Pregnancy does not increase risk of nevirapine side-effects

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 initiating  nevirapine-based 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 are conflicting.

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 middle-income.

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 antiretroviral therapy.”

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 remains limited.”