A demonstration project in three major US cities has shown a very low incidence of HIV infection, despite a high incidence of other sexually transmitted infections (STIs), in high-risk patients given free preexposure prophylaxis (PrEP) for HIV.
The study was published online November 16 in JAMA Internal Medicine.
The report represents the first from several large demonstration projects begun since the US Food and Drug Administration approved PrEP in 2012, and provides evidence for the effectiveness of PrEP in community settings.
"The low HIV incidence observed in the Demo Project likely reflects high overall adherence to PrEP and demonstrates that high levels of effectiveness can be achieved outside controlled studies," first author Albert Y. Liu, MD, MPH, from the San Francisco Department of Public Health in California, and coauthors write.
About two thirds of new HIV infections in the United States occur in men who have sex with men (MSM). Several randomized controlled trials have supported the efficacy of PrEP for HIV prevention. Outside of clinical trials, however, questions remain about adherence to and overall effectiveness of PrEP, as well as sexual practices of MSM treated at community STI clinics, according to the authors.
The open-label study took place at two municipal STI clinics in San Francisco and in Miami, Florida, and at a community health center in Washington, DC. The researchers enrolled 550 MSM and seven transgender women between October 2012 and February 2014, with follow-up occurring until February 2015.
Participants received free PrEP (combined daily oral tenofovir disoproxil fumarate and emtricitabine) and $25 for attending visits at 4, 12, 24, 36, and 48 weeks, at which points they received HIV testing, counseling, and clinical monitoring.
Researchers assessed PrEP blood levels from dried blood spot samples in 100 randomly selected participants at each site as well as in all African-American and transgender participants.
Interviewers assessed adherence using questionnaires, pill counts, and the medication possession ratio (number of dispensed pills divided by the number of days between visits). They also used questionnaires to evaluate sexual behavior, drug use, and depressive symptoms.
Of the 557 participants who started PrEP, 437 (78.5%) completed all 48 weeks of follow-up. Participants had mean PrEP adherence rates of 81.6% based on pill counts, 85.9% based on medication ratio, and 87.4% based on self-report.
African Americans, participants at the Miami clinic, those with lower socioeconomic status, and the uninsured had lower adherence.
Of 294 participants with tenofovir diphosphate levels tested, between weeks 4 and 48, from 80.0% to 85.6% had protective levels suggestive of four doses.
Protective levels were less likely among African Americans (56.8% of visits; P = .003) and those seen at the Miami clinic (65.1% of visits; P < .001).
Participants with stable housing (86.8%; P = .02) and those who reported at least two condomless anal sex partners in the last 3 months (88.6%; P = .01) had higher likelihood of having protective levels.
During follow-up, the mean number of anal sex partners in the last 3 months decreased from 10.9 to 9.3 (P = .04). The percentage who participated in condomless receptive anal sex stayed about the same, at between 65.5% and 65.6% (P = .99).
The incidence of STIs, although high overall, at 90 per 100 person-years, remained about the same during the study.
Two HIV infections occurred (HIV incidence, 0.43 [95% confidence interval, 0.05 - 1.54] infections per 100 person-years). Both participants had tenofovir diphosphate levels suggestive of less than two doses per week at the time of infection.
The authors note that the study underrepresented African Americans and transgender individuals, and that results may not generalize to a broader population. Cost and lack of insurance could also constitute major obstacles to PrEP access and adherence.
"These results provide support for expanding PrEP implementation in MSM in similar clinical settings and highlight the urgent need to increase PrEP awareness and engagement and to develop effective adherence support for highly affected African American and transgender populations," the authors conclude.
In an invited commentary, Raphael Landovitz, MD, from the David Geffen School of Medicine at the University of California, Los Angeles, notes that the overall news from the study is "good," but also provides "sobering lessons."
The Miami results may indicate that acceptance of PrEP may vary widely by region and culture, he points out. In addition, this study included highly motivated clinics experienced with PrEP, and the results may not generalize to other types of clinics. In particular, financial and insurance barriers, self-efficacy issues, and finding a clinic that can provide PrEP and do PrEP monitoring may represent major barriers.
"The so-called PrEP cascade requires identification of at-risk individuals, promotion of interest and knowledge of PrEP, linkage to PrEP-knowledgeable clinics, and PrEP initiation, persistence, and adherence," he emphasizes. "The benefits of PrEP will only fully be realized when we can identify ways of successfully moving persons at a high risk of HIV infection through this cascade."
One coauthor reports employment by Gilead Sciences. One or more authors report drug, contract work, or research support; serving on speakers bureaus and/or advisory boards; or research grants from one or more of the following: Gilead Sciences, Cepheid Inc, SeraCare Life Sciences, Melinta Therapeutics, Abbott Diagnostics, Roche Diagnostics, BMS, Janssen, Viv, and Merck. Dr Liu and two coauthors report leading trials in which the study drug was donated by Gilead Sciences. Dr Landovitz reports having previously served as a consultant to Gilead Sciences.
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Cite this: PrEP Effective in High-risk Group in Three-City Project - Medscape - Nov 17, 2015.