11th Conference on Retroviruses and Opportunistic Infections San Francisco, California - February 8 - 11, 2004

Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11;11th:Abstract No. 40LB

M Lallemant¹, G Jourdain², S Le Coeur³, J Y Mary⁴, N Ngo-Giang-Huong², S Koetsawang⁵, S Kanshana⁶, K McIntosh^7,8, V Thaineua⁶, and the Perinatal HIV Prevention Trial (Thailand)
¹PHPT- Inst. de Recherche pour le Développement, France and Thailand; ²Harvard Sch. of Publ. Hlth., Boston, MA, USA; ³Inst. Natl. d’Etudes Démographiques, Paris, France; ⁴INSERM Erm 0321, Paris, France; ⁵Family Hlth. Res. Ctr., Mahidol Univ., Bangkok, Thailand; ⁶Ministry of Publ. Hlth., Bangkok, Thailand; ⁷Children’s Hosp., Boston, MA, USA; and ⁸Harvard Med. Sch., Boston, MA, USA

BACKGROUND: Although zidovudine prophylaxis initiated at 28 weeks decreases in utero transmission of HIV to 1 to 2%, significant peripartum transmission still occurs. We hypothesized that, without additional toxicity, logistical complications, or significant cost, perinatal NVP added to ZDV could further reduce intrapartum transmission.

METHODS: All study women received prophylaxis during the third trimester of pregnancy, and infants received 1 week of zidovudine and formula feeding. Mother-infant pairs were randomized into 3 groups: single nevirapine dose to the mother (200 mg) and infant (6 mg), Nevirapine-Nevirapine; Nevirapine-Placebo; and Placebo-Placebo. The study endpoint was virologically proven HIV infection of the infant.

RESULTS: From January 2001 to March 2003, 1844 women were enrolled. After the first interim analysis, the Placebo-Placebo arm was discontinued. Among women delivering before interim analysis, the intent-to-treat Kaplan-Meier estimated transmission rate in the Nevirapine-Nevirapine arm was 1.1% (95%CI: 0.4 to 3.0), and 6.3% (4.2 to 9.5) in the Placebo-Placebo arm (p = 0.00026). Final as-treated transmission rates were 2.0% (1.2 to 3.4), and 2.8% (1.8 to 4.4) in the Nevirapine-Nevirapine and Nevirapine-Placebo arms, respectively (p for rejecting inferiority = 0.03). Intent-to-treat and as-treated analysis gave similar results. Maternal nevirapine was also associated with a significant decrease of transmissions detectable at birth. Although transmission was associated with viral load and CD4 count and marginally associated with prematurity and onset of ZDV prophylaxis, the effect of nevirapine was observed in most subgroups.

CONCLUSIONS: This study demonstrates the high efficacy of adding a single NVP dose in the mother, with or without a dose in the child, to oral ZDV prophylaxis for the reduction of perinatal HIV transmission. The observed reduction by 80% that led to the early interruption of enrolment in the Placebo-Placebo arm was much higher than we had hypothesized when the study was designed. The fact that the effect of infant and/or maternal NVP could be observed in most sub-groups suggests that there is no sub-population for whom NVP prophylaxis would not be beneficial.

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