Single-dose nevirapine not jeopardising mother's treatment, large Zambian study reports

Single-dose nevirapine used for prevention of mother-to-child transmission does not appear to be jeopardising the future treatment responses of mothers who take it, researchers from Zambia reported this week at the Sixteenth International AIDS Conference in Toronto, Canada. Their study is the largest investigation to date of the effects of single-dose nevirapine on subsequent maternal treatment response.

Two years ago at the Eleventh Conference on Retroviruses and Opportunistic Infections in San Francisco, French researchers presented findings that suggested a poorer virologic response to nevirapine-based combination antiretroviral therapy (ART) in women who had been exposed to single-dose nevirapine at the time of delivery in order to prevent transmission of the virus to their child. Subsequent concern about these findings led to numerous analyses of nevirapine resistance rates in women exposed to single-dose nevirapine at the time of delivery, and these studies showed alarmingly high rates of resistance – as much as 69% – in the early weeks after delivery.

With these nevirapine-resistant mutations declining in frequency as time went on, researchers were left with an important question: Will resuming nevirapine-based antiretroviral treatment in the future when the woman is in need of therapy lead to a resurgence of those mutations and the failure of treatment? In essence, what are the clinical implications of single-dose nevirapine resistance and does it jeopardise a woman’s future treatment options?

Researchers in Zambia, where a large number of women are receiving nevirapine-based ART, decided to observe treatment outcomes in 4,772 women who started nevirapine-based ART between May 2004 and November 2005. They found that 560 of the women had previously received single-dose nevirapine for prevention of mother-to-child transmission approximately 500 days before starting ART. Roughly 80% of the women were exposed to nevirapine more than 180 days prior to starting ART. At baseline, women with previous nevirapine exposure had a higher mean CD4 cell count (169 vs. 143 cells/mm³) and lower WHO clinical staging classification: 60% were stage 3 or 4 compared to 71% of those without nevirapine exposure.

After adjusting for baseline CD4 cell count, WHO clinical stage, TB status, BMI and age, no significant difference in immune response, as measured by CD4 cell increase, was documented between women previously exposed to nevirapine and those unexposed. After six and twelve months on therapy, there were no statistically significant differences observed in mean CD4 cell increases between the two groups: 178 vs. 200 CD4 cell increase (p = 0.14) at 6 months and 209 vs. 196 CD4 cell increase (p = 0.60) at twelve months. No difference in CD4 cell increases were observed in women who had been exposed to single dose nevirapine in the prior 180 days compared to women whose exposure was more remote. Lastly, no difference in clinical treatment failure or mortality was document between the nevirapine-exposed and unexposed women.

The authors did point out a few limitations of their study, including short duration of follow-up (18 month), lack of information regarding virologic treatment failure, and an inadequate sample size for detecting subtle difference in outcomes. Interestingly, loss to follow-up in the cohort was not revealed.

Nevertheless, this study offers promising news that single-dose nevirapine administration for prevention of perinatal transmission does not appear to jeopardize a woman’s short-term outcome when nevirapine-containing combination antiretroviral therapy is initiated. And dual or triple antiretroviral therapy is currently recommended for the prevention of perinatal transmission, single-dose nevirapine is still a viable and necessary option in settings where no other therapy is available or feasible.