1. Analyses of HIV-1 drug-resistance profiles among infected adolescents experiencing delayed antiretroviral treatment switch after initial nonsuppressive highly active antiretroviral therapy
- Author
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Agwu, Allison, Lindsey, Jane C., Ferguson, Kimberly, Zhang, Haili, Spector, Stephen, Rudy, Bret J., Ray, Stuart C., Douglas, Steven D., Flynn, Patricia M., and Persaud, Deborah
- Subjects
Highly active antiretroviral therapy -- Methods ,Highly active antiretroviral therapy -- Complications and side effects ,Drug resistance -- Physiological aspects ,Drug resistance -- Complications and side effects ,HIV infection -- Risk factors ,HIV infection -- Drug therapy ,Health - Abstract
Treatment failure and drug resistance create obstacles to long-term management of HIV-1 infection. Nearly 60% of infected persons fail their first highly active antiretroviral therapy (HAART) regimen, partially because of nonadherence, requiring a switch to a second regimen to prevent drug resistance. Among HIV-infected youth, a group with rising infection rates, treatment switch is often delayed; virologic and immunologic consequences of this delay are unknown. We conducted a retrospective, longitudinal study of drug resistance outcomes of initial HAART in U.S. youth enrolled between 1999-2001 in a multicenter, observational study and experiencing delayed switch in their first nonsuppressive treatment regimen for up to 3 years. HIV-1 genotyping was performed on plasma samples collected longitudinally, and changes in drug resistance mutations, CD[4.sup.+] T cell numbers and viral replication capacity were assessed. Forty-four percent (n = 18) of youth in the parent study experiencing virologic nonsuppression were maintained on their initial HAART regimen for a median of 144 weeks. Drug resistance was detected in 61% (11/18) of subjects during the study. Subjects on non-nucleoside reverse transcriptase inhibitor (NNRTI) regimens developed more (8/10) drug resistance mutations than those on protease-inhibitor (PI) regimens (2/7) (p = 0.058). Subjects developing NNRTI-resistance (NNRTI-R), showed a trend toward lower CD[4.sup.+] T cell gains (median: -6 cells/[mm.sup.3] per year) than those without detectable NNRTIR (median: +149 cells/[mm.sup.3] per year) (p = 0.16). HIV-1-infected youth maintained on initial nonsuppressive NNRTI-based HAART regimens are more likely to develop drug-resistant viremia than with PI-based HAART. This finding may have implications for initial treatment regimens and transmission risk in HIV-infected youth, a group with rising infection rates.
- Published
- 2008