Early archiving and predominance of nonnucleoside reverse transcriptase inhibitor-resistant HIV-1 among recently infected infants born in the United States. J Infect Dis 2007 May 15;195(10):1402-10
Date
04/17/2007Pubmed ID
17436219DOI
10.1086/513871Scopus ID
2-s2.0-34248165997 (requires institutional sign-in at Scopus site) 56 CitationsAbstract
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.
Author List
Persaud D, Palumbo P, Ziemniak C, Chen J, Ray SC, Hughes M, Havens P, Purswani M, Gaur AH, Chadwick EG, Pediatric AIDS Clinical Trials Group P1030 TeamMESH terms used to index this publication - Major topics in bold
Acquired Immunodeficiency SyndromeAnti-HIV Agents
Antiretroviral Therapy, Highly Active
CD4 Lymphocyte Count
DNA, Complementary
Drug Resistance, Viral
HIV-1
Humans
Infant
Lopinavir
Male
Pyrimidinones
RNA, Viral
Reverse Transcriptase Inhibitors
Reverse Transcriptase Polymerase Chain Reaction
Ritonavir
United States
Viral Load
Zidovudine