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Associations Between Anxiety and Adherence to Antiretroviral Medications in Low- and Middle-Income Countries: A Systematic Review and Meta-analysis

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Abstract

Untreated mental health disorders among people living with HIV (PLHIV) may prevent low- and middle-income countries (LMICs) from achieving the UNAIDS 90-90-90 targets. Anxiety disorders may be associated with decreased adherence to antiretroviral therapy (ART). We sought to review and meta-analyze studies estimating associations between anxiety and ART adherence in LMICs. We searched PubMed, PsychINFO, CINAHL and EMBASE for relevant studies published before July 18, 2018. We defined anxiety as reported anxiety scores from screening questionnaires or having a clinical diagnosis of an anxiety disorder, and poor ART adherence as missed doses, poor visit attendance, or scores from structured adherence questionnaires. We used a random effects model to conduct a meta-analysis for calculating a pooled odds ratio, and conducted sensitivity analyses by time on ART, anxiety evaluation method, and study region. From 472 screened manuscripts, thirteen studies met our inclusion criteria. Eleven studies were included in the meta-analysis. PLHIV who reported anxiety had 59% higher odds of poor ART adherence compared with those who did not report anxiety disorder (pooled odds ratio [pOR]: 1.59, 95% confidence interval [CI] 1.29–1.96, p < 0.001). When excluding PLHIV who initiated ART within 6 months, reported anxiety remained strongly associated with poor ART adherence (pOR: 1.61, 95% CI 1.18–2.20, p = 0.003). Among PLHIV in LMICs, reported anxiety was associated with poor ART adherence. This association persisted after the ART initiation period. Increased resources for mental health may be important for achieving virologic suppression in LMICs.

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Acknowledgements

The authors would like to thank Adrienne Shapiro MD, PhD, Rachel Kubiak, Haylea Hannah, and the other members of the Drain TB/HIV Research Lab for their mentorship and editing support.

Funding

Infectious Disease Society of America Medical Scholars Program. Research reported in this publication was supported by the Infectious Disease Society of America Education & Research Foundation (IDSA ERF) and National Foundation for Infectious Diseases (NFID), the National Institute of Allergy and Infectious Disease of the National Institutes of Health (K23 AI108293), the National Institute for Mental Health (F31 MH112397), the Harvard University Center for AIDS Research (P30 AI060354), the Massachusetts General Hospital Executive Committee on Research, and the University of Washington/Fred Hutch Center for AIDS Research, an NIH-funded program under Award Number AI027757 which is supported by the following NIH Institutes and Centers: NIAID, NCI, NIMH, NIDA, NICHD, NHLBI, NIA, NIGMS, NIDDK. The content is solely the responsibility of the authors and does not represent the official views of the National Institutes of Health or other funding agencies.

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Authors and Affiliations

  1. Department of Medicine, School of Medicine, University of Washington, 325 Ninth Ave, UW, Box 359927, Seattle, WA, 98104-2420, USA

    James Wykowski & Paul K. Drain

  2. Department of Global Health, School of Public Health, University of Washington, Seattle, USA

    Christopher G. Kemp, Jennifer Velloza, Deepa Rao & Paul K. Drain

  3. Department of Epidemiology, School of Public Health, University of Washington, Seattle, USA

    Jennifer Velloza & Paul K. Drain

  4. Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, USA

    Deepa Rao

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  1. James Wykowski
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Correspondence to James Wykowski.

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Appendices

Appendix 1: Anxiety and ART Adherence in Sub-Saharan Africa: Systematic Review

Search Protocol

Specific Aims

  1. 1.

    Meta-analyze associations between anxiety and ART adherence in Sub-Saharan Africa

    1. a.

      Sub-aim: anxiety and viral load, anxiety and CD4 count

Methods

Search Terms

PsycINFO, PubMed, CINAHL

(antiretroviral therapy, highly active OR ART OR anti-hiv agents OR hiv infections/drug therapy OR HAART OR antiretroviral* OR HIV treatment* OR hiv therap* OR HIV)

AND

(adherence OR nonadherence OR compliance OR noncompliance OR non-adherence OR non-compliance OR viral load OR CD4 OR viral suppress*)

AND

(anxiety OR anxious OR “GAD” OR “Generalized anxiety disorder” OR “BAI” OR “Beck Anxiety Inventory” OR “HADS-A” OR “HOSPITAL ANXIETY AND DEPRESSION SCALE-ANXIETY” OR “STAI” OR “STATE-TRAIT ANXIETY INVENTORY”)

AND

(Afghanistan OR Albania OR Algeria OR Samoa OR Angola OR Antigua OR Barbuda OR Argentina OR Armenia OR Azerbaijan OR Bangladesh OR Belarus OR Belize OR Benin OR Bhutan OR Bolivia OR Bosnia OR Herzegovina OR Botswana OR Brazil OR Bulgaria OR Burkina Faso OR Burundi OR Cambodia OR Cameroon OR Cabo Verde OR Central African Republic OR Chad OR Chile OR China OR Colombia OR Comoros OR Congo OR Costa Rica OR Côte d’Ivoire OR Cote d’Ivoire OR Ivory OR Cuba OR Djibouti OR Dominica OR Dominican OR Ecuador OR Egypt OR Salvador OR Eritrea OR Ethiopia OR Fiji OR Gabon OR Gambia OR Georgia OR Ghana OR Grenada OR Guatemala OR Guinea OR Guinea-Bissau OR Guyana OR Haiti OR Honduras OR India OR Indonesia OR Iran OR Iraq OR Jamaica OR Jordan OR Kazakhstan OR Kenya OR Kiribati OR Korea OR Kosovo OR Kyrgyz OR Lao OR Laos OR Latvia OR Lebanon OR Lesotho OR Liberia OR Libya OR Lithuania OR Macedonia OR Madagascar OR Malawi OR Malaysia OR Maldives OR Mali OR Marshall OR Mauritania OR Mauritius OR Mexico OR Micronesia OR Moldova OR Mongolia OR Montenegro OR Morocco OR Mozambique OR Myanmar OR Namibia OR Nepal OR Nicaragua OR Niger OR Nigeria OR Pakistan OR Palau OR Panama OR Papua New Guinea OR Paraguay OR Peru OR Philippines OR Romania OR Russia OR Russian OR Rwanda OR Samoa OR Sao Tome OR Senegal OR Serbia OR Seychelles OR Sierra Leone OR Solomon Islands OR Somalia OR South Africa OR Sri Lanka OR St. Lucia OR St. Vincent OR Grenadines OR Sudan OR Suriname OR Swaziland OR Syrian OR Syria OR Tajikistan OR Tanzania OR Thailand OR Timor-Leste OR Togo OR Tonga OR Tunisia OR Turkey OR Turkmenistan OR Tuvalu OR Uganda OR Ukraine OR Uruguay OR Uzbekistan OR Vanuatu OR Venezuela OR Vietnam OR “West Bank” OR Gaza OR Yemen OR Zambia OR Zimbabwe OR Africa OR sub-saharan OR developing countries[mh] OR “developing countries” OR “resource-limited” OR “resource-constrained” OR “low- and middle-income” OR LMIC OR “third world” OR “low income countries”)

EMBASE

(‘highly active antiretroviral therapy’ OR ART OR ‘anti-hiv agents’ OR ‘hiv infections/drug therapy’ OR HAART OR antiretroviral* OR ‘HIV treatment*’ OR ‘hiv therap*’ OR HIV)

AND

(adherence OR nonadherence OR compliance OR noncompliance OR non-adherence OR non-compliance OR ‘viral load’ OR CD4 OR ‘viral suppress*’)

AND

(anxiety OR anxious OR ‘GAD’ OR ‘Generalized anxiety disorder’ OR ‘BAI’ OR ‘Beck Anxiety Inventory’ OR ‘HADS-A’ OR ‘HOSPITAL ANXIETY AND DEPRESSION SCALE-ANXIETY’ OR ‘STAI’ OR ‘STATE-TRAIT ANXIETY INVENTORY’)

AND

(Afghanistan OR Albania OR Algeria OR Samoa OR Angola OR Antigua OR Barbuda OR Argentina OR Armenia OR Azerbaijan OR Bangladesh OR Belarus OR Belize OR Benin OR Bhutan OR Bolivia OR Bosnia OR Herzegovina OR Botswana OR Brazil OR Bulgaria OR ‘Burkina Faso’ OR Burundi OR Cambodia OR Cameroon OR ‘Cabo Verde’ OR ‘Central African Republic’ OR Chad OR Chile OR China OR Colombia OR Comoros OR Congo OR ‘Costa Rica’ OR Ivoire OR Ivory OR Cuba OR Djibouti OR Dominica OR Dominican OR Ecuador OR Egypt OR Salvador OR Eritrea OR Ethiopia OR Fiji OR Gabon OR Gambia OR Georgia OR Ghana OR Grenada OR Guatemala OR Guinea OR Guinea-Bissau OR Guyana OR Haiti OR Honduras OR India OR Indonesia OR Iran OR Iraq OR Jamaica OR Jordan OR Kazakhstan OR Kenya OR Kiribati OR Korea OR Kosovo OR Kyrgyz OR Lao OR Laos OR Latvia OR Lebanon OR Lesotho OR Liberia OR Libya OR Lithuania OR Macedonia OR Madagascar OR Malawi OR Malaysia OR Maldives OR Mali OR Marshall OR Mauritania OR Mauritius OR Mexico OR Micronesia OR Moldova OR Mongolia OR Montenegro OR Morocco OR Mozambique OR Myanmar OR Namibia OR Nepal OR Nicaragua OR Niger OR Nigeria OR Pakistan OR Palau OR Panama OR ‘Papua New Guinea’ OR Paraguay OR Peru OR Philippines OR Romania OR Russia OR Russian OR Rwanda OR Samoa OR ‘Sao Tome’ OR Senegal OR Serbia OR Seychelles OR ‘Sierra Leone’ OR ‘Solomon Islands’ OR Somalia OR ‘South Africa’ OR ‘Sri Lanka’ OR ‘St. Lucia’ OR ‘St. Vincent’ OR Grenadines OR Sudan OR Suriname OR Swaziland OR Syrian OR Syria OR Tajikistan OR Tanzania OR Thailand OR Timor-Leste OR Togo OR Tonga OR Tunisia OR Turkey OR Turkmenistan OR Tuvalu OR Uganda OR Ukraine OR Uruguay OR Uzbekistan OR Vanuatu OR Venezuela OR Vietnam OR ‘West Bank’ OR Gaza OR Yemen OR Zambia OR Zimbabwe OR Africa OR sub-saharan OR ‘developing countries’ OR ‘developing country’ OR resource-limited OR resource-constrained OR ‘low- and middle-income’ OR LMIC OR ‘third world’ OR ‘low income countries’)

Search Results (Date): 07/16/2018

Database

Number of results

PubMed

163

PsycINFO

248

CINAHL

127

EMBASE

126

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  • Reference lists of included articles

  • “Cited by” lists of included articles

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Wykowski, J., Kemp, C.G., Velloza, J. et al. Associations Between Anxiety and Adherence to Antiretroviral Medications in Low- and Middle-Income Countries: A Systematic Review and Meta-analysis. AIDS Behav 23, 2059–2071 (2019). https://doi.org/10.1007/s10461-018-02390-8

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