A landmark study – Effectiveness and Safety of Tenofovir Gel, an Antiretroviral Microbicide, for the Prevention of HIV Infection in Women

In what is being hailed as a landmark study, researchers running a trial in South Africa to test a vaginal microbicide with the antiretroviral (ARV) drug called tenofovir found that it significantly reduced women’s risk of becoming infected with HIV by 39 per cent compared with placebo.

Dr Quarraisha Abdool Karim and her husband Dr Salim S. Abdool Karim, announced the results of the CAPRISA 004 trial at the start of the International AIDS Conference (AIDS 2010), which takes place in Vienna this week. They also co-authored a paper on the trial that was published online on 19 July in the journal Science.

The Abdool Karims split their time between CAPRISA (Center for the AIDS Program of Research in South Africa) and the Mailman School of Public Health in Columbia University, New York.

The successful result has the potential to alter the course of the HIV epidemic and save millions of lives, Quarraisha Abdool Karim said at a news conference reported by WebMD.

She asked reporters to imagine a scenario: she is a doctor advising a young South African woman about how to avoid becoming infected with HIV. The woman’s partner is a migrant worker, he refuses to wear a condom and will not allow her to wear a female condom.

Currently, Abdool Karim, and thousands of doctors like her, have little to offer, but soon, she will be able to tell this young woman, and other like her, that if she uses this new gel she has a 39 per cent chance of avoiding infection, and if she always uses it, that protection could go up to 54 per cent.

This successful result from CAPRISA 004 is welcome news because the picture was looking distinctly gloomy for microbicides: around 60 are currently undergoing trials, they have proved effective and safe in animals, but until this recent result, the only news has been of three trials stopping early because the microbicide was either ineffective or even harmful.

In the CAPRISA 004 double-blind, randomized controlled trial, the researchers tested the effectiveness and safety of a 1% vaginal microbicidal gel containing the ARV tenofovir, described as a “a nucleotide reverse transcriptase inhibitor”, in preventing HIV infection in women.

The researchers recruited nearly 900 sexualy active, HIV-free women aged between 18 and 40 years living in urban and rural KwaZulu-Natal, South Africa, and randomly assigned them either to receive the active gel (445 women), or an inactive placebo gel (444).

Every month for 30 months, the women underwent HIV tests, and answered questions about their sexual behavior, precautions, and gel and condom use.

The results showed that:

  • The incidence of HIV in the active gel group was 5.6 per 100 women-years (38 women got HIV, with a total of their age in years being 680.6).
  • This compared to 9.1 per 100 women years in the placebo group (60 women, 660.7 women-years).
  • Overall, there was a significant 39 per cent lower rate of HIV incidence in the active gel compared to the placebo group.
  • Among high adherers (more than 80 per cent adherence), HIV incidence was 54 per cent lower in the active gel group.
  • Among intermediate (50 to 80 per cent) and low (under 50 per cent) adherers, the reduction in HIV infection rate was 38 and 28 per cent respectively.
  • There were no serious side effects.

The researchers concluded that:

“Tenofovir gel could potentially fill an important HIV prevention gap, especially for women unable to successfully negotiate mutual monogamy or condom use.”

Dr Anthony S Fauci, Director of the National Institute of Allergy and Infectious Diseases at the National Institutes of Health, congratulated the CAPRISA 004 researchers, and told the press that this finding is an important step because women make up the majority of new HIV infections around the globe, and the gel will empower this at-risk population with a safe and effective preventive tool.

He stressed the importance of continuing to pursue research into a range of HIV prevention methods, and mentioned that another NIAID sponsored study called VOICE, which began last year and is expected to enrol 5,000 female participants in four South African countries, will also test a tenofovir-based vaginal gel as an HIV prevention method.

VOICE (Vaginal and Oral Interventions to Control the Epidemic) will investigate the gel’s acceptability as a once-daily application rather than a before and after intercourse gel. It will also examine oral ARV tablets (either tenofovir on its own or tenofovir plus emtricitabine) as a pre-exposure prophylaxis (PrEP).

VOICE is being conducted by the Microbicide Trials Network (MTN), whose principal investigator is Dr Sharon Hillier, also professor and vice chair for faculty affairs, and director of reproductive infectious disease research in the department of obstetrics, gynecology and reproductive sciences at the University of Pittsburgh School of Medicine. Commenting on the significance of the CAPRISA 004 result, she said it has “reinvigorated” the field of HIV prevention research:

“This is an incredibly important achievement for which the CAPRISA team is to be congratulated. For all of us in the HIV prevention field, this result has shown that it may be possible to leverage this initial success using a single ARV at the time of sex into more potent approaches that could be 50, 60 or even 70 percent effective for prevention of HIV,” said Hillier.

However, there are mixed views on the potential impact microbicides will have on HIV prevention at population levels.

Last year, in September’s issue of The Lancet, Daniel Halperin, a senior research scientist at Harvard University School of Public Health, was quoted as saying that although microbicides are important we should “not set too much store by the whole enterprise”; they could “undoubtedly” save lives, but the effect at the population level in South Africa is not clear.

Halperin said it was also important to strengthen strategies to promote partner reduction, increase condom use in high risk groups like sex workers, and increasing the availability of safe male circumcision.

But Dr Anthony Mbewu, President of the Medical Research Council in South Africa, suggested the impact of an effective microbicide should not be underestimated. He said that mathematical modelling showed that even if services in 73 lower-income countries reached only 20 per cent of women so they used a 60 per cent effective microbicide, this could prevent 2.5 million HIV infections over 3 years.

“Averting HIV infection is not a light phrase. Infection is lethal for many women and saving a life is not a trivial matter,” he told The Lancet.

“Effectiveness and Safety of Tenofovir Gel, an Antiretroviral Microbicide, for the Prevention of HIV Infection in Women.”
Quarraisha Abdool Karim, Salim S. Abdool Karim, Janet A. Frohlich, Anneke C. Grobler, Cheryl Baxter, Leila E. Mansoor, Ayesha B. M. Kharsany, Sengeziwe Sibeko, Koleka P. Mlisana, Zaheen Omar, Tanuja N. Gengiah, Silvia Maarschalk, Natasha Arulappan, Mukelisiwe Mlotshwa, Lynn Morris, Douglas Taylor, and on behalf of the CAPRISA 004 Trial Group.
Science Published online 19 July 2010.
DOI:10.1126/science.1193748

Additional sources: NIH/NIAID, The Lancet (Sep 09), Microbicide Trials Network, WebMD.Written by: Catharine Paddock, PhD for Medical News Today

HIV/AIDS in South Africa, 2nd Edition, Edited by S. S. Abdool Karim, University of KwaZulu-Natal, South Africa, and Q. Abdool Karim, University of KwaZulu-Natal, South Africa is published by Cambridge University Press

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