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15 May 2007

Volume 195, Number 10
The Journal of Infectious Diseases 2007;195:1402–1410
© 2007 by the Infectious Diseases Society of America. All rights reserved.
0022-1899/2007/19510-0004$15.00
DOI: 10.1086/513871
MAJOR ARTICLE

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

Deborah Persaud,1

Paul Palumbo,3

Carrie Ziemniak,1

Jie Chen,4

Stuart C. Ray,2

Michael Hughes,4

Peter Havens,5

Murli Purswani,6

Aditya H. Gaur,7

Ellen Gould Chadwick,8 and the

Pediatric AIDS Clinical Trials Group P1030 Team

Departments of 1Pediatrics and 2Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland; 3Department of Pediatrics, University of Medicine and Dentistry of New Jersey, Newark; 4Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts; 5Department of Pediatrics, Medical College of Wisconsin, Milwaukee; 6Albert Einstein College of Medicine, New York, New York; 7St. Jude Children’s Research Hospital, Memphis, Tennessee; 8Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois

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.

Received 18 August 2006; accepted 16 November 2006; electronically published 5 April 2007.

  • (See the editorial commentary by Krogstad, on pages 1393–5.)

Reprints or correspondence: Dr. Deborah Persaud, 600 N. Wolfe St., Baltimore, MD 21287 ().

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L. Ross, N. Parkin, R. Lanier. (2008) Short Communication: The Number of HIV Major NRTI Mutations Correlates Directly with Other Antiretroviral-Associated Mutations and Indirectly with Replicative Capacity and Reduced Drug Susceptibility. AIDS Research and Human Retroviruses 24:4, 617-620
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Abstract-Full Text-PDF Version (457 kB)
Paul A. Krogstad. (2007) Resistance to Antiretroviral Drugs: A Threat to the Prevention and Treatment of Pediatric HIV Infection. The Journal of Infectious Diseases 195:10, 1393-1395
Online publication date: 15-May-2007.
Citation-Full Text-PDF Version (148 kB)

  • Potential conflicts of interest: E.G.C. has received research grants from Abbott Labs and GlaxoSmithKline and has equity interest in Abbott Labs, GlaxoSmithKline, Bristol‐Meyers Squibb, and Merck & Co. M.H. has had honoraria or consultancies with Abbott Labs, Boehringer Ingelheim, Bristol Myers Squibb, Chiron, Roche, and Tibotec. All other authors: no conflicts reported.

    Presented in part: 13th Conference on Retroviruses and Opportunistic Infections, Denver, CO, 5–8 February 2006 (abstract M183).

    Financial support: Elizabeth Glaser Pediatric AIDS Foundation (grant 14‐05 to D.P.); National Institutes of Health (grant RO1‐AI055312 to D.P.); Pediatric AIDS Clinical Trials Group of the National Institute of Allergy and Infectious Diseases (grant NCT00038480); Pediatric/Perinatal HIV Clinical Trials Network of the National Institute of Child Health and Human Development (grant N01‐HD‐3‐3345). Pharmaceutical support for the parent trial was provided by Abbott Laboratories.

    Clinical Trials number NCT00038480.

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