialist sector of gay men’s health.
The main emphasis is on facilitating the application of knowledge to real life situations and developing skills and abilities necessary to working in gay men’s health promotion. This will be accomplished by combining an academic and participative learning environment with professional practice.
This programme is a unique collaboration between the University of East London and Terrence Higgins Trust.
For further information on the programme visit www.uel.ac.uk
To speak with someone in person about the programme, contact Ilana Morrissey on i.morrissey@uel.ac.uk or 020 8223 4535.
Sector Development training courses
As part of Terrence Higgins Trust’s role in building the skills of workers working with people with HIV we are pleased to announce the dates for a series of training courses.
The courses will provide information and a discussion based environment so that workers can update their knowledge and skills in the area of health promotion for people with HIV. They will be delivered in a supportive, learning centred environment, encouraging participants to take responsibility for their own learning and development. For more details on the courses and dates please visit www.tht.org.uk/binarylibrary/trainingcourseguide.pdf
New resources from THT
Healthy Respect
The Healthy Respect web pages give advice and information for people who have experienced problems with their healthcare because of their HIV status. Problems with GPs, dentists and other healthcare professionals are highlighted and solutions are offered. For more information, visit www.tht.org.uk/healthyrespect
GPs and Gay Men (CHAPS)
This programme of work has launched with the aim of providing gay and bisexual men with information which will enable them to have a better understanding of how the healthcare system works and why being gay or bisexual is important to their health care.
The programme includes a website for gay men including issues such as how the health
system works, what it can do and how being gay might effect your health and healthcare.
This can be found at
http://gpsandgaymen.chapsonline.org.uk
The website also contain a health professionals’ section containing extra
resources to ensure their services are meeting the needs of their gay and bisexual
patients.
A booklet accompanying this site, ‘GP treatment for gay and bisexual men’ is also available by contacting James Glavin at james.glavin@tht.org.uk or can be ordered individually by calling THT Direct 0845 12 21 200.
Your next steps
This booklet is for you if you’ve just found out you have HIV. You might also find it helpful if you’ve known for a while, but have not wanted to think about it much until now.
The booklet covers things that we often want to know about at this time.
There’s straightforward information about what HIV is and how we can
look after our health. The booklet talks about having sex when you have HIV,
and whether or not it’s a good idea to share your news with other people.
‘Your next steps’ is available by contacting James Glavin at james.glavin@tht.org.uk or can be ordered individually by calling THT Direct 0845 12 21 200.
Advice services for Homeless LGBT people across London are saved and will expand
Stonewall Housing is delighted to announce that its vital advice service for
LGBT Londoners has been secured, due to new funding from London Councils. This
means that lesbian, gay, bisexual and transgender people who are homeless or
experiencing housing crisis will be able to access specialist, expert advice
from Stonewall Housing until 2012.
Anyone who is homeless or has a housing problem and needs advice can call the advice line: 020 7359 5767. www.stonewallhousing.org.
Other Services or events of interest to gay men in London.
Living Well
Living Well is an NHS funded programme and is one of the core healthcare initiatives being offered to people living with HIV across London. Living Well provides a wide range of options that are intended to promote long-term life skills, encourage the development of a supportive social community and empower participants with the ability to self manage their condition and work in partnership with their health care professionals.
Options provided are:
Positive Self Management Programme (PSMP)
A seven week course consisting of two and a half hour long sessions delivered by previous participants of the PSMP. The course explores the principles of self management with an emphasis on encouraging group members to actively assist each other in achieving individual goals.
The dates for the next Positive Self Management Programmes in London are as follows:
Dates Location Times 23 Jan - 5 March Soho Centre 6.00pm - 8.30pm 6 Feb - 19 March Soho Centre 6.00pm - 8.30pm 26 Feb - 15 April Alexandra Ave, Health and Social Care Centre Daytime 6 March - 17 April Monk's Park - Brent 11.00am - 1.30pm 6 March - 17 May Positively Women 6.00pm - 8.30pm 17 May - 27 June Soho Clinic 10.30am - 1.00pm (sessions 1 - 6) 6.00pm - 8.30pm (session 7) For more information contact the administrator on 020 8746 2274 or email admin@livingwelluk.com or write to Living Well, Devonport Centre, 111 Devonport Road, London W12 8PB.
Residential Weekend
Participants who have completed the PSMP are invited to attend an optional residential weekend. This is an opportunity to engage in workshops that will encourage a deeper experience and exploration of some of the issues and topics raised throughout the seven week programme
Facilitator Training
Training is offered to participants who have completed the PSMP and wish to become tutors, delivering the PSMP to their peers. Training is delivered under assessed conditions under license of Stanford University.
Life-Coaching
Twelve one-to-one sessions are offered with a qualified coaching psychologist. Coaching is suitable for clients who are keen to work strategically towards achieving future goals.
Counselling
Hour long sessions with a Living Well counsellor. These sessions are suitable for clients who are dealing with emotional issues which are usually related to their HIV status.
Positive East
The Gay Men's Team at Positive East offers a comprehensive range of services for gay men and men who have sex with men who are positive, negative or untested, who live or work in East London. For details visit www.gaymenswellbeing.com, email us at gaymen@positiveeast.org.uk or telephone Positive East on 020 7791 2855.
Himat, a group for South Asian gay, bisexual and men who have sex with men exploring issues of sexuality, culture, religion and race. For many South Asian gay men in London, facing up to being different can be full of unique problems. Being a minority within a minority can create a strong sense of isolation from other gay men. For details on Himat visit www.gaymenswellbeing.com or call on 020 7791 2855.
Positive Life is an activities group for HIV positive gay and bisexual men. The groups main aims are to offer a non-scene space for gay and bisexual men to meet and discuss topics of interest; to make friends with other positive gay men; be able to share experiences and where they can give and/or receive support, as well as an opportunity to learn new skills. For details on Positive Life go to www.gaymenswellbeing.com email positivelife@positiveeast.co.uk or call on 020 7791 2855
Signpost, a confidential telephone helpline for men who have sex with men provides basic information and guidance on sexual health, HIV/STI's as well as accessing services and groups across east London. Signpost operates every Tuesday and Thursday from 6.30 to 8.30pm on 020 7790 5795. For details on Signpost visit www.gaymenswellbeing.com
Interesting Articles:
Recreational drug use does not adversely affect CD4 cell counts
Use of the recreational drugs, cannabis, cocaine, poppers, or amphetamines, does not adversely affect the number or percentage of CD4 or CD8 cells in either HIV-positive or HIV-negative gay men, according to data from the Multicenter AIDS Cohort Study (MACS) published online on January 3rd in the journal Drug and Alcohol Dependence. However, the investigators did not measure the quality or function of these cells.
Animal and test tube studies have previously shown that recreational drugs such as cannabis (smoked as marijuana), cocaine, poppers, and amphetamines may adversely affect animal and human T cell responses.
Notably, cocaine given to HIV-infected mice greatly increased HIV levels and reduced CD4 cell counts to one ninth of the levels of the mice in the control group.
However, studies examining the impact of these recreational drugs on CD4 and CD8 T-cells in real life have reported inconsistent and conflicting findings, possibly due to confounding factors such as antiretroviral drug use, injecting drug use, and differences in the level and frequency of recreational drugs used over time.
Consequently, Dr Chun Chao of the University of California at Los Angeles, and her colleagues, sought to assess the association between cannabis, cocaine, poppers, and amphetamine use and CD4 and CD8 counts by examining survey data and medical records from HIV-positive and HIV-negative gay men and other men who have sex with men enrolled in the Multicenter AIDS Cohort Study (MACS).
In particular, they wanted to calculate the rate of CD4 and CD8 change as a function of drug use both at baseline and throughout the study period. In order to explore possible dose-response relationships, they looked specifically at frequency and duration of self-reported recreational drug use.
A total of 3236 HIV-negative men were included in the analysis (which included men enrolled from between April 1984 and April 2003). The average follow-up time for HIV-negative men was ten years.
A further 481 HIV-positive men were included in the analysis. These men were HIV-negative at MACS enrolment and acquired HIV before a cut-off date of December 31st1995, chosen to avoid any confounding effects of highly active antiretroviral therapy (HAART). The average follow-up time for HIV-positive men was five years.
Recreational drug use at baseline was high both for men who remained HIV-negative and those who became HIV-positive during the study.
Of the men who remained HIV-negative, 59% used cannabis, 27% used cocaine, 58% used poppers, and 16% used amphetamines at baseline.
Of the men who seroconverted during the study, 61% used cannabis, 30% used cocaine, 58% used poppers, and 17% used amphetamines at baseline.
Surprisingly, however, the investigators found that fater controlling for smoking (which can raise CD4 cell counts) and other factors known to affect CD4 cell levels, the men who said they used any of the four drugs either at baseline, or any time during the study, had a (non-statistically significant) higher average CD4 cell count throughout the follow-up period, compared to those men who said they did not use any of the drugs.
Consequently, they write, “we did not find any clinically meaningful associations, adverse or otherwise, between use of marijuana, cocaine, poppers, or amphetamines and T cell counts and percentages in either HIV-uninfected or HIV-infected men.”
They add that they “also did not observe any threshold effect by frequency of use or duration of use (at least not with weekly or more frequent use or continuous use in the past year).”
They note that although their study found that the use of poppers was significantly associated with a lower CD4 cell count, “the size of the effect was tiny, even the strongest effect (for weekly or more frequent use) amounting to only a 4% reduction relative to [men] who did not use poppers.”
They also say that although other studies have suggested that cocaine use had an adverse effect on CD4 cell counts “this association was not observed in our study, even in those who used cocaine weekly or more frequently.”
The investigators also looked at the effect of tobacco smoking, and found that “tobacco smoking was associated with approximately 6% (p < 0.01) and 7% increase (p = 0.04) in mean CD4 cell count in HIV-uninfected and HIV-infected men.”
However, in their conclusion, the investigators concede that “although the circulating numbers of CD4 and CD8 T cells do not appear to be significantly affected by use of these substances, these findings do not preclude the possibility that substance use may adversely affect the functional properties of T cells.”
They also fail to point out that recreational drug use can affect sexual risk-taking; that use of poppers was significantly correlated with seroconversion during gay men’s unprotected sexual encounters; that amphetamine use can affect adherence to HAART; and that smoking may undermine the benefits of HAART.
Reference Chao C, et al. Recreational drug use and T lymphocyte subpopulations in HIV-uninfected and HIV-infected men. Drug Alchol Depend doi:10.1016/j.drugalcdep.2007.11.010, 2008.
UNITED STATES: Post-Exposure HIV Drugs Won't Boost Risky Behaviour
Providing antiretroviral (ARV) treatment to people after they may have been exposed to HIV is an effective way to prevent them from becoming infected and does not appear to promote high-risk behaviour in people who know this option is available, a new study finds. "This is a viable way of helping people stay [HIV-] negative," said Dr. Steve Shoptaw of the University of California-Los Angeles' Department of Family Medicine, who was involved in the research.
Post-exposure prophylaxis (PEP) has long been available in occupational settings. In 2005, CDC expanded its PEP guidelines to cover people exposed to HIV outside the workplace, including through condom breakage, risky sex or drug use. However, Shoptaw and colleagues note that PEP is not widely used in such cases, in part because it is not covered by health insurance and is only very rarely offered by community health programs.
To examine the feasibility of a non-occupational PEP program organized and funded by the community, the researchers conducted a demonstration project in which people were offered a 28-day course of ARVs within 72 hours of potential HIV exposure.
One hundred people, 95 of them men, enrolled in the project. Participants were provided drug treatment, HIV testing and counselling for up to 26 weeks after enrolment. Fifty-eight participants reported having unprotected anal sex, while 18 percent reported condom breakage. Of the 84 people given the full course of ARVs, 75 percent actually took all the medicine. No one became HIV- positive during the study. Shoptaw noted that some health officials have been hesitant to offer PEP after risky sex or drug use for
UK sexual health clinics may be missing recent HIV infections in gay men
Sexual health clinics in the UK can do more to reduce the number of gay men with undiagnosed primary HIV infection, a study published in the online edition of Sexually Transmitted Infections suggests.
Although the study found that 86% of gay men attending sexual health services were being offered an HIV test, and that 82% of these men accepted a test, there were a range of reasons why clinics were not offering tests. One of these was the presence of risky sex within the “window period” for the development of HIV antibodies. This period can last up to three months. But the investigators note that this practice could mean that patients with recent HIV infection and high infectivity are being missed, particularly as newer HIV testing technology is now able to detect very recent HIV infections.
Surprisingly the investigators also found that clinics were more likely to offer tests to individuals attending for routine sexual health screens than to patients who were seeking care because they had symptoms of a sexually transmitted infection, even though the presence of such symptoms can be a good indicator of recent HIV risk activity.
Gay men remain the group most at risk of HIV infection in the UK. But it is thought that as many as a third of all HIV cases amongst gay men are undiagnosed, and there is good evidence that significant numbers of men with undiagnosed HIV are leaving sexual health clinics without such infection being diagnosed.
Late diagnosis of HIV is a concern at both a public health and individual level: patients with undiagnosed HIV are thought to be more infectious, and late HIV diagnosis is the underlying cause of much of the HIV-related illness and death seen in the UK. Reducing the number of late HIV diagnoses in the UK has been identified as a priority by the UK government and clinicians and as part of this strategy gay men attending sexual health clinics should now be offered annual, opt-out HIV tests.
Several studies have looked at the factors associated with the offer and acceptance of an HIV test to and by gay men. These studies suggest that clinic testing policy, waiting time for results, perceptions of risk and behaviour, age and ethnicity are all important.
To gain a better understanding of these issues investigators designed a cross-sectional or snap shot study. The aim was to determine the proportion of men being offered and accepting a test, and to describe the factors associated with the offer and acceptance of an HIV screen.
There are 238 sexual health clinics in the UK and questionnaires were sent to each requesting details of sexual health consultations with the first ten - 30 gay male patients seen in the week beginning February 7th 2005.
A total of 189 clinics participated in the study and provided details for 2,162 patients. Half of these individuals were new patients, 38% were re-attending and 12% were attending for follow-up appointments. Median age was 32 years and 82% of patients were white.
All the clinics reported offering an HIV test to gay men attending for their first sexual health appointment. However, only 61% said that they routinely offered tests to gay men who were re-attending.
Overall, 86% of gay men were offered an HIV test, this included 97% of new patients, 86% of patients who were re-attending, and 39% of those attending for follow-up appointments.
Reasons for not offering an HIV tests included: negative HIV test in the last three months (39%); patient declining the previous offer of an HIV test (6%); HIV risk activity was within the window period (5%); no new risks since last test (5%); and the patient of low perceived risk (4%).
The investigators found that patients attending for a routine sexual health screen were three times more likely to be offered an HIV test than those attending because they had symptoms of a sexually transmitted infection. (p < 0.01). An increasing number of partners increased the likelihood of an HIV test being offered (p < 0.01) as did a report of unprotected anal intercourse (p < 0.01).
Overall, the offer of an HIV test was accepted by 82% of men, including 84% of new patients and 79% of re-attenders.
Commonly reported reasons for refusing an HIV test were: HIV risk activity was within the “window period” (23%); low self-perceived risk (13%); anxiety about the result (11%); and deferral of testing to a later date (9%).
Patient characteristics significantly associated with accepting a test included routine attendance rather than seeking care for specific symptoms (p < 0.01), younger age (p < 0.01), increasing number of partners (p = 0.05), and shorter waiting time for results (p = 0.02).
Patients reporting unprotected anal sex in the previous three months were 81% more likely to request an HIV test than patients who reported never having unprotected anal sex. In addition, patients who had had unprotected sex more than three months ago were some 62% more likely to request a test than patients who had never had unprotected sex.
“This is the first national study of this kind and the aim was to aim was to examine rates of HIV testing and factors associated with offer an uptake of HIV testing among men who have sex with men. The data show that rates of offer and uptake are high”, write the investigators.
But the investigators do have concerns, particularly that patients with symptoms of sexually transmitted infections, which could indicate recent HIV risk activity, are less likely to be offered a test than individuals attending for routine screens.
The investigators are also concerned that patients were not being offered HIV tests because their risk activity was within the “window period.”
Both these reasons for not testing could, the investigators fear, lead to individuals with recent HIV infection, and a high risk of transmission to others, remaining undiagnosed.
Five recommendations are made by the investigators:
- All clinics should have written policy regarding HIV testing for gay men.
- All clinics should consider offering opt-out testing.
- Gay men re-attending clinics should be routinely offered an HIV test, at least annually.
- Patient attending with symptoms, reporting recent sexual risk, or within the “window period” should be encouraged to test at their first visit and be given appointments for retesting outside the window period.
- Waiting times for test results should be kept to a minimum.
Reference Munro HL et al. National study of HIV testing in men who have sex with men (MSM) attending genitourinary (GUM) clinics in the UK. Sex Transm Infect (online edition), 2008.
Recurrent hepatitis C in HIV-positive gay men: relapse or reinfection?
Genetic analysis suggests that HIV-positive gay men in London are being re-infected with sexually transmitted hepatitis C virus rather than experiencing relapse after treatment, according to a presentation at the Fifteenth Conference on Retroviruses and Opportunistic Infections in Boston on Monday.
There have been several outbreaks of apparently sexually transmitted hepatitis C infection amongst mostly HIV-positive men who have sex with men reported since the early 2000s. The largest epidemic is centred in the south of England (London and Brighton), but smaller clusters have also been seen in other major northern European cities, including Amsterdam, Paris, and several cities in Germany, as well as in Australia.
It is thought that men who have already been diagnosed as HIV-positive and have frequent, unprotected or ‘hard’ sex with other HIV-positive men (often in groups, and often under the influence of recreational drugs such as ketamine or GHB) are most at risk of acquiring hepatitis C via sex.
However, data from Brighton presented at last year’s Retrovirus conference showed that a small number of HIV-negative gay men are being diagnosed with hepatitis C as well; this report suggested that most of these men also become HIV-positive within a short time. Further, at the 2006 conference, researchers reported a few cases of apparent sexual transmission of hepatitis C to HIV-positive heterosexual women.
In a Monday afternoon session on HIV and hepatitis C co infection, Rachael Jones from London’s Chelsea and Westminster Hospital presented a late-breaker study that examined the incidence of subsequent acute hepatitis C infection amongst HIV-positive gay men who had previously been infected with hepatitis C and who had achieved sustained response following treatment of their first acute hepatitis C infection.
The study combined data from the two largest HIV treatment centres in London – Chelsea and Westminster Hospital and the Royal Free Hospital. Of 211 HIV/hepatitis C co infected individuals, 16 were identified as having two or more episodes of hepatitis C infection. Unlike some diseases, hepatitis C infection does not produce a lasting immune response that can protect against subsequent reinfection.
All were HIV positive gay or bisexual men with no known history of injecting drug use. The men had been diagnosed with HIV for an average of four years (range 1 – 17 years). The average age at first H hepatitis C infection was 38 years (range 26 – 51 years) and the average CD4 cell count at that time was 476 cells/mm3, indicating well preserved immune function.
All the men had previously undergone hepatitis C treatment with pegylated interferon plus ribavirin during their first acute infection, and had achieved sustained virological response, defined as undetectable HCV viral load on at least two measurements. While sustained virological response—more typically defined as continued undetectable hepatitis C RNA six months after completion of treatment—does not indicate complete hepatitis C eradication, it is usually considered a “cure,” and relapse more than six months after finishing interferon-based therapy is uncommon.
Subsequent hepatitis C infection in these men was detected following an increase in liver enzymes (ALT) during regular HIV clinic follow-up. Eleven of the 16 men were on antiretroviral therapy for HIV therapy at the time, and the average CD4 count was 499 cells/mm3. The average duration of sustained response before subsequent detection of hepatitis C viraemia was 28 months (range 6 – 55 months).
The investigators were able to obtain amplifiable, paired hepatitis C samples (from the first and subsequent HCV episodes) from eight of the men (all hepatitis C genotype 1). They performed a phylogenetic analysis to determine the likelihood that the two samples were related and to provide information about clusters of infection.
In two of the eight men, the samples were very closely related, suggesting either late relapse or subsequent re-infection from a common source. The other six men were found to have divergent paired sequences, suggesting that they were re-infected with a second hepatitis C strain of the same genotype.
In addition, the analysis found a clustering of most of the analysed hepatitis C strains which, the researchers suggested, may mean that a small “closed population” of gay HIV-positive men are re-infecting each other after treatment.
Importantly, the investigators found that all but two of the men with suspected hepatitis C reinfection had a concurrent sexually transmitted infection—usually syphilis (ten episodes), but also gonorrhoea (six cases) and new or recurrent herpes (three cases). This finding adds weight to their assertion that the men were continuing to practice sex that put them at a high risk of acquiring HCV.
Last year, Dr Mark Nelson, of the Chelsea & Westminster told the August/September issue of AIDS Treatment Update that he had observed syphilis and lymphogranuloma venereum (LGV) in many of his patients who had acquired hepatitis C via sex, both of which, he said, “make HIV and hepatitis C transmission even more likely.”
He added that the continued sexual transmission of hepatitis C amongst HIV-positive men “underlines the importance of safer sex messages for HIV-positive men. Some men are having condomless sex because they perceive that they won’t pass on HIV to someone who already has HIV, or if they have an ‘undetectable’ viral load for HIV, they can’t pass on HIV to anyone. But it does seem they’re passing on—and getting—hepatitis C.”
Along these lines, Dr Jones suggested that healthcare providers are “failing our patients,” since they are becoming infected with hepatitis C not once, but multiple times.
Indeed, she added, after the current presentation had been prepared, the researchers learned that two of the men who had been treated for a second episode of acute hepatitis C had become reinfected (or relapsed) yet a third time.
“We need a much stronger public health information and screening program” for hepatitis C, she said.
Reference Jones R et al. Hepatitis C viremia following sustained virological response to pegylated interferon and ribavarin in HIV+ men who have sex with men –re-infection or late relapse? Fifteenth Conference on Retroviruses and Opportunistic Infections, Boston. Abstract 61LB, 2008.
UNITED STATES: HPV Causing More Oral Cancer in Men
Human papillomavirus, the STD that is the leading cause of cervical cancer in women, could soon become one of the top causes of oral cancers in men, according to a new study.
In addition to cervical cancer, HPV can cause genital warts and increase the risk for penile and anal cancer for males. Previous research has established HPV as the primary cause of the estimated 5,600 cancers that occur annually in the tonsils, lower tongue, and upper throat - a role that has been rising over time.
In the new study, Dr. Maura Gillison of Johns Hopkins University and colleagues examined more than 30 years of National Cancer Institute data on oral cancers. They categorized approximately 46,000 cases by using a formula to divide them into those caused by HPV and those not linked to the virus.
The researchers found the incidence rate for HPV-related oral cancers increased steadily in men from 1973 to 2004, making it nearly as common as those from alcohol and tobacco. "If the current trend continues, within the next 10 years there may be more oral cancers in the United States caused by HPV than tobacco or alcohol," said Gillison.
Though studies indicate that oral sex is associated with HPV-related oral cancers, a cause-effect relationship has not been proved. Some research has suggested that unwashed hands can spread HPV to the mouth. Sex may explain the increase in male upper throat cancers, Gillison noted. However, HPV-related upper throat cancers among women declined significantly from 1973 to 2004.
Merck & Co. makes the only HPV vaccine currently available in the United States; it is now given only to girls and young women. Merck plans to seek Food and Drug Administration approval for use in boys later this year, primarily to prevent males from spreading HPV and help reduce the almost 12,000 cervical cancer cases diagnosed in US women annually. But the study's results point out there may be a direct benefit for males too. "We need to start having a discussion about those cancers other than cervical cancer that may be affected in a positive way by the
vaccine," said Gillison.
The study, "Incidence Trends for Human Papillomavirus-Related and -Unrelated Oral Squamous Cell Carcinomas in the United States," was published in the Journal of Clinical Oncology (2008;26(4):612-619).
Balance of evidence continues to show: undetectable viral load in blood does not equal zero infection risk
The level of HIV viral load in blood and semen is related, but studies looking at the correlation between HIV in blood and semen have yielded a wide variety of results, according to a review article analysing the results of 19 studies examining this issue published in the January 2008 edition of Sexually Transmitted Diseases. The review article’s authors found that the association between viral load in blood and semen was affected by a number of factors, with successful antiretroviral therapy strengthening the association and sexually transmitted infections weakening it.
Prevention messages should stress the importance of condoms and other risk reduction strategies, regardless of whether a patient is taking effective anti-HIV therapy, recommend the investigators, as HIV transmission is possible even if a patient has an undetectable viral load in their semen.
HIV is mainly transmitted by unprotected anal and vaginal sex. Since the earliest days of the HIV epidemic it has been known that the virus is present in both blood and genital fluids. Infection with HIV is dependent upon the exposure of susceptible cells to an infectious quantity of HIV and it is known that concentrations of HIV in genital fluids, such as semen can vary.
HIV viral load levels in blood and semen are related but are not equal. It is not possible to determine how infectious an HIV-positive individual is on the basis of their blood viral load unless the extent of the association between viral load in blood and semen is determined.
Understanding the relationship between viral load in blood and semen is essential for estimating the potential benefit for antiretroviral therapy to reduce the risk of HIV transmission.
Investigators from the University of Connecticut therefore reviewed studied that measured viral load in blood and semen at the same time. The investigators examined the correlation between viral load in the two and the factors affecting this.
A PubMed search in January 2007 together with a search of abstracts of research presented to the Conference on Retroviruses and Opportunistic Infections (CROI) and the conferences of the International AIDS Society yielded 19 eligible studies.
The investigators caution that most of these studies had a small sample size. Furthermore 17 had a cross-sectional design and only two were prospective.
Correlations between levels of HIV in blood and semen in the 19 studies ranged between 0.07 and 0.64.
But one study found an almost perfect (94%) concordance between viral load in blood and semen. The authors note that this was the most rigorously designed study, with all the men taking potent anti-HIV therapy and none having sexually transmitted infection.
A consistent finding of the study was that viral load was lower in semen than blood. In most of the studies, men who had undetectable virus in their semen also had an undetectable viral load in their blood. But two studies identified individuals who had levels of HIV in their semen that were equal to or greater than in their blood.
Four factors were identified that could potentially influence the relationship between viral load in blood and semen: sexually transmitted infections; anti-HIV therapy and adherence; drug resistance; and the stage of HIV infection.
Infections such as gonorrhoea and chlamydia (which cause inflammation in the urethra) were found to significantly increase levels of HIV in semen. Some studies also suggested that a greater numbers of sex partners and higher rates of sexual intercourse also increased genital shedding of HIV.
Because sexually transmitted infections increase viral load in semen but not in blood, the correlation between viral load in the two is lowered. The investigators stress, “in fact, the studies with the lowest correlations between blood plasma viral load and semen viral load are those that are most likely to have included men with co-occurring sexually transmitted infections.”
Most of the studies showed that anti-HIV therapy suppressed viral load in semen. But there was also evidence that some anti-HIV drugs did not penetrate the blood and semen with equal efficiency. But in ideal conditions, when men were taking an effective antiretroviral regimen, were fully adherent to their therapy, and did not have a sexually transmitted infection, then there was a 95% certainty that below 4% of men with an undetectable viral load in their blood would have a detectable viral load in their semen. However, the investigators note, “these optimal conditions are rarely met outside of research settings.”
Poor adherence to anti-HIV therapy was associated with detectable HIV in semen in some studies, and another study showed that the men who missed the fewest treatment doses had the greatest degree of HIV suppression in semen over time.
Men who are treated with anti-HIV therapy can develop drug-resistant virus in their semen, and there is evidence of multi-drug resistant strains of HIV developing in the genital tract but not blood. The investigators note, “there is considerable alarm about the potential spread of multiple drug-resistant HIV from men with resistant HIV in their semen who contract a co-occurring sexually transmitted infection…when HIV is poorly controlled, the risk of transmitting treatment-resistant variants is particularly high.”
There were conflicting findings about the relationship between CD4 cell count and the level of viral load in semen, but no study found that the presence of symptoms of HIV disease influenced the association between viral load in blood and semen.
The investigators note that there is research evidence that some men (HIV-positive and uninfected) who believe an undetectable viral load means a lower risk of transmission are more likely to have unprotected sex. The investigators are concerned that this could lead to an increase in the number of men who have risky sex, offsetting the “protective benefits of reductions in semen infectivity.”
Furthermore, the investigators note that semen that has an undetectable viral load is still potentially infectious, and that cells in semen can contain HIV proviral DNA and can act “as vehicles for sexual transmission of HIV.”
They also note that the antiretroviral-treated men most likely to report unprotected sex are those most likely to have poor adherence to antiretroviral therapy. Treatment non-adherence increases viral load and unprotected sex involves a risk of sexually transmitted infections. The investigators are concerned that unprotected sex occurring in the context of poor adherence and sexually transmitted infections could result in the transmission of drug-resistant virus.
The investigators recommend that “HIV prevention messages targeted to both infected and uninfected persons should communicate the importance of condoms and other risk reduction strategies regardless of HIV treatment status and at all stages of HIV disease. Perhaps most crucially, HIV prevention for people living with HIV…must include regular monitoring and aggressive treatment of co-occurring sexually transmitted infections.”
Reference Kalichman SC et al. Human immunodeficiency virus load in blood plasma and semen: review and implications of empirical findings. Sexually Transmitted Diseases 35: 55 – 60, 2008.
Swiss experts say individuals with undetectable viral load and no STI cannot transmit HIV during sex
Swiss HIV experts have produced the first-ever consensus statement to say that HIV-positive individuals on effective antiretroviral therapy and without sexually transmitted infections (STIs) are sexually non-infectious. The statement is published in this week’s Bulletin of Swiss Medicine (Bulletin des médecins suisses). The statement also discusses the implications for doctors; for HIV-positive people; for HIV prevention; and the legal system.
The statement, on behalf of the Swiss Federal Commission for HIV / AIDS was authored by four of Switzerland’s foremost HIV experts: Prof Pietro Vernazza, of the Cantonal Hospital in St. Gallen, and President of the Swiss Federal Commission for HIV / AIDS; Prof Bernard Hirschel from Geneva University Hospital; Dr Enos Bernasconi of the Lugano Regional Hospital; and Dr Markus Flepp, president of the Swiss Federal Office of Public Health’s Sub-committee on the clincal and therapeutic aspects of HIV / AIDS.
The statement’s headline statement says that “after review of the medical literature and extensive discussion,” the Swiss Federal Commission for HIV / AIDS resolves that, “An HIV-infected person on antiretroviral therapy with completely suppressed viraemia (“effective ART”) is not sexually infectious, i.e. cannot transmit HIV through sexual contact.”
It goes on to say that this statement is valid as long as:
- the person adheres to antiretroviral therapy, the effects of which must be evaluated regularly by the treating physician, and
- the viral load has been suppressed (< 40 copies/ml) for at least six months, and
- there are no other sexually transmitted infections.
The article begins by stating that the Commission “realises that medical and biologic data available today do not permit proof that HIV-infection during effective antiretroviral therapy is impossible, because the non-occurrence of an improbable event cannot be proven. If no transmission events were observed among 100 couples followed for two years, for instance, there might still be some such events if 10,000 couples are followed for ten years. The situation is analogous to 1986, when the statement ‘HIV cannot be transmitted by kissing’ was publicised. This statement has not been proven, but after 20 years’ experience its accuracy appears highly plausible.”
It then states that the evidence for the Commission’s current assertion about the relationship between treatment and sexual HIV transmisson is much more informed than what was available in 1986 regarding the transmission of HIV through kissing.
For example, they note, Quinn and colleagues found that in sero-discordant couples the risk of transmission depended on the viral load of the HIV-positive partner, and refer also to a prospective study of 393 heterosexual sero-discordant couples from Castilla and colleagues found that there were no infections among partners of persons on antiretroviral therapy, compared to a rate of transmission of 8.6% among partners of untreated patients. They also note that transmission from mother to newborn also depends on the maternal viral load, and can be avoided by taking antiretroviral therapy.
They go on to assert that effective antiretroviral therapy eliminates HIV from genital secretions. They say that HIV RNA, measured in sperm, declines below the limits of detection on antiretroviral therapy, and that HIV RNA is also below the limits of female genital secretions is, as a rule, during effective antiretroviral therapy. “As a rule,” they write, “it rises after, not before, an increase in plasma viral load.”
They also assert that although cell-associated viral genomes are present in genital secretions, even on antiretroviral therapy, these are not infectious virions since “HIV-containing cells in sperm lack markers of viral proliferations such as circular LTR-DNA.”
They note that the concentration of HIV RNA in sperm correlates with the risk of transmission and that “transmission risk declines towards zero with falling sperm viral load. These data indicate that the risk of transmission is greatly decreased by antiretroviral therapy.”
They add, however, several exceptions and caveats to the above statements:- After a few days or weeks of discontinuation of antiretroviral therapy, plasma viral load rises rapidly. There is at least one case report of transmission during this rebound.
- In patients not on treatment, STIs such as urethritis or genital ulcer disease increase the genital viral load; it falls again after the STI is treated.
- In a patient with urethritis, sperm viral load can rise slightly even while the patient is receiving effective treatment. This rise is small however, much smaller that the rise observed in patients not on treatment.
They conclude the scientific part of the article by saying that: “During effective antiretroviral therapy, free virus is absent from blood and genital secretions. Epidemiologic and biologic data indicate that during such treatment, there is no relevant risk of transmission. Residual risk can not be scientifically excluded, but is, in the judgment of the Commission, negligibly small.”
Implications for doctors
The Commission then discusses the implications for doctor-patient discussions. It says, "the following information aims to communicate to doctors criteria allowing them to establish whether or not a patient can sexually transmit HIV.
HIV cannot be transmitted sexually if:
- The HIV-positive individual takes antiretroviral therapy consistently and as prescribed and is regularly followed by his/her doctor.
- Viral load is ‘undetectable’ and has been so for at least six months
- The HIV-positive individual does not have any STIs."
Implications for HIV-positive people
The Commission states that an HIV-positive person in a stable relationship with an HIV-negative partner, who follows their antiretroviral treatment consistently and as prescribed and who does not have an STI, is "not putting their partner at risk of transmission by sexual contact."
"Couples must understand," they write, "that adherence will become omnipresent in their relationship when they decide not to use protection, and due to the importance of STIs, rules must be defined for sexual contacts outside of relationship."
"The same goes for people who are not in a stable relationship," they add. However due to the importance of STIs, use of condoms is still recommended.
They add that heterosexual women will have to consider eventual interactions between contraceptives and antiretrovirals before considering stopping using condoms.
They also say that insemination via sperm washing is no longer indicated when "antiretroviral treatment is efficient."
Implications for HIV prevention
The Commission says that it "is not for the time being, considering recommendations that HIV-positive individuals start treatment purely for preventative measures." Aside from the cost involved, they argue, it cannot be certain that HIV-positive people would be sufficiently motivated to follow, and apply to the letter, antiretroviral treatment on a long-term basis without medical indications. They note that poor adherence is likely to facilitate the development of resistance, and that, therefore, antiretroviral therapy as prevention is indicated only in "exceptional circumstances for extremely motivated patients."
The Commission also says that their statement should not change prevention strategies currently taking place in Switzerland. With the exception of stable HIV-positive couples where HIV-positivity and the efficacy of antiretroviral therapy can be established, measures to protect oneself must be followed at all times. "People who are not in a stable relationship must protect themselves," they note, "as they would not be able to verify whether their partner is positive or on efficient antiretroviral therapy."
Implications for the legal system
Finally, the Commission says that courts will have to take into account the fact that HIV-positive people on antiretroviral treatment and without an STI cannot transmit HIV sexually in criminal HIV exposure and transmission cases.
They conclude by stating that the Commission thinks that unprotected sex between a positive person on antiretroviral treatment and without an STI, and an HIV-negative person, does not comply with the criteria for an “attempt at propagation of a dangerous disease” according to section 231 of the Swiss penal code nor for “an attempt to engender grievous bodily harm” according to section122, 123 or 125.
Reference Vernazza P et al. Les personnes séropositives ne souffrant d’aucune autre MST et suivant un traitment antirétroviral efficace ne transmettent pas le VIH par voie sexuelle. Bulletin des médecins suisses 89 (5), 2008.
HIV therapy does not eliminate transmission risk-WHO
GENEVA, Feb 1 (Reuters) - Anti-retroviral drug treatments can dramatically reduce the level of HIV virus in the blood but transmission risks remain, United Nations health agencies said on Friday.
The World Health Organisation (WHO) and UNAIDS, responding to a study published by Switzerland's Federal AIDS Commission, said "correct and consistent use of condoms" was the best way to prevent the spread of the AIDS virus between sexual partners.
People taking anti-retrovirals can have undetectable amounts of HIV virus in their blood "at certain stages of their treatment", the Geneva-based agencies said in a statement.
"However, it has not been proven to completely eliminate the risk of transmitting the virus," UNAIDS and WHO said.
"More research is needed to determine the degree to which the viral load in blood predicts the risk of HIV transmission and to determine the association between the viral load in blood and viral load in semen and vaginal secretions."
They also stressed that other sexually transmitted diseases may contribute to transmission rates, further underscoring the need for "a comprehensive HIV prevention package" that includes mutual fidelity and a reduced number of sexual partners.
Antiretroviral therapy and sexual transmission of HIV
UNAIDS - Geneva, 1 February 2008 - Following the recent publication of an article on antiretroviral treatment and sexual transmission of HIV in the Swiss medical journal 'Bulletin des medecins suisses', UNAIDS and WHO reiterate the importance of a comprehensive approach to HIV prevention including correct and consistent use of condoms.
The article, published by Switzerland's Federal AIDS Commission (La Commission federale pour les probl mes lies au Sida), states that seropositive individuals do not risk transmitting HIV to a seronegative partner under the following conditions: The seropositive partner has to have had undetectable HIV in the blood for at least 6 months, there must be strict adherence to his/her antiretroviral regimen, and he/she must be free of any other sexually transmitted infections. In the article the Commission states that although available medical and biological evidence does not rule out the possibility of HIV transmission they feel that there is nonetheless enough information to support its statement.
To prevent transmission of HIV, UNAIDS and WHO strongly recommend a comprehensive package of HIV prevention approaches, including correct and consistent use of condoms.
People living with HIV who are following an effective antiretroviral therapy regimen can achieve undetectable viral loads (the amount of virus in a body fluid such as blood, semen or vaginal secretions) at certain stages of their treatment. Research suggests that when the viral load is undetectable in blood the risk of HIV transmission is significantly reduced. However, it has not been proven to completely eliminate the risk of transmitting the virus.
More research is needed to determine the degree to which the viral load in blood predicts the risk of HIV transmission and to determine the association between the viral load in blood and the viral load in semen and vaginal secretions. Research also needs to consider other related factors that contribute to HIV transmission including comorbidity with other sexually transmitted diseases. UNAIDS and WHO will continue to follow the science of HIV transmission and the effect of antiretroviral treatment on the transmission of HIV.
UNAIDS and WHO underline the importance of effective and proven HIV prevention methods for all people irrespective of their HIV status. In 2005 UNAIDS published a policy position paper on HIV prevention to provide policy guidance on intensifying HIV prevention efforts.
A comprehensive HIV prevention package includes, but is not limited to, delaying sexual debut, mutual fidelity, reduction of the number of sexual partners, avoidance of penetration, safer sex including correct and consistent male and female condom use, and early and effective treatment for sexually transmitted infections.
Patients who start anti-HIV treatment with a low CD4 cell count have a good chance of an undetectable viral load
Patients who start antiretroviral therapy with very low CD4 cell counts have a good chance of rapidly achieving and sustaining an undetectable viral load, according to UK data published in the February 1st edition of the Journal of Acquired Immune Deficiency Syndromes. The study also showed that despite having a median CD4 cell count of only 20 cells/mm3 when anti-HIV therapy was started, only 5% of patients died.
HIV treatment guidelines now recommend that antiretroviral therapy should be started when a patient’s CD4 cell count is in the region of 350 cells/mm3. There is good evidence that initiating treatment with a CD4 cell count of this level is associated with good long-term outcomes.
But late diagnosis of HIV is a significant problem in many countries, the UK included. Many patients only have their HIV diagnosed when they have CD4 cell counts below the recommended threshold for initiating treatment. Some individuals are already ill with an AIDS-defining illness when their HIV infection is diagnosed, and in many cases did not consider testing for HIV because they perceived their risk of infection to be low. Other individuals deferred testing because they feared the stigma that surrounds HIV, or arrived in the UK from overseas with profound immune suppression.
In 2001 approximately a fifth of patients who started anti-HIV therapy in the UK did so with a CD4 cell count below 50 cells/mm3, and most of these patients had had their HIV diagnosed late. Although access to HIV therapy is expanding around the world, between 25% - 55% of patients who start treatment in resource-limited settings do so with very severe immune suppression and a CD4 cell count below 50 cells/mm3.
Even though late initiation of antiretroviral therapy is a significant issue in many countries, few studies have evaluated the outcome of patients who start treatment with a CD4 cell count below 50 cells/mm3.
Therefore, investigators from the UK Collaborative HIV Cohort (UK CHIC) assessed the virological outcome in patients starting anti-HIV therapy with a very low CD4 cell count since 1996. They also calculated survival in these severely immuno-suppressed patients.
A total of 1117 patients from ten large HIV treatment centres in south east England and Edinburgh who started treatment with a low CD4 cell count between 1997 and 2005 were included in the study. All had a CD4 cell count below 50 cells/mm3 and a viral load above 1000 copies/ml when they commenced antiretroviral therapy.
The patients were divided into four groups according to the year in which they started antiretroviral therapy: 1997 - 98; 1999 – 2000; 2001 – 2002; 2003 – 2005.
Median CD4 cell count was just 20 cells/mm3 when the patients started treatment. Their median age was 37 years, 74% were men, and approximately 50% acquired HIV infection during heterosexual sex.
Antiretroviral therapy based upon a non-nucleoside reverse transcriptase inhibitor (NNRTI) was initiated by 58% of patients, with 36% starting treatment with a protease inhibitor-containing regimen, 4% triple nucleoside analogue treatment (which would now be considered suboptimal) and 2% with treatment from all three main classes of antiretrovirals. In the period since 1999, the proportion of patients starting NNRTI-based treatment has been steady at approximately 68%, with 25% starting protease inhibitor-based treatment in this time period.
Twelve weeks after starting anti-HIV treatment 80% of patients had a viral load below 400 copies/ml. At week 48, 83% of patients had a viral load below this level.
Since 1999 viral load tests have been in routine use in the UK with a lower limit of detection of 50 copies/ml. The proportion of patients since 1999 with a viral load below 50 copies/ml twelve weeks after starting treatment has averaged 49%, with 77% having a viral load below 50 copies/ml at week 48.
There have been significant improvements in anti-HIV therapy since 1996, with drugs that are easier to take, more potent and less toxic becoming available. There have also been improvements in HIV care. The investigators wanted to see if these improvements were associated with an increase in the proportion of patients achieving virological suppression over the course of the study. They found that the chances of achieving virological suppression increased year on year until 1999 and remained more or less stable thereafter before falling slightly between 2003- 2005.
They then looked to see if any particular patient characteristics were associated with an increased chance of HIV suppression. They found that women were more likely to have a viral load below 400 copies at week 48 than men (odds ratio [OR], 1.74; 95% CI, 1.07 – 3.02). Older patients were also more likely to achieve effective suppression of HIV (OR, 1.46; 95% CI, 1.11 – 1.96 for every ten years).
There was a trend for gay men to have a better response to treatment than individuals from other risk groups (p = 0.06). Patients of black ethnicity appeared less likely to have a good virological response to treatment than white patients, but the difference was not statistically significant (OR, 0.65; 95% CI, 0.37 – 1.42).
In the 2003 – 2005 calendar period the investigators estimated the probabilities of a women aged 25, 35 and 45 who started treatment with a CD4 cell count below 50 cells/mm3 achieving a viral load below 50 copies/ml at week 48 to be 71%, 75% and 79% respectively. For men the probabilities for these ages were 68%, 73% and 78%.
Of the patients who started anti-HIV treatment after 1999, 134 (15%) progressed to AIDS and 48 (5%) died. The investigators estimated that the probability of being alive twelve months after starting treatment was 98% for those who did so between 1999 – 2000, 97% for those starting treatment between 2001 – 2002, and 98% for those who initiated therapy between 2003 – 2005. The corresponding AIDS-free survival probabilities for each of these periods were 81%, 83% and 84%.
“It is encouraging to note that viral suppression can be achieved fairly rapidly in persons initiating therapy at a severely advanced state of immune deficiency”, conclude the investigators, adding “these data, albeit under conditions of good infrastructure for care delivery, are a useful comparator for other populations starting therapy at similar levels of immunodeficiency. Such information may be valuable for evaluating the success of antiretroviral therapy in rollout programmes.”
Reference Porter K et al. Changes in outcome of persons initiating highly active antiretroviral therapy at a CD4 cell count less than 50 cells/mm3. J Acquir Immune Defic Syndr 47: 202 – 205, 2008.
Less risk of AIDS for patients with low CD4 cell count and no treatment options who stay on failing therapy
HIV-positive patients with a low CD4 cell count and no new treatment options who are taking antiretroviral therapy which is not controlling their viral load should remain on their therapy rather than interrupt treatment, French researchers report in the January 15th edition of Clinical Infectious Diseases.
Patients who interrupted treatment were much more likely to experience disease progression and develop new AIDS-defining illnesses that patients who stayed on their virologically-failing regimen, the French researchers found.
Potent anti-HIV therapy significantly reduces the risk of HIV disease progression by suppressing HIV replication and allowing the recovery of the immune system. A detectable viral load during antiretroviral therapy can lead to the development of drug-resistant strains of HIV.
Two treatment strategies are often advocated for patients who have extensive experience of anti-HIV treatment, limited new drug options and ongoing replication of drug-resistant HIV: either maintain the existing treatment, often with additional “re-cycled” drugs; or, temporarily interrupt HIV treatment, hopefully allowing drug-sensitive HIV to once again emerge.
There are conflicting results from studies looking at both treatment strategies.
But no study has looked at HIV disease progression in extensively-treated patients who remain on a virologically failing treatment compared to such patients who interrupt treatment. It is therefore unknown if treatment interruption because of virologically failing treatment in patients with a low CD4 cell count – below 200 cells/mm3 - is a safe strategy.
Investigators therefore analysed data from the French HIV hospital database. They identified patients enrolled between 2000 – 2005 who had a CD4 cell count below 200 cells/mm3 and who had taken one or more antiretroviral regimens for six or months.
These patients were divided into three groups: patients who interrupted treatment; those who remained on treatment despite having a viral load above 500 copies/ml; and those who took anti-HIV treatment and maintained an undetectable viral load.
Information was gathered on the development of AIDS-defining illnesses in each of the three groups of patients.
A total of 12,765 patients were included in the investigators’ analysis, and 72% of these patients were men.
Anti-HIV therapy was interrupted by 2,399 patients and 39% of these had a viral load above 30,000 copies/ml. The number of patients who stayed on anti-HIV therapy with a detectable viral load was 8,783 and 46% of these patients had a viral load above 30,000 copies/ml. Overall, 4,351 patients who took anti-HIV treatment and had an undetectable viral load.
A new AIDS-defining illness was recorded in 348 patients in the treatment interruption arm, with an incidence of 18.5 cases per 100 patient years of follow-up. Of these, 99 (29%) occurred in the first month after treatment was stopped.
New AIDS events were recorded in 1483 patients who stayed on a virologically failing therapy, providing an incidence of 14.5 caser per 100 patient years of follow-up. Of these new AIDS-defining illnesses, 189 (13%) were diagnosed in the first month of follow-up.
A total of 310 patients who took anti-HIV therapy and had an undetectable viral load developed an AIDS-defining illness, an incidence of 4.5 cases per 100 patient years. Of these, 59 (19%) occurred during the first month of follow-up.
For each group of patients the incidence of new AIDS-defining events was higher for patients with a CD4 count below 50 cells/mm3 compared to those with a CD4 cell count between 150 – 200 cells/mm3. New AIDS-defining illnesses also occurred more frequently in patients with a baseline viral load above 30,000 copies/ml compared to patients with a baseline viral load below this value.
When the investigators looked at the incidence of individual AIDS-defining events, they found that each occurred with significantly greater frequency in patients who interrupted therapy than amongst patients who either remained on a virologically failing regimen, or amongst patients who took treatment and had an undetectable viral load.
Overall, amongst patients with a CD4 cell count below 50 cells/mm3, compared to individuals who interrupted therapy, those who remained on treatment with a detectable viral load were 22% less likely to develop a new AIDS-defining illness, with patients with an undetectable viral load some 62% less likely to progress to a new AIDS event.
For patients with a CD4 cell count between 50 – 200 cells/mm3, compared to patients who stopped anti-HIV treatment, individuals who continued therapy with a detectable viral load were 34% less likely to progress to a new AIDS event, with treated patients with an undetectable viral load being some 73% less likely.
“Patients with detectable viral load who continued antiretroviral therapy had lower incidence and risks of AIDS-defining events of all types than did patients who stopped their treatment, both in the overall population and after CD4 cell count stratification”, comment the investigators.
They add, “our study confirms that interruption of antiretroviral therapy has a negative prognostic impact, even in the most advance patients.”
“Maintenance of a failing drug regimen to which the patient’s HIV quasispecies is resistant may still interfere with viral replication and thereby slow the immunological and clinical deterioration”, suggest the investigators.
The investigators conclude, “our results suggest that, when profoundly immunodeficient HIV-infected patients have no further treatment options permitting effective viral control, maintaining a failing regimen is preferable to interrupting it.”
Reference Kousiginian I et al. Maintaining antiretroviral therapy reduces the risk of AIDS-defining events in patients with uncontrolled viral replication and profound immunodeficiency. Clin Infect Dis 46: 296 – 304, 2007.
Factors Associated with HIV Seroconversion in Gay Men in England at the Start of the 21st Century
In order to "detect and quantify current risk factors for HIV seroconversion among gay men seeking repeat tests at sexual health clinics," the authors conducted an unmatched case control study in London, Brighton, and Manchester.
The authors identified 75 case subjects (who had recently tested HIV-positive after having received a negative result within the past two years) and 157 control subjects (who had recently tested HIV-negative after having received a negative result within the past two years). The subjects all completed a computer-assisted self-interview that focused on their lifestyle and sexual behavior in the period between the tests.
The men in both groups were similar socio-demographically, in years since initiating sex with men, in lifetime number of HIV tests, in reasons for seeking previous HIV tests, and in the time since their last HIV test (mean=10.5 months). Risk factors noted in the period between tests included unprotected receptive anal intercourse (URAI) with partners not believed to be HIV-negative (adjusted odds ratio (AOR) and 95 percent confidence interval 4.1, 1.8 to 9.3), where increased risk was associated with concomitant use of nitrite inhalants, receiving ejaculate, and increasing numbers of partners. The researchers also noted independent risk for unprotected insertive anal intercourse (UIAI) with more than one man (AOR 2.7, 1.3 to 5.5) and use of nitrite inhalants (AOR 2.4, 1.1 to 5.2).
"HIV serodiscordant unprotected anal intercourse remains the primary context for HIV transmission among gay men, with increased risk associated with being the receptive partner, receiving ejaculate, and use of nitrite inhalants," the authors concluded. "Although the HIV transmission risk of URAI is widely acknowledged, this study highlights the risk of UIAI and that nitrite inhalants may be an important facilitator of transmission when HIV exposure occurs."
Scientists Study How HIV Hides in Body
WASHINGTON- The AIDS virus has hideouts deep in the immune system that today's drugs can't reach. Now scientists finally have discovered how HIV builds one of those fortresses - and they're exploring whether a drug already used to fight a parasite in developing countries just might hold a key to break in.
Researchers have long struggled unsuccessfully to attack what they call reservoirs of dormant HIV, and the new work is in very early stages.
But University of Rochester scientists say it may be fairly straightforward to attack one of these reservoirs, blood cells called macrophages that HIV hijacks and turns into viral hideaways.
The new discovery shows the exact steps that HIV takes to do that - and found that some existing drugs, including a long-used treatment for leishmaniasis called miltefosine, can block the main step and thus cause these cells to self-destruct.
"It's a very smart virus," said lead researcher Dr. Baek Kim. "They have to have a very good fence to protect their house for a long time. ... Get rid of the fence, and now their house is gone."
Today's drugs have turned HIV from a quick death sentence into, for many, a chronic infection. Yet those drugs don't eliminate HIV because they can't reach the two known pools of cells where the virus can lie dormant, ever ready to resurface.
So-called memory T cells form one such pool. As the name implies, these are the cells that ensure if you get, say, measles as a child, you're forever immune. They live for years, even decades, making them a logical HIV hideout, and one that scientists have repeatedly sought to dismantle to no avail.
Macrophages, another type of immune cell, form the second pool. They roam the body looking for invaders like bacteria to gobble up. If they get harmed, such as becoming infected by a virus, they're supposed to commit suicide. But HIV instead keeps them alive long past their normal lifespan.
"Up to now, nobody has really thought about how to eliminate the macrophage reservoir," said Dr. Kuan-Teh Jeang, an HIV specialist at the National Institutes of Health. "The imagination now has turned toward, 'How do we eliminate reservoirs?' ... The best way to address our problem is to simply kill those cells."
The Rochester team found that HIV produces a protein that turns on a particular cell-survival pathway. After a multistep process, it ultimately activates an enzyme called Akt that in turn prevents cell suicide, the researchers reported Thursday online in the journal Retrovirology.
That was good news, Kim said, because the Akt pathway is a culprit in certain cancers - meaning oncologists have been trying to target it for some time. So Kim put human HIV-infected macrophages in lab dishes and started adding drugs known to block the Akt pathway, to see if any killed the cells.
He had luck: Miltefosine and a cousin named perifosine both rapidly killed the macrophages, thus depriving HIV of this hideout.
Perifosine is currently being studied as a possible cancer drug. But miltefosine is known to be safe through its use in leishmaniasis patients. So Kim's goal is to rapidly study the already available miltefosine in animals, to see if it truly targets infected macrophages well enough to then test in HIV patients.
"The evidence they show is in fact pretty good," said NIH's Jeang, who says the next step should be a test of miltefosine in monkeys infected with SIV, the monkey version of the AIDS virus.
Experiment to treat genital herpes produces no protection
BOSTON -- A once-promising experiment to see if treating genital herpes with a common drug could dramatically reduce susceptibility to HIV infection has found no protection whatsoever - a shocking setback for researchers hoping to find a pill that would slow the spread of the AIDS epidemic.
Results of the long-awaited study, which included gay men in San Francisco, Seattle, New York and Peru, as well as women in Africa, were released here Monday at the 15th annual Retrovirus conference, the premiere annual scientific meeting of AIDS researchers.
Nearly 20 years of various studies on herpes had shown that herpes infection nearly tripled the risk of contracting HIV. The assumption was simple - use acyclovir, a proven anti-herpes drug, to knock down that infection, and the odds of avoiding HIV would dramatically improve - by at least 50 percent, on par with the prevention benefit now attributed to male circumcision.
Results of the study were shielded from researchers and subjects alike until the study period was completed, but when statisticians tabulated their data, the answer was certain: Those who took acyclovir to suppress their herpes infections acquired HIV infections at exactly the same rate as those who took a placebo.
"This was a huge setback for HIV prevention," said Dr. Sharon Hillier, a researcher at the Magee-Women's Research Institute at the University of Pittsburgh.
Scientists had a lot of reasons to think that the results of this study could be as exciting as the findings in 2005 and 2006 that adult male circumcision - the surgical removal of the foreskin - reduced by as much as 60 percent the risk that those man would contract HIV.
"Many people thought this was going to be a slam dunk," said Dr. Connie Celum, the University of Washington professor who led the study since it was approved in 2004.
"It was definitely disappointing, but it was also very clear," she said of the result.
Now, the long and difficult task is to find out why it did not work, and what might be done to come up with different outcome.
The theory that immediately jumped to the top of the list of possibilities is that suppressing herpes was not enough. Although acyclovir is a very effective treatment for Herpes Simplex 2, it does not eradicate it, and many of those who take it will continue to have occasional flareups of genital ulcers.
Dr. Kevin DeCock, director of the Department of HIV/AIDS at the World Health Organization, said he was disappointed, but not entirely surprised by the results of the study. "What we really need," he said, "is a herpes vaccine."
Could earlier ART reduce risk of death from non-AIDS related illnesses in people with HIV?
“Evidence suggests that HIV may well play a role in several serious non-AIDS defining events… and the use of ART (antiretroviral therapy) may well reduce the risk of some serious non-AIDS events,” said Professor Andrew Phillips of the Royal Free & University College Medical School in London, speaking on Monday morning in a plenary lecture at the Fifteenth Conference on Retroviruses and Opportunistic Infections (CROI) in Boston.
His presentation was based on an analysis of available morbidity and mortality data from a number of cohorts and large trials since the introduction of ART, which all seem to suggest that non-AIDS related illnesses are accounting for a growing proportion of the deaths in people with HIV — though even these causes of death have become less common on ART. The studies also suggest that, untreated, HIV could be increasing the risk of death from other serious conditions even at higher CD4 cell counts.
To further reduce the risk of these illnesses and death in people with HIV, he suggested increasing efforts to diagnose HIV as early as possible; research to better understand the risk factors for these non-AIDS events in people with HIV and to define ways to manage or prevent them; and finally, “we need to be looking at whether ART should to be initiated earlier in patients with CD4 counts above 500.”
Trends in death rates over time, and the reasons for those deaths: Since the introduction of highly active ART, starting around 1996, the rate of death among people with HIV has fallen sharply and data from the US HIV Outpatient Study (with over 8500 participants) show that the rate seems to keep falling over time. A very similar trend has been observed in a large cohort from the UK, with a death rate of just below 1% in 2006 among those seen for care during the year.
“That’s a relatively low rate,” said Prof Phillips, “but that death rate is still well above the general population [death] rate for people of the same ages. So what are people dying from?”
Data from a French cohort suggest that even though AIDS-related conditions are still the leading cause of death, they only account for slightly over a third of all deaths in people with HIV. Other causes accounted for the rest including most commonly cancer, hepatitis C, cardiovascular disease among others.
And importantly, failure of ART does not seem to explain why most people with HIV are dying, even among the AIDS-related deaths. According to a British audit of the AIDS-related deaths in 2005, clinicians listed the situations in which the death occurred — and the most common scenario was initiating treatment too late (explaining 40% of the cases). Of note, only 5% of the deaths were due to multidrug resistant HIV leaving the person with no remaining ART options. “With the new drugs coming through, and recently licensed, it seems like this situation will continue for some time,” said Prof Phillips.
Although other causes may account for a higher proportion of the deaths of people with HIV, the introduction of ART also produced a dramatic decrease in the incidence of non-AIDS related death according to unpublished data from the EuroSida cohort.
Could HIV increase risk of serious non-AIDS conditions and death? This suggests that, without treatment, HIV could be increasing the risk of death from certain non-AIDS related illnesses — and by implication, that ART might reduce the risk of death from those other diseases. So Prof Phillips focused on four disease areas including non-AIDS malignancies, end stage kidney disease, cardiovascular events, liver cirrhosis and death from other causes. He did not focus on the adverse effects of ART — but noted that it isn’t always easy to distinguish between the effects of HIV and the effects of ART in these cohorts.
HIV could increase the risk of non-AIDS illnesses in a number of ways. Some general mechanisms he listed that could potentially alter pathogenic processes include early loss of CD4 cells in the gastrointestinal tract, changes in the mucosal barrier allowing microbes to spread, generalised immune activation or fibrosis of lymphatic tissue.
But when it comes specifically to cancer, HIV-related immunodeficiency leads to a reduced capacity to control organisms (like certain viruses) that trigger cancerous processes; and allows infections that cause chronic inflammation that may in turn increase the risk of cancer. Or the immune system could lose the ability to recognise (and eliminate) transformed cells that develop into malignancies.
HIV has also been associated with a range of kidney disorders, such as HIV-associated nephropathy (which can be reversed by ART). But there is also a link with other pathologies such as immune complex glomerulonephritis and there is a high prevalence of proteinuria and raised creatinine levels (markers of kidney damage) that are associated with high HIV RNA levels and low CD4 cell counts. Proteinurea and elevated creatinine have both been associated with all causes of mortality in people with HIV (not just deaths due to kidney disease).
HIV infection has also been associated with some negative changes in biomarkers (or potential biomarkers) for cardiovascular disease such as HDL-cholesterol depletion, inflammation (as measured by IL-6 and C-reactive protein), endothelial activation/dysfuntion (as measured by VCAM/ICAM), activation of coagulation (as measured by D-dimer). Some of these chances seem to be at least partly reversed by ART.
Liver fibrosis also occurs more rapidly in people with hepatitis B or C virus (HBC and HCV) when they are coinfected with HIV though the mechanism for this isn’t entirely clear.
But 25 years into the HIV epidemic, and more than ten years since the introduction of ART, there is a large body of data that could show whether HIV is indeed increasing the risk of developing and dying from these serious conditions. Prof Phillips reviewed three types of evidence including 1) studies comparing of the risks between HIV-infected and uninfected people, 2) studies that looked at whether the risk of these conditions was associated with viral load and CD4 cell counts 3) and randomised trials that might show whether ART had an impact on these non-AIDS events.
The risk of serious non-AIDS events between people with HIV and people without HIV: There are certain limitations in making comparisons between people who are HIV-positive and those who are not because the groups may differ in other ways, besides HIV infection, that could confound the analysis and in ways that would be extremely difficult to adjust for. Dr Phillips mentioned smoking as one obvious example, but there are a host of others, such as the very factors that made some people more vulnerable to becoming HIV infected in the first place, and which could put people at a higher risk of other illnesses as well (economic or social situations, poor self-esteem, access to health services, etc). In addition, he noted that each non-AIDS condition has its own set of risk factors that could act differently in HIV infected people. Finally, in some of the studies, the HIV-infected people in the cohorts could have been taking ART, which could impact the data.
That being said, a recent meta-analysis, comparing the incidence of cancers in 444,172 people with HIV with that in 31,977 immune suppressed transplant patients versus the general population found that there was a significantly higher risk in both people with HIV and the transplant patients for 20 out of 28 cancers examined. Since these populations could be assumed to be quite different, the findings strongly suggest that these cancers are linked with immunodeficiency. A couple of studies last year also found an increased risk of lung cancer in people with HIV, independent of smoking.
The data on kidney disease isn’t as clear. In a study of US Veterans last year that looked at the risk of end stage renal disease (ESRD) in patients according to whether they were black or white patients, and according to HIV status. HIV appeared to have no significant impact on ESRD in the white patients. But black patients were at twice the risk of ESRD compared to whites, and in this population HIV appeared to increase the risk substantially (after adjustment for a range of factors).
Four major studies have found an increased risk of cardiovascular disease among HIV-positive patients compared to people without HIV. However, in one of the studies, this association was only observed in people who had been on a protease inhibitor for 18 months; and in another study, the link was only observed in younger patients.
As for liver disease, one study has reported that among 4855 men and boys with haemophilia (and probably HCV) 1218 who were HIV-infected had a markedly higher cumulative risk of death from liver disease within 25 years. Similar findings were reported for HBV in the Multicenter AIDS Cohort Study (MACS).
Findings to be presented on Wednesday this week at the conference, will highlight the risk of death from any cause in ART-naïve people with CD4 cell counts higher than 350 compared to the general population.
The association of CD4 and viral load with the risk of serious non-AIDS events: The data from two large collaborations, including the DAD collaboration (which contains 10 cohorts including CPCRA, EuroSida and others following over 33,000 people over time) and the CASCADE collaboration (which is in subjects with known dates of seroconversion — though Prof Phillips was only looking at the ART-naïve subjects) consistently show that the risk of death, whether from non-AIDS causes or all causes, increases with decreasing CD4 cell counts. At the higher CD4 counts, the rates of death from all causes and non-AIDS causes are virtually identical because, Prof Phillips said “virtually all the deaths were from non-AIDS causes.”
The association generally holds true for each of the four conditions. For instance, there is a significantly reduced risk of non-AIDS malignancy associated with higher CD4 cell count in the DAD and Cascade collaborations, and in pooled data from the First trial (a study comparing different starting strategies) though not in the SMART study. Further data from the Aquitaine Cohort supporting this conclusion were presented later at CROI.
There are less data (and fewer deaths) for kidney disease. The DAD collaboration and First both show a significantly higher risk of ESRD with lower CD4 cell counts but it is not significant in SMART.
The four studies show less of an association between CD4 cell counts and cardiovascular disease (a trend but the confidence intervals are wide). In the DAD collaboration that includes a very large number of events (including non-fatal events), the hazard ratio might only lie just below 1. However, these findings could be confounded by the fact that some drugs for HIV have also been associated with a higher rate of heart disease (including, at this conference, abacavir and ddI).
There is fairly strong evidence of an increasing risk of liver disease/death with lower CD4 cell counts, except in the First trial (where there were only 14 events and the confidence intervals were wide).
There is also a relation between decreasing CD4 cell counts and non-fatal hospitalisations due to AIDS-defining events reported in the Aquitaine cohort between 2000 and 2004. However, at CD4 cell counts above 200 almost all the hospitalisations were due to non-AIDS events.
There are fewer data on the association of viral load and serious non-AIDS events. SMART looked at the risk of events with a viral load > 400 versus ≤400 and when the events were pooled together, there was a significantly reduced risk of serious non-AIDS events with a suppressed viral load, even when the data were adjusted for the most recent CD4 cell count. The evidence was fairly consistent for each of the four conditions with the exception of non-AIDS malignancies.
The impact of effective ART on the risk of serious non-AIDS events: “The real test is: if you can induce a change in viral load and CD4 count, can you see a resulting change in the incidence of serious non-AIDS condition?” said Prof Phillips. Although no large study has yet addressed this specifically, some hints can be gleaned from the SMART trial.
Essentially, this was a treatment interruption study involving thousands, but — at least right after the start of the trial — one arm was on ART and the other (the intermittent arm) was not. Over the course of the trial, most participants had CD4 cell counts over 200, and 80% of the time, the CD4 cell counts were over 350.
The study found that there was a higher hazard ratio of serious non-AIDS events off of ART (1.6 for all events combined which was statistically significant). The findings were relatively consistent for the individual conditions, though not every one was significant on its own.
“Of the 85 deaths that occurred in SMART, only 7 (8%) were from AIDS causes, so this emphasizes again that in this higher CD4 cell count range, morbidity and mortality is dominated by non-AIDS events,” said Prof Phillips.
477 of the patients in ART were either treatment naïve or off of ART for over 6 months, which allowed for a comparison deferred ART versus immediate ART. Although the number of events were too small to be able to definitively conclude anything (12 vs 2), the hazard ratio of 7.02 (95% confidence interval 1.57-31.4) was significant with a p-value of 0.01.
Another analysis of the SMART data to presented later at the conference will examine how biomarkers such as IL-6 and d-dimer differed between the two arms, and could prove useful in explaining these differences in clinical endpoints.
Conclusion and recommendations
“On balance, the evidence suggests that HIV may well play a role in several serious non-AIDS defining events,” said Prof Phillips. It’s possible that starting ART much earlier could reduce these events..
In addition to earlier HIV diagnosis, Prof Phillips urged further research into the risk factors for these events in both people on and off ART, and “in order to do that, we need to standardise diagnostic criteria and data collection methods.”
In order to see whether ART should be started earlier, Prof Phillips recommended conducting a trial comparing ART initiation in people with CD4 cell counts above 500 versus waiting until CD4 cell counts are around 350. He believes such a study would be justified because:
- Serious non-AIDS illnesses are relatively common at higher CD4 cell counts
- The SMART study suggests that the risk/benefit of ART favours benefit
- The virological benefit of ART is more durable than expected when the drugs first became available
- Early use of therapy might be cost effective, especially if associated with a reduction in transmission risk
- Such a study would provide a basis for identifying the usefulness of biomarkers of the risk of these non-AIDS conditions, and provide insights into pathogenesis
“Research is needed to provide a basis for defining models of care for people with HIV which take into account the risk of all serious conditions,” said Prof Phillips. “Research into mechanisms by which HIV affects risk of non-AIDS conditions is needed, and it may help us understand more about the causes of such conditions outside of HIV.”
The START trial, which will evaluate early versus deferred treatment could prove to be an important resource for answering these questions and the pilot phase will begin in just a few months.
Reference: Phillips A. Morbidity and mortality in the HAART era. Fifteenth Conference on Retroviruses and Opportunistic Infections, Boston, 2008.
AIDS vaccine: additional infection risk restricted to uncircumcised men
The Merck ad5 candidate AIDS vaccine, which appears to have increased the HIV infection risk of some trial participants, may have done so because it specifically increased the vulnerability of uncircumcised men to infection through insertive anal sex, the Fifteenth Conference on Retrovirues and Opportunistic Infections was told today in Boston.
This implies that the vaccine may have abrogated an immune response that was protective to uncircumcised men. This may (or may not) have been related to pre-existing immunity to the ad5 adenovirus, which was the vaccine’s ‘delivery vehicle’.
To summarise briefly: the Merck V520 ad5 vaccine consisted of three stretches of HIV genome taken from HIV’s gag, pol and nef genes enclosed within a shell derived from adenovirus type 5, a common virus that in its natural state causes common cold symptoms.
This viral shell was made replication-incompetent so that while it could initially infect cells and therefore stimulate a cellular immune response, it could not produce further generations of virus.
In the STEP Trial, 1,500 volunteers at high risk of HIV in the Americas and Australia were originally recruited, starting in December 2004. They were largely gay men and female sex workers. Sixty-two per cent were male and the average age was 29. They were at high risk of infection, with 25% of men and 50% of women having had at least 20 sex partners in the previous six months.
Originally, people with high levels of pre-existing immunity to the Ad5 adenovirus had been excluded from the STEP trial, but a decision to double the trial’s size had been taken in August 2005 when reasonable immune responses were observed in this group. The trial had reached its target of 3,000 volunteers by March 2007.
The trial was stopped in September 2007 when its data and safety monitoring board realised that the vaccine conferred neither a protective effect against HIV infection nor any effect on the subsequent course of infection.
However analyses of the trial data revealed a more alarming fact: there were more infections in the vaccine recipients than the placebo recipients – 49 versus 33, to be exact.
There was only one infection in a female volunteer, which is probably due to there being rather low levels of prevalent HIV infection in heterosexual men in the trial countries: an African STEP trial might have produced more infections in women. All the following analyses are therefore for male volunteers only.
Over the whole trial group, the difference in infection rates between vaccine and placebo recipients was only marginally statistically significant, with a probability of 0.044 if the effect observed was caused by the vaccine alone (so-called ‘one-tailed’ probability), and 0.077 if the effect was caused by some combination of a direct vaccine effect and some kind of protective characteristic of the placebo group that was removed (‘two-tailed’ probability).
In the group that had high levels of adenovirus immunity, however, there were 21 infections in vaccine recipients and only nine in placebo recipients, and this was statistically significant (p = 0.02 one-tailed, 0.029 two-tailed).
Adenovirus immunity increased infection risk in vaccine group. This suggested that the vaccine may either have generated an immune activation response that, perhaps by stimulating HIV-receptor cells, made people more vulnerable to HIV, or it removed an immune defence against HIV that was somehow conferred by pre-existing ad5 immunity.
Merck’s Mark Robertson, presenting preliminary data on immune responses in the trial, showed that volunteers with high ad5 immunity levels had higher levels of generalised CD4 cell activation. This difference was even more marked in HIV seroconverters than those who remained uninfected, so some kind of inflammatory interaction with the vaccine vector may be to blame.
But presenter Susan Buchbinder of UCSF said that the latter possibility appeared stronger. The incidence of HIV infection, at about 4-5% a year, was the same in vaccine recipients regardless of their ad5 immunity level. However the incidence of infection was lower in placebo recipients who had higher levels of ad5 immunity, ranging from 4% a year in those with the lowest level to 1.2% a year in those with the highest level. The vaccine may therefore somehow have removed a protective effect of ad5 immunity.
Both in a univariate model and in a multivariate model that progressively eliminated other possible confounding factors, high ad5 immunity conferred a threefold higher risk of infection in vaccine recipients than in placebo recipients, compared to no increased risk in people with low ad5 immunity when compared to the placebo group.
However, Buchbinder added, the real reason for the additional risk in vaccine recipients may have had little to do with ad5 immunity, or it may only have had an accessory role.
Uncircumcised men at greater risk: There was one more important risk factor for HIV acquisition in vaccine recipients when compared to the placeo group: circumcision, or rather, the lack of it.
Uncircumcised vaccine recipients were, in univariate and multivariate analyses, four times more likely to become infected with HIV if they received vaccine than if they received placebo. In contrast there was no difference at all in infection rates between circumcised vaccine versus placebo recipients.
In questions after the presentation, Buchbinder commented that the risk to uncircumcised men was greater than the risk to men with high ad5 immunity, and that the latter may be a passive marker for the former. This was because the men with high ad5 immunity, who were largely recruited in the second wave, also tended to come from countries and communities with lower rates of circumcision; they were younger and more likely to come from Latin America, for instance.
She also commented that preliminary data hinted that the enhancement of infection risk was specifically seen in uncircumcised gay men who largely or exclusively had insertive anal sex. This would imply that the vaccine was abrogating some immune mechanism that normally protected uncircumcised ‘tops’ from infection through the mucosa of the foreskin.
However, this would not explain in itself why placebo recipients were less likely to get HIV if they had high ad5 immunity, so the two effects may be synergistic.
There are still many questions left unanswered by the STEP trial. Buchbinder said that the trial participants would be followed to find out if the apparent extra vulnerability to HIV conferred by the vaccine was long-lasting, and Mark
Robertson outlined a whole range of other factors that would be analysed, including other immune activation markers and CD4 subsets, markers of genetic vulnerability to infection such as HLA genotypes, herpes (HSV-2) status, seminal immune-cell subsets and seminal HIV viral load in seroconverters, and so on.
Are we wasting our time with current vaccine research? The STEP vaccine trial may, like another ‘failed’ trial, the SMART trial, generate a considerable amount of knowledge about HIV infection and vulnerability.
But it failed in its primary aim. After the STEP presentations, Ron Desrosiers of the New England Primate Research Centre at Harvard University and Neal Nathanson of the University of Pennsylvania mounted an elegant two-handed demolition of the entire current philosophy of HIV vaccine research, both saying that vaccine research had to go back to basic science and change its philosophy of generating similar ‘pipeline products’ to be tested in wasteful and expensive human trials.
Desrosiers said that the enormous genetic diversity of HIV, its ability “to replicate unrelentingly despite everything the immune system can throw at it”, the fact that the immune system cannot protect against superinfection, and the fact that we do not currently know what constitutes an immune response to HIV, all persuaded him that at the current time an effective HIV vaccine “is not feasible”.
We should not be surprised the Merck vaccine failed, he said, because strictly-designed monkey studies had already shown it was not protective; it also contained only one single genetic sequence of each of its three HIV antigens, compared with the thousands of variants HIV could throw up. For similar reasons, he believed that none of the products in the current vaccine pipeline stood any reasonable chance of showing efficacy.
He said that repeated trial failures might have serious ramifications both in terms of ‘donor fatigue’ – which could reduce funding for basic science as well as efficacy trials – and ‘volunteer fatigue’ in affected communities.
He accused the US National Institutes of Health, the largest single funder of HIV prevention technologies, of “losing its way” in its vaccine research strategy. And he said that advocates who bemoaned the lack of pharmaceutical company interest in vaccines were misled.
“The discoveries that are going to lead to a successful vaccine have not been made yet,” he said. “The drug companies know this, which is why, with the exception of Merck, they have not got involved. Once an HIV vaccine does become possible, pharma will jump on development and research.”
He urged a return to basic discovery research, and instanced work being done with artificial viral vectors that actually generate broadly neutralising antibodies against HIV (beginning to be recognised as essential in a vaccine) themselves, instead of trying to stimulate the body to make them.
Neal Nathanson, though less robustly, broadly agreed. He said that he and other researchers had long ago defined HIV as a virus “that defies vaccination”. He too urged a return to basic science such as the devising of genetic assays to search for broadly neutralising antibodies, and said that the marginal effects seen so far in lowering HIV viral load in human volunteers did not justify further large human studies such as the imminent PAVE study.
He ended on a note of optimism, saying that HIV could be controlled even in the absence of a vaccine, and citing Botswana as a country that was not only becoming able to treat all its citizens who needed antiretrovirals, but was also beginning to achieve reductions in HIV incidence.
References Robertson M, Buchbinder S et al. Efficacy results from the STEP Study (Merck V520 protocol 023/HVTN 502): a phase II test-of-concept trial of the MRKad5 HIV-1 gag/pol/nef trivalent vaccine. Fifteenth Conference on Retroviruses and Opportunistic Infections, Boston, abstract 88LB, 2008.
Robertson M et al. Immunological characterization of subjects from the STEP Study: a phase IIB test-of-concept trial of the MRKad5 HIV-1 gag/pol/nef trivalent vaccine. Fifteenth Conference on Retroviruses and Opportunistic Infections, Boston, abstract 89LB, 2008.
Desrosiers R. Scientific obstacles to an effective HIV vaccine. Fifteenth Conference on Retroviruses and Opportunistic Infections, Boston. Plenary presentation 91, 2008.
Nathanson N. AIDS vaccine at the crossroads. Fifteenth Conference on Retroviruses and Opportunistic Infections, Boston, plenary presentation 92, 2008.
Untreated HIV-positive individuals have a higher risk of death even at CD4 counts over 350
Even with CD4 counts above 350 cells/mm3, untreated HIV-positive individuals have an increased risk of death compared with the general population, according to data presented on Wednesday at the Fifteenth Conference on Retroviruses and Opportunistic Infections in Boston.
Rebecca Lodwick of University College London, assisted by Professor Andrew Phillips, presented findings from the Study Group in Death Rates at High CD4 Counts in Antiretroviral Naive Patients — the largest dataset yet to examine whether HIV-infected individuals with high CD4 counts who have not started antiretroviral therapy have an increased risk of death compared with the popul