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

I Fernández; E de Lazzari; A Inciarte; V Diaz-Brito; A Milinkovic; A Arenas-Pinto; F Etcheverrry; F García; L Leal; HIV-PEP Group

doi:10.1111/hiv.12964

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

HIV Med. 2021 Mar;22(3):218-224. doi: 10.1111/hiv.12964. Epub 2020 Oct 27.

Authors

I Fernández¹, E de Lazzari¹, A Inciarte², V Diaz-Brito¹, A Milinkovic³, A Arenas-Pinto³, F Etcheverrry¹, F García^{1

4}, L Leal^{1

4}; HIV-PEP Group

Collaborators

HIV-PEP Group:
E Fernandez, E Gonzalez, C Lucero, A Leon, F Garcıa, C Manzardo, D Nicolas, M Bodro, A Del Rıo, C Cardozo, C Cervera, J M Pericas, G Sanclemente, C de la Calle, L Morata, A Soriano, G Espinosa, J L Blanco, E Martınez, J Mallolas, J Miró, M Laguno, J Rojas, M Martınez-Rebollar, A Gonzalez-Cordon, C Cervera, H Knobel, J Peraire, P Domingo, B Clotet, D Dalmau, A Cruceta, J A Arnaiz, J M Gatell

Affiliations

¹ Infectious Diseases Department-HIV Unit, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain.
² Infectious Diseases Department-HIV Unit, Parc Sanitari Sant Joan de Déu, Sant Boi de Llobregat, Barcelona, Spain.
³ Chelsea and Westminster NHS Foundation Trust, London, UK.
⁴ Retrovirology and Viral Immunopathology, AIDS Research Group, (IDIBAPS), Hospital Clinic, University of Barcelona, Barcelona, Spain.

PMID: 33108035
DOI: 10.1111/hiv.12964

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.

Keywords: HIV; completion; integrase inhibitors; post-exposure prophylaxis.

Publication types

Meta-Analysis
Research Support, Non-U.S. Gov't

MeSH terms

Anti-HIV Agents* / therapeutic use
HIV Infections* / drug therapy
HIV Infections* / prevention & control
Homosexuality, Male
Humans
Male
Network Meta-Analysis
Post-Exposure Prophylaxis
Randomized Controlled Trials as Topic
Sexual and Gender Minorities*

Substances

Anti-HIV Agents