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| Comparison of Nevirapine Resistance (NVPR) Mutations in Women vs. Infants Receiving Single Dose NVP Prophylaxis to Prevent HIV-1 Vertical Transmission (HIVNET 012) |
SUSAN H. ESHLEMAN1, M. DESEYVE2, L. A. GUAY1, M. MRACNA1, M. FURTADO3, P. MUSOKE4, F. MMIRO4, J. B. JACKSON1;
1The Johns Hopkins Med. Inst., Baltimore, MD, 2Fred Hutchinson Cancer Res. Ctr., Seattle, WA, 3Applied Biosystems, Foster City, CA, 4Makerere Univ., Kampala, Uganda. |
| Presentation Number: 234 |
| Background In the HIVNET 012 trial, administration of a single dose of NVP to antiretroviral drug naïve pregnant Ugandan women at the onset of labor and a single dose to their infants within 72 hours of birth was shown to reduce the rate of HIV-1 mother-to-child transmission. We recently reported detection of NVPR mutations in 21/111 (19%) of women and 11/24 (46%) of infected infants in HIVNET 012 tested 6-8 weeks after delivery. The aim of this study was to compare the NVPR mutations detected in women vs. infants in this cohort.Methods HIV-1 from plasma collected 6-8 weeks after delivery was analyzed using the Applied Biosystems ViroSeq HIV-1 Genotyping System for the presence of NVPR mutations. Results Different patterns of NVPR mutations were detected in women vs. infants. In women, the most common mutation was K103N, whereas in infants it was Y181C. Among the 11 infants with NVPR, results were available for 10 of the corresponding mothers. Six of those women lacked NVPR. In 4 cases where both mother and infant had NVPR, the pattern of NVPR mutations in the mother and infant was different.Conclusion We detect different patterns of NVPR mutations in women vs. infants who received single dose NVP in HIVNET 012. This suggests that NVPR is independently selected in infants following NVP administration. The different rates of K103N vs. Y181C in women vs. infants could reflect a difference in the prevalence of pre-existing variants with those mutations, viral load, or the level of NVP exposure in women vs. infants. The fitness or NVP susceptibility of HIV-1 with K103N vs. Y181C could also influence selection of variants with each mutation in a given clinical setting. |
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