Nevirapine associated adverse events in a cohort of pregnant women

A case note review across five London hospitals reported lower overall rates of nevirapine associated adverse events than seen in other studies in a cohort of women receiving triple combination therapy.

Data from 193 women receiving nevirapine-containing regimens in pregnancy between January 2000 and December 2003 was collected from clinical notes and laboratory databases.

In this cohort the mean CD4 count at initiation of therapy was 337cells/mm³ including 125 (65%) of women with CD4 count above 200 cells/mm3. The most frequently used nucleoside backbone was zidovudine plus lamivudine, received by145 (76%) of women.

The authors reported nevirapine-associated toxicity in 8/125 (6.4%) of those with a CD4 count above 200 cells/mm³ and 1/63 (1.6%) of those with counts below 200 cells/mm3. Rash was seen in nine women including four with ALT or AST five times or more above the normal limit. None of the women experiencing nevirapine associated toxicities were hepatitis co-infected. There were no maternal deaths.

The authors write: “Although lower overall rates of adverse reaction were seen than in other studies, a majority occurred at CD4 counts above 200cells/mm³ where nevirapine should be used with careful monitoring.”

Comment

It is encouraging to see that side effects in this study were not particularly frequent nor severe. This cohort is followed fairly intensively, especially on initiation of therapy, so hopefully any side effects are detected early. When analysed with a CD4 cut-off of 250 cells/mm3, as used in other studies and in the Dear Dr letter from Boehringer, the authors saw no difference in rates of toxicity. The authors therefore postulated that the haemodilution of pregnancy might mean that the higher rate of side-effects seen in non-pregnant women with CD4 >250 cells/mm³ might not apply to pregnant women, and a lower cut-off of 200 cells/mm³ might be more appropriate.

Finally the study confirms the safety of using nevirapine up front in pregnant women with lower CD4 counts. This remains the preferred drug of choice for many doctors for women in this situation, with a Combivir backbone, and there has been considerable experience of this combination.

Women with higher CD counts are more at risk of toxicity with nevirapine than women with lower CD4 counts whether pregnant or not. This is the same group of patients who are also likely to use ARVs during pregnancy and stop therapy after delivery. So in addition to the risk of side effects the long half life of nevirapine needs careful consideration. Therefore it seems appropriate to use a PI in these mothers. The question is which PI?

Natarajan U, Pym A, Anderson J et al The side effect profile associated with use of NVP in a cohort of pregnant women in London. 7th ICDTHI,14-18 Nov, 2004, Glasgow. Abstract P190.