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Session 137 Poster Abstracts
Vertical Transmission and Antiretroviral Resistance
Friday, 1:30 - 3:30 pm
Hall B


802    
Infant Zidovudine Prophylaxis and Emergence of Nevirapine Resistance at 6 Weeks in Perinatally HIV-infected Infants Exposed to Intra-partum or Newborn Nevirapine
Nicole Ngo-Giang-Huong*1, G Jourdain1, P Tungyai2, W Boonprasit2, R Hansudewechakul3, S Kanjanavanit4, S Hongsiriwon5, C Ngampiyasakul6, P Layangool7, S Bhakeecheep8, P O Sukrakanchana2, S Tanasri2, M Lallemant2, and PHPT group
1Harvard Sch of Publ Hlth, Boston, MA, USA; 2PHPT-Ins de Recherche pour le Dévt, France and Thailand; 3Chiang Rai Prachanukroh Hospital, MOPH/PHPT-IRD054, Chiang Rai; 4Nakornping Hospital, MOPH/PHPT-IRD054, Chiang Mai; 5Chonburi Hospital, MOPH/PHPT-IRD054, Chonburi; 6Prapokklao Hospital, MOPH/PHPT-IRD054, Chantaburi; 7Bhumibol Adulyadej Hospital, MOPH/PHPT-IRD054, Bangkok; and 8Phayao Provincial Hospital, MOPH/PHPT-IRD054, Phayao, Thailand

Background:  The emergence of nevirapine (NVP)-resistance mutations after a single-dose intrapartum or newborn NVP to prevent mother-to-child transmission of HIV has been described in different settings. Whether the rate and pattern of NVP-resistance-associated mutations in HIV-infected children differ according to duration of infant ZDV prophylaxis is unknown.

Methods:  We studied 2 groups of perinatally HIV-infected children exposed to NVP and not breastfed. The first group consists of 33 infants born to mothers enrolled in PHPT-2, where mothers started ZDV from 28 weeks gestation and all received single-dose NVP at onset of labor while infants were randomized to receive NVP or placebo within 48 to 72 hours after birth. Within this group, 30 infants received 7 days of ZDV after birth and 3 infants received 6 weeks of ZDV after birth. The second group consists of 20 children born to mothers who received ZDV for < 2 weeks and were offered NVP at onset of labor. All children received a single dose of NVP 48 to 72 hours after birth and ZDV for 6 weeks. NVP-resistance mutations were assessed at 6 weeks after NVP exposure except for 4 samples:  2 tested 15 days after exposure; 2 tested at 4 months. HIV RNA was sequenced using the ViroSeq HIV-1 Genotyping system and mutations identified. Phylogenetic analysis was performed on the protease and RT genes. The prevalence of NVP-resistance mutations was compared according to the duration of infant and maternal ZDV prophylaxis.

Results:  Viral sequences could be amplified for 50 of 53 (94%) infants. All viruses were the circulating recombinant form CRF01_AE. NVP-resistance mutations were detectable in 4 of 50 (8%) children. Mutations observed were:  K103N alone or associated with the G190A in 3 children and Y181C in 1 child. Of the 4 NVP-resistance mutations detected, 3 occurred in infants who received 7 days of ZDV prophylaxis, and 1 occurred in an infant who received 6 weeks of ZDV.

Conclusions:  The incidence of NVP-resistance mutations in perinatally HIV-infected children exposed to perinatal NVP plus ZDV is lower than what has been described in others studies after exposure to NVP only. Our data do not show a difference in the prevalence of NVP-resistance mutations according to the duration of infant or maternal ZDV prophylaxis. The pattern of NVP mutations observed could be associated with the CRF01_AE subtype as well as ZDV prophylaxis.

Keywords: Nevirapine resistance; infants; zidovudine prophylaxis