Efavirenz or nevirapine in three‐drug combination therapy with two nucleoside‐reverse transcriptase inhibitors for initial treatment of HIV infection in antiretroviral‐naïve individuals
Abstract
Background
The advent of highly active antiretroviral therapy (HAART) has reduced the morbidity and mortality due to HIV. The World Health Organisation (WHO) antiretroviral treatment (ART) guidelines focus on three classes of antiretroviral drugs, namely: nucleoside/nucleotide reverse transcriptase inhibitors (NRTI), non‐nucleoside reverse transcriptase inhibitors (NNRTI) and protease inhibitors (PI). Two of the most common medications given in first‐line treatment are the NNRTIs, efavirenz (EFV) and nevirapine (NVP). It is unclear which NNRTI is more efficacious for initial therapy.
Objectives
To determine which NNRTI, EFV or NVP, is more efficacious when given in combination with two NRTIs as part of initial ART for HIV infection in adults and children.
Search methods
We used a comprehensive and exhaustive strategy in an attempt to identify all relevant studies, regardless of language or publication status, in electronic databases and conference proceedings from 1996 to 2009.
Selection criteria
All randomised controlled trials comparing EFV to NVP in HIV‐infected individuals without prior exposure to ART, irrespective of the dosage or NRTI backbone.
The primary outcome of interest was virologic response to ART. Other primary outcomes included mortality, clinical progression, severe adverse events, and discontinuation of therapy for any reason. Secondary outcomes were immunologic response to ART, treatment failure, development of ART drug resistance, and prevention of sexual transmission of HIV.
Data collection and analysis
Two authors assessed each reference for inclusion and exclusion criteria established a priori. Data were abstracted independently using a standardised abstraction form. Data were analysed on an intention‐to‐treat basis and reported as per dosage of NVP.
Main results
We identified seven randomised controlled trials that met our inclusion criteria.The trials were pooled as per dosage of NVP. None of these trials included children.The seven trials enrolled 1,688 participants and found no critical differences between EFV and NVP, except for different toxicity profiles. EFV is more likely to cause central nervous system side‐effects, while NVP is more likely to result in raised transaminases and neutropoenia. There was a higher mortality rate in the NVP 400mg once daily arm.The quality of literature to support these conclusions is moderate to high. Drug resistance was slightly less common with EFV than NVP, but the quality of this literature is low since only one of the seven studies reported on this outcome. No studies reported on sexual transmission of HIV. The length of follow‐up time, study settings, and NRTI backbone varied greatly.
Authors' conclusions
Both drugs have equivalent efficacies in initial treatment of HIV infection when combined with two NRTIs, but different side effects.
PICOs
Plain language summary
EFV and NVP are both equally effective in the suppression of HIV infection when compared as part of a three‐drug combination.
The introduction of highly active antiretroviral therapy as treatment for HIV infection has greatly reduced mortality and morbidity for adults and adolescents living with HIV around the world. The recommended initial treatments for HIV infection include two drugs from a class of drugs known as nucleoside reverse transcriptase inhibitors (NRTI) and one from a related class of drugs called non‐nucleoside reverse transcriptase inhibitors (NNRTI). The two NNRTIs currently in use are nevirapine (NVP) and efavirenz (EFV). NVP can cause liver damage and severe rash, both of which can be fatal. EFV may also cause a rash, impair mental function, and cause foetal malformations. The purpose of this review is to assess which of these two medications is better for initial treatment of HIV infection. We identified seven randomised controlled trials. A review of these trials shows that both drugs are equally effective in suppressing HIV infection but cause different side effects. Based on limited data, it appears that EFV is slightly less likely to cause side effects and more likely to prevent death than NVP. Future studies and recommendations should focus on specific toxicities and risk of resistance when comparing these two medications.
