Early Archiving and Predominance of Nonnucleoside Reverse Transcriptase Inhibitor-Resistant HIV-1 among Recently Infected Infants Born in the United States

Persaud, Deborah; Palumbo, Paul; Ziemniak, Carrie; Jie Chen; Ray, Stuart C.; Hughes, Michael; Havens, Peter; Purswani, Murli; Gaur, Aditya H.; Chadwick, Ellen Gould
May 2007
Journal of Infectious Diseases;5/15/2007, Vol. 195 Issue 10, p1402
Academic Journal
Background. The extent to which drug-resistant human immunodeficiency virus type 1 (HIV-1) acquired through mother-to-child transmission (MTCT) or failed chemoprophylaxis populates viral reservoirs and limits responses to antiretroviral treatment in infants is unknown. Methods. We evaluated the presence, type, and persistence of drug-resistant HIV-1 in pretreatment plasma and resting CD4+ T cells from US infants enrolled in a multicenter, open-label, phase 1/2 treatment trial of lopinavir/ritonavir (Pediatric AIDS Clinical Trials Group Protocol 1030) in young infants. Results. Twenty-two consecutively enrolled infants initiating highly active antiretroviral therapy at a median age of 9.7 weeks and treated for up to 96 weeks were studied. Drug-resistant HIV-1 was present in 5 (23.8%) of 21 infants analyzed; 4 (80.0%) had nonnucleoside reverse transcriptase inhibitor (NNRTI)—resistant HIV-1, only 1 of whom had a history of receiving nevirapine chemoprophylaxis. All 4 infants had NNRTI-resistant variants other than the K103N mutation. The fifth infant had the M184V mutation. Drug-resistant virus was archived in the resting CD4+ T cell latent reservoir in all 5 infants. Conclusions. The high rate, types, and early archiving of drug-resistant HIV-1 suggests that resistance testing be considered for infants, especially when an NNRTI-based regimen is planned. Furthermore, drug-resistance outcomes in infants should be an important secondary end point in MTCT trials.


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