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

TitleThe clinical impact of continuing to prescribe antiretroviral therapy in patients with advanced AIDS who manifest no virologic or immunologic benefit.
Publication TypeJournal Article
Year of Publication2013
AuthorsWohl DA, Kendall MA, Feinberg J, Alston-Smith B, Owens S, Chafey S, Marco M, Maxwell S, Benson C, Keiser P, van der Horst C, Jacobson MA
Corporate AuthorsA5030 Study Team
JournalPLoS One
Volume8
Issue11
Paginatione78676
Date Published2013
ISSN1932-6203
KeywordsAcquired Immunodeficiency Syndrome, Anti-Retroviral Agents, CD4 Lymphocyte Count, Drug Resistance, Viral, Female, Follow-Up Studies, HIV-1, Humans, Male, Medication Adherence, RNA, Viral, Survival Rate
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-AIDS-defining 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/mm(3) 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.

DOI10.1371/journal.pone.0078676
Alternate JournalPLoS ONE
PubMed ID24260125
PubMed Central IDPMC3829816
Grant List5-P30-AI-045008-07 / AI / NIAID NIH HHS / United States
A19418 / / PHS HHS / United States
AI 69513-01 / AI / NIAID NIH HHS / United States
AI069434 / AI / NIAID NIH HHS / United States
AI069501 / AI / NIAID NIH HHS / United States
AI069502-01 / AI / NIAID NIH HHS / United States
AI069556 / AI / NIAID NIH HHS / United States
AI27659 / AI / NIAID NIH HHS / United States
AI27660 / AI / NIAID NIH HHS / United States
AI27661 / AI / NIAID NIH HHS / United States
AI27664 / AI / NIAID NIH HHS / United States
AI27673 / AI / NIAID NIH HHS / United States
AI32782 / AI / NIAID NIH HHS / United States
AI32783-13 / AI / NIAID NIH HHS / United States
AI34853 / AI / NIAID NIH HHS / United States
AI46370 / AI / NIAID NIH HHS / United States
AI46376 / AI / NIAID NIH HHS / United States
AI46381 / AI / NIAID NIH HHS / United States
AI50410 / AI / NIAID NIH HHS / United States
AI68634 / AI / NIAID NIH HHS / United States
AI68636 / AI / NIAID NIH HHS / United States
AI69411 / AI / NIAID NIH HHS / United States
AI69423-01 / AI / NIAID NIH HHS / United States
AI69432 / AI / NIAID NIH HHS / United States
AI69439 / AI / NIAID NIH HHS / United States
AI69450 / AI / NIAID NIH HHS / United States
AI69470-01 / AI / NIAID NIH HHS / United States
AI69471 / AI / NIAID NIH HHS / United States
AI69474 / AI / NIAID NIH HHS / United States
AI69477-01 / AI / NIAID NIH HHS / United States
AI69494-01 / AI / NIAID NIH HHS / United States
AI69495 / AI / NIAID NIH HHS / United States
AI69532-01 / AI / NIAID NIH HHS / United States
M01-RR00096 / RR / NCRR NIH HHS / United States
P30 AI050410 / AI / NIAID NIH HHS / United States
RR00046 / RR / NCRR NIH HHS / United States
RR00051 / RR / NCRR NIH HHS / United States
U01 AI068634 / AI / NIAID NIH HHS / United States
U01 AI068636 / AI / NIAID NIH HHS / United States
UL1 TR001082 / TR / NCATS NIH HHS / United States
UM1 AI069423 / AI / NIAID NIH HHS / United States