Objective: In adults, nucleoside reverse transcriptase inhibitor–only antiretroviral regimens (NOARs) with ≥3 nucleoside reverse transcriptase inhibitors are less potent than highly active antiretroviral therapy (HAART). Published pediatric experience with NOARs is limited; thus, we wished to better define the virological, immunological and toxicological effects of NOARs in children and adolescents.
Methods: We analyzed data from NOAR-treated participants in LEGACY, a multicenter observational cohort study of HIV-infected children and adolescents. NOAR-treated case-participants were matched to participants without prior NOAR who initiated HAART during the same year for comparison.
Results: Of 575 participants with data from time of HIV diagnosis through 2006, 67 (12%) received NOARs for at least 24 weeks; most (46%) received the fixed dose combination of zidovudine/lamivudine/abacavir. NOAR use peaked in 2001 to 2002. NOAR-treated participants were significantly older and more treatment experienced than HAART-treated participants. Virologic outcomes, including the percentage of participants with a plasma HIV RNA viral load <400 copies/mL at week 24 (47% versus 34%) and the mean 24-week change in log10 plasma HIV RNA viral load from baseline (−0.63 versus −1.02), were similar between NOAR- and HAART-treated participants, but virologic rebound was more likely in NOAR-treated participants (77% versus 54%, P = 0.02). Increase in CD4 percentage points from baseline to 24 weeks was negligible in NOAR-treated participants compared with HAART-treated participants (0.95% versus 10.1%, P < 0.001). Anemia and leukopenia were more commonly reported with NOARs than HAART.
Discussion: Week 24 virologic outcomes were similar between NOAR- and HAART-treated participants, but NOAR durability was poorer and their use was associated with less immunologic reconstitution. NOARs should play a limited role in pediatric and adolescent antiretroviral therapy.
From the *Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, CA; †Children’s Hospital of Philadelphia, Philadelphia, PA; ‡University Texas Health Science Center at Houston, Houston, TX; §University Texas-Southwestern Medical Center, Dallas, TX; ¶Jacobi Medical Center, Bronx, NY; ‖Centers for Disease Control and Prevention; and **Northrop Grumman, Atlanta, GA.
Accepted for publication February 21, 2013.
M.N. was supported in part by NIH-NIAID 1 K23 AI076106, GM068968 and HD070886. The authors have no other funding or conflicts of interest to disclose.
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Address for correspondence: Michael Neely, MD, MSc, FCP, Laboratory of Applied Pharmacokinetics, 2250 Alcazar St. CSC 134B, Los Angeles, CA 90033. E-mail: email@example.com.