HIV contributes to stroke among young people

HIV, antiretroviral treatment, hypertension, and stroke in Malawian adults: A case-control study.

Benjamin LA, Corbett EL, Connor MD, Mzinganjira H, Kampondeni S, Choko A, Hopkins M, Emsley HC, Bryer A, Faragher B, Heyderman RS, Allain TJ, Solomon T. Neurology. 2015 Dec 18. pii: 10.1212/WNL.0000000000002278. [Epub ahead of print]

Objective: To investigate HIV, its treatment, and hypertension as stroke risk factors in Malawian adults.

Methods: We performed a case-control study of 222 adults with acute stroke, confirmed by MRI in 86%, and 503 population controls, frequency-matched for age, sex, and place of residence, using Global Positioning System for random selection. Multivariate logistic regression models were used for case-control comparisons.

Results: HIV infection (population attributable fraction [PAF] 15%) and hypertension (PAF 46%) were strongly linked to stroke. HIV was the predominant risk factor for young stroke (≤45 years), with a prevalence of 67% and an adjusted odds ratio (aOR) (95% confidence interval) of 5.57 (2.43-12.8) (PAF 42%). There was an increased risk of a stroke in patients with untreated HIV infection (aOR 4.48 [2.44-8.24], p < 0.001), but the highest risk was in the first 6 months after starting antiretroviral therapy (ART) (aOR 15.6 [4.21-46.6], p < 0.001); this group had a lower median CD4+ T-lymphocyte count (92 vs 375 cells/mm3, p = 0.004). In older participants (HIV prevalence 17%), HIV was associated with stroke, but with a lower PAF than hypertension (5% vs 68%). There was no interaction between HIV and hypertension on stroke risk.

Conclusions: In a population with high HIV prevalence, where stroke incidence is increasing, we have shown that HIV is an important risk factor. Early ART use in immunosuppressed patients poses an additional and potentially treatable stroke risk. Immune reconstitution inflammatory syndrome may be contributing to the disease mechanisms.

Abstract [1] Full-text [free] access [2]

Editor’s notes: Stroke incidence is increasing across sub-Saharan Africa. Globally, hypertension accounts for most of the strokes. However, in sub-Saharan Africa, stroke is not uncommon among younger people, among whom the prevalence of hypertension is low. Therefore other factors may play a role.

This article reports on a case-control study with prospective recruitment of cases and community controls, examining the role of HIV, antiretroviral therapy, and the interaction between HIV and hypertension as risk factors for stroke in a setting with high HIV prevalence.

The investigators confirmed 86% of their cases with brain imaging, and found that the majority (78%) had findings consistent with ischemic stroke. Not surprisingly they found that overall, hypertension accounted for about half (46%) of the stroke cases. Interestingly only one-quarter of all people with hypertension in the study (cases and controls) were on hypertensive treatment.

However, among younger people (≤45 years) with stroke, HIV infection was the most important risk factor and accounted for 42% of the cases. HIV-positive people experienced the greatest risk of stroke during their first six months after ART initiation.

The HIV-positive stroke cases had a lower CD4 cell count compared to HIV-positive controls on the same duration of ART. Immunosuppression is a risk factor for immune constitution inflammatory syndrome (IRIS), and IRIS could thus be a plausible mechanism of stroke among people initiating ART.

The results of this study reinforce the need to start ART before people have advanced immunosuppression, which will reduce IRIS-associated morbidity. The latest WHO guidelines, ‘Treat all’, which recommend starting all HIV-positive people on antiretroviral therapy as soon after diagnosis as possible, have the potential to contribute to this.  

Comorbidity [5], Epidemiology [6], HIV Treatment [7]
Africa [8]
Malawi [9]
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