Pregnancy does not increase the risk of
nevirapine (Viramune) associated
side-effects, according to the results of a systematic review and meta-analysis
published in the online edition of AIDS.
Investigators found that incidence of liver and skin toxicities – the major
side-effects of the drug – were high,
but no higher than the rate observed in the general HIV-positive adult
population treated with the drug. There was only weak evidence that nevirapine
therapy increased the risk of side-effects in pregnant women with a CD4 cell
count above 250 cells/mm3.
“This systematic review found no evidence
of increased risk of nevirapine-related adverse events associated with
pregnancy compared to non-pregnant adults, and only very weak evidence of
elevated risk of cutaneous and hepatic events among pregnant women
antiretroviral therapy at higher CD4
cell count,” comment the authors.
Current World Health Organization
(WHO) HIV treatment guidelines recommend the use of efavirenz- or nevirapine-based combinations. Nevirapine has been preferred for pregnant women because of
concerns about the safety of efavirenz in pregnancy. But there are also reservations
about the safety of nevirapine therapy, especially for pregnant women with a higher
CD4 cell count. However, the risks associated with the drug are uncertain and
the results from studies exploring the safety of nevirapine during pregnancy
Nevirapine has a pivotal role in
antiretroviral treatment programmes in resource-limited settings. Given the
uncertainty about its safety during pregnancy, especially for women with higher
CD4 cell counts, an international team of investigators conducted a systematic
review and meta-analysis, interrogating the results of 20 studies that reported
on nevirapine-associated side-effects in pregnant women.
The investigators compared the incidence of
hepatic and skin toxicities, as well as hypersensitivity reactions in pregnant
women treated with nevirapine, to the rates reported in research involving
non-pregnant adults with HIV taking the drug.
The studies included in the review and
meta-analysis were carried out in 14 separate countries, eight of which are poor or
When pooled together, the studies reported
on outcomes in 3582 pregnant women.
Overall, 7% of these women experienced a
hepatic event (3% serious); 7% developed a rash (3% serious); and 7% had a
hypersensitivity reaction to the drug. Treatment with nevirapine was stopped by
6% of pregnant women because of side-effects.
These incidences were comparable to those
reported in studies involving non-pregnant adults with HIV, whose
antiretroviral therapy was based on nevirapine.
A total of 15 studies compared the
incidence of side-effects according to whether pregnant women had a CD4 cell
count above or below 250 cells/mm3. There was a non-significant
trend for an increased incidence of cutaneous side-effects in people with
higher CD4 counts (OR, 1.1; 95% CI, 0.8-1.6). There was also non-significant
evidence of an association between a higher CD4 cell count and severe cutaneous
reactions (OR, 1.4; 95% CI, 0.8.2.4).
Six studies compared rates of side-effects
between pregnant and non-pregnant women. There was no significant evidence that
any toxicity occurred with increased frequency in pregnant women.
The investigators do not regard their
results as definitive. In particular, they highlight that 13 of the studies
included in their analysis had a retrospective design.
Nevertheless, they conclude: “the findings
of this review…suggest that there is little evidence to justify discrimination
according to pregnancy status when using nevirapine as part of combination
Despite this, the overall frequency of
side-effects associated with nevirapine was high and the authors suggested that
“where possible, the use of alternative drugs with better overall toxicity profiles
such as efavirenz should be considered. Such considerations are all the more
important in resource-limited settings where capacity for toxicity monitoring