Use of Nucleoside Reverse Transcriptase Inhibitor-only Regimens in HIV-infected Children and Adolescents

Overview

Journal Pediatr Infect Dis J

Specialty Pediatrics

Date 2013 Sep 7

PMID 24008749

Citations 1

Authors

Michael Neely

Richard Rutstein

Gabriela Del Bianco

Gloria Heresi

Theresa Barton

Andrew Wiznia

Ryan Wiegand

Travis Wheeling

Beverly Bohannon

Kenneth Dominguez

Affiliations

Soon will be listed here.

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.

Citing Articles

Efficacy and safety of abacavir-containing combination antiretroviral therapy as first-line treatment of HIV infected children and adolescents: a systematic review and meta-analysis.

Adetokunboh O, Schoonees A, Balogun T, Wiysonge C BMC Infect Dis. 2015; 15:469.

PMID: 26502899 PMC: 4623925. DOI: 10.1186/s12879-015-1183-6.

References

Landman R, Descamps D, Peytavin G, Trylesinski A, Katlama C, Girard P . Early virologic failure and rescue therapy of tenofovir, abacavir, and lamivudine for initial treatment of HIV-1 infection: TONUS study. HIV Clin Trials. 2006; 6(6):291-301. DOI: 10.1310/9DQP-R7JA-75ED-RBCP. View

Garvie P, Flynn P, Belzer M, Britto P, Hu C, Graham B . Psychological factors, beliefs about medication, and adherence of youth with human immunodeficiency virus in a multisite directly observed therapy pilot study. J Adolesc Health. 2011; 48(6):637-40. PMC: 3096841. DOI: 10.1016/j.jadohealth.2010.09.014. View

Shafer R . Rationale and uses of a public HIV drug-resistance database. J Infect Dis. 2006; 194 Suppl 1:S51-8. PMC: 2614864. DOI: 10.1086/505356. View

Barth R, Schim van der Loeff M, Schuurman R, Hoepelman A, Wensing A . Virological follow-up of adult patients in antiretroviral treatment programmes in sub-Saharan Africa: a systematic review. Lancet Infect Dis. 2010; 10(3):155-66. DOI: 10.1016/S1473-3099(09)70328-7. View

Ding H, Wilson C, Modjarrad K, McGwin Jr G, Tang J, Vermund S . Predictors of suboptimal virologic response to highly active antiretroviral therapy among human immunodeficiency virus-infected adolescents: analyses of the reaching for excellence in adolescent care and health (REACH) project. Arch Pediatr Adolesc Med. 2009; 163(12):1100-5. PMC: 3739292. DOI: 10.1001/archpediatrics.2009.204. View

Staszewski S, Keiser P, Montaner J, Raffi F, Gathe J, Brotas V . Abacavir-lamivudine-zidovudine vs indinavir-lamivudine-zidovudine in antiretroviral-naive HIV-infected adults: A randomized equivalence trial. JAMA. 2001; 285(9):1155-63. DOI: 10.1001/jama.285.9.1155. View

Castagna A, Cossarini F, Spagnuolo V, Gianotti N, Galli L . Prior therapy influences the efficacy of lamivudine monotherapy in patients with lamivudine-resistant HIV-1 infection. J Acquir Immune Defic Syndr. 2010; 56(1):e34-5. DOI: 10.1097/QAI.0b013e3181fbcc96. View

Katlama C, Fenske S, Gazzard B, Lazzarin A, Clumeck N, Mallolas J . TRIZAL study: switching from successful HAART to Trizivir (abacavir-lamivudine-zidovudine combination tablet): 48 weeks efficacy, safety and adherence results. HIV Med. 2003; 4(2):79-86. DOI: 10.1046/j.1468-1293.2003.00139.x. View

Vibhagool A, Cahn P, Schechter M, Smaill F, Soto-Ramirez L, Carosi G . Triple nucleoside treatment with abacavir plus the lamivudine/zidovudine combination tablet (COM) compared to indinavir/COM in antiretroviral therapy-naïve adults: results of a 48-week open-label, equivalence trial (CNA3014). Curr Med Res Opin. 2004; 20(7):1103-14. DOI: 10.1185/030079904125004006. View

10.

Kumar P, Rodriguez-French A, Thompson M, Tashima K, Averitt D, Wannamaker P . A prospective, 96-week study of the impact of Trizivir, Combivir/nelfinavir, and lamivudine/stavudine/nelfinavir on lipids, metabolic parameters and efficacy in antiretroviral-naive patients: effect of sex and ethnicity. HIV Med. 2006; 7(2):85-98. DOI: 10.1111/j.1468-1293.2006.00346.x. View

11.

Gulick R, Ribaudo H, Shikuma C, Lustgarten S, Squires K, Meyer 3rd W . Triple-nucleoside regimens versus efavirenz-containing regimens for the initial treatment of HIV-1 infection. N Engl J Med. 2004; 350(18):1850-61. DOI: 10.1056/NEJMoa031772. View

12.

Opravil M, Klimkait T, Louvel S, Wolf E, Battegay M, Fux C . Prior therapy influences the efficacy of lamivudine monotherapy in patients with lamivudine-resistant HIV-1 infection. J Acquir Immune Defic Syndr. 2009; 54(1):51-8. DOI: 10.1097/QAI.0b013e3181bef889. View

13.

Peacock-Villada E, Richardson B, John-Stewart G . Post-HAART outcomes in pediatric populations: comparison of resource-limited and developed countries. Pediatrics. 2011; 127(2):e423-41. PMC: 3025421. DOI: 10.1542/peds.2009-2701. View

14.

Clumeck N, Goebel F, Rozenbaum W, Gerstoft J, Staszewski S, Montaner J . Simplification with abacavir-based triple nucleoside therapy versus continued protease inhibitor-based highly active antiretroviral therapy in HIV-1-infected patients with undetectable plasma HIV-1 RNA. AIDS. 2001; 15(12):1517-26. DOI: 10.1097/00002030-200108170-00009. View

15.

Siberry G, Frederick T, Emmanuel P, Paul M, Bohannon B, Wheeling T . Methicillin-Resistant Staphylococcus aureus Infections in Human Immunodeficiency Virus-Infected Children and Adolescents. AIDS Res Treat. 2012; 2012:627974. PMC: 3447349. DOI: 10.1155/2012/627974. View

16.

Palma P, Romiti M, Cancrini C, Pensieroso S, Montesano C, Santucci M . Successful simplification of protease inhibitor-based HAART with triple nucleoside regimens in children vertically infected with HIV. AIDS. 2007; 21(18):2465-72. DOI: 10.1097/QAD.0b013e3282f1560b. View

17.

DEttorre G, Zaffiri L, Ceccarelli G, Andreotti M, Massetti A, Vella S . Simplified maintenance therapy with abacavir/lamivudine/zidovudine plus tenofovir after sustained HIV load suppression: four years of follow-up. HIV Clin Trials. 2007; 8(3):182-8. DOI: 10.1310/hct0803-182. View

18.

Castagna A, Danise A, Menzo S, Galli L, Gianotti N, Carini E . Lamivudine monotherapy in HIV-1-infected patients harbouring a lamivudine-resistant virus: a randomized pilot study (E-184V study). AIDS. 2006; 20(6):795-803. DOI: 10.1097/01.aids.0000218542.08845.b2. View

19.

Saez-Llorens X, Nelson Jr R, Emmanuel P, Wiznia A, Mitchell C, Church J . A randomized, double-blind study of triple nucleoside therapy of abacavir, lamivudine, and zidovudine versus lamivudine and zidovudine in previously treated human immunodeficiency virus type 1-infected children. The CNAA3006 Study Team. Pediatrics. 2001; 107(1):E4. DOI: 10.1542/peds.107.1.e4. View

20.

Greenland S . Modeling and variable selection in epidemiologic analysis. Am J Public Health. 1989; 79(3):340-9. PMC: 1349563. DOI: 10.2105/ajph.79.3.340. View