[61] EFFECT OF PERINATAL ZIDOVUDINE TREATMENT ON THE EVOLUTION OF CELL-FREE HIV-1 IN BREAST MILK ON POSTNATAL TRANSMISSION, ANRS 049 DITRAME-VIRO STUDY

2nd International AIDS Society Conference on HIV Pathogenesis and Treatment

Paris, France - July 13 - 16, 2003

[TITLE:] EFFECT OF PERINATAL ZIDOVUDINE TREATMENT ON THE EVOLUTION OF CELL-FREE HIV-1 IN BREAST MILK ON POSTNATAL TRANSMISSION, ANRS 049 DITRAME-VIRO STUDY

[AUTHOR(S):] O Manigart¹, M Crépin², V Leroy³, N Meda¹, D Valéa¹, EN Janoff⁴, F Rouet², L Dequae-Merchadoux³, F Dabis³, C Rouzioux⁵ and P Van de Perre¹ for the ANRS 049 DITRAME Study Group
¹Centre MURAZ, 01BP390 Bobo-Dioulasso, Burkina Faso; ²CEDRES, Programme PAC-CI, Abidjan, Côte d’Ivoire; ³Unité INSERM n° 593, Université Victor Segalen, Bordeaux, France; ⁴Mucosal and Vaccine Research Center, Veterans Affairs Medical Center, University of Minnesota School of Medicine, Minneapolis, MN, USA; and ⁵Laboratory of Virology, Necker-Enfants Malades Hospital, Paris, France

IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd: Abstract No. 61
Antiviral Therapy 2003; 8(Suppl. 1):S199

[ABSTRACT:] During the ANRS 049a trial, we characterized the effect of short course maternal ZDV regimen (from 36 weeks gestation to 7 days postpartum) on the evolution of HIV-1 RNA in breast milk and its relationship with the risk of postnatal transmission in African breastfed children. Study population was constituted of 98 transmitting mothers and 286 who did not transmit the virus within the first 24 months postpartum. Among those women who breastfed their infants who had remained free of peripartum transmission, 37 transmitted the virus postnatally, of whom 28 were available for breast milk measurements. In a nested case-control study, these cases were compared with 130 randomly-selected women who did not transmit postnatally (controls). Breast milk HIV-1 RNA was quantitated by RT-PCR on samples collected on days 8, 45 and 90. We compared these HIV-1 RNA levels in case and control mothers, after stratification according to treatment arm (ZDV or placebo). Levels of HIV-1 RNA in milk at day 8 were lower in mothers receiving ZDV (n=60) than in mothers receiving placebo (n=98) [median 29 vs 73 copies/ml (c/ml), respectively, P=0.0008]. Among non transmitters, median HIV-1 RNA remained under 50 c/ml over time in both ZDV- and placebo-treated groups. However, among transmitting mothers, median HIV-1 RNA at day 8 in milk of those who received placebo was significantly higher (n=15) than in other groups and declined over time from 1608 (day 8) to 346 (day 45) to 95.5 (day 90) c/ml. In contrast, median HIV-1 RNA in transmitting mothers treated with ZDV was comparable at day 8 (n=13) to that of non transmitters but increased by 8 to 16-fold by day 45 then day 90 [from 24 (day 8) to 470.5 (day 45) to 932.5 (day 90) c/ml]. In a multivariate analysis performed on data from 80 women with complete information, increase of HIV-1 RNA in milk from day 45 to day 90 was significantly associated with postnatal transmission and with previous ZDV prophylaxis. The substantial risk of postnatal transmission of HIV-1 are significantly associated with HIV-1 RNA levels in milk. The rebound of HIV-1 RNA levels in milk after discontinuation of maternal ZDV, but before cessation of breasfeeding may introduce additional risk of postnatal transmission.

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