Selection and fading of resistance mutations in women and infants receiving nevirapine to prevent HIV-1 vertical transmission (HIVNET 012)

被引:307
|
作者
Eshleman, SH
Mracna, M
Guay, LA
Deseyve, M
Cunningham, S
Mirochnick, M
Musoke, P
Fleming, T
Fowler, MG
Mofenson, LM
Mmiro, F
Jackson, JB
机构
[1] Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA
[2] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA
[3] Boston Univ, Sch Med, Dept Pediat, Boston, MA 02118 USA
[4] Makerere Univ, Dept Paediat, Kampala, Uganda
[5] Univ Washington, Dept Biostat, Seattle, WA 98195 USA
[6] NIAID, Div AIDS, NIH, Rockville, MD 20852 USA
[7] NICHHD, Pediat Adolescent & Maternal AIDS Branch, NIH, Rockville, MD USA
[8] Makerere Univ, Dept Obstet & Gynaecol, Kampala, Uganda
关键词
clinical trial; drug resistance; genotype; HIV-1; infant; nevirapine; pregnancy; prophylaxis; Uganda; vertical transmission;
D O I
10.1097/00002030-200110190-00006
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Objective: To examine the emergence and fading of NVP resistance (NVPR) mutations in HIV-1-infected Ugandan women and infants who received single dose NVP to prevent HIV-1 vertical transmission. Design: We examined NVPR in women and infants who received NVP in the HIVNET 012 clinical trial, including 41 out of 48 women with infected infants, 70 random ly-selected women with uninfected infants, and 33 out of 49 infected infants. Methods: Plasma HIV-1 was analyzed using the Applied Biosystems ViroSeq HIV-1 Genotyping System. Results: NVPR mutations were detected in 21 out of 111 (19%) women tested 6-8 weeks after delivery. The rate of NVPR was similar among women whose infants were or were not HIV-1 infected. K103N was the most common mutation detected. NVPR mutations faded from detection within 12-24 months in all 11 evaluable women. High baseline viral load and low baseline CD4 cell count were associated with development of NVPR. NVPR mutations were detected in 11 out of 24 (46%) evaluable infants who were infected by 6-8 weeks of age. The most common NVPR mutation detected in infants was Y181C. Those mutations faded from detection by 12 months of age in all seven evaluable infants. Of nine evaluable infants with late HIV-1 infection, only one had evidence of NVPR. Conclusions: NVPR was detected more frequently in infants than women following NVP prophylaxis, and different patterns of NVPR mutations were detected in women versus infants. NVPR was detected infrequently in infants with late HIV-1 infection. NVP-resistant HIV-1 faded from detection in women and infants overtime. (C) 2001 Lippincott Williams & Wilkins.
引用
收藏
页码:1951 / 1957
页数:7
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