Four-drug-class-resistant HIV linked to higher death risk

Individuals with HIV who were resistant to all four antiretroviral drug classes experienced higher mortality than those who were not resistant, a difference primarily due to lower CD4 cell counts.

METHODOLOGY:

• Researchers conducted a retrospective study to determine whether people living with HIV and resistance to four-drug classes (nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors, and integrase strand transfer inhibitors) faced a higher risk for death than those without such resistance.
• A total of 1097 patients with HIV were analysed, including 228 with four-drug class resistance (median age at baseline, 50 years; 72.4% men; median years of HIV diagnosis, 21.4 years) who were propensity score matched with 869 without such resistance, and followed up until a median of 8.67 years.
• The primary outcome was all-cause mortality.

TAKEAWAY:

• During the follow-up period, 12.3% of patients with HIV and four-drug class resistance vs 7.7% of those without such resistance died (incidence rate ratio, 1.51; P = .063).
• When controlling for comorbidities, patients who were resistant to the four drug classes had a significantly higher risk for mortality than those who were not resistant (adjusted hazard ratio [AHR], 1.68; P = .024).
• In the four-drug-class-resistant group, lower CD4 cell counts had a significant indirect effect on mortality (AHR, 1.62; P < .001); however, the direct effect was not statistically significant.

IN PRACTICE:

“The priority for this vulnerable population is achieving virological control to enable immune recovery,” the authors wrote.

SOURCE:

This study was led by Andrea Giacomelli, MD, Università degli Studi di Milano, Milan, Italy. It was published online on August 01, 2025, in Clinical Infectious Diseases.

LIMITATIONS:

This study was limited by its retrospective design and the small sample size of four-drug-class-resistant patients. Recruiting the control group from a single centre introduced selection and information bias. Moreover, approximately 30% of four-drug-class-resistant participants lacked data on causes of death.

DISCLOSURES:

This study was conducted as a part of routine work of the PRESTIGIO Registry, which received support from ViiV Healthcare, Gilead Sciences, Merck Sharp & Dohme, and Janssen-Cilag. Some authors reported receiving consultancy fees, speaker honoraria, and honoraria for lectures and presentations and having other ties with the registry funders and various pharmaceutical companies.