DURBAN, South Africa — Pre-exposure prophylaxis (PrEP) is proving to be an effective way to minimize the transmission of HIV infection, according to studies presented here at the International AIDS Conference 2016.
Wherever PrEP has been tested — whether in Africa or the United States — "we have consistently seen that adherence and the benefit from that adherence is better than it is in clinical trials," said Jared Baeten, MD, PhD, vice chair of the Department of Global Health and codirector of the International Clinical Research Center at the University of Washington in Seattle.
"And that's what we saw in the Partners Demonstration Project," he told reporters attending a news conference. The risk for HIV transmission was virtually eliminated in serodiscordant couples who adhered to an integrated regimen of antiretroviral therapy and PrEP.
"We have seen this now repeatedly — and I emphasize repeatedly," Dr Baeten said. "Knowing that something works, knowing that it's the real deal, and knowing that it's safe makes a huge difference in adherence," he explained. In contrast, in clinical trials, where neither the researchers nor the participants know the safety or efficacy of a drug, adherence can be an issue.
The open-label, prospective, interventional Partners Demonstration Project involved 1013 HIV-serodiscordant heterosexual couples recruited from four clinical sites in Kenya and Uganda. Participants were followed for 2 years.
Partners Demonstration Project
If the HIV-infected partner initiated antiretroviral therapy at study enrolment, the uninfected partner was offered PrEP for 6 months, allowing time for viral suppression in the infected partner. If the initiation of antiretroviral therapy was delayed, the use of PrEP could be prolonged.
"Ninety-seven percent of couples who were offered PrEP took it, and adherence was high — at over 80%," Dr Baeten reported.
Similarly, more than 90% of the HIV-positive partners initiated antiretroviral therapy, although about half delayed the initiation for 6 months or longer.
There were four incidents of HIV transmission during the study period — from November 2012 to June 2016 — but none of the people who seroconverted used PrEP.
The researchers estimated that 83 infections were prevented with the integrated regimen (risk reduction, 95%; P < .0001).
"Our results demonstrate that time-limited PrEP as a bridge to antiretroviral therapy is not only feasible, it is highly effective in preventing HIV transmission in serodiscordant couples," said Dr Baeten.
"This project is the first in Africa to demonstrate the effectiveness of PrEP outside of a clinical trial setting, and we observed the virtual elimination of HIV transmission," he pointed out.
In the United States, the open-label Project PrEPare evaluated the safety of PrEP, and adherence, in high-risk HIV-negative males 15 to 17 years of age.
Eligibility criteria included self-reports of at least one high-risk sexual behavior, such as condomless anal intercourse with an HIV-infected male partner or a partner of unknown HIV status.
Mean age of the 79 study participants was 16.5 years.
"Participants did not require parental consent to participate in this study," Sybil Hosek, PhD, from the Cook County Health and Hospitals System in Chicago, said during the news conference.
At baseline, about 15% of the adolescents had a sexually transmitted infection. At the end of the 48-week study period, the incidence had declined to 11%.
After the initiation of PrEP, participants were seen monthly. For the first 12 weeks of the study, levels of the drug were detectable in 95% of the cohort. And in more than half the adolescents, highly protective drug levels were detected, "indicating they were taking four or more doses a week," Dr Hosek reported.
PrEP was well tolerated and there were no discontinuations related to adverse events.
After week 12, visits were cut back to every 12 weeks. By week 24, "we started to see a pretty drastic decline in protective drug levels and an increase in participants who were not taking the medication at all," she reported.
There were three incidents of seroconversion during the study period.
"This, plus the presence of STIs, tells us that in the absence of PrEP, there are likely to be more HIV infections," Dr Hosek said. "This highlights the absolute need for access to PrEP for those under the age of 18."
The fact that tenofovir disoproxil fumarate and emtricitabine (Truvada, Gilead Sciences) is not licensed for anyone younger than 18 makes it extremely difficult for high-risk youth to access PrEP, she told Medscape Medical News.
"People are prescribing PrEP off-label, but that influences whether young people can get insurance for it," she explained. "They can't access the Gilead copayment plan if they are under 18 because the drug is being used off-label. That's really the critical piece here: to get the drug licensed. Hopefully, data from this study will allow young people access to PrEP."
Dr Hosek said she has no doubt that young people will consider taking PrEP for HIV prevention if they know it's an option.
"Taking a pill every day is outside the adolescent realm of thinking," she pointed out. "But adolescents enjoy taking control of their sexual health, and participants in our project all felt that they were doing something really good for themselves." They just need strategies and support to do it, she added.
Gilead Sciences is in the process of trying to secure an indication for people younger than 18.
"A theme that is emerging from this conference is how many young people, especially young women, are contracting HIV," said Katherine Gill, MD, from the Desmond Tutu HIV Centre in Cape Town, South Africa.
In fact, adolescent girls in South Africa, where PrEP is not currently funded, are up to eight times more likely to become infected with HIV than adolescent males, and this is the only age group in which death rates have been climbing since 2001.
"If we want to end AIDS, we cannot leave this group behind," Dr Gill told reporters.
In the PlusPills Project, sponsored by the National Institutes of Health, young men and women at risk for HIV infection were given 3 months of PrEP, after which they could choose to continue with the medication or abandon it.
Median age at study enrolment was 18 years, and median age of sexual debut was 15 years. Almost half the group reported infrequent condom use, and more than one-third tested positive for a sexually transmitted infection.
Of the 148 participants involved in the project, "90% chose to continue with PrEP after 3 months," Dr Gill reported.
At 3 months, 72% of the group reported that they took more than six pills a week, and roughly the same percentage had tenofovir plasma levels in excess of 40 ng/mL.
Preliminary results suggest that early adherence to PrEP was reasonable and adverse effects were minimal, said Dr Gill.
"We will continue to try to understand what motivates adolescents to make the choices they do and what we can do to keep them safe during this risky time of their lives," she added. "With this project, we now have something to offer adolescents for the first time."
Dr Baeten, Dr Hosek, and Dr Gill have disclosed no relevant financial relationships.
International AIDS Conference 2016: Abstracts WEACO105, TUAX0104LB, and LBPE018. Presented July 19 and 20, 2016.
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Cite this: Real-World PrEP Use Virtually Eliminates HIV Transmission - Medscape - Jul 21, 2016.