JMIR Publications

ABSTRACT

Background:

Pre-exposure prophylaxis (PrEP) programs have implemented in multiple countries, evidences from studies have shown that the biological protection conferred by PrEP. However, there are few data on tenofovir use alone as PrEP. We did a large succession of trials to verify the feasibility, effectiveness, safety and concomitant behavior change of PrEP among individuals at high risk of HIV infection in China.

Methods:

We conducted 3 phases of trials. Phase I contained a cross-sectional study, pharmacokinetic studies and a pilot trial of PrEP. Phase II was a multi-center, randomized, open label, parallel controlled clinical trial, participants were randomly assigned (1:1:1) to time driven group (tenofovir 300mg administered orally once daily), event driven group (tenofovir 300mg administered orally 24-48 hours before sexual activity and 2h after sexual activity, not exceding 300mg within 24 hours) and blank group. Phase III was multi-center, randomized, open label, parallel controlled clinical trial, participants were randomly assigned (1:1) to smart alert group (orally once daily medication with smart alert system) and normal medication group (orally once daily medication). The primary outcomes were the acceptance and pharmacokinetic characteristics of PrEP, the incidences of HIV infection and ADRs (adverse drug reaction) during individuals’ periods of PrEP use. The secondary outcomes included the adherence rates, hazard components of HIV infection and behavior change across individuals initiating PrEP to the last visit. For ethical principles, all participants were provided with condoms and received health education. This study was registered with Chinese Clinical Trial (ChiCTR-TRC-13003849, ChiCTR190026414).

Results:

In phase I (from Oct 2008 to Oct 2010), a total of 3493 high-risk participants were enrolled to a cross-sectional study, 2620 (75·1%) participants would use PrEP and 1100 (36·1%) was willing to participate in clinical trials of PrEP. Pharmacokinetic study of PrEP in 80 healthy subjects were shown that the Cmax, Tmax, T1/2 and AUC0-∞ of single dose and multiple dose of tenofovir were 290·71±63·21 vs 225·60±55·22(ng/ml), 1·05±0·16 vs 1·10±0·21 (h) , 18·78±3·28 vs 17·83±2·26(h) , 2284·16±373·54 VS 3155·87±928·26(μg/l×h) respectively. 480 participants were enrolled in pilot trial of PrEP, PAR (HIV positive partners) and MSM (men who sex with men) showed relatively high medication adherence. In phase II (from Jun 2013 to May 2016), a total of 1914 participants underwent randomization. During the follow-up of 3513·5 person-years, 30 HIV infections (2·02 per 100 person-years) were diagnosed in time-driven group (time-driven group versus blank group HR, 0·93; 95% CI, 058-1·51, P=0·777), 35(1·73 per 100 person-years) in event-driven group (event-driven group versus blank group HR, 0·83; 95% CI, 0·52-1·31, P=0·420) and 37(2·06 per 100 person-years) in blank group. Post-hoc analyses showed that participants with good medication compliance could reduce 53% hazard of HIV infection (P=0·011), and time driven medication with good compliance could reduce 62% hazard of HIV infection (P=0·009). We recorded no severe adverse event, and most commonly abnormal laboratory indicators were ALT, TG, UPRO, symptoms were diarrhea, nausea and vomit. A total of 1085 participants over 811·5 person-year were enrolled in phase III (from Jan 2019 to Jul 2021), result indicated that smart alert system significantly improved medication compliance (smart alert group versus normal medication group, HR, 0·79; 95% CI, 0·67-0·93, P=0·004).

Conclusions:

Tenofovir was effective when administrated with high medication compliance; on-demand use was recommended as an optimal medication regimen for PrEP. Tenofovir used as PrEP had good drug safety, combined with smart alert medication system was feasible for promotion as a medicine scheme in developing countries.