Network meta‐analysis of post‐exposure prophylaxis randomized clinical trials

Abstract

Objectives We performed a network meta‐analysis of PEP randomized clinical trials to evaluate the best regimen. Methods After MEDLINE/Pubmed search, studies were included if: (1) were randomized, (2) comparing at least 2 PEP three‐drug regimens and, (3) reported completion rates or discontinuation at 28 days. Five studies with 1105 PEP initiations were included and compared ritonavir‐boosted lopinavir (LPV/r) vs. atazanavir (ATV) (one study), cobicistat‐boosted elvitegravir (EVG/c) (one study), raltegravir (RAL) (one study) or maraviroc (MVC) (two studies). We estimated the probability of each treatment of being the best based on the evaluation of five outcomes: PEP non‐completion at day 28, PEP discontinuation due to adverse events, PEP switching due to any cause, lost to follow‐up and adverse events. Results Participants were mostly men who have sex with men (n = 832, 75%) with non‐occupational exposure to HIV (89.86%). Four‐hundred fifty‐four (41%) participants failed to complete their PEP course for any reason. The Odds Ratio (OR) for PEP non‐completion at day 28 in each antiretroviral compared to LPV/r was: ATV 0.95 (95% CI 0.58–1.56; EVG/c: OR 0.65 95% CI 0.30–1.37; RAL: OR 0.68 95% CI 0.41–1.13; and MVC: OR 0.69 95% CI 0.47–1.01. In addition, the rankogram showed that EVG/c had the highest probability of being the best treatment for the lowest rates in PEP non‐completion at day 28, switching, lost to follow‐up or adverse events and MVC for PEP discontinuations due to adverse events. Conclusions Our study shows the advantages of integrase inhibitors when used as PEP, particularly EVG as a Single‐Tablet Regimen.

Prophylaxis by doravirine-lamivudine-tenofovir disoproxil fumarate or elvitegravir-cobicistat-emtricitabine-tenofovir alafenamide after sexual exposure to HIV

“…Raltegravir (RAL/FTC/TDF) and dolutegravir (DTG/TDF/FTC) also showed completion rates above 90% [ 10 , 11 ]. A network analysis seems to show a higher completion rate of integrase inhibitor combinations than previous strategies with protease inhibitors [ 12 ]. Recently, co-formulated BIC/FTC/TAF was found to be safe and well tolerated, with a 90.4% completion rate [ 13 ], and could be a future PEP option, particularly in people with renal failure.…”

Safety and Tolerability of Once Daily Coformulated Bictegravir, Emtricitabine, and Tenofovir Alafenamide for Postexposure Prophylaxis After Sexual Exposure

“…32 The advent of integrase strand transfer inhibitors created new possibilities to construct effective 3-drug PEP regimens, given their excellent tolerability and potency, particularly when coupled with tenofovir and FTC, compared with zidovudine-containing regimens. 33 Combinations of NRTIs and raltegravir for PEP demonstrated a high level of safety and tolerability, but regimen completion was suboptimal, because many participants discontinued the medication prematurely or did not remember to take the second dose of raltegravir in the twice daily regimen. 11,[34][35][36] The fixeddrug single-pill coformulation of elvitegravir, cobicistat, FTC, and TDF allowed for the use of a single daily pill for PEP, but seemed to have higher rates of gastrointestinal symptoms and fatigue than raltegravir-based regimens, which may have led to product discontinuation.…”

Blocking CCR5 activity by maraviroc augmentation in post-stroke depression: a proof-of-concept clinical trial

“…The drug has been available in the US market since 2007 and has a known and satisfactory safety profile. Main adverse events include upper respiratory tract infections, cough, pyrexia, and rash [ 15 ].…”