Abstract
IntroductionDespite 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.MethodsWe 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.Results233 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/mm3 and lower baseline HIV RNA.ConclusionsAmong 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.
Highlights
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
In a number of randomized trials conducted in the early 1990s that were designed to test combination nucleoside reverse transcriptase inhibitor (NRTI) drug combinations or prophylaxis to prevent M. avium complex infection, crude mortality percentages of 32%–40% over one to two years of follow-up were reported [7,8,9]
It is not clear what clinical impact continuing to prescribe ART for late-stage AIDS patients who demonstrate neither suppression of HIV replication nor substantive improvement in absolute CD4+T cell count has in the modern ART era
Summary
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. In a number of randomized trials conducted in the early 1990s that were designed to test combination nucleoside reverse transcriptase inhibitor (NRTI) drug combinations or prophylaxis to prevent M. avium complex infection, crude mortality percentages of 32%–40% over one to two years of follow-up were reported [7,8,9]. It is not clear what clinical impact continuing to prescribe ART for late-stage AIDS patients who demonstrate neither suppression of HIV replication nor substantive improvement in absolute CD4+T cell count has in the modern ART era. Whether the causes of death among these individuals mirror those of the pre-modern ART era or are influenced by receipt of ART is not clear
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
