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 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 October and November 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.
For information about course dates or to book a place, please visit www.gmfa.org.uk/stopsmoking.
PACE Workshops
Risky Business - is a weekly on-going group where you will be able to share and talk about your experience with other gay/bi men, gain insight and make changes in your life. This group is for you if you find it a challenge to maintain safer sex, if your sex life feels out of control or if you have recently been prescribed PEP or used PEP in the past.
Every Tuesday at 6.30pm until 16th December.
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.
The third Sunday of the month, 6 till 9pm. Next date: 18th January.
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.
The third Monday of the month from 6.15pm till 9.15pm. Next date: Monday, 15th December 2008.
When Positive Meets Negative - 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.
Begins 6.30pm Friday 28th November. Continues Saturday 29th and Sunday 30th November.
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.
The last Sunday of the month from 6 till 9pm. Next date: 30th November.
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 18th December and every third Thursday of the month from 6pm to 9pm.
Book a place on 'Mind Your Backs Guys!'
Positively drug fucked
Are you HIV positive and been so 'out of it' that you've forgotten to take your pills or not taken them like you should? Would you like to know more about the impact that the recreational drugs you are taking are having on the virus. This group will guide you through the drugs that are out there, the impact that they can have on you, your meds, the virus and give you the information to help you make the right choice.
Saturday 22nd November and every fourth Saturday of the month from 10am to 12.30pm.
Book a place on 'Positively drug fucked'
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 27th November and every fourth Thursday of the month from 6pm to 9pm.
Book a place on 'How not to pick up'
Newly Diagnosed Men's Support Group
A safe environment where newly diagnosed gay men in London can be supported in coming to terms with their diagnosis and discuss relevant issues for example disclosure, relationships and sex and adherence.
Six week course begins Tuesday 13th January 2009 from 6.30pm to 9pm.
Book a place on 'Newly Diagnosed Men's Support Group'
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
London Lesbian & Gay Switchboard (LLGS) www.llgs.org.uk provides an information, support and referral service for the LGBT community and anyone who needs to consider issues around their sexuality. Our helpline number is 020 7837 7324.
You can call us between 10am and 11pm any day of the week, 365 days a year to talk to a fully trained volunteer who will be helpful, friendly and supportive. Operated entirely by lesbian, gay and bisexual volunteers, we offer support and information to any caller on any subject to do with sexuality.
Sex and sexual health – You can ask us anything you like about sex; wanting it, having it, safer sex, sexual health and where to go if you have an itch or a sore. Perhaps you're worried about HIV and AIDS - we'll tell you what the risks are and what precautions you can take.
Coming out – Call us if you want to talk about your feelings; are frightened, confused, isolated or coming to terms with your sexuality.
Going out – Find out where to go; bars, clubs, saunas, social and sports groups or support groups etc – we have comprehensive London listings as well as most of the regional options.
Oh by the way – we won't tell you what to do, we won't judge you and we won't tell anyone else about your call.
The helpline operates from 10am to 11pm, seven days a week, 52 weeks year.
Our helpline number is 020 7837 7324.
The recruitment hotline for volunteers is 020 7837 7606.
Our text phone number is 020 7689 8501.
Our information web site www.queery.org.uk provides 24 hour access to our database of information and resources relevant to the LGBT community.
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.
HIV treatment and health information
Terrence Higgins Trust and NAM are working together to provide face to face, printed and on-line treatment and health information for people living with HIV in London.
HIV Health Support Service
The HIV Health Support Service will be useful if you have just been diagnosed with HIV, or if you are thinking of starting treatment, changing treatment or experiencing side effects. Your local health trainer can help you gain more knowledge about anti-HIV drugs and how the virus affects your body. They can also help you make changes so you can lead a healthier life.
The service is available across the capital in clinics, at HIV and other community organisations, and if necessary at home. If you prefer you could meet other people with HIV by attending a group health skills session. To find out more information or to make an appointment with your local health trainer call 020 7737 9740.
Publications
NAM and THT’s treatment and health publications are pitched at different levels to suit different people’s needs.
The publications are:
- a summary resource setting out the ten most important things it is good to know about HIV and its treatment;
- over 100 factsheets on specific health issues;
- a range of entry-level booklets, covering broad topics. These may be particularly helpful if you are newly diagnosed. Click for an example of a booklet called Your Treatment;
- a range of booklets on specific treatment and health topics, providing more detailed information;
- a monthly newsletter: HIV Treatment Update;
- a comprehensive directory of symptoms, illnesses, treatments and side-effects;
- a treatments information website.
All printed resources are available free of charge to anyone living with HIV in London. Simply call 020 7840 0050 or e-mail info@nam.org.uk
FS magazine
The winter 2008 issue of FS is available online and in bars and clubs across
London from the end of November 2008. 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 Know Your HIV Status Campaign:
One third of HIV positive gay men don't know they have HIV. If you know you have HIV, you can make informed decisions about your health, the sex you have and your future.
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:
Free 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, without charge and 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
- Other forms of 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 volunteering@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.
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
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.
Interesting articles and news from around the world:
High rate of death amongst patients with HIV diagnosed late
Patients who have an AIDS-defining illness at the time of their HIV diagnosis have a high rate of mortality, an international team of investigators report in the November 30th edition of AIDS. The researchers believe that their results show the importance of earlier diagnosis of HIV. However, they found that significant numbers of patients diagnosed late achieved an undetectable viral load and an increase in their CD4 cell count above the key level of 200 cells/mm 3 after antiretroviral therapy was started.
The amount of HIV-related illness and death fell dramatically after the introduction of effective HIV treatment in the late 1990s. However, in the UK, there are still approximately 800 HIV-related deaths a year, despite the provision of free HIV treatment and care. Many of these deaths occur in patients who have their HIV diagnosed late when they are already severely ill with HIV. Last year, doctors, policy makers and activists developed an action plan to reduce the number of late HIV diagnoses.
An international team of investigators from Europe and Canada wished to obtain a better understanding of the characteristics of patients who had were already ill with an AIDS-defining illness at the time of their HIV diagnosis, their outcome (progression to another AIDS-defining illness or death) and response to HIV treatment.
Information from eight cohorts was therefore pooled. A total of 760 patients diagnosed late between 1997-2004 were included in the investigators’ analysis. Most of the patients (78%) were male, however they came from a broad spectrum of risk groups with 36% being defined as heterosexual, 19% as homosexual and 12% as injecting drug users. Average age at the time of diagnosis was 39 years. The data revealed that the average CD4 cell count at diagnosis was dangerous low, the median being 42 cells/mm 3, and median viral load at the time of diagnosis was 120,000 copies/ml.
The two most common AIDS-defining illnesses at the time of diagnosis were PCP (35%) and tuberculosis (22%), followed by candida (12%), Kaposi’s sarcoma and toxoplasmosis (both 9%), CMV (7%) and lymphoma (4%).
Information on prognosis was available for 584 patients and a total of 110 (19%) of these individuals developed a second AIDS-defining illness after their diagnosis. A total of 125 patients, and 28% of these individuals had developed a new AIDS-defining illness prior to their death. Median CD4 cell count at the time of death was 28 cells/mm 3, with median viral load being 86,000 copies/ml.
Death occurred a median of 21 days after HIV diagnosis amongst the patients who did not receive antiretroviral therapy, and a median of thirteen months after diagnosis amongst the patients who received treatment with anti-HIV drugs.
The only baseline factors associated with a higher risk of death were older age (p = 0.0001) and higher viral load (p = 0.002).
HIV treatment was started by 624 patients (82%). HIV treatment was started a median of 31 days after diagnosis with HIV. Treatment was started sooner in patients diagnosed in 2004 and in those who were older or had KS at the time of their diagnosis. Patients with TB at the time of their diagnosis started treatment significantly later than other patients. The investigators believe that this is because the treating doctors wished to avoid the occurrence of an immune reconstitution inflammatory syndrome.
Median CD4 cell count at the time treatment was initiated by 41 cells/mm 3. Two-thirds of patients started HIV treatment with a combination based upon a protease inhibitor, with 25% initiating an NNRTI-based regimen. One-in-ten patients started therapy with a triple NRTI regimen, a combination of drugs that was revealed to be suboptimal during the follow-up period.
Most (505, 89%) of the patients who took HIV treatment had at least one viral load measurement below 500 copies/ml. Viral load fell to this level a median of 90 days after antiretroviral therapy was started. The only factors significantly associated with an increased chance of achieving a viral load below this level were calendar year in which treatment was initiated (2003/04, p = 0.004),and lower baseline viral load (p = 0.01).
Viral load subsequently rebounded in 186 (37%) individuals. Factors significantly associated with this outcome included treatment with a triple NRTI regimen ((p = 0.04), TB at the time of HIV diagnosis (p = 0.001) and diagnosis before 1999 (p = 0.003). Factors associated with a lower risk of rebound included treatment based upon a protease inhibitor (p = 0.02), diagnosis in 2003/04 (p = 0.03), a time when more powerful and durable HIV treatment was available, and older age at diagnosis (p = 0.0006).
Within three months of starting HIV therapy, median CD4 cell count had increased to 111cells/mm 3 and after a year of treatment, median CD4 cell count was 211 cells/mm 3. Of the 587 patients whose CD4 cell count was below 200 cells/mm 3 at the time of diagnosis, 58% had two consecutive counts above this level a median of one year and two months after starting treatment with anti-HIV drugs.
“Our study highlights the fact that patients who present for the first time with an AIDS event are likely to remain a clinical problem for the foreseeable future and deaths remain common in this group”, conclude the investigators, adding “steps to encourage earlier HIV testing and diagnosis among all groups and to increase clinical awareness of the possibility of an AIDS diagnosis among individuals ho are not perceived to be at risk of HIV infection are required.”
Reference
Mussini C. et al. Patients presenting with AIDS in the HAART era: a collaborative cohort analysis. AIDS 22: 2461-69, 2008.
Raltegravir may have role in PEP if exposure involves drug-resistant HIV
Raltegravir (Isentress) can be safely used as part of a post-exposure prophylaxis regimen and may be of particular value if the possible exposure involves highly drug-resistant HIV, according to a letter published in the November 30th edition of AIDS.
Raltegravir is the first integrase inhibitor to be approved and its use is currently restricted to patients with extensive experience of antiretroviral therapy. Clinical trials investigating its safety and effectiveness in individuals starting HIV treatment for the first time are currently underway and the interim results are promising.
Doctors from Washington State in the USA have explored another possible use for raltegravir – as part of a post-exposure prophylaxis regimen following possible occupational exposure to HIV.
Two cases when raltegravir was used effectively and safely as part of a post-exposure prophylaxis are reported by the doctors. They occurred between July 2007 and January 2008 and both cases involved possible exposure from the same highly treatment-experienced patient with drug-resistant virus.
The first healthcare worker experienced a deep wound when removing a venous catheter from the patient, whose viral load was 215,000 copies/ml at the time. Raltegravir was not licensed at this time, so special permission had to be obtained for its use as part of a post-exposure prophylaxis regimen. This regimen also included atazanavir (Reyataz) boosted by ritonavir, plus Truvada (tenofovir and FTC). However, because of nausea and hyperbilirubinaemia treatment with atazanavir/ritonavir was stopped and therapy with Truvada and raltegravir was provided for 28 days.
The second case involved a laboratory worker who was cut by a test tube containing the patient’s blood. This individual received treatment with a well-tolerated post-exposure prophylaxis regimen including darunavir (Prezista), boosted by ritonavir with Truvada and raltegravir.
Neither individual became infected with HIV. The authors write. “raltegravir was well tolerated in these two occupational exposures and appears to be an optimal choice for these individuals exposed to blood from an HIV patient with extensive drug resistance, given its novel mechanism of action, potent and rapid killing of HIV, and favourable side-effect profile.”
Reference
Siegel M.O. et al. Raltegravir for postexposure prophylaxis following occupational exposure to HIV. AIDS 22: 2552-54, 2008.
Immune Cells Worn Out from HIV Fight Given New Life to Assault Disease: Study
Researchers report they have found a way to revivify "killer" CD8 immune cells, which could some day be used to assist the body's natural infection-fighting power against HIV. CD8 cells normally seek and destroy infected cells, but they become "exhausted" by HIV infection, said study co-author Dr. Mario Ostrowski.
With HIV infection, CD8 cells "don't produce all the chemicals required to kill infected cells," Ostrowski said. "They can't perform any function. They're just totally wimpy and exhausted."
Worn-out CD8 cells also exhibit high levels of a molecule called Tim-3 normally used to slow the immune system down after an infection has been successfully dispatched. In test tubes, researchers blocked Tim-3 in CD8 cells taken from HIV patients and found the cells were revitalized. "We observed that blocking the Tim-3 pathway rescued those cells and restored their ability to fight off infection," said Ostrowski.
"We still do not know how the virus triggers Tim-3 or if this is restricted to HIV infection," said Dr. Lishomwa Ndhlovu, a study co-principal at the University of California-San Francisco. "But our findings may provide a new direction to vaccines and therapies that will potentially reverse these dysfunctional cells and allow them to control HIV-1 replication."
The full report, "Tim-3 Expression Defines a Novel Population of Dysfunctional T Cells with Highly Elevated Frequencies in Progressive HIV-1 Infection," was published in the Journal of Experimental Medicine (2008;doi:10.1084/jem.20081398).
UNITED KINGDOM OF GREAT BRITAIN AND NORTHERN IRELAND; UNITED STATES OF AMERICA: Souped-Up Immune Cells Catch Even Disguised HIV
Researchers on Sunday reported that they genetically engineered immune cells that can detect HIV even when it tries to disguise itself, potentially suggesting a new way to treat HIV infection. Engineered versions of cytotoxic T lymphocytes (CTLs), also known as CD8 killer T cells, were able to recognize other cells infected by HIV and slow HIV's spread in lab dishes.
"Billions of these anti-HIV warriors can be generated in two weeks," said study co-leader Angel Varela-Rohena of the University of Pennsylvania.
HIV not only attacks CD4 immune cells that help mount the body's defense: The virus also can disguise itself from CTLs by hiding a protein called HLA-I-associated antigen. "CTLs are crucial for the control of HIV infection," the researchers wrote. "Unfortunately, HIV has an arsenal of mutational and nonmutational strategies that aid it in escaping from the CTL response mounted against it by its host."
To counter this, Varela-Rohena and colleagues took CTLs from an HIV patient and genetically engineered them to detect HIV that had escaped natural T cells. "It is possible to improve on nature when it comes to preventing HIV CTL escape," the scientists wrote. In addition, "the engineered T cells responded in a much more vigorous fashion so that far fewer T cells were required to control infection," said James Riley, a study co-author at the University of Pennsylvania.
"In the face of our engineered assassin cells, the virus will either die or be forced to change its disguises again," said co-author Andy Sewell of Britain's Cardiff University, a step the researchers hope will further weaken the virus. The researchers plan to begin testing the treatment in HIV patients in 2009.
"We have managed to engineer a receptor that is able to detect HIV's key fingerprints and is able to clear HIV infection in the laboratory," said Bent Jakobsen, chief scientific officer at Adaptimmune Ltd., the British firm that owns the technology.
The full report, "Control of HIV-1 Immune Escape by CD8 T Cells Expressing Enhanced T-Cell Receptor," was published ahead of print by Nature Medicine online (2008;doi:10.1038/nm.1779).
Could treatment interruptions make a comeback?
Two and half years after a major study of HIV treatment interruption was halted because of a higher risk of death in people who stopped treatment, results from a four-year Italian study reported this week suggest no elevated risk of illness or death as a result of interrupting treatment. The findings were presented this week at the Ninth Congress on Drug Therapy in HIV Infection in Glasgow.
The SMART study was a major international randomised trial of structured treatment interruption versus continuous antiretroviral therapy. Participants with CD4 counts above 350 cells/mm 3 on antiretroviral treatment were randomised to interrupt treatment until their CD4 counts fell below 250 cells/mm 3, or take antiretroviral therapy continuously.
The study was halted after two years because people who interrupted treatment had an increased risk of death and HIV disease progression, and subsequent analysis showed that they also had a higher risk of non-AIDS related serious adverse events including cancers and cardiovascular disease.
As a consequence of those findings, treatment interruptions, once popular, have been warned against and discarded as a potential strategy for managing long-term treatment.
So it was with some trepidation that Dr Franco Maggiolo of Bergamo, Italy, presented results from the LOTTI study, a lengthy Italian study of structured treatment interruption (STI). “My task this morning is not easy: it’s a difficult thing to talk about Strategic Treatment interruptions (STIs) since the SMART Trial, but I’m here to convince you there are some good options for patients,” he told the conference.
The LOTTI study showed that intermittent treatment of patients with CD4 counts over 350 produced clinical results equivalent to continuous treatment.
Alongside Maggiolo’s presentation, a study from Dr Cal Cohen of the Community Research Initiative in Boston, USA found that it was safe for patients to stop taking a regimen of Truvada (tenofovir+FTC) and efavirenz at weekends.
The LOTTI study is a lengthy (four years follow-up and still continuing) study in which 329 patients were randomised either to receive continuous antiretroviral therapy (ART) or to stop treatment when their CD4 counts reached 700 and to resume when they fell below 350. In addition to having a baseline CD4 count of over 700, patients had to have a nadir (lowest-ever) CD4 count of over 200 and be on stable ART with a viral load below 50 copies/ml.
Half the patients had a baseline CD4 count over 500. The average age was 40 and 73% were male, with an even spread of risk groups (37% heterosexual, 23% gay men and 39% injecting drug users). The average time participants had been on ART was six years.
The study’s primary endpoint was death from any cause, progression to AIDS or any condition requiring hospital admission. Secondary endpoints included any disease symptom not requiring admission and any grade 3 or 4 laboratory abnormality in tests.
After four years, the proportion of patients reaching the primary endpoint was 12.1% of those on STIs and 11.6% of those on continuous treatment, a non-significant difference. These results were achieved with the STI patients staying off therapy two-thirds of the time compared with less than 2% of the time in the continuous-therapy patients. Patients with CD4 nadirs exceeding 500 were able to stay off therapy 85% of the time.
After the presentation an audience member asked if Maggiolo’s study just proved that “those who should never have started can safely stop,” but Maggiolo said that only a third of participants had a CD4 nadir over 350 cells/mm 3, so the majority had been eligible for ART under current guidelines.
Maggiolo detailed the clinical endpoints observed in the trial. Four patients on continuous treatment had cardiovascular disease requiring hospitalisation compared to none on STI, and six controls developed diabetes (a secondary endpoint) compared with none on STIs. In contrast, seven patients on STIs got bacterial pneumonia compared with no controls, and this was statistically significant.
There were significant differences in cardiovascular and metabolic events (primary and secondary endpoints) between controls and people on STIs: they occurred in 10.5% of controls and 1% of STIs, an incidence of 0.2% a year in STI patients compared with 3.3% a year in controls. This contrasted with the SMART study which found an incidence of 1.1% per year each in both control and intervention groups for this combined endpoint.
Maggiolo commented that the average follow-up time in SMART had been just over a year compared with four years in his study and that if the LOTTI study had been stopped at the same timepoint as SMART, no difference would have been observed in cardiovascular and metabolic events either. His study demonstrated that it took a long time for the benefits of therapy-sparing regimes to become evident.
He also said that in his study 95% of patients had CD4 counts over 350 compared with 65% on SMART and 0.5% below 250 compared with 8.6% on SMART, which might explain the higher mortality and morbidity rate seen in patients off treatment in the latter.
Maggiolo commented that doctors might like to see more evidence before making STI’s on the LOTTI model standard clinical practice, but when asked what it would take to change clinical practice commented, “It already is mine. It’s not for every clinician or every patient, but it’s a safe option for some”.
Following Maggiolo’s presentation Cal Cohen presented results from the FOTO (Five On, Two Off) study which randomised 60 largely gay male patients either to continue treatment with Truvada plus efavirenz or to stop taking it at weekends.
The patients were 83% male and 77% of white ethnicity, with an average age of 47 in controls and 42 in the intervention arm and an average CD4 count of 670.
After 24 weeks, 80% in the control arm and 83% in the intervention arm had a viral load under 50, a non-significant difference. There were five dropouts in the FOTO arm and two in the control arm. Excluding these, a ‘on treatment’ analysis shows that 100% of the intervention arm had viral loads under 50 by week 24 compared with 85% in the control arm. Most dropouts were due to the frequent monitoring required of participants, but one participant in the FOTO arm dropped out due to efavirenz-related side effects (dizziness and insomnia) and one before the study even began because he was anxious about stopping his drugs.
Eighteen patients – eight controls and ten FOTO patients - had viral load ‘blips’ during the study, defined as a single viral load between 50 and 500; the highest reading was 160 on FOTO and 465 on control.
CD4 cells at week 24 were 705 in the control arm and 635 on FOTO, but this apparent difference, Cohen commented, has adjusted since then and the latest CD4 results are the same in both arms.
Did patients adhere to the strategy? In the FOTO arm, three patients took over five doses a week at some point while eight took more than two days off, though none took more than three. No patient who took three days off developed a detectable viral load (viral loads were measured on Mondays). Unlike the Maggiolo strategy, the FOTO protocol also kept patients undetectable, meaning that it did not entail the problem of raising the infectiousness of patients.
However Cohen said he had not yet determined adherence rates in the control arm, which is obviously crucial to determining the feasibility and risks of the strategy.
Why do the strategy? Cohen asked. Apart from saving 29% of drug costs, patients much preferred it. When asked on a scale of 0-10 whether they preferred stopping their drugs at weekends, where zero indicated total disapproval and 10 total approval, the average score was 9.5.
References
Maggiolo F et al. CD4-guided STI in patients responding to HAART. Ninth International Congress on Drug Therapy in HIV Infection, Glasgow. Abstract O213. 2008.
Cohen C. The FOTO Study: 24-week results support the safety of a 2-day break on efavirenz-based antiretroviral therapy. Ninth International Congress on Drug Therapy in HIV Infection, Glasgow. Abstract O214. 2008.
Non-nucleoside resistance is efficiently transmitted within infection ‘clusters’
HIV that is resistant to the non-nucleoside drugs (NNRTIs) efavirenz and nevirapine is efficiently transmitted between members of sexual networks, a study from Canada has found. The proportion of NNRTI-resistant HIV could even be amplified by rapid, ‘chain reaction’ transmission between members of large networks, the study finds.
In contrast, other types of HIV drug resistance are more likely to appear within isolated cases of infection and seem to be ‘filtered out’ by such chain transmission.
An important study last year of HIV transmission in Quebec, Canada, in which people (largely gay men) recently infected with HIV had their virus subjected to extremely precise analysis of its entire polymerase gene, found that half of HIV infections in the province occurred in smaller or larger clusters of anything between two and 17 people, where a ‘cluster’ was defined as the occurrence of HIV viruses that were genetically identical or near-identical in different people.
Estimating the dates of transmission and the rate of change in the HIV polymerase gene showed that about half of all infections were transmitted by people in primary HIV infection, in the first six weeks or so when people’s viral loads are high.
Subsequent studies from other parts of the world including the UK have confirmed that a high proportion (25%-50%) of HIV infections is acquired from people who are themselves in primary infection. Dr Mark Wainberg of the team at the McGill AIDS Centre in Montreal that conducted the initial study undertook a further evaluation of the same cohort to establish the frequency of transmission of drug-resistant virus.
They found worrying evidence that clustering of transmissions and therefore rapid-fire ‘cascades’ of transmission were getting more common, with the proportion of infections that were in a cluster increasing from 49% in December 2005 to 56% by June 2007. The average number of people in transmission clusters had also increased, from 6.6 to 10.3. People infected in clusters were also younger, with an average age of 30 as opposed to 40 in unique infections.
Wainberg’s team found 64 small clusters (defined as having four members or fewer) and 31 large ones (five or more members). Infection with virus resistant to the nucleoside analogue (NRTI) drugs – AZT, tenofovir, abacavir, 3TC and the like – was more common in one-off infections than in ones in clusters. Nine per cent of unique infections had NRTI resistance compared with 3.8% in small clusters and only 2.1% in large clusters.
In contrast NNRTI resistance was no more common in small clusters than in unique infections (5.9% and 6.7% respectively), but it was a lot more common within large clusters, at 15.5% of all virus acquired by large-cluster members. Individual NNRTI mutations were also more common in large clusters while individual NRTI mutations were less common. Protease inhibitor (PI) resistance was also less common in clusters than in unique infections (2.4% versus 4.0%).
Why is this happening? NRTI and PI resistance tends to make the virus carrying it less fit. It reproduces more poorly and people carrying it tend to have lower viral loads than people with NNRTI-resistant virus, so it is transmitted less often. This also means it tends to decrease as a proportion of the total virus carried by people with multiple strains. so, if they transmit HIV, they tend to transmit fitter, non-resistant virus.
NNRTI resistance on the other hand exacts no fitness penalty and also persists longer in the body. In a group of people who are rapidly transmitting HIV to each other and where people are infected with genetically near-identical strains, therefore, any introduction of NNRTI-resistant virus into the group results in a high likelihood that it will be transmitted to multiple individuals in the group. In this way transmission clusters can act as amplifiers of NNRTI resistance.
“NNRTIs [in combination therapy] may be more fragile than long term clinical trials suggest,” said Wainberg. “It is only logical that the transmission of NNRTI mutations will continue to increase in settings in which they are used extensively in first-line therapy.”
However he also added that he was hopeful that the new-generation NRTIs, etravirine and the yet-to-be-license rilpivirine, which do not acquire resistance so easily, would not show the same pattern of cluster amplification.
The findings have particular relevance for resource-limited settings where first-line therapy is almost entirely dependent on NNRTIs, and where treatment failure may not be detected for months or even years due to the lack of viral load testing. In these settings recently reported evidence suggests that anywhere from 30-90% of patients failing NNRTI-containing regimens have NNRTI resistance by the time that treatment failure is detected.
The World Health Organization is working with national AIDS programmes to develop surveillance systems in resource-limited settings that can detect if NNRTI resistance is becoming a serious problem in newly-infected people.
Further information about the transmission of drug-resistant HIV can be found here on www.aidsmap.com
If you can't switch, better to stay on failing treatment than stop it, studies show
Patients on failing drug regimens maintain stable CD4 counts with detectable viral load levels up to 10,000 copies/ml, as long as they remain on HIV treatment, a study presented at the Ninth International Congress on Drug Therapy in HIV in Glasgow showed this week.
In contrast, patients who stop treatment begin to suffer CD4 cell declines at viral load levels as low as 500 copies/ml. It is therefore better to stay on a failing therapy than to stop, the investigators concluded.
Meanwhile, another study found that it is better to stay on therapy in the opposite scenario, where patients achieve an undetectable viral load but never achieve a good CD4 response. Such patients had a much lower risk of AIDs or death than patents who came off therapy, the study found.
Stay on treatment if you have a detectable viral load...
The first study, co-ordinated by the Royal Free and University College Medical School (UCMS), reviewed European patients in seven countries, but will likely have greatest applicability to resource-poor settings where patients are more likely to be maintained on treatment while having a detectable viral load, presenter Amanda Mocroft said.
“We don’t actually know the rate of CD4 count change or at what level of viral load CD4 counts start to decline in developing countries,” she commented.
To address this gap in knowledge, the survey looked at the relationship between viral load and rate of CD4 count change in 7231 European patients from 1997 to 2004.
The study looked at CD4 ‘slopes’. In order to calculate a CD4 slope for a patient, there had to be at least three CD4 measurements taken over a time period when a patient’s viral load and therapy regimen were both stable, with the viral load varying by no more than 0.5 logs (no more than threefold). The researchers could then use the three CD4 tests to calculate a slope, expressed as the average number of CD4 cells gained (or lost, in the case of a negative slope) per year.
‘Stable’ antiretroviral therapy (ART), in this case, meant no change in any regimen component over the duration of the CD4 slope, even in cases of failure.
The majority of patients included in the survey were white men. Over a quarter had had AIDS diagnoses, with an average pre-therapy minimum CD4 count of 168 and a baseline viral load of 4.6 logs (40,000). The 7231 patients contributed about 59,000 CD4 slopes between them, an average of six per patient.
The study confirmed that being on ART was better than not taking it, regardless of viral load. Patients on stable ART with viral loads under 500 copies/ml had an average gain of about 40 CD4 cells a year.
If the viral load was between 500 and 10,000 copies/ml, the CD4 count neither increased nor declined as long as patients stayed on ART. But at viral loads over 10,000 the CD4 slope became negative and patients who stayed on failing ART lost an average 42 cells a year.
Patients who had never started therapy, however, lost 40 cells a year at any level of detectable viral load (defined for this study as over 500 copies/ml). When viral load rose above 10,000 copies/ml, CD4 cell loss accelerated to around 70 cells a year.
Worst off were people on treatment interruptions, and this study added yet more weight to the evidence that once you start on ART, it is a bad idea to stop. Patients on treatment interruptions lost nearly twice as many cells at viral loads between 500 and 10,000 as patients who’d never started ART (about 70 cells a year) and lost about 110 cells a year at viral loads above 10,000 copies/ml – nearly three times as many as patients maintained on so-called ‘failing’ ART.
The types of drug used in the ART regimen also had an effect on the CD4 slope. Patients on protease inhibitors (PIs - boosted and unboosted) had better CD4 increases than patients on other regimens, about 50 versus 25 cells a year at viral loads below 500 copies/ml. At viral loads above 10,000 copies/ml everyone experienced CD4 declines but patients taking PIs still had slower declines. Mocroft therefore recommended that second-line regimens should all contain a boosted PI.
Stay on treatment if you have a low CD4 count...
Another cohort study also found that it was much better to stay on therapy than come off it in the situation where, despite achieving viral undetectability, patients do not make a full CD4 count recovery. Wendy Bannister, also of University College Medical School, told the conference that patients with CD4 counts under 200 who came off ART were ten times more likely to die than patients who remained on ART – even if those on ART had a detectable viral load.
Bannister was reporting on findings from the EUROSIDA Cohort, a group of patients from seven European countries. To be included in the study, patients had to have a CD4 count under 200 within six months of a viral load test. The patients were then divided into three groups according to whether they were on ART with a viral load under 500 (Group A), on ART with a viral load over 500 (Group B), or not on ART (Group C).
Clearly, patients could be in any of the three groups at different times, and Bannister gave an example of a fictitious patient who’d originally been on failing dual therapy and had stopped it (group C), subsequently started triple combination therapy but still had a detectable viral load (group B), then finally became undetectable (group A).
The three groups were similar, though the ones off therapy were less likely to be male and more likely to be injecting drug users, a possible confounding factor. Forty-five per cent of those off ART and 40% of those on it but with a detectable viral load had CD4 counts under 100 compared with 20% of those with an undetectable viral load. The average viral load in patients off ART was 72,000 copies/ml and in those on ART but detectable, 25,500 copies/ml.
The combined rate of AIDS or death was 5% a year in group A, 12% in group B and no less than 60% in group C. However when it came to the risk of death alone, patients on ART (groups A and B) had an equal risk of dying (about 3% a year) regardless of viral load, whereas in group C patients the risk of death was about 30%.
When this was further resolved into deaths from AIDS conditions and non-AIDS conditions, being on ART and having undetectable viral load protected patients from AIDS-related conditions, but viral undetectability did not protect them from non-AIDS conditions; indeed those in group B had the lowest risk of death from non-AIDS-related conditions. The risk of AIDS deaths was 0.4%, 1% and 11% in groups A,B and C respectively while of non-AIDS deaths it was 2%, 1% and 11%.
The tenfold higher risk of death and disease in people off ART can be partly explained by terminally ill people being taken off ART or having died before starting it, Bannister commented; but the difference between AIDS and non-AIDS deaths is intriguing and warrants further investigation.
References
Phillips AN et al (presenter Mocroft A). Rate of change in CD4 counts in patients with stable HIV viremia. Ninth International Congress on Drug Therapy in HIV Infection, Glasgow. Abstract O212. 2008.
Bannister W P et al. Opportunistic infections in immunocompromised but virologically suppressed HIV-1 infected patients. Ninth International Congress on Drug Therapy in HIV Infection, Glasgow. Abstract O332. 2008.
Continued antiretroviral therapy reduces bone mineral density in SMART study
A sub-study of the SMART trial has found greater losses of bone mineral density in people who stayed on continuous antiretroviral therapy, compared to those who periodically interrupted their treatment. The study also found that people on continuous treatment were almost five times more likely to experience a serious fracture during the follow-up period than those who interrupted treatment.
HIV-positive individuals generally have lower bone-mineral density than their HIV-negative peers. There is conflicting evidence about the relationship between antiretroviral treatment (ART) and long-term HIV infection as contributing causes, and the question continues to be investigated. Investigators from the SMART study presented findings from a body composition sub-study in a poster at the 48 th Interscience Conference on Antimicrobial Agents and Chemotherapy in Washington DC on Monday.
The SMART study was designed to compare the outcomes of continuous ART versus therapy involving treatment interruptions. Participants were randomised to either take their antiretrovirals continually or, if their viral load was undetectable, to discontinue treatment when their CD4 cell count was above 350 cells/mm 3, recommencing treatment when it fell to around 200 cells/mm 3. The study was terminated early when it was found that patients who interrupted treatment were more likely to have both HIV-related and non-HIV-related illnesses.
A total of 275 patients in the SMART study were prospectively enrolled in a sub-study designed to evaluate the impact of ART on bone mineral density; data was available on 214 of these. Between May 2002 and January 2006, 98 of these patients took continuous ART and the remaining 116 interrupting their treatment according to the study protocol. The two groups of patients were very similar, with an average age of about 44 years; races were fairly even mixed and about 20% were women. A significant number smoked (41% in the interruption group and 51% in the continuous group). Smokers suffer more bone mineral loss as they age, several large studies have shown.
Over the four-year course of the sub-study, patients on continuous therapy received ART for 93% of follow-up time, compared with 37% in the treatment interruption group. The majority of the time off treatment occurred in the first year of the study.
Bone mineral density (BMD) was checked at baseline and then annually in the hip and spine using a technique called dual-energy X-ray absorptiometry (DEXA). BMD in the spine was also checked using a CT scan.
Overall, spine BMD steadily declined in the continuous-therapy group. In the treatment-interruption group, it increased over the first year, when the greatest number of participants were off therapy. It declined after that but still remained higher than the levels of those on continuous therapy. Although the differences fell below statistical significance at further time points (due to the declining numbers with follow-up data available, as well as the gradually decreasing differences themselves), the overall longitudinal difference (summed over time) remained significant.
Compared to patients who interrupted their antiretroviral therapy, those who took ART continuously experienced a 0.9% decline in bone mineral density in the hip each year, a 2.9% decline in density in the spine (as measured by CT scan), and a 0.4% fall in density in the spine (as measured by DEXA). In the spine (as measured by DEXA), the difference in BMD favoured the interrupted-therapy group by 1.7% at year 1 (p = 0.003) and 1.2% over the entire period (p=.05). In the hip, the differences were 1.3% at year 1 (p = 0.002) and 1.4% over the duration (p = 0.002).
Although differences between outcomes were observed in people on different antiretroviral agents, the study was not powered to evaluate such differences.
In the larger SMART study, grade 4 bone fractures occurred at a rate of 0.13 per 100 person-years in patients who took their treatment all the time, versus 0.03 per 100 person-years in those who interrupted therapy (hazard ratio 4.9, 95% confidence interval 1.1 – 22.5, p = 0.04).
The investigators concluded that "continuous antiretroviral therapy contributes to bone mineral density loss and may increase the risk of fractures" relative to intermittent ART. However, they stress that interrupting HIV treatment is not recommended, as the SMART study showed that it increases the risk of both HIV disease progression and death.
Reference
Grund B. et al. Continuous antiretroviral therapy decreases bone mineral density: results from the SMART study. Interscience Conference on Antimicrobial Agents and Chemotherapy, abstract H-2312a, Washington, 2008.
A First Step Toward a Cure for AIDS? Novel Procedure Appears to Have Eliminated HIV by Jeffrey Laurence, M.D.
We need a cure for AIDS. We can't treat our way out of this epidemic. Anti-HIV therapy is a lifelong commitment, accompanied by many life-altering and some potentially life-threatening side effects. And for every person placed on treatment, two to three are newly infected. In 2007 alone there were 2.7 million new infections, and only 31 percent of those who needed treatment received it. Viral reservoirs—cells and tissues in which HIV remains dormant, beyond the reach of anti-HIV drugs but poised to grow at any moment—persist for the life of an infected person. And while all currently available anti-HIV drugs suppress the virus, they cannot eliminate it.
Given this context, a brief report in February 2008 by a group of physicians from Germany appeared to change everything when presented as a poster at the annual Conference on Retroviruses and Opportunistic Infections in Boston. It described a 40-year-old man—an American working in Berlin—whose HIV had been under good control for several years using a typical cocktail of drugs known as HAART. Then he developed acute leukemia.
In an attempt to cure the leukemia, he underwent a course of radiation therapy and chemotherapy in preparation for a stem cell transplant. But in his case, rather than simply using the best match among available stem cell donors, his physicians did something very clever. They also screened potential donors for a natural mutation known as delta32 CCR5. CCR5 is the primary means by which most types of HIV infect cells. Individuals lacking this CCR5 receptor—the 1.5 percent of the Caucasian population in America and Europe with the delta32 mutation—are completely resistant to infection by the most common forms of HIV.
The patient's stem cell transplant was a success, although relapse of his leukemia required a second transplant using the same donor. Now off all anti-HIV drugs for almost two years, the patient continues to show no detectable signs of HIV in his blood, bone marrow, lymph nodes, intestines, or brain. To the limits of our ability to detect HIV, it appears that the virus has been eradicated from his body. At the very least this patient represents a functional cure: he is off all anti-HIV meds, has a normal T-cell count, and exhibits no evidence of virus.
amfAR quickly called together 10 experts in clinical AIDS, stem cell transplantation, and HIV virology for a two-day think tank at the MIT Endicott House to evaluate these data. The patient's physician, Gero Hutter, presented details of the case, which were closely scrutinized by all. In a summary statement, attendees indicated that this case does indeed represent at least a functional cure. Dr. Hutter agreed to ask his patient to provide additional blood samples so that scientists attending the amfAR meeting could perform even more sensitive tests to attempt to further document that the virus has been erased from the patient. amfAR is coordinating distribution of these samples.
But amfAR's involvement doesn't end there. It is possible that the patient may have been cured of HIV/AIDS. But the cost of such a stem-cell transplant procedure can run up to $250,000. It is associated with a relatively high death rate from infectious and immunologic complications, and the number of delta32-CCR5 donors of appropriate tissue type would be very small. Here further research may yield key answers.
For example, it is unknown whether the use of a delta32-CCR5 donor is essential. Perhaps the transplant procedure itself was the most important element. The potential to genetically engineer stem cells to remove CCR5 from a patient's own stem cells also exists, and strategies to do so were discussed at the think tank. These and related issues will serve as topics for an upcoming amfAR grant cycle.
New research shows how HIV damages the brain
ScienceDaily (Nov. 18, 2008) — Scientists have unraveled in unprecedented detail the cascade of events that go wrong in brain cells affected by HIV, a virus whose assault on the nervous system continues unabated despite antiviral medications that can keep the virus at bay for years in the rest of the body.
The new research reveals key steps taken in the brain by Tat, a protein that is central to HIV's attack on cells called neurons. Researchers discovered the receptor that Tat uses to attack neurons, and they were able to reverse the effects of Tat in the laboratory by blocking the receptor.
The discovery of a major molecular player in the process opens up a new avenue for researchers to explore in their efforts to prevent or treat HIV's neurological effects, for which there is no currently approved treatment. Researchers say that much of the molecular action that underlies HIV's attack on the brain also occurs in other diseases, such as Parkinson's and Alzheimer's diseases, and that the results spell progress for those conditions as well.
The team from the University of Rochester Medical Center and other institutions published its results online Nov. 13 in the journal PloS One.
The powerful antiviral drugs that keep many HIV patients healthy for years don't completely eradicate the virus from the body, and in the brain, even the very low levels of that remain cause relentless damage. Scientists have observed that a large percentage of HIV patients – perhaps up to half – show evidence of neurologic disease from the virus,
"The current medications give many patients a new lease on life. But the virus is still taking a toll on the brain, even when the virus appears to be much less active elsewhere in the body," said the paper's corresponding author, neurologist Harris "Handy" Gelbard, M.D., Ph.D. of the University of Rochester Medical Center.
Gelbard was a newly minted pediatric neurologist embarking on his career when a good friend of his – a doctor with whom Gelbard had trained – became ill and died of AIDS in less than two years. His friend's struggle, and the severity of his neurological symptoms, touched Gelbard. Gradually, with the support of mentors, Gelbard came to focus on the neurological effects of HIV. He now leads a group of researchers funded by the National Institute of Mental Health that is trying to identify or create the first treatment for the neurological effects of HIV, known collectively as neuroAIDS or HIV dementia.
Scientists have known that Tat, which helps HIV operate, replicate, and infect cells, is at the forefront of HIV's attack on the brain, bringing about severe inflammation. Immune cells within the brain go into overdrive, churning out substances that attract more immune cells, and white blood cells from the body flood in and join the fray, all clumping together to form destructive entities known as multinucleated giant cells.
"Suddenly the brain environment turns from nurturing to toxic, and the brain has to work much harder to send messages. Cells are on overdrive, spending a lot more energy to do the same things they used to do easily," said Gelbard, who is director of the Center for Neural Development and Disease at Rochester.
Other changes occur throughout the brain as well. Neurons that normally reach throughout the brain by forming networks of far-reaching, delicate extensions crucial for cell communication become damaged. Instead of sprouting healthy dendrites – projections that resemble tiny trees – neurons in the brain of an HIV patient have had parts of their dendrites abruptly torn off, in a process known as "synaptic pruning." The dendrites begin to look like a patch of severely damaged trees after a bad ice storm.
Such damage occurs in parts of the brain crucial for thinking, decision-making, and movement and memory. That accounts for symptoms like difficulties concentrating, forgetfulness, poor coordination, confusion, and gait disturbances. In later stages, neuroAIDS can cause outright dementia.
Gelbard's team discovered that Tat works through the ryanodine receptor to sicken neurons in two ways. Scientists have known that Tat makes vulnerable the mitochondria, organelles within neurons and other cells that are commonly considered the "power packs" or energy sources for cells. The team discovered that Tat destroys the ability of mitochondria to protect themselves from changes in levels of calcium.
The scientists discovered another effect of Tat as well. Tat has a dramatic effect on an organelle known as the endoplasmic reticulum, where proteins are actually assembled and folded. Gelbard's team discovered that it's Tat's effects on the ryanodine receptor that cause an "unfolded protein response" seen in the brains of HIV patients. Shape is everything for proteins, and they're nearly always useless or harmful when they are unfolded or misfolded. The problem in HIV patients is exacerbated because protein folding requires a great deal of energy – energy that cells whose mitochondria are petering out aren't likely to have.
The team also showed, in mice, that a single exposure to Tat has long-lasting effects on the brain, causing problems with mitochondria and endoplasmic reticulum weeks later. Perhaps most striking, Gelbard says, is the observation that the exact same types of damage were seen in brain tissue of patients with HIV and neurologic disease but not in tissue from patients with HIV who did not have the neurologic disease.
The findings are in line with past findings from the team, which has shown that the central problem in HIV dementia is not that brain cells simply die. Rather, they become sick and lose their ability to communicate with each other. Because the cells are still alive, there is hope that the condition could be stopped or even reversed with proper treatment. Indeed, doctors commonly see patients who begin antiviral therapy and immediately are less confused and have improved brain functioning, but the effect generally fades as the disease progresses.
In their experiment, Gelbard's team was able to stop the harmful effects of Tat in neurons from mice by using the drug dantrolene, which blocks the ryanodine receptor. While the work offers a new target in the search for a drug that could be used in people to stop the effects of HIV dementia, Gelbard cautions that dantrolene has side effects and would not be appropriate.
"A lot of people are under the impression that HIV has been 'solved,' that somehow, it's no longer a problem. But the disease never went away, and it's a huge problem," said Gelbard, who is professor of Neurology, Pediatrics, and Microbiology and Immunology.
"There are a fair number of similarities between this brain disease and other diseases, such as Parkinson's or Alzheimer's," said Gelbard. "We hope that what we are learning can be applied to other diseases as well."
The first author of the paper is former graduate student John P. Norman, Ph.D., now with Exxon-Mobil. Other authors were Seth Perry, Ph.D., research assistant professor of Neurology; graduate students Holly Reynolds and Michelle Kiebala; Sanjay Maggirwar, Ph.D., and Stephen Dewhurst, Ph.D., professors of Microbiology and Immunology; Karen De Mesy Bentley; David Volsky, Ph.D., of Columbia University Medical Center; and Margarita Trejo and Eliezer Masliah, M.D., of the School of Medicine at the University of California at San Diego.
Using the immune-stimulating drug interleukin-2 (IL-2) alongside conventional antiretroviral therapy (ART) can produce a more rapid CD4 increase than usual in people who are diagnosed with very low CD4 counts, and may help to prevent AIDS-related illnesses in the first few months, an Italian study has found.
IL-2 is a naturally-occurring cytokine (immune-modulating protein) that can also be made artificially. It produces significant rises in CD4 counts in the majority of people who take it by lengthening the lives of CD4 cells. It has been the subject of two long-running drug trials in people with HIV, ESPRIT and SILCAAT, which are expected to report in 2009.
These trials were initiated at a time when IL-2 was envisaged as a possible alternative to ART, or at least a way of delaying its initiation. However IL-2 produced unpleasant (and unpopular) flu-like side-effects in many trial subjects, and with the improvement in tolerability of antiretrovirals, enthusiasm for it as a long-term alternative to ART has waned.
However it could be used in other ways, including as a short-term emergency CD4 booster for people with very low CD4 counts, in order to reduce the risk of opportunistic infections until antiretroviral therapy has boosted the immune system enough for the risk to have passed. This is the strategy Camilla Tincati and colleagues from two HIV clinics in Milan decided to try.
Tincati started 73 recently diagnosed patients on ART, then after two weeks randomised patients either to continue on ART as normal (40 patients) or to receive IL-2 as well (33 patients). The IL-2 patients received three ‘cycles’ of IL-2; these consisted of ten average-size doses of IL-2 given as a subcutaneous injection once daily, spread over two weeks with a weekend break. This was repeated three times in the first three months on therapy.
Patients’ progress was followed for 18 months after the first three-month cycle of IL-2 treatment. Those failing to show a recovery of more than 30% in CD4 count from baseline after six months received three more IL-2 cycles in months 6 to 9.
The patients had low CD4 counts at baseline, with an average count of 48 cells/mm 3 in the ART patients and 61 cells/mm 3 in the IL-2 patients. Twenty-seven (67.5%) of the ART patients and 15 (45.5%) of the IL-2 patients had AIDS-defining illnesses at the start of the study. All patients responded to ART with declining viral loads.
Interleukin-2 therapy provided a significant degree of what Tincati and colleagues called ‘CD4 rescue’. At the end of three months, and three cycles of IL-2 in the patients who took it, the average CD4 count increase in patients on ART alone was 20 cells/mm 3, and their CD4 counts now averaged 68 cells/mm 3; in patients taking IL-2 it was 145 cells/mm 3, and the average count was now 206 cells/mm 3.
However, the CD4 count increases did not last. By the end of six months, the average CD4 count increase was identical in patients whether or not they received IL-2: 59 cells/mm 3. In other words while the patients on ART experienced a slow increase to an average of 107 cells/mm 3, the IL-2 patients actually experienced a considerable CD4 decline in the second three months and the average CD4 cell count in the IL-2 group now stood at 120 cells/mm 3.
By the end of 18 months, ART patients had an average CD4 count of 145 cells/mm 3 (up 97) and the IL-2 patients had an average count of 168 cells/mm 3 (up 107) – not a significant difference.
Response to IL-2, however, varied considerably between patients. Tincati and colleagues divided the patient group into 23 (70%) IL-2 ‘responders’ and ten (30%) ‘non-responders’. Both responders and non-responders had an initial CD4 boost in response to the first cycle: a 161 cells/mm 3 increase in responders and a 95 cells/mm 3 increase in non-responders, meaning that non-responders still had an initial increase far in excess of that seen in patients on ART alone.
However although the CD4 count rises were quite well sustained in responders (up 61 cells/mm 3 at six months and up 135 cells/mm 3 at 18 months from baseline), they were not sustained in non-responders (up only 28 cells/mm 3 at six months, and 74 cells/mm 3 at 18 months, meaning they ended up with slightly lower CD4 counts than patients on ART alone). Further cycles of IL-2 did not produce any more significant CD4 rises in non-responders.
Nonetheless, the IL-2 therapy did appear to reduce considerably the danger of new AIDS-defining illnesses in the first few months on therapy. While new AIDS illnesses were diagnosed in six (15%) patients on ART, only one was diagnosed in a patient receiving IL-2 (3%). Although this difference just escaped statistical significance (p = 0.06), the researchers commented that “the finding of a reduced prevalence of patients developing AIDS-defining conditions suggests a possible efficacy” in the strategy of boosting with IL-2, “which may translate into earlier clinical benefit.”
Reference
Tincati C et al. Clinical effect of interleukin-2 (IL-2) immuno-adjuvant treatment in HIV+ advanced naïve patients. Ninth International Congress on Drug Therapy in HIV Infection, Glasgow, Abstract P1, 2008.
Obama Likely to Reverse Some Bush Administration HIV/AIDS Prevention, Family Planning Policies, Adviser Says
President-elect Barack Obama likely will undo U.S. family planning and HIV/AIDS prevention efforts that long linked funding to antiabortion and abstinence-only policies, Susan Wood -- co-chair of Obama's advisory committee for women's health and a professor at George Washington University's School of Public Health and Health Services -- said recently, Bloomberg reports. Wood said that although President Bush's global health programs -- such as the President's Emergency Plan for AIDS Relief -- have brought more HIV/AIDS treatment to developing countries than under any other president, spending requirements for abstinence-only education have hampered family planning and the prevention of sexually transmitted infections worldwide.
"We have been going in the wrong direction, and we need to turn it around and be promoting prevention and family planning services and strengthening public health," Wood said. She added that Obama "is committed to looking at all this and changing the policies so that family planning services -- both in the U.S. and the developing world -- reflect what works, what helps prevent unintended pregnancy, reduce maternal and infant mortality, prevent the spread of disease."
According to Bloomberg, one of Bush's policies that has been cited for hindering STI and HIV/AIDS prevention efforts is restrictions on condom education. Gill Greer, director-general of the International Planned Pregnancy Federation, said CDC has pulled some condom information from its Web site. Greer said, "The U.S. administration has certainly succeeded in demonizing condoms rather than showing that they can be part of prevention of both unplanned pregnancy and sexually transmitted infections."
Valerie Huber, executive director of the National Abstinence Education Association, said the Bush administration's emphasis on abstinence and fidelity "been shown to have demonstrable success in Africa," adding, "It would be more than unfortunate if that policy was changed." According to Huber, both Republicans and Democrats have cited support for PEPFAR's focus on abstinence and education, which has reduced the spread of HIV in countries such as Uganda. "If the president-elect wants to be science-based in foreign sex education policies, it would be wisest to continue this way because it's shown to be effective," Huber added.
Wendy Turnbull, a senior policy analyst with Population Action International, said that because of the "Mexico City" policy -- which restricts U.S. international foreign aid to family planning programs abroad using their own funds to provide abortion services or lobby their governments regarding abortion rights -- many family planning associations that rejected the terms of the rule "lost funding ... lost technical assistance and ... lost contraceptives." Under the basis of the policy, Bush also halted support for the United Nations Population Fund in 2002, saying it supported "coercive" abortion programs in China, an allegation the agency has denied, Bloomberg reports (Gale/Lauerman, Bloomberg, 11/10). The Los Angeles Times "Top of the Ticket" blog reports that the Mexico City policy is likely to be "quickly rescinded" after Obama takes office (Hoffecker, "Top of the Ticket," Los Angeles Times, 11/10).
According to Wood, the U.S. government in recent years has influenced and "tightly vetted" international organizations to reflect its own policies. She added that Obama will bring "back a sense of balance and perspective and the use of good science and good medicine in these positions, and not just this narrow, political ideology"(Bloomberg, 11/10).
Disclaimer: Please don’t assume that GMFA or the Pan London 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 londonservices@gmfa.org.uk.
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