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
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%
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”.