title: Analyses of HIV-1 drug-resistance profiles among infected adolescents experiencing delayed antiretroviral treatment switch after initial nonsuppressive highly active antiretroviral therapy.
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, CD4+ 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 CD4+ T cell gains (median: -6 cells/mm(3) per year) than those without detectable NNRTI-R (median: +149 cells/mm(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.
authors.affiliation: Department of Pediatrics, Division of Infectious Diseases, Johns Hopkins Medical Institution, Baltimore, Maryland, USA.
authors.forename: Allison
authors.initials: A
authors.lastname: Agwu
authors.forename: Jane C
authors.initials: JC
authors.lastname: Lindsey
authors.forename: Kimberly
authors.initials: K
authors.lastname: Ferguson
authors.forename: Haili
authors.initials: H
authors.lastname: Zhang
authors.forename: Stephen
authors.initials: S
authors.lastname: Spector
authors.forename: Bret J
authors.initials: BJ
authors.lastname: Rudy
authors.forename: Stuart C
authors.initials: SC
authors.lastname: Ray
authors.forename: Steven D
authors.initials: SD
authors.lastname: Douglas
authors.forename: Patricia M
authors.initials: PM
authors.lastname: Flynn
authors.forename: Deborah
authors.initials: D
authors.lastname: Persaud
mesh_terms: D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D004334:Drug Administration Schedule; D024882:Drug Resistance, Viral / Q000235:genetics; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D017422:Sequence Analysis, DNA; D017211:Treatment Failure; D019562:Viral Load; D014779:Virus Replication
chemical_list: D019380:Anti-HIV Agents; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors