Antiretroviral Therapy Shows Benefit, Even Without a Virologic or Immunologic Response

A study suggests that antiretroviral therapy has benefits even in patients who do not show a virologic or immunologic response.

Patients with advanced AIDS who appear to receive little virologic or immunologic benefit from antiretroviral therapy (ART) should continue to receive therapy, as it reduces crude morality percentages more than earlier therapies, the results of a recent study suggest.

The study appeared in the November 2013 edition of PLOS One and assessed the causes and predictors of mortality in participants in a clinical trial of preemptive therapy for cytomegalovirus disease. Researchers focused on participants who did not achieve virologic suppression or substantive immune reconstitution, despite treatment with ART.

“In a cohort of individuals with very advanced HIV disease who had been prescribed ART and failed to achieve complete virologic suppression and substantive immune reconstitution prior to enrollment between 2000 and 2004, mortality was lower than reported in comparable cohorts studied in the early 1990s,” the authors wrote. “This suggests that even in the most advanced AIDS patients who obtain little, if any, objective immunologic or virologic benefit from modern antiretroviral treatment, ART may improve survival compared to NRTI [nucleoside reverse transcriptase inhibitor]-only therapy.”

The study involved 233 participants, recruited between 2000 and 2004, who received ART prescriptions from a health care provider for at least 3 months, and had shown no virologic suppression below 1000 copies/mL, and did not have substantive immunologic reconstitution. Although racially diverse, the cohort was primarily male, with a median age of 42 years. There was minimal alteration to the participants’ therapy during the study follow-up, the authors noted.

Study endpoints included time to death, AIDS-defining conditions, and serious non-AIDS events. Causes of death were reported by site investigators and were reviewed by study chairs, who then categorized each death as being AIDS-defining, non-AIDS defining, or of uncertain etiology.

At the 96-week follow-up point, 56 of the participants died; 42.8% of the deaths were related to an AIDS-defining condition or AIDS progression, the authors noted. The conditions included pneumocystis jirovecii pneumonia, cytomegalovirus, candidiasis, cryptococcosis, wasting syndrome, Kaposi’s sarcoma, lymphoma, progressive multifocal leukoencephalopathy, and cryptosporidia infection, and accounted for 90% of fatalities.

Meanwhile, 44.6% of deaths at the 96-week follow-up point were believed to be due to non—AIDS-related factors, and 12.5% were of unknown cause.

New AIDS-defining conditions developed in 25.3% of participants receiving ART prescriptions during the study, assessed at a median follow-up period of 78 weeks after entering the study. Five participants had died with an AIDS-defining condition by the median follow-up period.

Serious non—AIDS-defining events were reported in 17.2% of participants in the study, assessed at a median follow-up of 81 weeks after entering the study. The most frequently seen serious non–AIDS-defining events included sepsis and pulmonary diseases.

The change in deaths from AIDS-related events to conditions that are not associated with AIDS suggests that ART provides more protective benefits than earlier therapies, despite its apparent failure in certain patients, the authors noted.

“The shift over time in mortality from the AIDS events of the pre-modern-ART era to conditions that have not traditionally been considered a consequence of HIV disease progression suggests a potential protective effect of modern ART regimens in preventing death from AIDS-defining conditions, even among patients with persistent low CD4+ T cell counts and uncontrolled HIV replication,” the authors wrote.