Exploring the impact of therapeutic advances in HIV-related mortality in the United States

•Over the last 20 years, most HIV-related deaths occurred because of infectious diseases and neoplasms.•Men and African American individuals had a higher HIV-related mortality.•HIV-related mortality was highest in Southern states and urban areas.•Decreasing mortality trends were seen in all racial and gender groups secondary to highly active antiretroviral therapy. Mortality from HIV has significantly declined with the introduction of highly active antiretroviral therapy (HAART). This study sought to examine the longitudinal trends in mortality from HIV-related diseases by race, sex, geographical region, and over time as HAART trends changed. We queried the Centers for Disease Control and Prevention's Wide‐Ranging Online Data for Epidemiologic Research database and performed serial cross‐sectional analyses of national death certificate data for all-cause mortality with comorbid HIV from 1999 to 2020. HIV diseases (International Classification of Diseases, Tenth Revision codes B20-B24, O98.7, R75) were listed as the contributing cause of death. We calculated the age-adjusted mortality ratio (AAMR) per 1,000,000 individuals and determined mortality trends using the Joinpoint Regression Program. Subgroup analyses were performed by sex, race, region, and organ system. The study period was further stratified into three groups when specific drug regimens were more prevalent. In the 22-year study period, 251,759 all-cause mortalities with comorbid HIV were identified. The leading cause of death was infectious disease (84.0%, N = 211,438). Men recorded a higher AAMR than women (4.66 vs 1.65, P < 0.01). African American individuals had the highest AAMR (13.46) compared to White, American Indian, and Asian individuals (1.70 vs 1.65 vs 0.47). The South region had the highest AAMR (4.32) and urban areas had a higher AAMR compared to rural areas (1.77 vs 0.88). More than 80% of deaths occurred because of infectious disease over the last 2 decades with a decreasing trend over time when stratified by race, sex, and geographical region. Despite advances in HAART, mortality disparities persist which emphasizes the need for targeted interventions in these populations.