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
Science Express Index
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
Science Express Index
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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