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Association of Maternal ZDV Use during Pregnancy and Infant ZDV Genotypic Resistance with Rapid Disease Progression among Infants in the WITS J. PITT*1‚2, R. COLGROVE3, B. THOMPSON2‚4, A. JAPOUR5, and S. WELLES6. 1Columbia Univ., New York, NY; 2Women and Infants Transmission Study (WITS); 3Harvard Med. Sch., Boston, MA; 4C-TASC, Baltimore, MD; 5Abbott Labs., Chicago, IL; and 6Univ. of Minnesota, Minneapolis Factors associated with ZDV genotypic drug resistance (RT mutations at codons 41, 67, 70, 210, 215, or 219) in infant isolates from birth through 6 mos., and the impact of resistance on rapid disease progression (CDC Category 3 CD4 cell decline or Clinical Category C disease within the first year) were evaluated in 57 HIV+ infants enrolled in the WITS through March 1994. 17 women were treated with ZDV for HIV symptoms; 40 received no ZDV. Overall, 19/57 (33%) of infants were rapid progressors. While maternal ZDV use during pregnancy was significantly associated with resistance in infants [OR= 5.0 (95% CI: 1.5,17.5)], maternal plasma HIV RNA level had a trend towards association as well [OR = 11.4 (0.9,142.9) per each 500,000 copies]. Infant ZDV use during the first 6 mos. was not associated with resistance (p=0.48). Univariate analysis identified maternal ZDV use during pregnancy [OR = 4.9 (1.5,16.6)] and infant 1–2 mo. peak plasma HIV RNA levels [OR = 1.2 (>1.0,1.43) per 500,000 copies] as significantly associated with progression. Maternal plasma HIV RNA at delivery [OR = 5.4 (0.6,51.8) per 500,000 copies] and genotypic resistance in infants [OR = 2.6 (0.8,8.9)] were not significant. Infant ZDV use during the first 6 mos. was not associated with progression (p=.66). In 2-parameter models, maternal ZDV use during pregnancy remained significantly associated with progression [OR = 4.6 (1.1,19.3)] when adjusted for infant peak plasma HIV RNA [OR = 1.13(<1.0,1.4) per 500,000 copies]. Infant genotypic resistance after adjustment for infant peak plasma HIV RNA was not significant [adjusted OR= 3.5 (0.8,15.4]. While maternal antenatal ZDV use reduces perinatal transmission, ZDV use during pregnancy and early infant peak RNA levels may impact progression in infants who acquire HIV despite maternal ZDV use. Further studies with a larger sample size are needed to better define the role of infant genotypic resistance. Key Words: infant disease progression, perinatal ZDV exposure, ZDV resistance |
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© 7th
Conference on Retroviruses and Opportunistic Infections, |