AEGiS-13IAC: Selection of Nevirapine (NVP) resistance mutations in Ugandan women and infants receiving NVP prophylaxis to prevent HIV-1 vertical transmission (HIVNET 012).

13th International AIDS Conference

Durban, South Africa - July 9-July 14, 2000

Selection of Nevirapine (NVP) resistance mutations in Ugandan women and infants receiving NVP prophylaxis to prevent HIV-1 vertical transmission (HIVNET 012).

Int Conf AIDS 2000 Jul 9-14; 13:19 (abstract no.. LbOr13)

Jackson JB, Mracna M, Guay L, Dileanis JA, Musoke P, Mmiro F, Eshleman SH
The Johns Hopkins Medical Institutions, Baltimore, MD 21287. Fax: 410-614-2907, E-mail: bjackso@jhmi.edu.

BACKGROUND: In HIVNET 012, treatment naive Ugandan women and infants received a single dose of NVP for prevention of HIV-1 perinatal transmission. Women received NVP at the onset of labor, and infants received NVP within 72 hours of birth. In this trial, 36 infants were HIV-1 infected by 6 weeks of age despite NVP prophylaxis. We determined whether NVP resistance mutations could be detected in these women and infants 6 weeks following intrapartum NVP administration.

METHODS: Plasma collected 6 weeks after NVP administration was analyzed from 30 women whose infants were infected, and 7 of the infected infants. 2 infants were RNA positive at birth and 5 were positive for the first time at 6 weeks of age. The median HIV-1 viral load of the 30 women prior to NVP administration was 70,953 RNA copies/ml (range:8,925-659,755). Plasma HIV-1 RT sequences were analyzed using the PE Biosystems ViroSeq HIV Genotyping System.

RESULTS: NVP resistance mutations were detected at 6 weeks post partum in 7 (23%) of 30 women whose infants were HIV-1 infected. The K103N NVP resistance mutation was detected in all 7 women. In addition, 1 woman had they Y181C mutation, and 1 woman had the Y181C and V106A mutations. NVP resistance mutations were also detected in 3 of the 7 infected infants. The K103N mutation was detected in 1 infant and the Y181C mutation was detected in 2 infants. The maternal and infant HIV-1 genotypes were different for each mother-infant pair. Follow-up of these women and infants is ongoing to determine the persistence of HIV-1 variants with these mutations.

CONCLUSIONS: HIV-1 with NVP resistance mutations can be detected in a minority of HIV-1 infected women and infants 6 weeks after single dose NVP prophylaxis. The clinical significance of this finding is not known. The different genotypes in each mother-infant pair suggest that NVP-resistant HIV-1 variants in the infants may have been selected by NVP, rather than transmitted from mother to child.

Keywords: AEGIS, Nevirapine, Disease Transmission, Vertical, HIV-1, HIV Infections, Viral Load, HIV-1 Reverse Transcriptase, Mutation, Selection (Genetics), HIV Seropositivity, Genotype, Infant, Adult, Human, Female, Child, prevention & control, transmission, genetics, therapy, AIDS
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