12th Conference on Retroviruses and Opportunistic Infections Boston, Massachusetts - February 22-25, 2005

Conf Retrovir Opportunistic Infect 2005 Feb 22-25;12:abstract no. 72LB

M L Chaix¹, Francois Dabis², D Ekouevi², F Rouet³, B Tonwe-Gold⁴, I Viho⁴, L Bequet⁴, G Peytavin⁵, H Toure⁴, H Menan³, V Leroy², and C Rouzioux^1
1Virologie,EA3620, Universite Rene Descartes, CHU Necker, Paris, France; ²INSERM U593, ISPED, Université Victor Segalen, Bordeaux, France; ³CeDReS, CHU de Treichville, Abidjan, Côte d'Ivoire; ⁴Projet ANRS DITRAME PLUS, Programme PACCI, CHU Treichville, Abidjan, Côte d'Ivoire; and ⁵Toxicologie, CHU Bichat-Claude Bernard, Paris, France

BACKGROUND: In Africa, single-dose nevirapine (sdNVP) and short-course of zidovudine (ZDV)+ lamivudine (3TC) frequently induce viral resistance when used to prevent mother-to-child HIV-1 transmission. The ANRS DITRAME Plus study is an open-label cohort evaluating the combination of a short-course of ZDV+3TC and sdNVP, ending with 3 days of ZDV+3TC post-partum. We describe the frequency of genotypic resistance mutations with this regimen to prevent mother-to-child transmission.

METHODS: In Abidjan in 2002 to 2003, 329 consenting pregnant women started oral ZDV+3TC at ≥ 32 weeks of gestation, received an extra dose of ZDV+3TC and sdNVP at beginning of labor, then ZDV+3TC for 3 days post-partum. Neonates received ZDV for 7 days + sdNVP on day 2. Mothers’ plasma HIV-1 RNA levels (viral load) were quantified at baseline and at day 2 post-partum. Genotypic resistance analysis was performed by sequencing reverse transcriptase gene at week 4 post-partum among transmitting mothers (n = 16), in a random sample of 80 non-transmitting mothers stratified on baseline viral load and CD4 cell count distributions and in infected children (n = 16). In case of mutations detected at week 4 post-partum, baseline samples were also tested. Mothers’ NVP plasma concentrations were determined by a validated HPLC assay at day 2 post-partum.

RESULTS: The 6-week HIV-1 transmission rate was 4.7% (95%CI 2.4 to 7.0%). Median baseline CD4+ cell count was 293/mm³ for transmitting mothers and 416/mm³ for non-transmitters; median viral load was 5.16 and 4.45 log₁₀ copies/mL, respectively. Most of the HIV-1 isolates were subtype CRF02. At day 2 post-partum, viral load was < 2.3 log₁₀ copies/mL for 52% of the women. Only 1 non-transmitting woman had detectable NVP resistance mutations (103N, 181C) and 3TC resistance mutations (184V); 7 other women had 184V resistance mutations. The overall frequency of resistance mutations was 1.14% (CI 0.03 to 6.17%) for NVP and 8.33% (CI 3.66 to 15.76%) for 3TC. No resistant virus was detectable at baseline for these 8 women. The median plasma NVP concentration was 713 ng/mL (31 to 2111) at day 2 post-partum. In multivariate analysis, duration of ZDV+3TC pre-partum prophylaxis was significantly associated with detection of 184V variant (p = 0.009). Of 16 infected children, 1 developed NVP and 3TC mutations and 3 had 3TC mutations.

CONCLUSIONS: A short-course regimen of ZDV+3TC with sdNVP, together with 3 days of ZDV+3TC post-partum prevents most peri-partum HIV-1 transmission in Africa and minimizes viral resistance to NVP.

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Copyright © 2005 - Foundation for Retrovirology and Human Health. Reproduction of this abstract (other than one copy for personal reference) must be cleared through the Foundation for Retrovirology and Human Health. Licensed (AIDSLINE) from National Library of Medicine.