14th International HIV Drug Resistance Workshop 7-11 June 2005, Québec City, Canada

INFANT NEVIRAPINE RESISTANCE CAN BE SUBSTANTIALLY REDUCED AFTER SINGLE DOSE NEVIRAPINE BY AVOIDING MATERNAL NEVIRAPINE DOSING AND PROVIDING INFANTS WITH ZIDOVUDINE IN ADDITION TO SINGLE DOSE NEVIRAPINE AFTER BIRTH

Antivir Ther. 10, Suppl 1:S3 (abstract no. 1)

SH Eshleman¹, DR Hoover², SE Hudelson¹, S Chen¹, A Mwatha³, SA Fiscus⁴, JB Jackson¹, NI Kumwenda¹ and T Taha^1
1Johns Hopkins University, Baltimore, MD, USA ²Rutgers University, Piscataway, NJ, USA ³Fred Hutchinson Cancer Res. Ctr., Seattle, WA, USA ⁴University of North Carolina, Chapel Hill, NC, USA

BACKGROUND: The NVAZ trial in Malawi compared four regimens for prevention of HIV-1 mother-to-child transmission: Group 1: women and infants received single dose nevirapine (HIVNET 012 regimen); Group 2: women received single dose nevirapine, infants received single dose nevirapine+zidovudine twice a day for 7 days; Group 3: women (presenting in late labour) received no nevirapine, infants received single dose nevirapine; Group 4: women (presenting in late labour) received no nevirapine, infants received single dose nevirapine+zidovudine as above. The HIV- 1 transmission rate was similar for Groups 1, 2 and 4, but was statistically higher for Group 3.

METHODS: We analysed nevirapine resistance 6–8 weeks after single dose nevirapine in 78 infants who became HIV-1 infected despite antiretroviral prophylaxis (23 in Group 1, 21 in Group 2, 19 in Group 3, 15 in Group 4). Infant plasma (0.1 ml) was analysed with the ViroSeq system.

RESULTS: The frequency of nevirapine resistance differed significantly among infants in Groups 1–4 (P=0.001). In Group 1 (HIVNET 012 regimen), 20/23=87% of infants had resistance. The frequency of resistance was lower when the mother received no nevirapine (14/19=74%, Group 3), or when the infant received nevirapine+zidovudine (12/21=57%, Group 2). The frequency of resistance was lowest when the mother received no nevirapine and the infant received nevirapine+zidovudine (4/15=27%, Group 4). In a factorial logistic repression fit using the entire data set, both avoiding nevirapine in women (P<0.001) and providing infants with zidovudine (P=0.04) independently predicted reduced nevirapine resistance. No infants had zidovudine resistance.

CONCLUSION: Nevirapine resistance in infants who became HIV-1 infected despite antiretroviral prophylaxis was significantly reduced by avoiding pre-delivery maternal nevirapine and providing infants with nevirapine+zidovudine. In NVAZ, the overall transmission rates at 6–8 weeks were not statistically different for this regimen (no maternal nevirapine, infants receive nevirapine+zidovudine, 15.3%) and the HIVNET 012 regimen (14.1%). By not exposing women to nevirapine, this regimen also prevents emergence of maternal nevirapine resistance, which could potentially compromise the efficacy of nevirapine prophylaxis in subsequent pregnancies or the efficacy of antiretroviral regimens for treatment of their HIV-1 infection.

PRESENTING AUTHOR: SH Eshleman

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2005-06-07
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