No New HIV Infections Seen Over 2.5 Years in Kaiser San Francisco PrEP Program

The number of people accessing Truvada pre-exposure prophylaxis (PrEP) through the large Kaiser Permanente San Francisco healthcare system has increased dramatically since 2012, and no new HIV infections have been reported so far, according to study results published in the September 1 advance edition of Clinical Infectious Diseases. Rates of sexually transmitted infections (STIs) were high -- reaching 50% after a year on PrEP -- and some gay men reported a drop-off in condom use, but PrEP offers an opportunity for timely STI diagnosis and treatment, the researchers said.

Jonathan Volk, Bradley Hare, and colleagues from Kaiser Permanente San Francisco analyzed patterns of PrEP use among members seen at the Kaiser Permanente Medical Center in San Francisco, looking at trends in PrEP referrals and initiation, incidence of HIV and STIs among PrEP users, and self-reported changes in condom use and number of sexual partners. Hare previously reported some preliminary findings at a December 2014 World AIDS Day forum in San Francisco.

The Food and Drug Administration approved Gilead Sciences' Truvada (tenofovir/emtricitabine) for PrEP in July 2012, and In May 2014 the Centers for Disease Control and Prevention (CDC) recommended that people at substantial risk for HIV infection should consider PrEP. The approval and recommendation were based in part on data from the iPrEx trial of mostly gay and bisexual men, which showed that once-daily Truvada reduced the risk of HIV infection by 42% overall compared to placebo, rising to 92% among participants with blood drug levels indicating regular use. More recently 2 other randomized PrEP trials for men who have sex with men (MSM) -- the U.K. Proud and French Ipergay studies -- found that daily or "on demand" Truvada reduced the risk of HIV infection by 86%.

As reported last month, a non-randomized PrEP Demo Project in San Francisco, Miami, and Washington, DC saw good adherence overall, and the 2 new HIV infections during follow-up occurred in men with low or undetectable tenofovir levels at the time of seroconversion. But there is not yet much data on PrEP use in regular clinical practice.

Kaiser's primary care and other providers refer clients to a specialized PrEP program after risk assessment or upon request. People seeking PrEP are tested for HIV infection and STIs and screened for medical contraindications to Truvada (such as pre-existing kidney or bone problems). The program provides adherence support and clinical monitoring including safety assessments and HIV and STI screening every 1 to 3 months while on PrEP. Beginning in July 2014 participants were surveyed about changes in their sexual behavior after starting PrEP.

This analysis included more than 1000 Kaiser SF members -- mostly gay and bi men -- evaluated for PrEP from its July 2012 FDA approval through February 2015. The researchers looked at cumulative HIV and STI incidence (new infections) after 6 and 12 months, comparing people who started PrEP and those who decided not to do so after referral.

Results

• From July 2012 through February 2015 there were 1045 total referrals for PrEP, of which 835 (80%) led to an in-person evaluation.
• Of the 801 participants with at least 1 intake visit, 657 people (82%) opted to start PrEP -- including 20 who restarted PrEP after discontinuing it -- while 144 people (18%) decided not to do so.
• PrEP referrals and the number of people starting PrEP began to rise around September 2013, with a steeper increase after the CDC recommendation in May 2014.
• Among the 657 people who started PrEP, 99% were men who have sex with men, 3 were heterosexual women, and 1 was a transgender man with male sexual partners; the mean age was 37 years (range 20-68 years).
• 1 PrEP user reported injection drug use, and 15 reported using post-exposure prophylaxis (PEP) during the 3 months prior to PrEP initiation.
• There were no differences in age or gender between people who started or decided against PrEP.
• PrEP users were significantly more likely than non-users to report multiple sex partners (84% vs 69%), but were similarly likely to report having an HIV-positive partner (30% vs 25%).
• Among the 144 people who decided against PrEP, the reasons included low HIV risk (35%), cost (15%), not wanting to do required follow-up (10%), preferring PEP as a prevention strategy (6.3%), concern about side effects (2.8%), and concern about potentially increasing their sexual risk behavior (1.4%).
• Only a small number of people were ineligible for PrEP for medical reasons, including 2.8% with pre-existing HIV infection, 1.4% with impaired kidney function, and 0.7% with osteoporosis.
• No new HIV diagnoses occurred among PrEP users during 388 person-years of follow-up.
• 187 PrEP users were diagnosed with at least 1 STI during follow-up -- including 78 with multiple STIs -- giving a total of 344 STI diagnoses.
• After 6 months on PrEP, 30% of participants were diagnosed with any STI, 18% had a rectal STI, 17% had chlamydia, 15% had gonorrhea, and 3.3% had syphilis; after 12 months, the corresponding percentages were 50%, 33%, 33%, 28%, and 5.5%, respectively.
• Among the 143 PrEP users who completed a survey about changes in sexual behavior after 6 months on PrEP, 56% said their condom use was unchanged, 41% reported a decrease, and 3% reported an increase; 74% said their number of sexual partners stayed the same, 15% reported a decrease, and 11% reported an increase.
• No factors were found to predict decreased condom use or an increased number of sexual partners, including age, history of STIs, having an HIV-positive partner, recent methamphetamine or cocaine use, or self-reported PrEP adherence.

"We observed a dramatic increase in PrEP use in a clinical practice setting, with no new HIV infections among PrEP users," the researchers summarized. "This was despite high rates of STIs -- rectal STIs in particular -- and self-reported decreases in condom use in 41% of a subset of PrEP users."

The authors noted that based on data from the placebo arm of a PrEP trial with a similar high rate of rectal STIs, they would have expected an HIV incidence as high as 8.9 per 100 person-years without effective PrEP.

The high rates of STIs in this study are a concern, and "reinforce that ongoing screening and treatment for STIs, including hepatitis C, remain an essential component of PrEP delivery," they wrote. "Given that STIs are independently associated with HIV acquisition, the frequent STI screening in our PrEP program may have facilitated earlier diagnosis and treatment of these infections and thus contributed to the protective benefit of PrEP against HIV infection."

Hare and colleagues previously reported in the February 18 issue of Clinical Infectious Diseasesthat 2 HIV-negative men gay receiving PrEP at Kaiser had been newly infected with hepatitis C virus (HCV), with sex being their only apparent risk factor.

The decline in condom use by many men in this study conflicts with findings from PrEP clinical trials that mostly have not shown evidence of so-called "risk compensation," or use of one prevention strategy leading to an increase in other risky practices. But in the pivotal randomized PrEP trials such as iPrEx, participants did not know whether they were getting the active drug or placebo, and it was not yet clear that PrEP was highly effective for preventing HIV infection.

"Interest in and use of PrEP was almost exclusively among MSM, reflecting the HIV epidemic in San Francisco and a rapid increase in awareness and acceptance of PrEP use in this community," Volk and colleagues concluded. "While demand for PrEP is growing among MSM, outreach is needed to others at risk for HIV, including transgender women, heterosexual men and women, and people using injection drugs."

The Volk study showed a "dramatic increase" in PrEP uptake approximately 1 year after FDA approval, Kimberly Koester and iPrEx lead investigator Robert Grant from the University of California at San Francisco noted in an accompanying editorial commentary.

"This striking uptake produced an expected and most desired outcome -- no new HIV infections -- among a population vulnerable to HIV," they wrote. "Given the historical devastation wrought by HIV/AIDS within the city of San Francisco and elsewhere, this is tremendously good news…The data published by Volk and colleagues demonstrates meaningful progress towards the goal of halting new infections."

Regarding the high rate of STIs seen in this study, they wrote, "The increased frequently of STI testing offered during PrEP services affords more timely diagnosis and treatment of STIs, and high rates of diagnosis may reflect greater diagnostic yield rather than changes in sexual behavior…What appears to be high rates of STI diagnosis may reflect appropriate use of PrEP by people who have the most to benefit and people staying closer to their medical home for sexual health services."

"It is time for a vigorous conversation about sexually transmitted infections, too long eclipsed by fear of HIV infection," Koester and Grant advised. "Feeling safer from HIV infection while using PrEP creates space for a more robust discussion of STIs."

9/2/15

References

JE Volk, JL Marcus, T Phengrasamy, CB Hare, et al. No New HIV Infections with Increasing Use of HIV Preexposure Prophylaxis in a Clinical Practice Setting. Clinical Infectious Diseases. September 1, 2015 (Epub ahead of print).

KA Koester and RM Grant. Keeping Our Eyes on the Prize: No New HIV Infections with Increased Use of HIV Pre-exposure Prophylaxis (Editorial commentary). Clinical Infectious Diseases. September 1, 2015 (Epub ahead of print).

Other Source

Kaiser Permanent. Large Study of PrEP Use in Clinical Practice Shows No New HIV Infections. Press release. September 1, 2015.