15th International AIDS Conference Bangkok, Thailand — July 11-July 16, 2004

Int Conf AIDS. 2004 Jul 11-16;15:Abstract No. LbOrB09

J McIntyre¹, N Martinson¹, Investigators for the Trial 1413², V Boltz³, S Palmer³, J Coffin³, J Mellors⁴, M Hopley⁵, T Kimura⁶, P Robinson⁶, D Mayers^6
1Perinatal HIV Research Unit, Univ of Witwatersrand, Johannesburg, South Africa; ²Study , Investigators, South Africa; ³NCI Drug Resistance Program, Frederick, MD, United States; ⁴Univ of Pittsburgh, Pittsburgh, PA, United States; ⁵Boehringer Ingelheim ZA, Johannesburg, South Africa; ⁶Boehringer Ingelheim Pharm, Ridgefield, CT, United States

BACKGROUND: SdNVP given at the time of delivery has reduced MTCT transmission in resource poor settings, but concerns have been raised about development of NNRTI-resistance limiting future treatment. A trial of sdNVP+short course CBV was conducted to determine whether post-partum maternal HIV-1 resistance can be avoided.

METHODS: A prospective, randomized three-arm study compares sdNVP, sdNVP+4 days CBV and sdNVP+7 days CBV for pMTCT, conducted is South Africa; 300 mother-infant pairs are planned. SdNVP was given to the mother during active labor and to the infant within 24-72 hours after delivery. CBV BID was initiated in mother during labor and in infants soon after delivery. Maternal NNRTI resistance at weeks 2 and 6 post-partum was the primary endpoint. Genotypic resistance was determined by population sequencing of plasma HIV. Studies of minority drug resistant populations of virus using differential PCR confirmed by clonal sequencing are in progress. Infant HIV-1 transmission was determined by HIV DNA or RNA at birth, 2 and 6 wks.

RESULTS: We evaluated the first 61 mothers with 6-week follow-up and population sequencing. Median entry CD4 count was 318 cells/mm³; median viral load was 32,600 copies/ml. All isolates were clade C. Population sequencing of 2 and 6 week specimens showed NNRTI resistance in 9/18 (50%) patients in sdNVP; sdNVP+CBV4: 1/20(5%); sdNVP+CBV7: 3/23(13%). The most common NNRTI resistance mutations were: K103N (8), Y181C (7), A190G (5), Y188C (4), V106A (3), and V106M (3). No NRTI mutations, including 184, were detected. Among 68 evaluable infants, intrauterine transmission was observed in four; one additional infant (sdNVP) experienced peri/post partum transmission. No treatment-related serious adverse event concerns have been identified.

CONCLUSIONS: SdNVP is effective in decreasing MTCT of HIV, but sdNVP+CBV can significantly decrease the subsequent development of drug resistant maternal HIV-1. The optimal duration of CBV is uncertain.

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LbOrB09

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