Studies confirm ART prevented HIV in uninfected heterosexual partners

Results from three recent trials indicate that once-daily antiretroviral therapy may reduce the risk for HIV infection among uninfected men and women exposed to HIV through heterosexual sex with an infected partner.

“Treatment is prevention, and these three studies provide the proof,” Elly Katabira, MD, IAS 2011 international chair and president of the International AIDS Society, said in a press release. “The XI International AIDS Conference in Vancouver in 1996 is remembered as the conference that heralded the arrival of combination antiretroviral treatment. The IAS 2011 Conference will be remembered as the beginning of the treatment as prevention revolution.”

As previously reported in Infectious Disease News, results from the HPTN 052 trial indicated HIV-infected men and women with otherwise healthy immune systems who initiated immediate oral ART were 96.3% less likely to infect their uninfected partners and remained healthier compared with those assigned delayed treatment.

Results from two new trials, TDF2 and the Partners PrEP study, were both presented today at the 6th IAS Conference on HIV Pathogenesis, Treatment and Prevention in Rome. After the unexpected release of the Partners PrEP data last week, the CDC released the TDF2 results early, “to ensure that all emerging trial data are concurrently available to fully inform public health and policy discussions moving forward,” according to a CDC press release.

TDF2 study

Data from the CDC’s TDF2 study conducted in collaboration with the Botswana Ministry of Health indicated that once-daily tenofovir disoproxil fumerate combined with emtricitabine (Truvada, Gilead Sciences) effectively reduced the risk for HIV infection by approximately 63% among uninfected heterosexual men and women.

Michael C. Thigpen, MD, of the division of HIV/AIDS Prevention at the CDC, and colleagues randomly assigned 1,219 HIV-seronegative participants aged 18 to 39 years (45.7% female) to either once-daily oral tenofovir disoproxil fumarate-emtricitabine or once-daily placebo.

Of the 33 participants who became infected with HIV (63.6% female), nine were assigned once-daily tenofovir disoproxil fumerate plus emtricitabine and 24 to placebo. This translated into an overall protective efficacy of 62.6% (95% CI, 21.5-83.4). After including only those on ART regimen when infected, efficacy increased to 77.9% (95% CI, 41.2-93.6).

Partners PrEP study

Preliminary findings from the phase 3, randomized, double blind, Partners PrEP study indicate that two different regimens, tenofovir (Viread, Gilead Sciences) and tenofovir disoproxil fumerate plus emtricitabine, both reduced HIV transmission among 4,758 couples in which one partner is infected with HIV and the other is not. This trial was halted early due to strong evidence of effectiveness of the drugs.

The trial was conducted by researchers at the University of Washington in collaboration with others across nine sites in Kenya and Uganda.

Compared with a 73% (95% CI, 49-85) reduction in HIV risk with tenofovir disoproxil fumerate plus emtricitabine, those assigned tenofovir had a 62% (95% CI, 34-78) reduced risk for HIV.

“These are exciting results for global HIV prevention. We now have findings from two studies showing that [pre-exposure prophylaxis] can work for heterosexuals, the population hardest hit by HIV worldwide,” said Kevin Fenton, MD, Infectious Disease News Editorial Board member and director of the CDC’s National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention. “Taken together, these studies provide strong evidence of the power of this prevention strategy.”

“These studies mark a turning point in HIV science and in HIV prevention,” Stefano Vella, MD, IAS 2011 local co-chair and research director at the Istituto Superiore di Sanità (ISS) in Rome, said in a press release. “The urgent challenge now is to implement treatment as prevention in the developing world."

For more information:

• Cohen M. # MOAX0102.
• Thigpen MC. # WELBC01. Both presented at: The 6th IAS Conference on HIV Pathogenesis, Treatment and Prevention; July 17-20, 2011; Rome.

PrEP with antimicrobial agents has been used successfully to block the transmission of infectious diseases, including influenza and malaria, and has been suggested for use in high-risk individuals to block HIV transmission. Data to date for PrEP in HIV had been less than exciting. Published in December 2010 in the New England Journal of Medicine, the iPrEx trial found that once-daily TDF/FTC conferred only a 44% reduction in HIV acquisition among men and transgender women who have sex with men. While resistance to either TDF or FTC was not seen in breakthrough infections, the protective effect was less than anticipated. In April 2011 the FEM-PrEP study was halted early, because HIV transmission in high-risk women was not affected by TDF/FTC. Nearly 2,000 women in Kenya, South Africa and Tanzania, were enrolled in this study. The same number of new HIV infections occurred in the placebo and TDF/FTC groups (n=28 in each group).

Data presented in Rome at the IAS meeting are much more encouraging. In TDF2, more than 1,200 heterosexual males and females in Botswana were enrolled. TDF/FTC decreased HIV incidence by 62.6%. Currently, there is no clear reason for the different efficacy rates seen in the different studies. TDF2 enrolled males and females, while FEM-PrEP studied women only. However, early analyses suggest that women in TDF2 were protected by TDF/FTC.

Similarly, TDF/FTC or TDF alone was used on heterosexual, discordant couples in Partners PrEP study. TDF/FTC use in the uninfected partner reduced HIV transmission by 73%, while TDF alone reduced it by 62%. As in TDF2, PrEP protected both men and women from HIV infection. Of course data from HPTN 052 established that treatment of the infected partner in discordant couples is very effective (96%) in blocking HIV transmission to the uninfected partner. Perhaps there are settings when one would choose to expose the uninfected partner to two drugs rather than treat the infected partner with three drugs.

Several other PrEP studies, phase 2 or 3, are on-going; each is testing TDF/FTC. One observation, TDF and FTC were arbitrarily chosen, because they are well tolerated, once-daily and coformulated. There is no priori reason for not using other drugs, either alone or combination, for chemoprophylaxis. In high-risk populations, post-exposure prophylaxis, three-drug regimens are recommended. Given the conflicting data from PrEP studies, perhaps consideration of other combinations is warranted.

Finally, PrEP for HIV raises many issues. If a PreP regimen is found to be unequivocally effective, several new questions need to be addressed. Who gets PreP and for how long? Who pays for PreP? How frequently do individuals on PrEP need to be tested for breakthrough infections or monitored for drug toxicity? Will condom use decrease, and the rates of other STI’s increase? Still, given the paucity of effective options, search for a clearly effective PrEP regimen must continue.

– Stephen Smith, MD

Infectious Disease News Editorial Board member

Disclosure: Dr. Smith reports no relevant financial disclosures.

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