Adverse events associated with nevirapine and efavirenz-based first-line antiretroviral therapy: a systematic review and meta-analysis.
BACKGROUND
Since 2002, the WHO has recommended either nevirapine (NVP) or efavirenz (EFV) as part of first-line antiretroviral therapy. These two drugs are known to have differing toxicity profiles, but the risk of these toxicities overall is not well established.


METHODS
We systematically reviewed adverse events among treatment-naive HIV-positive adults and children receiving either NVP or EFV as part of first-line antiretroviral therapy. The primary outcome was drug discontinuation as a result of any adverse event; specific toxicities were evaluated as secondary outcomes. Point estimates and 95% confidence intervals (95% CIs) were calculated and proportions and odds ratios (ORs) pooled using fixed-effects meta-analysis.


RESULTS
We reviewed data on 26,446 adults and 3975 children from eight randomized trials and 26 prospective cohorts. Overall, adults on NVP were more than two times more likely to discontinue treatment due to any adverse event compared to patients on EFV (OR 2.2, 95% CI 1.9-2.6). Severe hepatotoxicity (OR 3.3, 95% CI 2.5-4.2), severe skin toxicity (OR 3.9, 95% CI 2.5-5.4), and severe hypersensitivity reactions (OR 2.4, 95% CI 1.9-2.9) were more likely to occur among patients on NVP. Patients receiving EFV were more likely to experience severe central nervous system events (OR 3.4, 95% CI 2.1-5.4). Similar associations were seen in children.


CONCLUSIONS
Compared to NVP, EFV is associated with a lower frequency of severe adverse events, in particular treatment discontinuations. This finding supports a move toward EFV-based therapy as the preferred first-line treatment regimen for HIV treatment within a public health approach.
Department of Infectious Disease Epidemiology, Faculty of Medicine, Imperial College, London, UK.
Zara
Z
Shubber
Alexandra
A
Calmy
Isabelle
I
Andrieux-Meyer
Marco
M
Vitoria
Françoise
F
Renaud-Théry
Nathan
N
Shaffer
Sally
S
Hargreaves
Edward J
EJ
Mills
Nathan
N
Ford
D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects*; D048588:Benzoxazines / Q000008:administration & dosage / Q000009:adverse effects*; D002648:Child; D003521:Cyclopropanes; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D019829:Nevirapine / Q000008:administration & dosage / Q000009:adverse effects*; D016032:Randomized Controlled Trials as Topic; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*
D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D018894:Reverse Transcriptase Inhibitors; D019829:Nevirapine; C098320:efavirenz