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Choice of Antiretroviral Drugs for Postexposure Prophylaxis for Adults and Adolescents: A Systematic Review

Publication year: 
2015
Author (s): 
Ford, Nathan [et al.]
Corporate author: 
WHO
Publication details: 
UK, Oxford University Press, 2015
Publication in: 
S170 • CID 2015:60 (Suppl 3) • Ford et al
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%– 8.6%; TDF+ FTC+raltegravir [RAL], 74.7%; 95% CI, 41.4%–100%; TDF+FTC+ boosted darunavir [DRV/r], 3.9%; 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.