855 Resistance Mutations Following a Single-dose Intrapartum Administration of Nevirapine to HIV-infected Thai Women and Their Infants Receiving Short-course Zidovudine T. Chaowanachan*1, T. Chotpitayasunondh2, N. Vanprapar3, W. Leelawiwat1, M. Culnane1,4, B. Jetsawang1, T. Tasaneeyapan1, P. Mock1, J. W. Tappero1,4, RJ Simonds 4 1Thailand MOPH-U S CDC Collaboration, Nonthaburi; 2Queen Sirikit Natl Inst of Child Hlth, Bangkok, Thailand; 3Siriraj Hosp, Mahidol Univ, Bangkok, Thailand; and 4CDC, Atlanta, GA
Background: Single-dose intrapartum/newborn nevirapine (NVP) reduces mother-to-child HIV transmission (MTCT). We assessed the development of genotypic resistance mutations in pregnant HIV-infected women and their infants receiving short-course zidovudine (ZDV) therapy and single-dose intrapartum/newborn NVP. Given the widespread use of NVP for MTCT, data documenting the development of resistance following this regimen alone or in combination with other drugs are critical.
Methods: From Jan 2001 through Aug 2002, 195 antiretroviral (ARV) naive mother-infant pairs have been enrolled in an ongoing open label ZDV/NVP trial. Women received ZDV 300 mg BID from 34-36 wks gestation until labor, and ZDV 300 mg every 3 hrs and NVP 200 mg once during labor. Infants received NVP, 2 mg/kg at 48-72 hrs of life, plus ZDV syrup 2 mg/kg x 4 wks. Pre-ZDV, delivery, and 1 mo postpartum (pp) maternal blood plasma samples were collected from all women and 1 wk and 4 mo pp samples from a subset. Infant samples were collected at birth, 1 mo, 2 mos, and 4 mos and from a subset at 1 wk. Samples were tested for CD4 cell count enumeration (FACScan 2 color), viral load (VL) (Amplicor Monitor v1.5), and NVP/ZDV genotypic resistance (Visible Genetics Tru-Gene HIV-1).
Results: As of Sept 2002, 177/195 (91%) women had a 1 mo pp visit. Antiretroviral (ARV) resistance testing was done for 133/177 (75%). Of those tested, median baseline CD4 count was 366 cells/mL (8-914); median VL was 3,857 copies/ml (0-376,871) at delivery and 36,994 copies/ml (0-614,410) at 1 mo pp. At 1 mo pp, 21/133 women exhibited mutations; 20 (15%) associated with NVP resistance and 1 (0.8%) associated with ZDV resistance. K103N was the most common NVP mutation found alone (5/20) or in combination with other mutations (5/20). Of the 20 women with NVP resistance, 3 women had pre-ZDV, delivery, 1 wk and 4 mos pp samples tested; no mutations were detected. Nine (9) out of 195 (4.6%) infants were HIV-infected; 3/9 had resistance testing. One (1; 33%) exhibited NVP resistance (K103N) in the 2 mo sample. Virus remained resistant at 4 mos of age.
Conclusions: Of 133 ARV naive women receiving short-course ZDV + intrapartum NVP, 20 demonstrated NVP and 1 a ZDV genotypic resistance mutation at 1 mo pp. Of the 3 HIV-infected infants tested, 1 demonstrated NVP resistance. The clinical relevance of transient NVP genotypic resistance with single dose NVP alone or in combination for MTCT is currently unknown.