AEGiS-15IAC: Profile of NNRI associated mutations in women exposed to a single dose of nevirapine during delivery in Thailand.

15th International AIDS Conference

Bangkok, Thailand - July 11-16, 2004

Profile of NNRI associated mutations in women exposed to a single dose of nevirapine during delivery in Thailand.

Int Conf AIDS 2004 Jul 11-16; 15:(abstract no. WeOrB1289)

Ngo-Giang-Huong N, Tungyai P, Kummee A, Jenjaroen K, Winiyakul N, Malitong P, Chonladarat T, Ruangsirinusorn S, Sangsawang S, Srichandraphan W, Jitphiankha W, Laphikanont W, Haesungcharern A, Lallemant MJ
Harvard School of Public Health/IRD054/Chiang Mai University, Chiang Mai, Thailand

BACKGROUND: Studies performed in Africa and Europe using a single intrapartum dose of nevirapine (NVP) to reduce HIV vertical transmission has shown that NVP exposure was followed by the selection of viruses with NNRTI resistance associated mutations in a significant proportion of women. These studies were performed in areas where HIV subtypes A, B, C and D were most prevalent. In Thailand, most of the circulating viruses are the recombinant CRF01_AE for which the pattern of NVP induced resistance mutations has not yet been described in detail.

METHODS: Plasma samples from women enrolled in the perinatal HIV prevention trial in Thailand (PHPT-2) and exposed to SD NVP were collected 10 days and 6 weeks postpartum. HIV RNA was sequenced using the HIV ViroSeq kit v2.0 and analyzed with the ViroSeq HIV-1 Genotyping System Software v2.5 (Applied Biosystems, USA). Sequences were assessed for NNRTI associated mutations codons (100, 101, 103, 106, 108, 181, 188, 190, 225, 230 and 236) and examined for subtypes by phylogenetic analysis.

RESULTS: Within this group of 310 immunocompromized women, most of whom had to initiate therapy relatively soon after pregnancy, the overall frequency of NNRTI mutation was 38% (118/308), with 72.9% (86/118) with a single mutation and 27.1% (32/118) with at least 2 mutations. Prevalence of specific mutations was 65% (77/118) for K103N, 30% (35/118) for G190A, 13% (16/118) for V108I and 12% for Y181C mutations. Conclusion These results indicate that for women exposed to an intrapartum single dose of NVP, the selection of NNRTI mutations may occur as early 10 days postpartum, with K103N being the common mutation as reported for other subtypes. However, the pattern of mutations for CRF01-AE differed from other subtypes with the G190A as the second most prevalent mutation

Keywords: AEGIS, Nevirapine, Disease Transmission, Vertical, HIV-1, Acquired Immunodeficiency Syndrome, Single Person, HIV-1 Reverse Transcriptase, Thailand, Mutation, HIV Seropositivity, Africa, Europe, Humans, Female, Pregnancy, transmission, genetics

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