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Antiretroviral drugs protect against HIV
Results of three large studies, presented at the recent International AIDS Society (IAS) Conference on HIV Pathogenesis, indicate that pre-exposure prophylaxis of antiretrovirals can prevent HIV when used by heterosexual men and women.1,2
These studies mark a turning point in HIV science and in HIV prevention, stated Stefano Vella, MD, IAS 2011 co-chairman and research director at the Istituto Superiore di Sanità in Rome. The urgent challenge now is to implement treatment as prevention in the developing world, Vella urged in remarks issued during the conference presentation.
Margaret Chan, MD, MSc, director-general of the Geneva, Switzerland-based World Health Organization (WHO), said in a statement issued in tandem with the conference presentation, "Effective new HIV prevention tools are urgently needed, and these studies could have enormous impact in preventing heterosexual transmission. WHO will be working with countries to use the new findings to protect more men and women from HIV infection."
The Centers for Disease Control and Prevention (CDC) is reviewing the data from the conference. It and will begin working with a range of stakeholders and with established guidelines development working groups to prepare guidance specific to the use of PrEP among U.S. heterosexuals.
Take a closer look
The Partners PrEP (pre-exposure prophylaxis) Study is a phase III, randomized, double-blind, placebo-controlled trial of daily oral tenofovir and emtricitabine/tenofovir for the prevention of HIV-1 acquisition among HIV-1 seronegative partners in heterosexual HIV-1 serodiscordant partnerships. Coordinated by the University of Washington in Seattle in collaboration with investigators at nine sites in Kenya and Uganda, the study enrolled 4,758 HIV-1 serodiscordant couples. The HIV-1 uninfected partners were randomly assigned in equal numbers to one of three study groups: those receiving tenofovir, emtricitabine/tenofovir, or placebo. All study participants received a comprehensive package of HIV-1 prevention services.
Study results indicate tenofovir reduced HIV-1 risk by 62% (95% confidence interval [CI] 34 to 78, p = 0.0003), emtricitabine/tenofovir by 73% (95% CI 49 to 85, p < 0.0001). Efficacy for tenofovir and emtricitabine/tenofovir were not statistically different. More than half (62%) of HIV negative participants were male, 38% were female; both PrEP medications reduced HIV-1 risk in men and women, researchers report. Adherence to the daily PrEP medication was high; more than 97% of dispensed doses of the study medications were taken. More than 95% of participants were retained in study follow-up.1
An independent data and safety monitoring board recommended in July 2011 that study results be reported and the placebo arm discontinued due to definitive demonstration of HIV-1 protection from PrEP in the study population.
What now happens to those enrolled in the study? Participants on the active PrEP arms are continuing in the study to gather additional comparative information about the safety, efficacy, and tolerability of tenofovir versus emtricitabine/tenofovir PrEP, according to Jared Baeten, MD, PhD, co-chair of the study and associate professor of global health and medicine at the University of Washington in Seattle. Participants in the placebo arm are discontinuing study medication; they will be offered active PrEP at the study clinics, he states.
Check the data
The TDF2 study, conducted by the CDC in partnership with Botswana Ministry of Health study, is a randomized, placebo-controlled trial designed to study the safety and efficacy of a once-daily tablet of tenofovir disoproxil fumarate and emtricitabine (TDF/FTC, Truvada, Gilead Sciences, Foster City, CA) for reducing the risk of HIV acquisition among heterosexual men and women at two sites in Botswana. In addition to study medication, all participants received a comprehensive package of HIV prevention services.
Researchers report that TDF/FTC reduced the risk of acquiring HIV infection by about 63% overall in the study population (95% CI, 21.5 to 83.4; p = 0.0133) and by 78% among trial participants believed to be taking study medications (95% CI 41.2 to 93.6, p = 0.0053). Adherence as measured by pill count was high, both among those receiving TDF/FTC (84.1%) and those receiving placebo (83.7%). Reported sexual risk behavior was similar between the two study arms.2
More proof offered
In the third study presented at the IAS conference, researchers from the HIV Prevention Trials Network (HPTN) 052 study reported that men and women already infected with HIV had a reduced risk of transmitting the virus to their uninfected sexual partners by 96% through early initiation of combination antiretroviral therapy (cART). HPTN 052 also found that early initiation of cART benefits the HIV-infected individual, researchers note.
The trial was conducted at 13 study sites in nine countries: Botswana, Brazil, India, Kenya, Malawi, South Africa, Thailand, the United States and Zimbabwe. It was designed to evaluate whether early versus delayed use of cART by HIV-infected individuals would reduce transmission of HIV to their uninfected partners and benefit the HIV-infected individuals as well. During the study, 39 participants who had been HIV-uninfected at the start of the study became infected with HIV. Of those, 29 were linked transmissions, where the virus from the originally infected sexual partner was confirmed by genetic analysis to be the source of infection in the newly infected partner. Only one of the 29 infections occurred in the early cART arm, researchers report. Based on the latest analyses, the lone transmission most likely occurred close to the time the couple enrolled in the study and before HIV viral replication could have been suppressed by cART in the infected participant, scientists hypothesize.3
The new analyses also shed light as how early initiation of cART benefits the HIV-infected person. Individuals who were put on early cART maintained higher absolute CD4 counts than those in the delayed arm, who received treatment when their CD4 counts fell below 250 cells/mm3 or an AIDS-related event occurred. Data indicates early cART was associated with a 41% reduction in HIV-related illnesses or death, a direct benefit for the HIV-infected partner.3
Initial results of the HPTN 052 study were released in May 2011 by an independent data safety monitoring board. Those results have just been published.4 How do the results presented at the IAS conference differ from those initially reported?
Myron Cohen, MD, J. Herbert Bate Distinguished Professor of Medicine, Microbiology and Immunology, and Public Health at the University of North Carolina at Chapel Hill and lead investigator of the HPTN 052 trial, says, "Critically important, we showed novel methods to link cases with virology. We explained the single transmission event from the person on ART, and using virology, provided the most likely explanation for the rare slippage.'"