Use of nucleoside reverse transcriptase inhibitor-only regimens in HIV-infected children and adolescents.

Abstract

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.

• Authors: Michael Neely, Richard Rutstein, Gabriela Del Bianco, Gloria Heresi, Theresa Barton, Andrew Wiznia, Ryan Wiegand, Travis Wheeling, Beverly Bohannon, Kenneth Dominguez, LEGACY Consortium
• Journal: The Pediatric infectious disease journal (Pediatr Infect Dis J) Vol. 32 Issue 9 Pg. e370-6 (Sep 2013) ISSN: 1532-0987 [Electronic] United States
• PMID: 24008749 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Anti-HIV Agents
• Nucleosides
• RNA, Viral
• Reverse Transcriptase Inhibitors

Topics

• Adolescent
• Anti-HIV Agents (adverse effects, therapeutic use)
• CD4 Lymphocyte Count
• Child
• Child, Preschool
• Cohort Studies
• Drug Therapy, Combination (adverse effects, methods)
• Drug-Related Side Effects and Adverse Reactions (epidemiology, pathology)
• Female
• HIV (isolation & purification)
• HIV Infections (drug therapy, immunology, virology)
• Humans
• Immune Reconstitution Inflammatory Syndrome (epidemiology, pathology)
• Infant
• Nucleosides (adverse effects, therapeutic use)
• Prospective Studies
• RNA, Viral (blood)
• Reverse Transcriptase Inhibitors (adverse effects, therapeutic use)
• Treatment Outcome
• Viral Load
• Young Adult