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January 26, 2016; 86 (4) ArticleOpen Access

HIV, antiretroviral treatment, hypertension, and stroke in Malawian adults

A case-control study

Laura A. Benjamin, Elizabeth L. Corbett, Myles D. Connor, Henry Mzinganjira, Sam Kampondeni, Augustine Choko, Mark Hopkins, Hedley C.A. Emsley, Alan Bryer, Brian Faragher, Robert S. Heyderman, Theresa J. Allain, Tom Solomon
First published December 18, 2015, DOI: https://doi.org/10.1212/WNL.0000000000002278
Laura A. Benjamin
From the Malawi-Liverpool-Wellcome Trust Clinical Research Programme (L.A.B., E.L.C., A.C., R.S.H.) and the Department of Medicine (L.A.B., H.M., S.K., R.S.H., T.J.A.), College of Medicine, University of Malawi, Blantyre; the Brain Infections Group (L.A.B., T.S.), Institute of Infection and Global Health, University of Liverpool (L.A.B., H.C.A.E., T.S.); the Walton Centre NHS Foundation Trust (L.A.B., T.S.), Liverpool; the Department of Clinical Research (E.L.C.), London School of Hygiene and Tropical Medicine; the NHS Borders and Division of Clinical Neuroscience (M.D.C.), University of Edinburgh, UK; the School of Public Health (M.D.C.), University of the Witwatersrand, Johannesburg, South Africa; the Royal Liverpool Hospital (M.H.); the Royal Preston Hospital (H.C.A.E.), Liverpool, UK; the Department of Medicine (A.B.), Division of Neurology, Groote Schuur Hospital, University of Cape Town, South Africa; the Liverpool School of Tropical Medicine (B.F.); the Division of Infection and Immunity (R.S.H.), University College London; and the National Institute for Health Research (T.S.), Health Protection Research Unit in Emerging and Zoonotic Infections, Liverpool, UK.
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Elizabeth L. Corbett
From the Malawi-Liverpool-Wellcome Trust Clinical Research Programme (L.A.B., E.L.C., A.C., R.S.H.) and the Department of Medicine (L.A.B., H.M., S.K., R.S.H., T.J.A.), College of Medicine, University of Malawi, Blantyre; the Brain Infections Group (L.A.B., T.S.), Institute of Infection and Global Health, University of Liverpool (L.A.B., H.C.A.E., T.S.); the Walton Centre NHS Foundation Trust (L.A.B., T.S.), Liverpool; the Department of Clinical Research (E.L.C.), London School of Hygiene and Tropical Medicine; the NHS Borders and Division of Clinical Neuroscience (M.D.C.), University of Edinburgh, UK; the School of Public Health (M.D.C.), University of the Witwatersrand, Johannesburg, South Africa; the Royal Liverpool Hospital (M.H.); the Royal Preston Hospital (H.C.A.E.), Liverpool, UK; the Department of Medicine (A.B.), Division of Neurology, Groote Schuur Hospital, University of Cape Town, South Africa; the Liverpool School of Tropical Medicine (B.F.); the Division of Infection and Immunity (R.S.H.), University College London; and the National Institute for Health Research (T.S.), Health Protection Research Unit in Emerging and Zoonotic Infections, Liverpool, UK.
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Myles D. Connor
From the Malawi-Liverpool-Wellcome Trust Clinical Research Programme (L.A.B., E.L.C., A.C., R.S.H.) and the Department of Medicine (L.A.B., H.M., S.K., R.S.H., T.J.A.), College of Medicine, University of Malawi, Blantyre; the Brain Infections Group (L.A.B., T.S.), Institute of Infection and Global Health, University of Liverpool (L.A.B., H.C.A.E., T.S.); the Walton Centre NHS Foundation Trust (L.A.B., T.S.), Liverpool; the Department of Clinical Research (E.L.C.), London School of Hygiene and Tropical Medicine; the NHS Borders and Division of Clinical Neuroscience (M.D.C.), University of Edinburgh, UK; the School of Public Health (M.D.C.), University of the Witwatersrand, Johannesburg, South Africa; the Royal Liverpool Hospital (M.H.); the Royal Preston Hospital (H.C.A.E.), Liverpool, UK; the Department of Medicine (A.B.), Division of Neurology, Groote Schuur Hospital, University of Cape Town, South Africa; the Liverpool School of Tropical Medicine (B.F.); the Division of Infection and Immunity (R.S.H.), University College London; and the National Institute for Health Research (T.S.), Health Protection Research Unit in Emerging and Zoonotic Infections, Liverpool, UK.
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Henry Mzinganjira
From the Malawi-Liverpool-Wellcome Trust Clinical Research Programme (L.A.B., E.L.C., A.C., R.S.H.) and the Department of Medicine (L.A.B., H.M., S.K., R.S.H., T.J.A.), College of Medicine, University of Malawi, Blantyre; the Brain Infections Group (L.A.B., T.S.), Institute of Infection and Global Health, University of Liverpool (L.A.B., H.C.A.E., T.S.); the Walton Centre NHS Foundation Trust (L.A.B., T.S.), Liverpool; the Department of Clinical Research (E.L.C.), London School of Hygiene and Tropical Medicine; the NHS Borders and Division of Clinical Neuroscience (M.D.C.), University of Edinburgh, UK; the School of Public Health (M.D.C.), University of the Witwatersrand, Johannesburg, South Africa; the Royal Liverpool Hospital (M.H.); the Royal Preston Hospital (H.C.A.E.), Liverpool, UK; the Department of Medicine (A.B.), Division of Neurology, Groote Schuur Hospital, University of Cape Town, South Africa; the Liverpool School of Tropical Medicine (B.F.); the Division of Infection and Immunity (R.S.H.), University College London; and the National Institute for Health Research (T.S.), Health Protection Research Unit in Emerging and Zoonotic Infections, Liverpool, UK.
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Sam Kampondeni
From the Malawi-Liverpool-Wellcome Trust Clinical Research Programme (L.A.B., E.L.C., A.C., R.S.H.) and the Department of Medicine (L.A.B., H.M., S.K., R.S.H., T.J.A.), College of Medicine, University of Malawi, Blantyre; the Brain Infections Group (L.A.B., T.S.), Institute of Infection and Global Health, University of Liverpool (L.A.B., H.C.A.E., T.S.); the Walton Centre NHS Foundation Trust (L.A.B., T.S.), Liverpool; the Department of Clinical Research (E.L.C.), London School of Hygiene and Tropical Medicine; the NHS Borders and Division of Clinical Neuroscience (M.D.C.), University of Edinburgh, UK; the School of Public Health (M.D.C.), University of the Witwatersrand, Johannesburg, South Africa; the Royal Liverpool Hospital (M.H.); the Royal Preston Hospital (H.C.A.E.), Liverpool, UK; the Department of Medicine (A.B.), Division of Neurology, Groote Schuur Hospital, University of Cape Town, South Africa; the Liverpool School of Tropical Medicine (B.F.); the Division of Infection and Immunity (R.S.H.), University College London; and the National Institute for Health Research (T.S.), Health Protection Research Unit in Emerging and Zoonotic Infections, Liverpool, UK.
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Augustine Choko
From the Malawi-Liverpool-Wellcome Trust Clinical Research Programme (L.A.B., E.L.C., A.C., R.S.H.) and the Department of Medicine (L.A.B., H.M., S.K., R.S.H., T.J.A.), College of Medicine, University of Malawi, Blantyre; the Brain Infections Group (L.A.B., T.S.), Institute of Infection and Global Health, University of Liverpool (L.A.B., H.C.A.E., T.S.); the Walton Centre NHS Foundation Trust (L.A.B., T.S.), Liverpool; the Department of Clinical Research (E.L.C.), London School of Hygiene and Tropical Medicine; the NHS Borders and Division of Clinical Neuroscience (M.D.C.), University of Edinburgh, UK; the School of Public Health (M.D.C.), University of the Witwatersrand, Johannesburg, South Africa; the Royal Liverpool Hospital (M.H.); the Royal Preston Hospital (H.C.A.E.), Liverpool, UK; the Department of Medicine (A.B.), Division of Neurology, Groote Schuur Hospital, University of Cape Town, South Africa; the Liverpool School of Tropical Medicine (B.F.); the Division of Infection and Immunity (R.S.H.), University College London; and the National Institute for Health Research (T.S.), Health Protection Research Unit in Emerging and Zoonotic Infections, Liverpool, UK.
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Mark Hopkins
From the Malawi-Liverpool-Wellcome Trust Clinical Research Programme (L.A.B., E.L.C., A.C., R.S.H.) and the Department of Medicine (L.A.B., H.M., S.K., R.S.H., T.J.A.), College of Medicine, University of Malawi, Blantyre; the Brain Infections Group (L.A.B., T.S.), Institute of Infection and Global Health, University of Liverpool (L.A.B., H.C.A.E., T.S.); the Walton Centre NHS Foundation Trust (L.A.B., T.S.), Liverpool; the Department of Clinical Research (E.L.C.), London School of Hygiene and Tropical Medicine; the NHS Borders and Division of Clinical Neuroscience (M.D.C.), University of Edinburgh, UK; the School of Public Health (M.D.C.), University of the Witwatersrand, Johannesburg, South Africa; the Royal Liverpool Hospital (M.H.); the Royal Preston Hospital (H.C.A.E.), Liverpool, UK; the Department of Medicine (A.B.), Division of Neurology, Groote Schuur Hospital, University of Cape Town, South Africa; the Liverpool School of Tropical Medicine (B.F.); the Division of Infection and Immunity (R.S.H.), University College London; and the National Institute for Health Research (T.S.), Health Protection Research Unit in Emerging and Zoonotic Infections, Liverpool, UK.
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Hedley C.A. Emsley
From the Malawi-Liverpool-Wellcome Trust Clinical Research Programme (L.A.B., E.L.C., A.C., R.S.H.) and the Department of Medicine (L.A.B., H.M., S.K., R.S.H., T.J.A.), College of Medicine, University of Malawi, Blantyre; the Brain Infections Group (L.A.B., T.S.), Institute of Infection and Global Health, University of Liverpool (L.A.B., H.C.A.E., T.S.); the Walton Centre NHS Foundation Trust (L.A.B., T.S.), Liverpool; the Department of Clinical Research (E.L.C.), London School of Hygiene and Tropical Medicine; the NHS Borders and Division of Clinical Neuroscience (M.D.C.), University of Edinburgh, UK; the School of Public Health (M.D.C.), University of the Witwatersrand, Johannesburg, South Africa; the Royal Liverpool Hospital (M.H.); the Royal Preston Hospital (H.C.A.E.), Liverpool, UK; the Department of Medicine (A.B.), Division of Neurology, Groote Schuur Hospital, University of Cape Town, South Africa; the Liverpool School of Tropical Medicine (B.F.); the Division of Infection and Immunity (R.S.H.), University College London; and the National Institute for Health Research (T.S.), Health Protection Research Unit in Emerging and Zoonotic Infections, Liverpool, UK.
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Alan Bryer
From the Malawi-Liverpool-Wellcome Trust Clinical Research Programme (L.A.B., E.L.C., A.C., R.S.H.) and the Department of Medicine (L.A.B., H.M., S.K., R.S.H., T.J.A.), College of Medicine, University of Malawi, Blantyre; the Brain Infections Group (L.A.B., T.S.), Institute of Infection and Global Health, University of Liverpool (L.A.B., H.C.A.E., T.S.); the Walton Centre NHS Foundation Trust (L.A.B., T.S.), Liverpool; the Department of Clinical Research (E.L.C.), London School of Hygiene and Tropical Medicine; the NHS Borders and Division of Clinical Neuroscience (M.D.C.), University of Edinburgh, UK; the School of Public Health (M.D.C.), University of the Witwatersrand, Johannesburg, South Africa; the Royal Liverpool Hospital (M.H.); the Royal Preston Hospital (H.C.A.E.), Liverpool, UK; the Department of Medicine (A.B.), Division of Neurology, Groote Schuur Hospital, University of Cape Town, South Africa; the Liverpool School of Tropical Medicine (B.F.); the Division of Infection and Immunity (R.S.H.), University College London; and the National Institute for Health Research (T.S.), Health Protection Research Unit in Emerging and Zoonotic Infections, Liverpool, UK.
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Brian Faragher
From the Malawi-Liverpool-Wellcome Trust Clinical Research Programme (L.A.B., E.L.C., A.C., R.S.H.) and the Department of Medicine (L.A.B., H.M., S.K., R.S.H., T.J.A.), College of Medicine, University of Malawi, Blantyre; the Brain Infections Group (L.A.B., T.S.), Institute of Infection and Global Health, University of Liverpool (L.A.B., H.C.A.E., T.S.); the Walton Centre NHS Foundation Trust (L.A.B., T.S.), Liverpool; the Department of Clinical Research (E.L.C.), London School of Hygiene and Tropical Medicine; the NHS Borders and Division of Clinical Neuroscience (M.D.C.), University of Edinburgh, UK; the School of Public Health (M.D.C.), University of the Witwatersrand, Johannesburg, South Africa; the Royal Liverpool Hospital (M.H.); the Royal Preston Hospital (H.C.A.E.), Liverpool, UK; the Department of Medicine (A.B.), Division of Neurology, Groote Schuur Hospital, University of Cape Town, South Africa; the Liverpool School of Tropical Medicine (B.F.); the Division of Infection and Immunity (R.S.H.), University College London; and the National Institute for Health Research (T.S.), Health Protection Research Unit in Emerging and Zoonotic Infections, Liverpool, UK.
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Robert S. Heyderman
From the Malawi-Liverpool-Wellcome Trust Clinical Research Programme (L.A.B., E.L.C., A.C., R.S.H.) and the Department of Medicine (L.A.B., H.M., S.K., R.S.H., T.J.A.), College of Medicine, University of Malawi, Blantyre; the Brain Infections Group (L.A.B., T.S.), Institute of Infection and Global Health, University of Liverpool (L.A.B., H.C.A.E., T.S.); the Walton Centre NHS Foundation Trust (L.A.B., T.S.), Liverpool; the Department of Clinical Research (E.L.C.), London School of Hygiene and Tropical Medicine; the NHS Borders and Division of Clinical Neuroscience (M.D.C.), University of Edinburgh, UK; the School of Public Health (M.D.C.), University of the Witwatersrand, Johannesburg, South Africa; the Royal Liverpool Hospital (M.H.); the Royal Preston Hospital (H.C.A.E.), Liverpool, UK; the Department of Medicine (A.B.), Division of Neurology, Groote Schuur Hospital, University of Cape Town, South Africa; the Liverpool School of Tropical Medicine (B.F.); the Division of Infection and Immunity (R.S.H.), University College London; and the National Institute for Health Research (T.S.), Health Protection Research Unit in Emerging and Zoonotic Infections, Liverpool, UK.
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Theresa J. Allain
From the Malawi-Liverpool-Wellcome Trust Clinical Research Programme (L.A.B., E.L.C., A.C., R.S.H.) and the Department of Medicine (L.A.B., H.M., S.K., R.S.H., T.J.A.), College of Medicine, University of Malawi, Blantyre; the Brain Infections Group (L.A.B., T.S.), Institute of Infection and Global Health, University of Liverpool (L.A.B., H.C.A.E., T.S.); the Walton Centre NHS Foundation Trust (L.A.B., T.S.), Liverpool; the Department of Clinical Research (E.L.C.), London School of Hygiene and Tropical Medicine; the NHS Borders and Division of Clinical Neuroscience (M.D.C.), University of Edinburgh, UK; the School of Public Health (M.D.C.), University of the Witwatersrand, Johannesburg, South Africa; the Royal Liverpool Hospital (M.H.); the Royal Preston Hospital (H.C.A.E.), Liverpool, UK; the Department of Medicine (A.B.), Division of Neurology, Groote Schuur Hospital, University of Cape Town, South Africa; the Liverpool School of Tropical Medicine (B.F.); the Division of Infection and Immunity (R.S.H.), University College London; and the National Institute for Health Research (T.S.), Health Protection Research Unit in Emerging and Zoonotic Infections, Liverpool, UK.
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Tom Solomon
From the Malawi-Liverpool-Wellcome Trust Clinical Research Programme (L.A.B., E.L.C., A.C., R.S.H.) and the Department of Medicine (L.A.B., H.M., S.K., R.S.H., T.J.A.), College of Medicine, University of Malawi, Blantyre; the Brain Infections Group (L.A.B., T.S.), Institute of Infection and Global Health, University of Liverpool (L.A.B., H.C.A.E., T.S.); the Walton Centre NHS Foundation Trust (L.A.B., T.S.), Liverpool; the Department of Clinical Research (E.L.C.), London School of Hygiene and Tropical Medicine; the NHS Borders and Division of Clinical Neuroscience (M.D.C.), University of Edinburgh, UK; the School of Public Health (M.D.C.), University of the Witwatersrand, Johannesburg, South Africa; the Royal Liverpool Hospital (M.H.); the Royal Preston Hospital (H.C.A.E.), Liverpool, UK; the Department of Medicine (A.B.), Division of Neurology, Groote Schuur Hospital, University of Cape Town, South Africa; the Liverpool School of Tropical Medicine (B.F.); the Division of Infection and Immunity (R.S.H.), University College London; and the National Institute for Health Research (T.S.), Health Protection Research Unit in Emerging and Zoonotic Infections, Liverpool, UK.
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Citation
HIV, antiretroviral treatment, hypertension, and stroke in Malawian adults
A case-control study
Laura A. Benjamin, Elizabeth L. Corbett, Myles D. Connor, Henry Mzinganjira, Sam Kampondeni, Augustine Choko, Mark Hopkins, Hedley C.A. Emsley, Alan Bryer, Brian Faragher, Robert S. Heyderman, Theresa J. Allain, Tom Solomon
Neurology Jan 2016, 86 (4) 324-333; DOI: 10.1212/WNL.0000000000002278

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Abstract

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.

GLOSSARY

3TC=
lamivudine;
aOR=
adjusted odds ratio;
ART=
antiretroviral therapy;
AZT=
zidovudine;
d4T=
stavudine;
IRIS=
immune reconstitution inflammatory syndrome;
NIHSS=
NIH Stroke Scale;
NVP=
nevirapine;
PAF=
population attributable fraction

Footnotes

  • Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article. The Article Processing Charge was paid by Wellcome Trust.

  • Supplemental data at Neurology.org

  • Editorial, page 316

  • Received November 21, 2014.
  • Accepted in final form August 19, 2015.
  • © 2015 American Academy of Neurology

This is an open access article distributed under the terms of the Creative Commons Attribution License 4.0 (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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