title: Choice of antiretroviral drugs for postexposure prophylaxis for adults and adolescents: a systematic review.
abstract: BACKGROUND
  The choice of preferred regimens for human immunodeficiency virus postexposure prophylaxis (PEP) has evolved over the last 2 decades as more data have become available regarding the safety and tolerability of newer antiretroviral drugs. We undertook a systematic review to assess the safety and efficacy of antiretroviral options for PEP to inform the World Health Organization guideline revision process.
  
  
  METHODS
  Four databases were searched up to 1 June 2014 for studies reporting outcomes associated with specific PEP regimens. Data on PEP completion and discontinuation due to adverse events was extracted and pooled estimates were obtained using random-effects meta-analyses.
  
  
  RESULTS
  Fifteen studies (1830 PEP initiations) provided evaluable information on 2-drug regimens (zidovudine [ZDV]- or tenofovir [TDF]-based regimens), and 10 studies (1755 initiations) provided evaluable information on the third drug, which was usually a protease inhibitor. The overall quality of the evidence was rated as very low. For the 2-drug regimen, PEP completion rates were 78.4% (95% confidence interval [CI], 66.1%-90.7%) for people receiving a TDF-based regimen and 58.8% (95% CI, 47.2%-70.4%) for a ZDV-based regimen; the rate of PEP discontinuation due to an adverse event was lower among people taking TDF-based PEP (0.3%; 95% CI, 0%-1.1%) vs a ZDV-based regimen (3.2%; 95% CI, 1.5%-4.9%). For the 3-drug comparison, PEP completion rates were highest for the TDF-based regimens (TDF+emtricitabine [FTC]+lopinavir/ritonavir [LPV/r], 71.1%; 95% CI, 43.6%-98.6%; TDF+FTC+raltegravir [RAL], 74.7%; 95% CI, 41.4%-100%; TDF+FTC+ boosted darunavir [DRV/r], 93.9%; 95% CI, 90.2%-97.7%) and lowest for ZDV+ lamivudine [3TC]+LPV/r (59.1%; 95% CI, 36.2%-82.0%). Discontinuations due to adverse drug reactions were lowest for TDF+FTC+RAL (1.9%; 95% CI, 0%-3.8%) and highest for ZDV+3TC+boosted atazanavir (21.2%; 95% CI, 13.5%-30.0%).
  
  
  CONCLUSIONS
  The findings of this review provide evidence supporting the use of coformulated TDF and 3TC/FTC as preferred backbone drugs for PEP. Choice of third drug will depend on setting; for resource-limited settings, LPV/r is a reasonable choice, pending the improved availability of better-tolerated drugs with less potential for drug-drug interactions.
authors.affiliation: Department of HIV/AIDS, World Health Organization, Geneva, Switzerland.
authors.forename: Nathan
authors.initials: N
authors.lastname: Ford
authors.affiliation: Department of Infectious Disease Epidemiology, Imperial College London, United Kingdom.
authors.forename: Zara
authors.initials: Z
authors.lastname: Shubber
authors.affiliation: HIV/AIDS Unit, Infectious Disease Service, Geneva University Hospital, Switzerland.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Calmy
authors.affiliation: Department of HIV/AIDS, World Health Organization, Geneva, Switzerland.
authors.forename: Cadi
authors.initials: C
authors.lastname: Irvine
authors.affiliation: Riscobiologico.org Network, Rio de Janeiro, Brazil.
authors.forename: Cristiane
authors.initials: C
authors.lastname: Rapparini
authors.affiliation: Clinton Health Access Initiative.
authors.forename: Olawale
authors.initials: O
authors.lastname: Ajose
authors.affiliation: Department of HIV/AIDS, World Health Organization, Geneva, Switzerland.
authors.forename: Rachel L
authors.initials: RL
authors.lastname: Beanland
authors.affiliation: Department of HIV/AIDS, World Health Organization, Geneva, Switzerland.
authors.forename: Marco
authors.initials: M
authors.lastname: Vitoria
authors.affiliation: Department of HIV/AIDS, World Health Organization, Geneva, Switzerland.
authors.forename: Meg
authors.initials: M
authors.lastname: Doherty
authors.affiliation: The Fenway Institute, Fenway Health Department of Medicine, Beth Israel Deaconess Medical Centre and Harvard Medical School, Boston, Massachusetts.
authors.forename: Kenneth H
authors.initials: KH
authors.lastname: Mayer
mesh_terms: D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D004359:Drug Therapy, Combination; D000068679:Emtricitabine / Q000627:therapeutic use; D006678:HIV / Q000187:drug effects; D015658:HIV Infections / Q000517:prevention & control*; D006801:Humans; D061466:Lopinavir / Q000627:therapeutic use; D056990:Post-Exposure Prophylaxis; D019438:Ritonavir / Q000627:therapeutic use; D000068698:Tenofovir / Q000627:therapeutic use; D014944:World Health Organization
chemical_list: D019380:Anti-HIV Agents; D061466:Lopinavir; D000068698:Tenofovir; D000068679:Emtricitabine; D019438:Ritonavir
keywords: adverse events; antiretroviral; postexposure prophylaxis; safety; tolerability