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

**Authors:** Stanley ZIMBA, Owen NGALAMIKA, Emmanuel MUKAMBO, Theresa SHANKANGA, Taonga MSIMUKO, Diwell MWANSA, Bwalya MULENGA, Mike CHISHA, Mashina CHOMBA, Melody ASUKILE, Lorraine CHISHIMBA, Violet KAYAMBA, Lloyd MULENGA, Omar SIDDIQI, Owen A. ROSS, Masharip ATADZHANOV, Deanna SAYLOR

PMC · DOI: 10.21203/rs.3.rs-6945551/v1 · Research Square · 2025-07-01

## TL;DR

This study in Zambia found that certain HIV medications, like Tenofovir Disoproxil Fumarate, are linked to a higher risk of stroke in people with HIV, while Dolutegravir is associated with a lower risk.

## Contribution

The study identifies specific antiretroviral drugs associated with increased or decreased stroke risk in a Zambian HIV population.

## Key findings

- Tenofovir Disoproxil Fumarate (TDF) use was associated with increased odds of stroke.
- Dolutegravir use was associated with reduced odds of stroke.
- Stroke patients on long-term ART were more likely to be using Dolutegravir and TDF.

## Abstract

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.

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.

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).

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.

## Linked entities

- **Chemicals:** Tenofovir Disoproxil Fumarate (PubChem CID 5486830), Dolutegravir (PubChem CID 54726191)
- **Diseases:** stroke (MONDO:0005098)

## Full-text entities

- **Genes:** CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}
- **Diseases:** Hypertension (MESH:D006973), Stroke (MESH:D020521)
- **Chemicals:** Dolutegravir (MESH:C562325), alcohol (MESH:D000438), TDF (MESH:D000068698), ARTand (-)
- **Species:** Human immunodeficiency virus 1 (no rank) [taxon 11676], Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

39 references — full list in the complete paper: https://tomesphere.com/paper/PMC12236916/full.md

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Source: https://tomesphere.com/paper/PMC12236916