News and upcoming events
Gay Men's Sex Survey 2008
The Gay Men's Sex Survey, conducted by Sigma Research, is the largest annual survey of gay and bisexual men in the world. It is completely anonymous and takes about 15 minutes to complete. The information that we gain from this research informs and motivates our work, ensuring that our efforts have the maximum impact in preventing new HIV infections. Visit www.demographix.com to complete the survey.
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 Good Sexual Health Team small media resources
What do you do when you're Wasted? This is a new, mini version of Camden'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.
Other small media resources for gay men.
Upcoming Courses & Workshops for gay men:
Workshops and courses in August and September 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 Thursday 7th August for 7 weeks
- The following course begins 7pm Tuesday 26th 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: 18 August, 15 September. 6.15 till 9.15pm.
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: 17 August, 21 September. 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: 31 August, 28 September. 6 till 9pm
Friend or Foe - is a weekend workshop on self-esteem, exploring how you can relate to yourself in more compassionate, supportive and constructive ways and move away from being critical, nasty or destructive to yourself.
Begins 6.30pm Friday 29 August. Continues Saturday 30 and Sunday 31 August.
Positive Sex - is a weekend workshop for gay men living with the virus to talk with other men and find their own way forward.
Begins 6.30pm Friday 26 September. Continues Saturday 27 and Sunday 28 September.
To book a place or for more information call 020 7700 1323.
THT Courses
Mind Your Backs Guys! All you'll ever need to know about your arse and his
Ever been curious about prostates, the male G-spot, buttock exercising or douching? Whether you want to learn more about how to enjoy anal sex or have questions about the health of your posterior, this group is for you.
Thursday 21th August and every fourth Thursday of the month from 6pm to 9pm.
Book a place on 'Mind Your Backs Guys!'
How not to pick up
Have you ever found yourself with more than a phone number as a memory of that night of fun? Many of us will get a sexually transmitted infection at some time, even if we have safe sex or sex with only a few men. "How not to pick up" is a gay men's group which will guide you through what's out there, how to avoid it and what to do if you do "pick up".
Thursday 28th August and every fourth Thursday of the month from 6pm to 9pm.
Book a place on 'How not to pick up'
Sex Addicts Course
If you see yourself as a sex addict or a sexual compulsive and feel that
your sexual behaviours are having an overwhelming and negative impact
on your life, then we may be able to help. In July, Terrence Higgins Trust
will commence a weekly group programme for gay men who feel that their
relationship with sex is somehow out of control.
Ten week programme begins Thursday 25th September 2008 at 6.30pm.
For more information, venue details or to book an assessment, call 0207 812 1773.
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 - 020 7837 7324
LLGS normal opening helpline hours are 10am to 11pm daily.
THT Gay Men's Sexual Health Helpline - 020 7998 4161
This is a new helpline to give, information, advice and support about sexual health to gay men in London, whether they have HIV or not.
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 summer 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 three (out now) is about sex for gay men with HIV – dealing with HIV treatment, who's who at your clinic, other ways to look after your body and mind. 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 Arse Facts Campaign:
It's tricky getting to know your arse; it's not something you look at everyday.
But whether you're a top, bottom or flip both ways, there are a few essential
facts that you should know to help keep you and your partners safe and healthy.
After reading the facts, why not
enter The Arse Factor for a chance to
win £100 of underwear or swimwear.
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 The GMI Partnership
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 Behavioural Therapy
- Peer mentoring
- Sexual health counselling
For further information or to make an assessment appointment please call 020 8305 5002 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 020 7812 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 020 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
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)
One of the first steps for those who join Living Well is the Positive Self-Management Programme; better known as the PSMP. The PSMP is run by trained facilitators, some of whom are living with HIV themselves, and consists of seven weekly sessions of two and a half hours each and an optional residential weekend. Some of the areas covered include:
- Goal setting
- Action planning
- Problem solving
- Coping Skills
- Support and information
- Planning for the future
The PSMP is delivered in a supportive group environment. Through discussion and sharing of information participants are encouraged to attain new skills and direction to help them make better informed decision about managing their condition.
The PSMP allows participants to meet other people facing similar concerns and challenges, helping them to overcome isolation and build a supportive social network.
Non-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 and news from around the world:
PEPFAR reauthorisation approved by President Bush; HIV travel ban will end
President Bush today signed into law a President’s Emergency Plan for AIDS Relief re-authorised by Congress for five years with more than twice the funds used between 2003 and 2008, with a mandate to provide care and support to 12 million people by 2013.
The reauthorisation is vastly more than the White House requested, and is the result of a concerted campaign by advocates to extend the scope as well as the volume of US funding for AIDS relief. A total of $48 billion will be available over the next five years, of which $12.6 billion will go towards malaria and TB programmes. $2 billion could go to the Global Fund to Fight AIDS, TB and Malaria in 2009, a substantial increase in US support.
The bill, passed by both Democrat-controlled houses of Congress, removes the controversial requirement that one-third of prevention expenditure go to programmes that promote abstinence and faithfulness. Instead PEPFAR chiefs in countries with generalised epidemics will need to explain to Congress if they do not spend at least 50% of their prevention allocations on a broader range of interventions that promote abstinence, faithfulness, partner reduction and delayed sexual debut, which may still have the effect of biasing prevention activities towards extrenal targets rather than local realities.
The provision has been criticised by some advocates because it still falls short of comprehensive prevention programmes. Although the bill requires that prevention activities should address gender-based violence and legal protection for women and girls, it does not mention the importance of integrating family planning into HIV prevention activities.
On treatment no specific target is given for the numbers who should receive antiretroviral treatment, except to specify a minimum level of 2 million.Targets could fluctuate according to the level of appropriations in each year of the re-authorisation, making it difficult to plan ahead and creating a potential disincentive to recruit new patients onto treatment. The bill also sets down a target of 80% coverage of interventions to prevent mother-to-child transmission in the 15 PEPFAR focus countries.
The bill also contains an amendment inserted by the Senate that ends the ban on entry of HIV-positive people to the United States as visitors, refugees or asylum seekers. HIV-positive people will no longer be required to seek a special visa waiver through a US embassy abroad if they wish to visit the US, a decision that has been widely welcomed by advocates worldwide.
Australasians reject Swiss statement - model predicts fourfold increase in HIV transmission over 10 years
HIV transmission among serodiscordant monogamous couples in which the HIV-positive partner has an undetectable viral load due to effective treatment might rise fourfold over a decade if condom use is abandoned, suggests a mathematical model published this week.
The study, published in the July 26 th edition of The Lancet coincides with the publication of a joint Australasian statement developed in response to the Swiss statement, which concludes that consistent condom use and early and effective treatment for sexually transmitted infections “is the only way to prevent HIV spread.”
The impact of antiretroviral therapy on sexual transmission has been the subject of intense debate this year, following publication of guidance from the Swiss Federal AIDS Commission (EKAF) stating that an individual with a blood plasma undetectable viral load is not infectious under certain conditions.
Although much of the debate has been due to concerns about increased sexual risk-taking on a population level cancelling out any gains in antiretroviral therapy’s effect on infectiousness some of the concerns have been about the scientific accuracy of the Swiss statement.
In particular there are no data on the residual transmission risk that may exist when an individual has an undetectable viral load on therapy, even when they are in a monogamous relationship – which may reduce the risk of acquiring new sexually transmitted infections ( STIs), but does not address the potential impact of untreated chronic viral STIs such as herpes. Other factors that may affect the risk of unprotected sex while taking effective treatment include potential variations in concentrations between individual antiretroviral drugs in the genital tract and anal mucosa; the effect of adherence on antiretroviral drug levels; and the impact of intermittent viraemia (‘blips’).
In order to estimate the per act and cumulative risks of HIV transmission from individuals with a blood plasma viral load below 10 copies per mL, investigators from the National Centre in HIV Epidemiology and Clinical Research at the University of New South Wales in Sydney used a simple mathematical model.
The model used previous published data estimating the relationship between viral load and transmission risk (based on data from heterosexual couples in Uganda practising vaginal sex) as well as previously published estimates of HIV transmission risk per sexual act for men to women; women to men; and men to men. It also assumed that each monogamous couple had 100 instances of sexual intercourse each year; that no heterosexual couple had anal intercourse; and that men in same-sex relationships had equal amounts of insertive and receptive anal sex.
Importantly, however, the model assumes that HIV transmission is possible at all viral load levels, rather than assuming that there is threshold below which transmission cannot occur.
An accompanying editorial commentary from Professor Geoffrey Garnett of Imperial College London and Professor Brian Gazzard, of Chelsea and Westminster Hospital, London notes, “the authors extrapolate the model beyond the available data, assuming that there is continuous reduction in risk rather than a threshold below which no transmission is possible. The Swiss statement is based on the different assumption that there is such a threshold, as was observed in a study in Rakai, Uganda, where no transmission event occurred when viral copy numbers were below 1500 copies per mL. Unfortunately, small sample sizes mean that neither assumption is secure.”
Nevertheless, the model found that the cumulative probability of transmission to the serodiscordant partner for each year is 0.0022 (range 0.0008–0·0058) for female-to-male transmission; 0.0043 (range 0·0016–0·0115) for male-to-female transmission; and 0.043 (range 0·0159–0·1097) for male-to-male transmission.
The investigators point out the public health implications if their calculations were to hold true: over ten years and 10,000 serodiscordant couples they would expect to see 215 (range, 80–564) female-to-male transmissions; 425 (range, 159–1096) male-to-female transmissions; and 3524 (range, 1477–6871) male-to-male transmissions, “corresponding to an increase in incidence of four times compared with incidence under current rates of condom use.”
In their discussion, however, they point out that “under our assumptions, the effectiveness of treatment in reducing the risk of HIV transmission per sexual act was about the same as has been reported for condoms. Although we agree that effective antiretroviral treatment which leads to undetectable viral load is likely to have a substantial effect on reducing infectiousness, our analyses suggest that it should not replace condoms.”
On the basis of the data presented here, the Australian researchers conclude, “we believe that the Swiss statement is not a sensible public-health message because its logical outcome would be the abandonment of condoms by people with effectively treated HIV infection… As a population strategy, treatment as prevention has the potential to reduce HIV epidemics only if consistent condom use is maintained. Indeed, our analysis suggests that there is large potential for more harm than good.”
That was also the conclusion of the Australasian consensus statement to which the study’s authors contributed. The statement, from the Australasian Society for HIV Medicine, the Australian Federation of AIDS Organisations, the National Association of People Living with HIV/AIDS, and the National Centre in HIV Epidemiology and Clinical Research notes the following:
“Consistent use of effective antiretroviral therapy (ART) will, in most cases, lead to an undetectable viral load (VL), as measured in blood, semen and vaginal fluids. As a result, the average viral load of the community of people living with the human immunodeficiency virus (HIV) will be reduced. By reducing the VL, ART will also complement the benefits of consistent condom use and effective sexually transmitted infections (STI) detection and treatment, in preventing HIV transmission that may otherwise occur due to condom failure. However, there are no data to suggest that a population HIV prevention strategy based solely or predominately on the use of ART and associated with a reduction in condom use, will lead to fewer people becoming infected in the Australian and New Zealand populations, especially in the context of rising rates of STI.”
The statement then summarises available knowledge on the effect of treatment on transmission and weighs the pros and cons of making a public statement that encourages individuals with an undetectable viral load to abandon safer sex. It also acknowledges the legal implications for jurisdictions that have HIV exposure laws, such as New South Wales.
It concludes by saying that, “for the present and in light of our current knowledge, safe sex is the only way to prevent HIV spread. Safer sex includes correct and consistent male and female condom use, and early and effective detection and treatment for STIs.”
The editorial commentary from Professors Garnett and Gazzard is more pragmatic: “Denying an effect of treatment on risk of transmission would be dishonest and futile, because well-informed patients will assume an effect,” they write.
It is also more welcoming of the Swiss statement that marked the end of “muted discussion” on the effects of treatment on prevention. “In many ways,” it concludes, “the Swiss statement provides the opportunity for positive public-health messages, by promoting adherence to treatment and concern over other sexually transmitted infections. The use of condoms, in addition to antiretrovirals, to further reduce risk and prevent other sexually transmitted infections can then also be promoted.”
References
Wilson DP et al. Relation between HIV viral load and infectiousness: a model-based analysis. Lancet 372: 314-20, 2008.
Garnett GP and Gazzard B. Risk of HIV transmission in discordant couples. Lancet 372: 270-71, 2008.
Australasian Society for HIV Medicine, National Centre in HIV Epidemiology and Clinical Research, Australian Federation of AIDS Organisations and National Association of People Living with HIV/AIDS. Australasian statement on HIV antiretroviral therapy and infectiousness. Published online July 18, 2008.
UNITED KINGDOM : Doctors 'Miss Early HIV Symptoms'
BBC (07.22.08) - Monday, July 28, 2008
Almost half of all early-stage HIV infections in the United Kingdom are being missed, the National AIDS Trust (NAT) said recently. Approximately 7,000 new HIV cases occur annually in Britain, and as many as 50 percent are believed to be transmitted by people who are in the early stages of their own infection.
The first few weeks of infection are often marked by severe flu-like symptoms such as sore throat, fever, and rashes. After about six weeks, these symptoms typically recede and the infected person will feel normal again, even though he or she has HIV. People seeking medical treatment for these symptoms are often told they have a trivial viral infection and to return if they see no improvement, said NAT.
A study in Brighton found that 48 percent of HIV patients who had sought medical attention for their early symptoms were not diagnosed with HIV during that appointment.
"It is very worrying that [general practitioners] and other health care professionals are often missing the signs and symptoms of HIV infection," said NAT CEO Deborah Jack. "This can mean they become seriously ill in the longer term and respond less well to treatment. It also means they are likely to be putting partners at risk of infection as they may live undiagnosed for a number of years."
"HIV testing needs to be more widespread and routine," said Dr. Martin Fisher, a consultant in HIV medicine. The symptoms that accompany early infection represent a "golden opportunity" to spot new cases, he said.
NEW YORK : City HIV Budget Cuts, Gay Men React
Duncan Osborne Gay City News ( New York City) (07.17.08) - Monday, July 28, 2008
Many gay men in New York City reacted ambivalently to news that the city is cutting HIV/AIDS spending, even as new infections, especially among younger men of color, continue to increase.
The administration of Mayor Michael Bloomberg said it cut only about $1.3 million from the health department's HIV/AIDS services budget of about $116 million for the fiscal year that began July 1. However, the City Council said the cut was actually $10.1 million. It restored $5.8 million and says the result is a cut of about $4.3 million. The mayor required across-the-board city agency cuts to help close budget gaps and pay down debt.
"When it comes to the gay community, they say 'Forget about it, what can we do?'" said Esau Reyes, referring to City Hall as he sat outside the Lesbian, Gay, Bisexual and Transgender Community Center. "They don't care about us." "I don't think it's the government's fault," Hiram Lopez rebutted. "I believe it's each individual. It's kind of an every-man-for-himself kind of thing."
In the park, Keith Laskey empathized with a city having to manage limited resources. "I want to be educated about AIDS, but I also don't want to break my neck on the subway steps," he said. "I think [Bloomberg] knows what he's doing," said Laskey's friend, Gary Hall.
"I guess I've read that the numbers are on the rise" among young gay minorities, said Lee Fiver. Asked the prospects of successfully lobbying for more money to tackle HIV, Fiver's friend said, "My knee-jerk reaction would be no. I think it's lost its sense of urgency."
"Everyone's getting very careless," said another man. "Honestly, everyone I speak with, they're not afraid of HIV anymore. I'm not hopeful about what's going on." "People just don't care anymore," agreed Joseph Spagner. "Out of sight, out of mind."
Meditation slows AIDS progression, study finds
Reuters NewMedia - July 24, 2008 Maggie Fox, Health and Science Editor
WASHINGTON, July 24 (Reuters) - Meditation may slow the worsening of AIDS in just a few weeks, perhaps by affecting the immune system, U.S. researchers reported on Thursday.
If the findings are borne out in larger studies, it could offer a cheap and pleasant way to help people battle the incurable and often fatal condition, the team at the University of California Los Angeles said.
They tested a stress-lowering program called mindfulness meditation, defined as practicing an open and receptive awareness of the present moment, avoiding thinking of the past or worrying about the future.
The more often the volunteers meditated, the higher their CD4 T-cell counts -- a standard measure of how well the immune system is fighting the AIDS virus. The CD4 counts were measured before and after the two-month program.
"This study provides the first indication that mindfulness meditation stress-management training can have a direct impact on slowing HIV disease progression," David Creswell, who led the study, said in a statement.
His team tested 67 HIV-positive adults from the Los Angeles area, 48 of whom did some or all of the meditation. Most were likely to have highly stressful lives, Creswell said.
"The average participant in the study was male, African American, homosexual, unemployed and not on ARV (antiretroviral) medication," they wrote in the journal Brain, Behavior, and Immunity.
The meditation classes included eight weekly two-hour sessions, a day-long retreat and daily home practice. "The people that were in this class really responded and just really enjoyed the program," Creswell said.
"The mindfulness program is a group-based and low-cost treatment, and if this initial finding is replicated in larger samples, it's possible that such training can be used as a powerful complementary treatment for HIV disease, alongside medications," he added.
Quality of life
About 30 percent of the volunteers were taking HIV drug cocktails, which can help suppress the virus.
"Even when we controlled for ARV use, we still saw these effects. Whether you are on or off the drugs you are going to see these benefits," Creswell said in a telephone interview.
Creswell said it was unclear how the stress-reducing effects of meditation work. It may directly boost CD4 T-cell levels, or suppress the virus, he said. "We know that stress has direct effects on viral load," he said.
Creswell said he believes the program can help people infected with a variety of viruses and from all walks of life. HIV patients are especially highly stressed, he noted. "These marginalized folks typically are experiencing the highest stress levels," he said.
But middle-class workers also experience stress. "Most people do report a lot of daily stress," Creswell said.
And for AIDS patients, HIV drug cocktails are known to have a variety of side effects, from weight gain to nausea.
"One of the main side-effects of this particular treatment was an increase in their quality of life," Creswell said.
Trial for Vaccine Against H.I.V. Is Canceled
The New York Times - July 18, 2008 Lawrence K. Altman
Plans for a large human trial of a promising government-developed H.I.V. vaccine in the United States were canceled Thursday because a top federal official said scientists realized that they did not know enough about how H.I.V. vaccines and the immune system interact.
The decision is a major setback in an effort to develop an H.I.V. vaccine that began 24 years ago when government health officials promised a marketed vaccine by 1987. Health officials have long contended that such a vaccine would be their best weapon to control the AIDS pandemic.
A number of other H.I.V. vaccines are in various stages of testing around the world. But there had been high hopes for the government's trial because the potential vaccine was among a new class that sought to stimulate the immune system in a different way.
The official who canceled the government trial, Dr. Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases, said it was becoming clearer that more fundamental research and animal testing would be needed before an H.I.V. vaccine was ever marketed.
Scientists say that developing a vaccine against H.I.V. is one of the most difficult scientific endeavors in history because of the uncanny nature of the virus.
The government vaccine - known as PAVE, for Partnership for AIDS Vaccine Evaluation - was similar to a much-heralded vaccine that failed last year. That vaccine was developed by Merck, and Dr. Fauci's agency helped pay for the Merck trials.
Dr. Fauci said he reached his decision to cancel the coming trial after meeting with scientists to try to understand why the Merck vaccine had failed. He said he had concluded that scientists must go a step at a time because they did not yet know fundamental facts like which immune reactions are the most important in preventing the infection.
Dr. Fauci said the new trial was intended to determine whether the vaccine could significantly lower the amount of H.I.V. in the blood of those who become infected. He said a smaller trial was needed to figure out whether the vaccine could do that before large trials were conducted.
"Show me that the vaccine works by lowering the amount of H.I.V. in the blood," Dr. Fauci said. "Then we will move to a larger trial that will document the link with a particular immune response." He added that until then, "doing a large trial is not justified."
Dr. Alan Bernstein, executive director of the Global HIV Vaccine Enterprise, said that his organization supported Dr. Fauci's decision and that there was an "urgent need for a diversity of new approaches to H.I.V. vaccine design."
For instance, Dr. Bernstein said, recent laboratory advances, which allow scientists to look at hundreds of genes simultaneously, "offer immense promise in helping us understand how to design new H.I.V. vaccine candidates that can achieve long-lasting immune protection."
The trial canceled Thursday was supposed to have started enrolling 8,500 volunteers last October to receive the PAVE vaccine, developed by the infectious diseases agency. PAVE is a consortium of federal agencies and key federally financed organizations involved in developing and evaluating experimental H.I.V. vaccines. It seeks to create an effective H.I.V. vaccine that no pharmaceutical company or institution is likely to accomplish on its own.
The PAVE trial had been postponed after a test of the Merck vaccine failed in its two main objectives: to prevent infection and to lower the amount of H.I.V. in the blood among those who became infected. Also, the findings among the 3,000 participants in nine countries in which the Merck vaccine was tested suggested it might have increased the risk of becoming infected.
After a safety monitoring committee detected the problems with the Merck vaccine in September, the company quickly halted its study. Scientists have found no obvious explanation for the failure of the Merck vaccine, which had been considered the most promising candidate. The Merck vaccine was the first of a new class of H.I.V. vaccines to get to an advanced stage in human testing. The vaccine was made from a weakened version of a common cold virus, adenovirus type 5, which served as a way to deliver three synthetically produced genes - gag, pol and nef - from the AIDS virus. Three doses of the vaccine were injected over six months.
Scientific analyses found that the highest risk of H.I.V. infection among recipients of the Merck vaccine was in males who both were uncircumcised and had pre-existing antibodies to adenovirus type 5. After the failure of Merck trial, the government reduced the number of potential volunteers to 2,400; they would have included circumcised gay men who had no pre-existing antibodies to adenovirus type 5. The scaled-back study would have cost about $63 million, compared with $140 million for the initial design.
At a news conference in 1984, top federal officials said they were optimistic that a marketable H.I.V. vaccine would be available in three years. Since then, AIDS researchers have been divided about how fast to test experimental vaccines. Many urge caution out of fear that failures could destroy confidence among uninfected people most at risk who would be needed as volunteers in future trials. But equally vocal groups call for testing everything as soon as the research shows promise because of the urgent need for a vaccine.
In an unrelated development, researchers at Duke University reported new findings Thursday showing that H.I.V. stuns the immune system earlier than scientists previously understood. The window of opportunity in stopping H.I.V. may be a matter concerning the first few days, not weeks, after the virus enters the body, a team headed by Dr. Barton Haynes reported in The Journal of Virology.
The findings were based on a study of 30 individuals newly infected with H.I.V., and the National Institutes of Health paid for the study.
Need for vigilance: two cases of abacavir allergy despite pre-treatment screening all-clear
Healthcare workers and patients need to be vigilant about the possibility of an allergic reaction after starting abacavir (Ziagen), even if the HLA-B*5701 screening test is negative, emphasise investigators in separate reports in the July 31 st edition of AIDS.
It is now well known that abacavir can cause a severe allergic reaction in about 8% of patients. Symptoms include rash, fever, stomach or chest problems. Most cases occur within six weeks of starting treatment with the drug.
Research has found an association between hypersensitivity to abacavir and the presence of the HLA-B*5701 gene. This gene is most common among, but not limited to, individuals with a northern European racial origin.
It is possible to test patients for the presence of this gene, and only patients with a confirmed negative result should start treatment with abacavir.
But doctors in London provided care to a patient who developed an usual hypersensitive reaction to abacavir, despite being HLA-B*5701-negative.
The case involved a 45-year-old Kenyan man. He was diagnosed with tuberculosis and subsequently HIV. At the time of his HIV diagnosis his CD4 cell count was 70 cells/mm 3 and his viral load 500,000 copies/ml. A test at this point also showed that the patient was HLA-B*5701- negative.
Standard four drug tuberculosis treatment was provided to the patient, and within five days the patient’s temperature had returned to normal. Five weeks later anti-HIV drugs were started.
Considerable care was taken to ensure that the patient’s anti-tuberculosis drug and HIV treatment regimen did not interact. He therefore initiated antiretroviral therapy with a highly unusual combination of AZT, Truvada (tenofovir and FTC), and abacavir.
Within five hours of receiving his first dose of anti-HIV drugs, the patient developed a fever of 39 degrees C, and felt generally unwell, nauseous, and had abdominal pain. There was no rash. With the exception of the fever, these symptoms disappeared. However for the next 13 days the patient had a temperature above 39 degrees C.
A range of tests were conducted to see if the patient’s high temperature was due to a cancer or infection. These investigations found nothing significant.
Sixteen days after antiretroviral therapy was started, the patient’s doctors decided to eliminate a drug allergy as a possible cause of the fever. Treatment with abacavir was therefore stopped and a new antiretroviral regimen consisting of Combivir (3TC and AZT), tenofovir, and Kaletra (lopinavir/ritonavir) was started.
Within hours the patient’s temperature returned to normal. Treatment with anti-tuberculosis drugs was continued and three weeks later the patient was still without a fever and had a CD4 cell count of 160 cells/mm 3 and a viral load of 500 copies/ml. A second HLA-B*5701 test was negative
The investigators suggest that this case raises three important issues:
- This is the first case to involve such a rapid onset of the symptoms of abacavir hypersensitivity and (with the exception of the fever) such a quick recovery. They note that abacavir is quickly absorbed and that this could explain the rapid appearance of the fever.
- This is the most severe report of abacavir hypersensitivity in an HLA-B*5701-negative individual.
- This case could represent an unusual hypersensitivity reaction to the drug.
But the investigators acknowledge that they did not perform a skin-patch test to confirm their diagnosis of an abacavir hypersensitivity reaction.
“Overall, this case demonstrates that not all abacavir drug reactions occur as a result of classic hypersensitivity reactions and can occur irrespective of HLA-B*5701 status”, write the investigators. They conclude, “as such, clinical vigilance must continue to be an essential part of the management of individuals commencing abacavir.”
A separate case report in the same edition of AIDS concerns a severe abacavir hypersensitivity reaction, also in an HLA-B*5701-negative patient.
Doctors in Amsterdam report that their patient had both negative HLA and skin patch tests, but nevertheless developed symptoms including a breakdown of muscle fibres ( rhabdomyolysis), muscle aches, watery diarrhoea and a high temperature. These symptoms had developed ten days after the patient replaced AZT with abacavir in his antiretroviral regimen.
Anti-HIV therapy was stopped because of the symptoms and the patient slowly recovered. HLA-B*5701 tests were negative before the patient started abacavir therapy and after treatment with the drug was stopped. The results of an abacavir skin patch test were also negative.
“Even if a patient is tested HLA-B*5701 or skin patch negative or both, severe abacavir hypersensitivity reaction can still occur, and prudent clinical management remains necessary”, write the investigators. They conclude that although the HLA-B*5701 gene has been strongly associated with hypersensitivity to abacavir, “a second mechanism might be involved, and future…testing for abacavir hypersensitivity is open for improvement.”
Reference
Fox J. et al. An unusual abacavir reaction. AIDS 22: 1520 – 22, 2008.
Bonta P. et al. Severe abacavir hypersensitivity reaction in a patient tested HLA-B*5701 negative. AIDS 22: 1522 – 23, 2008.
Nukes and diabetes—is there a link?
Sean Hosein CATIE News: July 14, 2008
In Canada and other high-income countries, the widespread availability of highly active antiretroviral therapy (HAART) has resulted in a dramatic decline in AIDS-related deaths. However, HIV therapy is associated with side effects, many of which were not expected when HAART first became available.
For instance, a group of drugs called thymidine analogues, such as d4T ( Zerit, stavudine) and AZT ( Retrovir, zidovudine), has been linked to the disappearance of the fatty layer just under the skin (subcutaneous fat).
Another group of drugs called protease inhibitors is generally associated with increased levels of lipids (fatty substances)—cholesterol and triglycerides— in the blood. If left untreated, this increase in lipids leads to a heightened risk for cardiovascular disease.
Now researchers involved with a very large database called DAD suggest that the use of d4T or AZT is associated with an increased risk of diabetes. However, there are some issues with DAD that make drawing firm conclusions problematic. These issues are explored further in this report.
Study details
The study team analysed health-related information collected from clinics mostly in Europe but also from the United States, Australia and Argentina. At the time participants entered the study their average profile was as follows:
- 26% female, 74% male
- age – 38 years
- 34% were smoking tobacco
- CD4+ count – 410 cells
24% had previously experienced a life-threatening infection
The study team focused on the time between April 2001 and January 2005.
Results—focus on fat
At the start of the study, 952 out of a total of 32,437 participants had diabetes. Over the course of the study, 742 more participants (3%) developed diabetes.
Taking into account many possible factors, the study team found that the following had an impact on the development of diabetes:
- total cholesterol: an increase of 1 mmol/L raised the risk of diabetes by 9%
- triglycerides : a doubling of triglyceride levels increased the risk of diabetes by 81%
- an increase in body fat content was associated with a 57% increase in the risk of diabetes
- a decrease in body fat content was associated with a 28% increase in the risk of diabetes
These changes in body fat are likely related to the HIV lipodystrophy syndrome. In people with lipodystrophy, some parts of the body, such as the belly and breasts (in women) gain fat while other parts, such as the limbs and face, lose fat. In HIV negative people, changes in body fat content can increase the risk of diabetes, so it is not surprising that a link between changes in body fat in the DAD study were also associated with an increased risk of diabetes.
Results—treatment
For each year of d4T use, the risk of diabetes increased by 20%. The drugs AZT and ddI ( Videx EC, didanosine) were also associated with a heightened risk of developing diabetes (but lesser so than the risk with d4T).
Results—other factors
In addition to the factors mentioned above, the study team also found that several other risk factors were linked to developing diabetes in the DAD study, as follows:
- older age
- being male
- being overweight or obese
- being heterosexual
- being a person of colour
Nukes and diabetes
Insulin is a hormone produced by the pancreas gland. Insulin helps move sugar (glucose) from the blood into cells where it can be burned as a source of energy. It is possible that d4T and other nukes might trigger insulin resistance, a condition whereby cells grow increasingly insensitive to the effects of insulin. The body tries to compensate for this by producing ever-increasing amounts of
insulin but eventually the pancreas becomes exhausted and diabetes develops. Researchers are not sure exactly how d4T might cause insulin resistance, but they suspect that it damages the energy-producing parts of cells (mitochondria), causing them to malfunction.
A large randomized trial has confirmed that d4T and ddI are associated with the development of insulin resistance in HIV positive people. Results from a small study suggest that AZT may also cause similar problems. The good news is that two commonly used nukes— abacavir ( Ziagen and in Kivexa and Trizivir) and tenofovir ( Viread and in Truvada and Atripla) —are not linked to insulin resistance.
Protease inhibitors and diabetes
Experiments with cells, animals and people suggest that exposure to the protease inhibitor ritonavir ( Norvir and in Kaletra) increases the risk of insulin resistance. Yet the DAD researchers found that exposure to ritonavir in their study was linked to a reduced risk for diabetes. How their study found such a link is puzzling. Concerned by this finding, the DAD team noted that this result about ritonavir “should be viewed cautiously.”
Non-nukes and diabetes
The DAD analysis suggests that use of the non-nuke nevirapine ( Viramune) is associated with a reduced risk of developing diabetes.
Points to consider
In addition to the findings mentioned above, there are some important issues brought about by the way DAD conducted its data-capture and analysis that readers may wish to note. Here are some of these points:
Design flaw
Perhaps the most important point is this: DAD was an observational study. Such studies can find associations. However, because they are not randomized, observational studies cannot entirely rule out the possibility of bias when interpreting their findings. Therefore, the DAD study cannot be certain about its findings.
Missing in action
While the DAD researchers tried to collect as much data as possible, their analysis may have been affected by the lack of important information. For instance, there appears to be little or no information, certainly in the published paper, about participants with close family members who had a history of diabetes. At least one other study of HIV positive people found that participants who had family members with diabetes were themselves at high risk for developing this complication.
Still useful
Perhaps the good news from the DAD study is that the proportion of participants who developed diabetes after starting treatment was small—only 2%. Another useful outcome of the DAD study is that it may remind both physicians and HIV positive people that diabetes is a potential complication. Therefore, regular monitoring of fasting blood samples for glucose levels is important.
Developing good dietary habits is equally important (eating more fibre, whole grains and colourful fruit and vegetables, and much less food containing refined flour and sugar). This can be done with advice from a nutritionist or dietician. Regular exercise is also helpful for reducing weight and staying healthy.
Sean R. Hosein
REFERENCES:
- 1. Fleischman A, Johnsen S, Systrom DM, et al. Effects of a nucleoside reverse transcriptase inhibitor, stavudine, on glucose disposal and mitochondrial function in muscle of healthy adults. Am J Physiol Endocrinol Metab. 2007 Jun;292(6):E1666-73.
- 2. Blümer RM, van Vonderen MG, Sutinen J, et al. Zidovudine/lamivudine contributes to insulin resistance within 3 months of starting combination antiretroviral therapy. AIDS. 2008 Jan 11 ;22(2):227-36.
- 3. Carper MJ, Cade WT, Cam M, et al. HIV-protease inhibitors induce expression of suppressor of cytokine signaling-1 in insulin-sensitive tissues and promote insulin resistance and type 2 diabetes mellitus. American journal of physiology. Endocrinology and metabolism. Am J Physiol Endocrinol Metab. 2008 Mar ;294(3):E558-67.
- 4. Hruz PW, Yan Q, Struthers H, et al. HIV protease inhibitors that block GLUT4 precipitate acute, decompensated heart failure in a mouse model of dilated cardiomyopathy. FASEB J. 2008 Jul;22(7):2161-7.
- 5. Caumo A, Guffanti M, Perseghin G, et al. Effects of atazanavir/ritonavir and lopinavir/ritonavir on glucose uptake and insulin sensitivity. AIDS. 2007 Nov 12 ;21(17):2366-7.
- 6. Blass SC, Ellinger S, Vogel M, et al. Overweight HIV Patients with Abdominal Fat Distribution Treated with Protease Inhibitors are at High Risk for Abnormalities in Glucose Metabolism - A Reason for Glycemic Control. Eur J Med Res. 2008 May 26 ;13(5):209-14.
- 7. De Wit S, Sabin CA, Weber R, et al. Incidence and risk factors for new-onset diabetes in HIV-infected patients: the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study. Diabetes Care. 2008 Jun ;31(6):1224-9.
- 8. Dagogo-Jack S. HIV therapy and diabetes risk. Diabetes Care. 2008 Jun ;31(6):1267-8.
Exhausted B Cells Hamper Immune Response to HIV
NIAID Online Update - July 14, 2008
CONTACT: NIAID Office of Communications, 301-402-1663, niaidnews@niaid.nih.gov
WHAT: Recent studies have shown that HIV causes a vigorous and prolonged immune response that eventually leads to the exhaustion of key immune system cells--CD4+ and CD8+ T-cells--that target HIV. These tired cells become less and less able to
fight the virus, and the cells' fatigue contributes to the inability of an HIV-infected person's immune system to clear the virus from the body.
Now, researchers at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, have shown that a similar type of exhaustion strikes another important brigade of immune system soldiers: the B cells that make virus-fighting proteins called antibodies.
In most HIV-infected individuals not receiving antiretroviral therapy, the virus replicates continuously, causing systemic disturbances that include changes in certain subsets of B cells that circulate in the blood. One of these subsets, known as "tissue-like memory B cells," is abundant in HIV-infected individuals who do not control their viral burden. These particular cells show signs of premature exhaustion and a reduced ability to make the high-quality antibodies needed to fight HIV.
As with studies of exhausted CD4+ and CD8+ T cells, these new findings related to exhausted B cells help illuminate the complex immune system damage caused by HIV, and the challenges to rebuilding or bolstering an HIV-infected person's immune system.
NIAID's HIV vaccine research program aims to increase the understanding of B cells to help inform the development of an effective vaccine, and this study contributes to this effort. The authors note that the design of a therapeutic vaccine designed to slow HIV disease progression will need to overcome or circumvent the challenge posed by the inability of certain exhausted B cells to make high-quality antibodies.
ARTICLE: S Moir et al. Evidence for HIV-associated B cell exhaustion in a dysfunctional memory B cell compartment in HIV-infected viremic individuals. Journal of Experimental Medicine DOI 10.1084/jem.20072683.
The Coming Crisis in HIV Drug Development
By Paul Dalton, June 16, 2008
The last few years have seen tremendous progress in treating people with advanced and drug-resistant HIV. Four powerful drugs became available that either overcame drug resistance (Prezista [darunavir, TMC-114], Intelence [etravirine, TMC-125]) or were from entirely new classes [Selzentry (maraviroc), Isentress (raltegravir)].
This marked an important and unique moment in HIV drug development. Never before have so many new and effective drugs come out so close together. People with extensive experience taking HIV drugs have been able to put together powerful regimens with two or more fully active agents -- often for the first time.
Project Inform took pains to highlight both the tremendous promise of these new drugs as well as the importance of using them correctly -- emphasizing that this moment, or anything resembling it, is unlikely to recur. Our message was clear: 'Seize this opportunity, use the new drugs carefully, and don't waste this once-in-a-lifetime chance'.
As good as some of these newer drugs have looked in studies, there are emerging signs of trouble in the real world. Dr. Steven Deeks, a prominent HIV physician and researcher says, "Although the current generation of drugs are generally doing great, many patients are not responding in a durable manner. We are now following about 25 individuals who have failed all six drug classes. The key now is to design regimens to maintain immunologic and clinical stability while we wait for more drugs. I am concerned, however, as it will likely be a few years before we have another shot at getting the virus under control. We desperately need a second generation integrase inhibitor that works against viruses resistant to raltegravir."
Dr. Deeks' experience is far from typical. He follows many of the most treatment experienced people in the San Francisco Bay Area, many of whom have been on therapy since 1987. Although not typical, his experiences have been reported elsewhere, if in smaller numbers.
This suggests a burgeoning problem of people beginning to run out of treatment options, as has happened a couple of times during the epidemic. Project Inform is concerned that the most vulnerable people living with HIV will be left with few or no viable treatment options, possibly for many years.
One of the unintended effects of the recent successes in drug development is that fewer people are available for studies of experimental drugs aimed at treatment experienced folks. We saw this coming and have been counseling drug companies and the Food and Drug Administration (FDA) that the era of 'TORO-like' studies was coming to a close. These studies give volunteers optimized background therapy (the best combination of HIV drugs chosen with resistance test results) with either the experimental drug or a placebo. The design allows regulators, scientists and activists to clearly see the benefit of the new drug. (Some call these studies 'TORO-like' after those that led to the approval of Fuzeon [ enfuvirtide, T20]).
This contrasts with how studies of first line treatment are done. When studying HIV drugs as first line, the basic model is head-to-head non-inferiority studies, which are designed to tease out the relative contribution of the entire regimens rather than the individual drugs. (Non-inferiority means that one drug or regimen is equivalent or 'close enough' to another.)
The FDA has allowed non-inferiority studies for drugs being studied as first line, but has insisted on placebo controlled superiority studies for treatment experienced studies. This made a good deal of sense when there were many people signing up for these studies. The situation is now quite different.
While there aren't enough people signing up for these kinds of studies, there's still a sizeable need for studying new HIV drugs. This, combined with the thin drug pipeline and the current difficulty recruiting for studies, may add up to real trouble down the line.
In meetings with many drug companies Project Inform has warned of this impending problem and recommended that they adopt new ways of studying their drugs. The reaction has been mixed. While some companies have been quite open to new ideas, it's fair to say that most would prefer to stick with models that have proven successful.
We have struggled to argue -- to the companies and the FDA -- that ways of studying and developing drugs are both necessary and possible. Gilead Sciences is one of the first to grapple with this. When it came time to do large, pivotal studies of their experimental integrase inhibitor, elvitegravir, there simply were not enough people in the US to enroll a typical study for treatment experienced people. Project Inform had warned Gilead, and others, of this eventuality and argued for studies that would more closely resemble the head-to-head, non-inferiority studies used for studying first-line drugs.
Over time Gilead came to agree that this was the way forward and submitted such a plan to the FDA. The FDA eventually allowed Gilead to move forward with this study design for elvitegravir. This is a great victory for people living with HIV. There is a great need for new treatments to be developed and for the FDA and companies to think and act creatively to ensure this happens.
An Overview of the Current State of HIV Drug Development
The Industry
As a whole, pharma has done a tremendous job developing HIV drugs. However, many visible signs are showing their fading commitment to HIV. Fewer new companies are getting into HIV, and some well established ones are either cutting back or eliminating their drug development plans. The marketplace for HIV drugs is both crowded and competitive. The scientific hurdles for developing new HIV drugs have also grown more difficult, making it a less attractive market for companies.
The FDA
The FDA is responsible for ensuring that drugs are safe and effective before they become available outside clinical studies. Recent media stories that focused on drug safety, particularly on Vioxx and Heparin, have created a somewhat fearful climate inside the FDA where new ideas are met skeptically. Their recent decision to green light elvitegravir's development shows that at least its antiviral division is open to creative drug development plans.
The Current Pipeline
All in all, the pipeline is both thin and unimpressive. There are a few 'me too' drugs (slight changes in existing drugs) which are helpful but not game changing. A few novel compounds may prove promising down the line, but they're struggling right now, due to either study results or in one case the company being bought by a company that doesn't want to work in HIV.
As for those drugs in human studies, the closest to approval is rilpivarine (TMC-278), an NNRTI for first line treatment being studied against Sustiva. Vicriviroc, Schering's CCR5 drug, continues to flounder but is still viable. Bevirimat, a maturation inhibitor from Panacos, has been hamstrung by formulation problems. Other drugs we are following are Pharmasset's racivir, and Avexa's apricitabine.
The Bottom Line
The past two years have been a boon to people with extensive treatment experience. Four successful new drugs, including two new classes, have meant most people can put together powerful, effective and tolerable regimens, even if they've never been able to get to undectable before. However, this period is now over, and we're experiencing a major downturn in the number of promising drugs in the pipeline.
This reinforces the importance of using the current crop of new drugs correctly. Your best chance at getting to and staying undetectable is to start a regimen with at least two and hopefully three fully active drugs. If you're able to do this and get your HIV level to undetectable, good adherence is the best way of keeping it there.
This also points to the need for treatment activists, like Project Inform, to continue to work with the companies, scientists and regulators to ensure that new drugs are developed.
Lastly, this situation points toward the need for a cure. It is only going to become more difficult to keep the companies, their researchers and the general public interested in HIV drugs. There's a growing sense that HIV is not that much of a problem anymore, at least not in wealthy countries.
The only real solution is a cure. While some may discount its possibility, we do not. Many promising approaches are under study, as well as a resurgence in community activism aimed at cure research. A conscientious program mounted by academia, industry, government and community is necessary to reach this goal.
http://www.thebody.com/content/art47196.html?mtrk=9029755
Dutch study finds increased sexual risk-taking amongst gay men counteracts 'ART as prevention'
The ability of antiretroviral therapy to reduce sexual infectiousness has not been enough to compensate for increases in risky sex among gay men in the Netherlands, according to a recently published study in the journal AIDS. The investigators, who used mathemetical modelling to explain recent increases in HIV diagnoses, conclude that sexual risk behaviour must be reduced to pre-1996 levels for treatment to have an impact on the Dutch gay HIV epidemic.
The impact of antiretroviral therapy (ART) on sexual transmission has been the subject of intense debate this year, following publication of guidance from the Swiss Federal AIDS Commission (EKAF) stating that an individual with a blood plasma undetectable viral load is not infectious.
Although some of the concerns have been about the scientific accuracy of that statement, much of the debate has been due to concerns about increased sexual risk-taking on a population level cancelling out any gains in ART’s effect on infectiousness.
In 2000, a mathematical modelling study from San Francisco suggested that the availability of ART had resulted in rates of risky sexual behaviour amongst gay men equal to, or greater than, the beneficial impact of ART on per contact HIV transmission. Another mathematical model, focusing on gay men in Australia, came to similar conclusions in 2004.
However, a more recent mathematical model examining the impact of ART in resource-limited settings suggested that it may have a positive impact on the HIV epidemic, particularly in population where these is less frequent partner change, and a similar model also appeared to show benefits when examining the epidemic in in the Canadian province of British Columbia (B.C.). So much so, in fact, that last week, B.C. announced that it was planning to expand access to ART as a prevention tool.
To determine the impact of a decade of potent ART on the HIV epidemic investigators from Amsterdam and London evaluated the impact of sexual risk behaviour, HIV testing behaviour and ART uptake on the HIV epidemic between 1980 and 2004 using a mathematical model fitted to data from several national databases that provided them with extensive information on epidemic trends amongst gay men in the Netherlands.
The model’s most important factor was its estimation of the prevalence of infectious individuals, weighted by their relative infectiousness – which depended on their stage of infection, whether they were diagnosed, and whether or not they were on fully suppressive ART – and the incidence of new infections.
They did this by using data from 130 gay men from the Amsterdam Cohort who were identified during seroconversion prior to 1996. They estimated that there were six periods of HIV infectiousness, starting with primary infection (which lasted an average of 0.24 years, or just under three months) followed by five more periods (undiagnosed untreated; diagnosed untreated; time after first treatment failure; time after second treatment failure; and time after third treatment failure, or AIDS) each lasting an average of 1.89 years.
They also assumed that time on successful treatment did not result in being sexually infectious, and also accounted for the relative infectiousness of different stages of HIV disease (where primary infection and AIDS were the periods of highest viral load and transmission risk) based on data from heterosexual couples in Uganda practicing vaginal sex.
They then fitted the model to data from the ATHENA cohort that included annual new HIV diagnoses and annual new AIDS cases, as well as country of infection (they calculated that 14% of diagnosed infections in gay men did not take place in the Netherlands).
Finally, they analysed four time periods: 1980-1983; 1984-1995; 1996-1999; and 2000-2004. Their calculations suggest that new HIV infections peaked in 1983, fell again due to the widespread uptake of 'safer sex', and started rising again in 2000 following increased sexual risk behaviour among gay men.
Their model produced a ‘reproduction number’ for these time periods, which was the average number of people an HIV-positive gay man could infect over his whole infectious lifespan, and which incorporated sexual risk behaviour, the impact of diagnosis, and the impact of ART. A reproduction number above 1 would increase the HIV epidemic and one below 1 would decrease the epidemic.
They found that after 1996, once potent ART was introduced, the reproduction number declined to 0.76 although this was not as great as it could have been due to an estimated 18% increase in the risk behaviour rate.
Even though a number of factors should have reduced the reproduction number further between 2000 and 2004 – including a reduction in the estimated time between infection and diagnosis, and widespread uptake of treatment – a further increase in risk behaviour during this period (an estimated 66% increase, just 29% lower than before the concept of ‘safer sex’ was created in 1984) meant that the estimated reproduction number for 2000-2004 was 1.04.
This, they write, is “near or above the critical epidemic threshold, and thus indicates that HIV may once again be spreading epidemically among MSM in the Netherlands."
Their model estimated that in 2005, just under one in four (24%) gay men with HIV in the Netherlands were unaware of their infection, and that these 24% accounted for 90% of sexual HIV transmission. However, they had assumed that gay men reduced sexual risk-taking by 50% following diagnosis, based on data from a 2005 meta-analysis of previous studies.
A more recent UK study found that diagnosed gay men were between 1.6-times and 3.29-times more likely to have sex that risked onward HIV transmission than undiagnosed gay men. It is possible, therefore, that the investigators may have overestimated the impact of undiagnosed individuals on transmission.
"On the basis of these model estimates," they write, "we conclude that HAART has played an important role in limiting transmission but that any gains made have been more than offset by increases in the risk behaviour rate. Had these increases not occurred in the HAART era, the reproduction number would have declined to 0.6, and the epidemic would have been in convinced decline.”
Although mathematical models are notoriously difficult to reliably estimate the dynamics of HIV epidemics, due to the use of so many assumptions, the investigators argue that their model is more robust than others because it used “several national databases recording diagnoses of HIV infection and AIDS, and deaths, allowing the diagnosis rate to be estimated reliably.”
They add that although gay men in the Netherlands are testing more frequently than before, their model suggests that testing frequency alone does not explain recent increases in diagnoses, but rather “a substantial increase in transmission. Our estimates were corroborated by changing trends in CD4 cell count at diagnosis, where a recent increase in the proportion of newly diagnosed individuals with high CD4 cell counts is apparent.”
They conclude that their model “suggests that the only way to reverse epidemic spread...is to reduce the risk behaviour rate from current levels” and that “the most effective intervention is to bring risk behaviour back to pre-HAART levels.”
Reference
Bezemer D et al. A resurgent HIV-1 epidemic among men who have sex with men in the era of potent antiretroviral therapy. AIDS. 22(9):1071-1077, 2008.
Disclaimer: Please don’t assume that GMFA or the London Gay Men’s HIV Prevention Partnership endorse or oppose the points of view of the authors. Please read these articles critically. Sometimes articles may contain mis-statements, we believe they are important to include because of the information they contain or the arguments they put forward. If you have a story or article on STI or HIV prevention which you would like to be distributed please forward it to lgmhpp.update@gmfa.org.uk.
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