Early archiving and predominance of nonnucleoside reverse transcriptase inhibitor-resistant HIV-1 among recently infected infants born in the United States.
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.
Persaud
Deborah
D
Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. dpers@jhmi.edu
Palumbo
Paul
P
Ziemniak
Carrie
C
Chen
Jie
J
Ray
Stuart C
SC
Hughes
Michael
M
Havens
Peter
P
Purswani
Murli
M
Gaur
Aditya H
AH
Chadwick
Ellen Gould
EG
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000276:immunology; D019380:Anti-HIV Agents / Q000627:therapeutic use / Q000633:toxicity; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D018076:DNA, Complementary / Q000235:genetics; D024882:Drug Resistance, Viral; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D007223:Infant; D061466:Lopinavir; D008297:Male; D011744:Pyrimidinones / Q000627:therapeutic use / Q000633:toxicity; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use* / Q000633:toxicity; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019438:Ritonavir / Q000627:therapeutic use / Q000633:toxicity; D014481:United States; D019562:Viral Load; D015215:Zidovudine / Q000627:therapeutic use / Q000633:toxicity
D019380:Anti-HIV Agents; D018076:DNA, Complementary; D011744:Pyrimidinones; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D061466:Lopinavir; D015215:Zidovudine; D019438:Ritonavir