TY - JOUR
T1 - HIV-1 genotypic zidovudine drug resistance and the risk of maternal-infant transmission in the Women and Infants Transmission Study
AU - Welles, Seth L.
AU - Pitt, Jane
AU - Colgrove, Robert
AU - McIntosh, Kenneth
AU - Chung, Pei Hua
AU - Colson, Amy
AU - Lockman, Shahin
AU - Fowler, Mary Glenn
AU - Hanson, Celine
AU - Landesman, Sheldon
AU - Moye, John
AU - Rich, Kenneth C.
AU - Zorrilla, Carmen
AU - Japour, Anthony J.
PY - 2000
Y1 - 2000
N2 - Objectives: Although the treatment of pregnant women and their infants with zidovudine (ZDV) has been remarkably effective in preventing the perinatal transmission of human HIV-1, many potentially preventable infections still occur. To examine whether the risk of perinatal infection is increased among women who carry ZDV-resistant HIV-1, the role of genotypic ZDV resistance in perinatal transmission was evaluated. Methods: The reverse transcriptase (RT) region of clinical isolates from culture supernatants of 142 HIV-1-infected women enrolled in the Women and Infants Transmission Study (WITS), who had been treated with ZDV during pregnancy was sequenced. Results from genotypic sequencing were linked to demographic, laboratory, and obstetrical databases, and the magnitude of association of having consensus drug-resistant HIV-1 RT mutations with transmission was estimated. Results: Twenty-five per cent (34/142) of maternal isolates had at least one ZDV-associated resistance mutation. A lower CD4 cell percentage and count (P = 0.0001) and higher plasma HIV-1 RNA (P = 0.006) were associated with having any ZDV resistance mutation at delivery. Having any RT resistance mutation [odds ratio (OR): 5.16; 95% confidence interval (CI): 1.40, 18.97; P = 0 0.01], duration of ruptured membranes [OR: 1.13 (1.02, 1.26) per 4 h duration; P = 0.02], and total lymphocyte count [OR: 1.06 (1.01, 1.10) per 50 cells higher level; P = 0.009] were independently associated with transmission in multivariate analysis. Conclusion: Maternal ZDV resistant virus was predictive of transmission, independent of viral load, in these mothers with moderately advanced HIV-1 disease, many of whom had been treated with ZDV before pregnancy. (C) 2000 Lippincott Williams and Wilkins.
AB - Objectives: Although the treatment of pregnant women and their infants with zidovudine (ZDV) has been remarkably effective in preventing the perinatal transmission of human HIV-1, many potentially preventable infections still occur. To examine whether the risk of perinatal infection is increased among women who carry ZDV-resistant HIV-1, the role of genotypic ZDV resistance in perinatal transmission was evaluated. Methods: The reverse transcriptase (RT) region of clinical isolates from culture supernatants of 142 HIV-1-infected women enrolled in the Women and Infants Transmission Study (WITS), who had been treated with ZDV during pregnancy was sequenced. Results from genotypic sequencing were linked to demographic, laboratory, and obstetrical databases, and the magnitude of association of having consensus drug-resistant HIV-1 RT mutations with transmission was estimated. Results: Twenty-five per cent (34/142) of maternal isolates had at least one ZDV-associated resistance mutation. A lower CD4 cell percentage and count (P = 0.0001) and higher plasma HIV-1 RNA (P = 0.006) were associated with having any ZDV resistance mutation at delivery. Having any RT resistance mutation [odds ratio (OR): 5.16; 95% confidence interval (CI): 1.40, 18.97; P = 0 0.01], duration of ruptured membranes [OR: 1.13 (1.02, 1.26) per 4 h duration; P = 0.02], and total lymphocyte count [OR: 1.06 (1.01, 1.10) per 50 cells higher level; P = 0.009] were independently associated with transmission in multivariate analysis. Conclusion: Maternal ZDV resistant virus was predictive of transmission, independent of viral load, in these mothers with moderately advanced HIV-1 disease, many of whom had been treated with ZDV before pregnancy. (C) 2000 Lippincott Williams and Wilkins.
KW - HIV-1
KW - RT drug-resistant mutations
KW - Zidovudine drug-resistance
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U2 - 10.1097/00002030-200002180-00008
DO - 10.1097/00002030-200002180-00008
M3 - Article
C2 - 10716502
AN - SCOPUS:0034105783
SN - 0269-9370
VL - 14
SP - 263
EP - 271
JO - AIDS
JF - AIDS
IS - 3
ER -