The clinical impact of continuing to prescribe antiretroviral therapy in patients with advanced AIDS who manifest no virologic or immunologic benefit

David A. Wohl, Michelle A. Kendall, Judith Feinberg, Beverly Alston-Smith, Susan Owens, Suzette Chafey, Michael Marco, Sharon Maxwell, Constance Benson, Philip Keiser, Charles Van Der Horst, Mark A. Jacobson

Research output: Contribution to journalArticle

Abstract

Introduction: Despite the efficacy and tolerability of modern antiretroviral therapy (ART), many patients with advanced AIDS prescribed these regimens do not achieve viral suppression or immune reconstitution as a result of poor adherence, drug resistance, or both. The clinical outcomes of continued ART prescription for such patients have not been well characterized. Methods: We examined the causes and predictors of all-cause mortality, AIDS-defining conditions, and serious non-AIDSdefining events among a cohort of participants in a clinical trial of pre-emptive therapy for CMV disease. We focused on participants who, despite ART had failed to achieve virologic suppression and substantive immune reconstitution. Results: 233 ART-receiving participants entered with a median baseline CD4+ T cell count of 30/mm3 and plasma HIV RNA of 5 log10 copies/mL. During a median 96 weeks of follow-up, 24.0% died (a mortality rate of 10.7/100 patient-years); 27.5% reported a new AIDS-defining condition, and 22.3% a new serious non-AIDS event. Of the deaths, 42.8% were due to an AIDS-defining condition, 44.6% were due to a non-AIDS-defining condition, and 12.5% were of unknown etiology. Decreased risk of mortality was associated with baseline CD4+ T cell count ≥25/mm 3 and lower baseline HIV RNA. Conclusions: Among patients with advanced AIDS prescribed modern ART who achieve neither virologic suppression nor immune reconstitution, crude mortality percentages appear to be lower than reported in cohorts of patients studied a decade earlier. Also, in contrast to the era before modern ART became available, nearly half of the deaths in our modern-era study were caused by serious non-AIDS-defining events. Even among the most advanced AIDS patients who were not obtaining apparent immunologic and virologic benefit from ART, continued prescription of these medications appears to alter the natural history of AIDS - improving survival and shifting the causes of death from AIDS- to non-AIDS-defining conditions.

Original languageEnglish (US)
Article numbere78676
JournalPloS one
Volume8
Issue number11
DOIs
StatePublished - Nov 15 2013

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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