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PrEP News from IAS 2013

, by Liz Highleyman

IAS2013THUMBSeveral studies presented at the 7th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2013) in Kuala Lumpur shed further light on pre-exposure prophylaxis, or PrEP, including how it might be made more effective.

Gay Men

Robert Grant from UCSF’s Gladstone Institutes discussed the latest findings from iPrEx, the groundbreaking trial of Truvada (tenofovir plus emtricitabine) PrEP for men who have sex with men (abstract WELBC02). As previously reported, the study showed that PrEP reduced the risk of HIV sexual transmission by 42% overall, and up to 99% among those with drug levels in their blood corresponding to daily use.

At the IAS meeting, Grant reported the first data from an open-label extension of the trial after the randomized Truvada versus placebo phase, known as iPrEx OLE. A majority (65%) of the original 2,340 iPrEx participants who remained HIV-negative said they would like ongoing access to Truvada for prevention. Older participants, those with less education, those reporting sexual risk behavior, and those with detectable drug levels in the original trial were more likely to continue PrEP. But nearly two-thirds of people with undetectable blood drug levelsindicating they did not take Truvada regularlystill wanted to continue.

The most common reason for not continuing on Truvada was side effects, reported by 49%. In addition, 15% did not like taking daily pills, 14% decided they could manage their HIV risk without PrEP, and 9% were concerned about drug resistance. Smaller numbers worried that taking PrEP would make others think they were HIV positive or gay.

Blood drug level testing during the first 12 weeks of iPrEx OLE revealed that more participantsdouble at some siteshad detectable levels in the extension than in the original randomized trial. This suggests that people might be more adherent once they know they are receiving Truvada rather than placebo, and once they know PrEP works.

Injection Drug Users

As reported last month, the Bangkok Tenofovir Study found that daily tenofovir reduced the risk of HIV infection among more than 2,400 people who inject drugs. Risk fell by 49% overall and by 74% among participants who took tenofovir via directly observed therapy. But the study could not determine whether PrEP worked by preventing infections due to needle-sharing or sex.

Michael Martin (photo: Jan Brittenson)

Michael Martin (photo: Jan Brittenson)

Michael Martin from the Centers for Disease Control and Prevention presented detailed findings from the study (abstract WELBC05). As in iPrEx, the protective effect in the Bangkok study increased with greater adherence as measured by blood drug levels. Preventive efficacy was 54% among participants with 67% adherence, rising to 68% for those with 90% adherence, 72% with 95% adherence, and 84% with 98% adherence.

A poster by the Bangkok Study Team (abstract MOLBPE27) looked at factors associated with infection. Over time, fewer participants reported sharing needles or injecting at all, which could help explain why PrEP appeared more effective later in the study. Sexual risk behavior also declined during the trial. These changes, the researchers suggested, were likely due to risk-reduction counseling, HIV education, and methadone maintenance offered to study participants.

Only three factors were significantly associated with higher risk: needle-sharing (8.9-fold higher), incarceration (2.7-fold higher), and being under age 30 (1.9-fold higher). No sexual risk factors were found to be significant predictors. Since needle-sharing was the strongest risk factor, this suggests new infections were largely attributable to injection, and PrEP did in fact reduce injection-associated HIV transmission.

PrEP for Women

Unlike iPrEx, the Bangkok study, and the Partners PrEP study of heterosexual couples, the Fem-PrEP and VOICE studies could not demonstrate that oral tenofovir or Truvada had a protective effect for women in Africa because adherence was so low. Drug level measurements revealed that less than 40% of the women in Fem-PrEP had taken their pills within the past 48 hours, and even fewer did so daily. Still, more than 80% remained in the study and returned for regular follow-up visits, with most reporting good adherence.

Christina Wong from FHI 360 presented findings from in-depth interviews with a randomly selected 5% of the more than 2,100 Fem-PrEP participants in Kenya and South Africa (abstract WEAC0104).

The most commonly mentioned reason for joining and staying in the trialcited by more than 60%was personal benefits besides PrEP, including regular health care, prevention education, free condoms, pregnancy testing, and monthly HIV testing. In fact, the women appeared to be relying on the prevention support and regular testing they received in lieu of actually taking PrEP as directed. One-third said they participated in the trial to help other people or their community.

One situation where PrEP may be useful is when an HIV-negative woman and HIV-positive man wish to conceive a child. Researchers with the Partners PrEP trialwhich showed that Truvada reduced transmission risk within heterosexual couples in Africa by 73%looked at outcomes among women who became pregnant during the study (abstract WEAC0101).

About 10% of participating women became pregnant. Although they stopped tenofovir after a positive pregnancy test, many infants were exposed in the womb early in the first trimester. Comparing women who took tenofovir alone, Truvada, or placebo, there were no differences in number of pregnancies, miscarriages, stillbirths, pre-term deliveries, birth defects, birth weight, or early infant growth.

The researchers concluded that PrEP is safe for pregnant women. However, a mathematical model suggested it may not offer much additional benefit for women whose positive partners are on effective antiretroviral therapy (abstract TUAC0104). The HPTN 052 trial showed “treatment as prevention” can reduce transmission risk by 96% among heterosexual couples.

For couples who only had unprotected sex during fertile periods, treatment for the man and PrEP for the woman both reduced transmission risk, but adding PrEP to treatment did not provide significant extra protection, according to the model.

PrEP Delivery

Taken together, these findings confirm that antiretroviral PrEP can be highly effective, but only when used consistently, which many study participants did not do. Roy Gulick from Weill Medical College gave an overview of new drugs and delivery systems during a special session on antiretrovirals for primary HIV prevention.

Key features of agents most suitable for PrEP include penetration into target tissues (such as genital mucosa), long-lasting activity to allow convenient dosing, a high barrier to resistance, and being affordable and easy to use.

Among the potential PrEP drugs Gulick discussed, maraviroc (Selzentry) has demonstrated protection in animal studies and is now being tested for gay men and women in the ongoing NEXT-PrEP (HPTN 069) trial.

Newer antiretrovirals under investigation for PrEP include the NNRTIs dapivirine and rilpivirine (Edurant), the entry inhibitor ibalizumab, and the integrase inhibitor GSK1265477. In addition to pills, other delivery methods include injections and vaginal rings.

One study presented at the conference showed that two antiretroviral drugs in long-acting nanosuspensionsthe GSK1265477 and TMC278-LA, an extended formulation of rilpivirineproduced adequate blood levels when taken once-monthly or even quarterly, and appeared safe in HIV-negative study volunteers (abstract WEAB0103).

Advances such as these in PrEP delivery could help people adhere better to therapy, yielding benefits for HIV prevention as well as treatment.

The full IAS 2013 program is available online.

Liz Highleyman (liz (at) hivandhepatitis.com) is a freelance medical writer and editor-in-chief of HIVandHepatitis.com.

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