Systematic review confirms that efavirenz is a safer option than nevirapine for adults and children starting HIV therapy

Michael Carter
Published: 29 January 2013

Efavirenz is a safer option than nevirapine for adults and children starting antiretroviral therapy, according to the results of a meta-analysis published in the online edition of AIDS.

Treatment discontinuations were twice as likely among people treated with nevirapine (Viramune) than those taking efavirenz. Nevirapine was also associated with a higher frequency of liver toxicities, rash and hypersensitivity reactions. In contrast, efavirenz (Sustiva, also in the combination pill Atripla) was associated with an increased frequency of central nervous system (CNS) side-effects.

The investigators believe their results support “a move towards efavirenz-based therapy as the preferred first-line treatment regimen for HIV treatment”.

Since 2002, the World Health Organization has recommended either efavirenz or nevirapine as part of first-line antiretroviral therapy. The 2010 edition of WHO guidance states that the drugs have similar efficacy but different side-effect profiles. It is well known that rash and liver toxicities are potential side-effects of nevirapine, whereas efavirenz has been associated with CNS toxicities.

However, there is emerging evidence that efavirenz may be both a more potent and safer treatment option than nevirapine. In order to get a clearer understanding of the safety of the two drugs, an international team of researchers performed a systematic review and meta-analysis. Randomised and prospective studies were eligible for inclusion if they included treatment-naive adults or children who initiated HIV therapy based on either of these drugs.

The primary aim of the authors was to compare rates of treatment discontinuations. Their secondary objective was to investigate the frequency of specific side-effects. These included liver toxicity, rash, hypersensitivity reaction, CNS disorders, elevations in lipids and toxicity-related mortality.

A total of 22 prospective and eight randomised studies involving approximately 26,000 adults met the inclusion criteria. In addition, there were four cohort studies involving 4000 children.

The investigators first examined outcomes in adults.

The overall rate of toxicity-related treatment discontinuations for people taking nevirapine was 9%. This compared to a rate of 6% for those initiating therapy with efavirenz. Thus, the authors calculated that patients on nevirapine were twice as likely to discontinue treatment due to side-effects compared to those taking efavirenz (OR = 2.2; 95% CI, 1.9-2.6).

As regards specific side-effects, people receiving nevirapine were more likely to experience liver toxicities of any grade (OR = 1.5; 95% CI, 1.3-1.8) and severe liver toxicities (OR = 3.3; 95% CI, 2.5-4.2) than people treated with efavirenz.

Nevirapine was also associated with a greater risk of skin toxicity (OR = 3.9; 95% CI, 2.5-5.4) and hypersensitivity reactions (OR = 2.4; 95% CI, 1.9-2.9).

In contrast, people treated with efavirenz were more likely than individuals taking nevirapine to develop CNS side-effects (OR = 2.1; 95% CI, 1.9-2.4) and severe CNS toxicities (OR = 3.4; 95% CI, 2.1-5.4).

“This systematic review supports prior findings of individual studies reporting a greater frequency of both liver and skin toxicities associated with nevirapine compared to efavirenz, and a greater frequency of CNS toxicity associated with efavirenz compared to nevirapine,” write the authors.

Side-effects leading to mortality were extremely rare with both drugs.

Results from the four studies involving children were broadly similar to those of the adult studies, showing that nevirapine was associated with an increased frequency of rash and that efavirenz therapy involved a greater risk of CNS side-effects.

The authors conclude that their findings “support the move towards tenofovir/3TC/efavirenz as the preferred first-line regimen for scale up of ART”.


Shudder Z et al. Adverse events associated with nevirapine and efavirenz-based first-line antiretroviral therapy: a systematic review and meta-analysis. AIDS 27, online edition, DOI: 10.1097/QAD.0b013e32835f1db0, 2013.

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