en
Scientific article
Review
English

Choice of antiretroviral drugs for postexposure prophylaxis for adults and adolescents : a systematic review

Published inClinical infectious diseases, vol. 60, no. Suppl. 3, p. S170-S176
Publication date2015-06-01
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.

eng
Keywords
  • Adverse events
  • Antiretroviral
  • Postexposure prophylaxis
  • Safety
  • Tolerability
  • Adolescent
  • Adult
  • Anti-HIV Agents / therapeutic use
  • Antiretroviral Therapy, Highly Active / adverse effects
  • Drug Therapy, Combination
  • Emtricitabine / therapeutic use
  • HIV / drug effects
  • HIV Infections / prevention & control
  • Humans
  • Lopinavir / therapeutic use
  • Post-Exposure Prophylaxis
  • Ritonavir / therapeutic use
  • Tenofovir / therapeutic use
  • World Health Organization
Research group
Citation (ISO format)
FORD, Nathan et al. Choice of antiretroviral drugs for postexposure prophylaxis for adults and adolescents : a systematic review. In: Clinical infectious diseases, 2015, vol. 60, p. S170–S176. doi: 10.1093/cid/civ092
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Article (Published version)
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ISSN of the journal1058-4838
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