[2] SINGLE DOSE NEVIRAPINE COMBINED WITH A SHORT COURSE OF COMBIVIR FOR PREVENTION OF MOTHER TO CHILD TRANSMISSION OF HIV-1 CAN SIGNIFICANTLY DECREASE THE SUBSEQUENT DEVELOPMENT OF MATERNAL AND INFANT RESISTANT VIRUS

14th International HIV Drug Resistance Workshop

7-11 June 2005, Québec City, Canada

SINGLE DOSE NEVIRAPINE COMBINED WITH A SHORT COURSE OF COMBIVIR FOR PREVENTION OF MOTHER TO CHILD TRANSMISSION OF HIV-1 CAN SIGNIFICANTLY DECREASE THE SUBSEQUENT DEVELOPMENT OF MATERNAL AND INFANT RESISTANT VIRUS

Antivir Ther. 10, Suppl 1:S4 (abstract no. 2)

JA McIntyre¹, N Martinson¹, GE Gray¹ for the Trial 1413 Investigator Team, and DB Hall², V Boltz³, S Palmer³, J Coffin³, J Mellors⁴, M Hopley⁵, T Kimura², P Robinson², DL Mayers²
¹Perinatal HIV Research Unit, Univ of Witwatersrand, Johannesburg, RSA; ²Boehringer Ingelheim Pharmaceuticals, Inc. Ridgefield, CT, USA; ³NCI Drug Resistance Program, Frederick, MD, USA; ⁴University of Pittsburgh, Pittsburgh, PA, USA; ⁵Boehringer Ingelheim ZA, Johannesburg, RSA

BACKGROUND: Single dose nevirapine (sdNVP) given at the time of delivery has decreased mother-to-child transmission (MTCT) in resource poor settings, but concerns have been raised about development of NNRTI-resistance limiting future treatment. A trial of sdNVP+short course combivir (CBV) was conducted to determine whether post-partum maternal and infant HIV-1 resistance can be reduced.

METHODS: A prospective, randomized three-arm study compares sdNVP, sdNVP+4 days CBV and sdNVP+7 days CBV for pMTCT, conducted in South Africa; 300 mother-infant pairs were planned. The sdNVP arm was closed to accrual after an interim analysis. All 226 mothers randomized to the three arms have reached 6 weeks of follow up. SdNVP was given to the mother during active labour and to the infant within 24–72 hours after delivery. CBV BID was initiated in mother during labour and in infants soon after delivery. Maternal NNRTI resistance at weeks 2 and 6 post-partum was the primary endpoint. Infant HIV-1 transmission was determined by HIV DNA or RNA at birth, 2 and 6 weeks.

RESULTS: We evaluated 226 mothers and 228 infants with 6-week follow-up. Median entry CD4 count was 314 cells/mm³; median viral load was 4.49 log₁₀ copies/mL. Population sequencing of 2 and 6 week specimens showed NNRTI resistance in 39/68 (57%) mothers in sdNVP; sdNVP+CBV4: 9/67 (13%); sdNVP+CBV7: 6/68 (9%). The most common maternal NNRTI resistance mutations were: K103N, Y188C, Y181C, V106M, A190G, and V106A. No NRTI mutations, including M184V, were detected. Among 228 evaluable infants, in utero transmission was 21/228 (9.2%) and at 6 weeks total transmission rate was 24/228 (10.5%). NNRTI resistance was detected in 7/9 (78%) infants in sdNVP; sdNVP+CBV4: 1/8 (13%); sdNVP+CBV7: 0/7 (0%). No M184V mutations or K103N mutations were observed in sdNVP infants. The sdNVP+CBV4 infant was an in utero transmission with K103N and Y181C and her mother did not develop NNRTI resistance.

CONCLUSIONS: SdNVP+CBV can significantly decrease the subsequent development of maternal and paediatric NNRTI resistant HIV-1 without risk of 3TC resistance. The optimal duration of CBV is uncertain and the two sdNVP+CBV arms remain open to accrual.

PRESENTING AUTHOR: DB Hall

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2005-06-07
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