Lower CD4 cell count and higher virus load, but not antiretroviral drug resistance, are associated with AIDS-defining events and mortality

An ACTG Longitudinal Linked Randomized Trials (ALLRT) analysis

Susan Swindells, Hongyu Jiang, A. Lisa Mukherjee, Mark Winters, Ronald J. Bosch, David Katzenstein

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Background: We hypothesized that drug resistance mutations would impact clinical outcomes associated with HIV-1 infection. Methods: A matched case-control study of participants in AIDS Clinical Trials Group Longitudinal Linked Randomized Trials (ALLRT). Cases experienced an AIDS-defining event (ADE) or mortality, and controls did not. One hundred thirty-four cases were identified and matched to a total of 266 controls by age, sex, treatment regimen, and length of follow-up. Both cases and controls had HIV RNA levels of ≥500 copies/mL within 24 weeks of an event. Population-based genotyping at or near the time of the event was used to evaluate the impact of resistance mutations on incidence of ADE and/or death using conditional logistic regression models. Results: One hundred four cases and 183 controls were analyzed. Median time to event was 99 weeks; 6 cases were deaths. At baseline, cases had lower CD4 (median 117 vs 235 cells/mm 3; P < .0001) and higher HIV RNA levels (median 205,000 vs 57,000 copies/mL; P = .003). No significant differences in resistance were seen between cases and controls. Conclusions: In this rigorously designed case-control study, lower CD4 cell counts and higher virus loads, not antiretroviral drug resistance, were strongly associated with ADE and mortality.

Original languageEnglish (US)
Pages (from-to)79-88
Number of pages10
JournalHIV Clinical Trials
Volume12
Issue number2
DOIs
StatePublished - Jan 1 2011

Fingerprint

CD4 Lymphocyte Count
Drug Resistance
Acquired Immunodeficiency Syndrome
Viruses
Mortality
Case-Control Studies
Logistic Models
HIV
RNA
Mutation
HIV Infections
HIV-1
Clinical Trials
Incidence
Population

Keywords

  • acquired immunodeficiency syndrome
  • human immunodeficiency virus
  • mortality
  • opportunistic infection
  • virologic resistance

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)

Cite this

Lower CD4 cell count and higher virus load, but not antiretroviral drug resistance, are associated with AIDS-defining events and mortality : An ACTG Longitudinal Linked Randomized Trials (ALLRT) analysis. / Swindells, Susan; Jiang, Hongyu; Mukherjee, A. Lisa; Winters, Mark; Bosch, Ronald J.; Katzenstein, David.

In: HIV Clinical Trials, Vol. 12, No. 2, 01.01.2011, p. 79-88.

Research output: Contribution to journalArticle

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abstract = "Background: We hypothesized that drug resistance mutations would impact clinical outcomes associated with HIV-1 infection. Methods: A matched case-control study of participants in AIDS Clinical Trials Group Longitudinal Linked Randomized Trials (ALLRT). Cases experienced an AIDS-defining event (ADE) or mortality, and controls did not. One hundred thirty-four cases were identified and matched to a total of 266 controls by age, sex, treatment regimen, and length of follow-up. Both cases and controls had HIV RNA levels of ≥500 copies/mL within 24 weeks of an event. Population-based genotyping at or near the time of the event was used to evaluate the impact of resistance mutations on incidence of ADE and/or death using conditional logistic regression models. Results: One hundred four cases and 183 controls were analyzed. Median time to event was 99 weeks; 6 cases were deaths. At baseline, cases had lower CD4 (median 117 vs 235 cells/mm 3; P < .0001) and higher HIV RNA levels (median 205,000 vs 57,000 copies/mL; P = .003). No significant differences in resistance were seen between cases and controls. Conclusions: In this rigorously designed case-control study, lower CD4 cell counts and higher virus loads, not antiretroviral drug resistance, were strongly associated with ADE and mortality.",
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