BACKGROUND: Single-dose nevirapine (sd-NVP) is the mainstay of prevention of mother-to-child transmission programs in developing countries. Exposure to sd-NVP selects for resistance mutations, however. We longitudinally assessed these mutations in HIV-1-infected infants from Soweto and Durban, South Africa. METHODS: We prospectively followed 465 infants who received sd-NVP after enrolling their mothers when pregnant. If HIV infected, their virus was genotyped, using the ViroSeq HIV-1 Genotyping System, to detect resistant mutations. Those with resistance were genotyped at 6 months and then every 6 months out to 18 months if resistance was detected at the previous visit. RESULTS: Of 53 HIV-infected infants, 24 (45.3%) had detectable resistance at their first visit, when the most frequent mutations were Y181C (75%), K103N (25%), and Y188C (12%). Of those whose visit was before 12 weeks of age, 2 of 42 infants shared identical resistance mutations with their mothers. By 18 months of age, 11 of 24 infants with resistance had died and 1 still had the Y181C mutation. CONCLUSIONS: Resistant mutations were selected in half of the infants exposed to sd-NVP, but fewer were detected over time and, unlike the case in their mothers, Y181C dominated initially and persists. Transient resistance mutations may have a negative impact on highly active antiretroviral therapy in infants and children.
BACKGROUND: Single-dose nevirapine (sd-NVP) is the mainstay of prevention of mother-to-child transmission programs in developing countries. Exposure to sd-NVP selects for resistance mutations, however. We longitudinally assessed these mutations in HIV-1-infectedinfants from Soweto and Durban, South Africa. METHODS: We prospectively followed 465 infants who received sd-NVP after enrolling their mothers when pregnant. If HIV infected, their virus was genotyped, using the ViroSeq HIV-1 Genotyping System, to detect resistant mutations. Those with resistance were genotyped at 6 months and then every 6 months out to 18 months if resistance was detected at the previous visit. RESULTS: Of 53 HIV-infectedinfants, 24 (45.3%) had detectable resistance at their first visit, when the most frequent mutations were Y181C (75%), K103N (25%), and Y188C (12%). Of those whose visit was before 12 weeks of age, 2 of 42 infants shared identical resistance mutations with their mothers. By 18 months of age, 11 of 24 infants with resistance had died and 1 still had the Y181C mutation. CONCLUSIONS: Resistant mutations were selected in half of the infants exposed to sd-NVP, but fewer were detected over time and, unlike the case in their mothers, Y181C dominated initially and persists. Transient resistance mutations may have a negative impact on highly active antiretroviral therapy in infants and children.
Authors: William I Towler; Linda Barlow-Mosha; Jessica D Church; Danstan Bagenda; Patrick Ajuna; Micheal Mubiru; Philippa Musoke; Susan H Eshleman Journal: AIDS Res Hum Retroviruses Date: 2010-05 Impact factor: 2.205
Authors: Jessica Fogel; Donald R Hoover; Jin Sun; Lynne M Mofenson; Mary G Fowler; Allan W Taylor; Newton Kumwenda; Taha E Taha; Susan H Eshleman Journal: AIDS Date: 2011-04-24 Impact factor: 4.177
Authors: Jessica D Church; Wei Huang; Neil Parkin; Natalia Marlowe; Laura A Guay; Saad B Omer; Philippa Musoke; J Brooks Jackson; Susan H Eshleman Journal: AIDS Res Hum Retroviruses Date: 2009-07 Impact factor: 2.205
Authors: Tamara S Flys; Michelle S McConnell; Flavia Matovu; Jessica D Church; Danstan Bagenda; Leila Khaki; Paul Bakaki; Michael C Thigpen; Chineta Eure; Mary Glenn Fowler; Susan H Eshleman Journal: J Infect Dis Date: 2008-08-15 Impact factor: 5.226
Authors: James A McIntyre; Mark Hopley; Daya Moodley; Marie Eklund; Glenda E Gray; David B Hall; Patrick Robinson; Douglas Mayers; Neil A Martinson Journal: PLoS Med Date: 2009-10-27 Impact factor: 11.069