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Session 10 Oral Abstracts and Mini-Lecture
Transmission, Selection, and Persistence of Drug-Resistant Virus
Monday, 10 am - 12:15 pm
Presentation Time: 10:45 am
Room 3000


38
HIV Resistance and Transmission following Single-dose Nevirapine in a PMTCT Cohort
N Martinson*1,2,3, L Morris1,2,3, G Gray1,2, D Moodley4, P Lupondwana1,2, C Chezzi1,2, S Cohen1, C Pillay1,2, A Puren1, M Ntsala1, J Sullivan5, J Steyn2, and J McIntyre2
1Natl. Inst. for Communicable Diseases, Johannesburg, South Africa; 2Perinatal HIV Res. Unit, Johannesburg, South Africa; 3Sch. of Med., Johns Hopkins Univ., Baltimore, MD, USA; 4King Edward Hosp., Durban, South Africa; and 5Univ. of Massachusetts Med. Sch., Worcester, USA

Background:  Nevirapine (NVP), given to mothers in labor and to neonates within 72 hours of delivery, is an effective, simple PMTCT regimen. Previous studies have shown that transient resistance develops in those exposed to this regimen. This study was designed to assess genotypic resistance induced by NVP (NVPR).

Methods:  We enrolled 623 HIV-infected mothers at 2 tertiary hospitals in South Africa from 32 to 38 weeks’ gestation. We report preliminary findings on baseline and follow-up visits scheduled at 6 weeks postpartum. High-level NVPR was defined as K103N, V106A/M, Y181C, YI88C, and G190A.

Results:  The median CD4 and viral load of pregnant women was 393 x106/l (IQR 266 to 585) and 28 700 copies/mL (IQR 6560 to 100,000). No drug naïve women had resistance at baseline; 456 were followed at a median time of 7.0 weeks postpartum (IQR 6.3 to 10.3); all but 4 were clade C; 38.8% (95%CI:  34 to 44) of mothers and 42.4% (95%CI:  30 to 55) of their infants were found to have NVPR. Maternal resistance in the first (4 to 6 weeks postpartum), second (6 to 7 weeks), third (7 to 10 weeks), and fourth quartiles (10 to 36 weeks) of the follow-up visit was 43%, 44%, 44%, and 24%, respectively (test for trend p = 0.006). Maternal mutations included K103N (31%), Y181C (12%), and Y188C (8.1%); 21% had a single mutation, 13% had 2, and 5%, 3 or 4 mutations. Infants’ mutations included Y181C (32%), K103N (12%) and Y188C (5%). The 10-week HIV MTCT rate was 8.6% (95%CI:  6.0 to 11.2). There was an association between postpartum NVPR and transmission (OR 2.9, 95%CI:  1.4 to 6.1) confounded by maternal viral load and CD4 count. Baseline CD4, log baseline viral load, the time from labor NVP dose to the postpartum blood draw and the total number of times a mother took NVP in her pregnancy were statistically significantly associated with development of resistance.

Conclusions:  Maternal and infant resistance induced by NVP is high. Its effect on subsequent pregnancies and choice of HAART regimen remains to be explored.

Keywords: nevirapine resistance; mother-to-child transmission; HIV-1 subtype C