Antiretroviral Therapy and Risk of Stroke in People with HIV in Zambia

Background People with HIV (PWH) are at increased risk of stroke likely due to many factors including antiretroviral therapy (ART). We sought to evaluate the association between ARTand risk of stroke in PWH. Methods We conducted a prospective case-control study at the University Teaching Hospital in Lusaka, Zambia between March 2022 and October 2024 in PWH comparing those with stroke (cases) and without (controls) matched (1:2) for age, sex and race. Standardized data collection instruments were used to collect demographic, clinical, laboratory and imaging information. Comparisons were made between the cases and controls, and subgroup analysis by ART duration was done for the cases. Results We analyzed results for 205 cases and 410 controls. Compared to controls, cases were more likely to have hypertension (71% vs. 18%, p =0.001), lower CD4 counts [293(163-592) cells/µl vs. 533 (376-688) cells/µl, p =0.0001] and to be on second line ART (23% vs. 4%, p =0.001). Hypertension (aOR 19.7, 95% CI 3.1-126.4, p =0.002) and Tenofovir Disoproxil Fumarate (TDF) use (aOR 85.3, 95% CI 5.3-1380.7, p =0.002) were associated with increased odds of stroke, whereas Dolutegravir (aOR 0.03, 95% CI 0.001-0.58, p =0.02) and alcohol use (aOR 0.24, 95% CI 0.06-0.95) were associated with reduced odds of stroke. The majority of stroke patients on long-term ART were using Dolutegravir (80% vs. 35%, p =0.001) and TDF (72% vs. 42%, p =0.01). Conclusion In PWH, TDF associates with higher odds of stroke. Although Dolutegravir associates with reduced odds of stroke, stroke patients on long-term ART are more likely to be on it.