Methods: We analyzed data from the CDC WONDER Underlying Cause of Death dataset (1999 -2020), identifying HHR deaths using ICD-10 codes B20-B24 and related conditions among individuals ≥15 years. Mortality trends were stratified by the six-level urban-rural classification. Crude and age-adjusted mortality rates (per 100,000) and 95% confidence intervals were calculated using the 2000 U.S. Standard Population across the 69,234 county-year observations.

Results: In 1999, large central metro (urban) counties exhibited the highest crude and age-adjusted mortality rates (26.3 per 100,000), declining to 9.9 by 2020. In contrast, noncore (rural) counties saw a smaller decline, from 15.5 to 9.6 per 100,000. Crude rates declined from 24.8 to 8.9 in large central metros and from 17.0 to 11.8 in noncore counties. Despite overall national declines, reductions were slower in rural areas. Notably, the southern states exhibited persistently higher HHR compared to other regions, with several southern states consistently in the top percentiles for mortality throughout the study period.

Conclusions: Although HHR mortality declined nationwide, rural areas continue to bear a disproportionate burden. Addressing these disparities will require expanded rural HIV services, stigma reduction, and tailored interventions targeting structurally underserved communities.