Background: PEP is recommended after a potential exposure to HIV. In animal models, PEP has to be maintained 4 weeks to be effective. However, with the recommended regimens in humans, side effects are frequent and are the main reason for poor adherence and a high rate of discontinuation. The objective of these 2 trials was to assess the rate of discontinuation of PEP at 28 days comparing the standard of care Lopinavir/r (LPV/r) vs Maraviroc (MVC) or Raltegravir (RAL) both with Tenofovir/Emtricitabine (TVD).
Methods: Individuals coming to the emergency room (ER) for potential sexual exposure to HIV were randomized to: TVD 200/245 QD plus LPV/r 400/100 BID (n=117) or plus MVC 300 BID (n=120) in one trial (n=237) and TVD plus LPV/r (n=121) or plus RAL 400 BID (n=122) in the second trial (n=243). After randomization, 4 follow-up visits were scheduled: day 0, 28, 90 and 180. The primary end-point was rate of discontinuation at day 28. Secondary end-points were adherence to PEP, side effects and rate of seroconversions.
Results: In MVC and RAL trials, median age was 35 and 33 years and 92% and 90% were males respectively. The median interval between exposure and presentation at ER was 15h and 13.5h. Type of exposition was male homosexual sex in 83% and 81%. The level of risk was high in only 13% and 9% of individuals. The source patient was known to be HIV infected in 30.8% and 31%. In MVC trial, only 187/237 (79%) who were randomized and started PEP attended the first scheduled visit (day 0) and differences between arms were not observed (p=0.92). Similar results were found in RAL trial [198/243 (81.5%) attended the day 0 (p=0.62)]. The rate of discontinuation of PEP before day 28 of follow-up was significantly higher in LPV/r (31.5%) vs MVC (11.6%) arm (p=0.001) and in LPV/r (36.6%) vs RAL (23.7%) arm (p=0.04). The proportion of patients with low adherence to PEP was similar in LPV/r vs MVC arms (54% vs 46%, respectively, p=0.56), but was higher in LPV/r vs RAL arms (49.2% vs 30.8%, respectively, p=0.03). Adverse effects were reported in 122 out of 187 (50.8%) patients in MVC study attending at least the day 0 visit [70/92 (76.1%) in LPV/r and 52/95 (54.7%) in MVC arm, p=0.002] and in in 134 out of 198 (67.7%) patients in RAL study [75/101 (74.3%) in LPV/r and 59/97 (60.8%) in RAL arm, p=0.04]. No seroconversions were observed.
Conclusions: The rate of discontinuation of PEP and side effects were higher in patients allocated to TVD plus LPV/r as compared with those with TVD plus MVC or TVD plus RAL.