Session 21 Oral Abstracts
Pregnancy and Prevention of Perinatal HIV Transmission
Thursday, 10 am - 12:30 pm
Presentation Time: 11:45 am
302-304

74LB
Maternal Single-dose Nevirapine May Not Be Needed to Reduce Mother-to-Child HIV Transmission in the Setting of Maternal and Infant Zidovudine and Infant Single-dose Nevirapine: Results of a Randomized Clinical Trial in Botswana
Roger Shapiro*¹, I Thior², P Gilbert³, S Lockman⁴, C Wester², L Smeaton⁵, L Stevens², T Ndung'u², V Novitsky⁵, E van Widenfelt², P Mazonde⁶, T H Lee⁵, R Marlink⁵, S Lagakos⁵, M Essex⁵, and The Mashi Study Group
¹Beth Israel Deaconess Med Ctr, Boston, MA, USA; ²Botswana-Harvard Sch of Publ Hlth AIDS Initiative Partnership, Gaborone; ³Univ of Washington, Seattle, USA; ⁴Brigham and Women's Hospital, Boston, MA, USA; ⁵Harvard Sch of Publ Hlth, Boston, MA, USA; and ⁶Botswana Ministry of Health, Gaborone, Botswana

Background: Single-dose nevirapine (SD-NVP) given to mothers and infants has been shown to reduce mother-to-child transmission of HIV when added to zidovudine (ZDV)-based prophylaxis in a formula-fed population. However, the development of NVP resistance in women limits enthusiasm for this MTCT prevention strategy.

Methods: HIV⁺ pregnant women at 4 sites in Botswana were randomized to a partially double blinded, 2x2 factorial clinical trial to prevent perinatal and breast-feeding mother-to-child transmission. All women received ZDV from 34 weeks gestation through delivery, and all infants received 1 month of ZDV. Mother-infant pairs were randomized to receive blinded maternal and infant SD-NVP (N/N) or maternal and infant placebo (P/P), and randomized to formula feed or breastfeed with 6 months of infant ZDV prophylaxis. In response to external data, the perinatal NVP intervention was revised 17 months after study initiation to compare maternal and infant SD-NVP (N/N) with maternal placebo and infant SD-NVP (P/N). Maternal ART became available to women with AIDS in the revised study era. The original study was designed to assess superiority of N/N over P/P, and the revised study to assess equivalence of P/N to N/N. Final perinatal transmission results are presented.

Results: Among 1179 live births in both study periods, 56 (4.7%) were HIV⁺ by 1 month, and 41 of these (73%) were HIV⁺ at birth. In the original study, 13 (5.3%) of 243 in the N/N group were HIV⁺ by 1 month, compared with 15 of 242 (6.2%) in the P/P group (Fisher’s exact p = 0.70, 95% CI for difference = –5.2% to 3.5%). In the revised study, 15 (4.3%) of 345 in the N/N group were HIV⁺ by 1 month, compared with 13 (3.7%) of 349 in the P/N group (p = 0.70, 95% CI for difference = –2.4% to 3.8%), meeting pre-determined criteria for equivalence. A statistical interaction between assigned feeding strategy and treatment arm was detected in the original study (Zelen’s exact p = 0.02), but not in the revised study (p = 1.0). Toxicity rates were low and similar between SD-NVP and placebo in both study periods. NVP resistance mutations occurred in 44% of 157 women receiving SD-NVP tested at 1 month post-partum.

Conclusions: Adding N/N to ZDV was not superior to ZDV alone, but these results need to be interpreted in the context of feeding strategy and the in utero infection rate. If perinatal SD-NVP is added to ZDV, P/N is similar to N/N and may avoid maternal NVP resistance.

Keywords: Perinatal; Mother-to-Child Tansmission; Nevirapine