The stubborn persistence and commitment of microbicide researchers, advocates and trial participants has finally seen some reward with positive results from a South African trial of the gel form of the antretroviral drug tenofovir. Originally due to be released on July 20th, the results were disclosed tonight after the UK Financial Times and two unnamed individuals who had been briefed on the findings apparently decided an exclusive story was more important than the normal ethical practice of honoring media embargoes. The news was quickly followed by official press releases and the publication of the paper describing the outcome of the trial – named CAPRISA 004 – in the journal Science. The lead authors are the wife-and-husband team of Quarraisha and Salim Abdool Karim.
Among a cohort of women at high risk of HIV infection followed for an average of 18 months, there were 38 infections in the group of 445 tenofovir gel recipients and 60 in the 444 placebo recipients. The HIV incidence rates were 5.6 per 100 women-years and 9.1 per 100 women-years, respectively, for an overall reduction in risk of 39% (95% confidence interval 6-60%). Efficacy was greater among the subgroup of women reporting high adherence to the gel with a 54% reduction in risk of HIV acquisition, albeit with an inevitably wider 95% confidence interval spanning 4-80% (the 95% confidence interval is a statistical assessment of the degree of uncertainty associated with the result). Although the data are not included in the Science paper, a fact sheet released by CAPRISA (Center for the AIDS Programme of Research in South Africa) and Family Health International reports that an analysis of HSV-2 incidence found a statistically significant 51% reduction in risk associated with receipt of tenofovir gel. The fact sheet notes that while several related compounds are known to have anti-HSV-2 activity, tenofovir has not been shown to be effective against the virus at standard doses, so the mechanism underlying this outcome remains to be clarified. The confidence intervals around the 51% efficacy against HSV-2 have not yet been reported but are likely to be made available when the official presentation of CAPRISA 004 is made at 1pm Central European Summer Time (7am EST) tomorrow at the 2010 International AIDS Conference. Further details about next steps and confirmatory trials should also emerge at that time.
A huge number of media outlets have now picked up on the story and these articles can be found via Google news.
Published Online July 19, 2010
Science DOI: 10.1126/science.1193748
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RESEARCH ARTICLES
Quarraisha Abdool Karim,1,2,*, Salim S. Abdool Karim,1,2,3,* Janet A. Frohlich,1 Anneke C. Grobler,1 Cheryl Baxter,1 Leila E. Mansoor,1 Ayesha B. M. Kharsany,1 Sengeziwe Sibeko,1 Koleka P. Mlisana,1 Zaheen Omar,1 Tanuja N. Gengiah,1 Silvia Maarschalk,1 Natasha Arulappan,1 Mukelisiwe Mlotshwa,1 Lynn Morris,4 Douglas Taylor,5 on behalf of the CAPRISA 004 Trial Group
The CAPRISA 004 trial assessed effectiveness and safety of a 1% vaginal gel formulation of tenofovir, a nucleotide reverse transcriptase inhibitor, for the prevention of HIV acquisition in women. A double-blind, randomized controlled trial was conducted comparing tenofovir gel (n = 445) with placebo gel (n = 444) in sexually active, HIV-uninfected 18- to 40-year-old women in urban and rural KwaZulu-Natal, South Africa. HIV serostatus, safety, sexual behavior, and gel and condom use were assessed at monthly follow-up visits for 30 months. HIV incidence in the tenofovir gel arm was 5.6 per 100 women-years, i.e., person time of study observation (38/680.6 women-years), compared to 9.1 per 100 women-years (60/660.7 women-years) in the placebo gel arm (incidence rate ratio = 0.61; P = 0.017). In high adherers (gel adherence >80%), HIV incidence was 54% lower (P = 0.025) in the tenofovir gel arm. In intermediate adherers (gel adherence 50 to 80%) and low adherers (gel adherence <50%), the HIV incidence reduction was 38% and 28%, respectively. Tenofovir gel reduced HIV acquisition by an estimated 39% overall and by 54% in women with high gel adherence. No increase in the overall adverse event rates was observed. There were no changes in viral load and no tenofovir resistance in HIV seroconverters. Tenofovir gel could potentially fill an important HIV prevention gap, especially for women unable to successfully negotiate mutual monogamy or condom use.
1 Centre for the AIDS Program of Research in South Africa (CAPRISA), Durban, South Africa.
2 Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA.
3 University of KwaZulu-Natal, Durban, South Africa.
4 National Institute for Communicable Diseases, Johannesburg, South Africa.
5 FHI, North Carolina, USA.
* These authors contributed equally to this work.
Published Online July 19, 2010
Science DOI: 10.1126/science.329.5990.374
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NEWS OF THE WEEK
At Last, Vaginal Gel Scores Victory Against HIV
Jon Cohen
For the first time ever, a vaginal gel has unequivocally blocked the transmission of HIV. In a trial that involved nearly 900 South African women, those who received a vaginal gel that contains an anti-HIV drug had a 39% lower chance of becoming infected by the virus than those who received a placebo. As reported today online in Science and in a presentation at the 18th International AIDS Conference in Vienna, of the 444 women who received a placebo gel, 60 became infected with HIV, versus 38 infections in the 445 women who received the microbicide. The result was statistically significant, and no serious side effects occurred.
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