Introduction: Food insecurity is a potentially important barrier to the success of antiretroviral therapy (ART) programs in resource-limited settings. We undertook a longitudinal study in rural Uganda to estimate the associations between food insecurity and HIV treatment outcomes.
Design: Longitudinal cohort study.
Methods: Participants were from the Uganda AIDS Rural Treatment Outcomes study and were followed quarterly for blood draws and structured interviews. We measured food insecurity with the validated Household Food Insecurity Access Scale. Our primary outcomes were: ART nonadherence (adherence <90%) measured by visual analog scale; incomplete viral load suppression (>400 copies/ml); and low CD4+ T-cell count (<350 cells/μl). We used generalized estimating equations to estimate the associations, adjusting for socio-demographic and clinical variables.
Results: We followed 438 participants for a median of 33 months; 78.5% were food insecure at baseline. In adjusted analyses, food insecurity was associated with higher odds of ART nonadherence [adjusted odds ratio (AOR) 1.56, 95% confidence interval (CI) 1.10–2.20, P < 0.05], incomplete viral suppression (AOR 1.52, 95% CI 1.18–1.96, P < 0.01), and CD4+ T-cell count less than 350 (AOR 1.47, 95% CI 1.24–1.74, P < 0.01). Adding adherence as a covariate to the latter two models removed the association between food insecurity and viral suppression, but not between food insecurity and CD4+ T-cell count.
Conclusions: Food insecurity is longitudinally associated with poor HIV outcomes in rural Uganda. Intervention research is needed to determine the extent to which improved food security is causally related to improved HIV outcomes and to identify the most effective policies and programs to improve food security and health.
aDivision of HIV/AIDS, San Francisco General Hospital, University of California, San Francisco (UCSF), San Francisco
bDepartment of Health Policy and Management, Fielding School of Public Health, University of California, Los Angeles, Los Angeles, California
cDepartment of Health Promotion, Education, and Behavior, Arnold School of Public Health, University of South Carolina, Columbia, South Carolina
dMassachusetts General Hospital Center for Global Health, Boston, Massachusetts, USA
eMbarara University of Science and Technology; Mbarara, Uganda
fUnited Nations World Food Programme, Rome, Italy
gDepartment of Epidemiology and Biostatistics, UCSF, San Francisco, California
hRagon Institute of MGH, MIT and Harvard University
iDepartment of Global Health and Social Equity, Harvard Medical School
jDepartment of Global Health and Populations, Harvard School of Public Health, Boston, Massachusetts, USA.
Correspondence to Sheri D. Weiser, MD, MPH, Division of HIV/AIDS, San Francisco General Hospital, POB 0874, University of California, San Francisco, California, 94143, USA. Tel: +1 415 314 0665; fax: +1 415 869 5395; e-mail: Sheri.Weiser@ucsf.edu
Received 4 April, 2013
Revised 24 June, 2013
Accepted 4 July, 2013
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Food insecurity, defined as having insufficient access to safe, nutritionally adequate foods or needing to acquire foods in social unacceptable ways , is common in resource-poor settings, particularly among HIV-infected populations [2,3]. Food insecurity contributes to worse health-related quality of life , depression [5,6], increased hospitalizations [4,7], and higher morbidity [4,7] among HIV-infected individuals. Cross-sectional and qualitative studies suggest that food insecurity may negatively impact antiretroviral therapy (ART) response [8,9], thereby jeopardizing the success of new ART programs. As a result, improving food security may be an effective way to support HIV treatment adherence and retention in care [10,11], and international organizations have begun to integrate food, nutrition, and HIV/AIDS care initiatives [12–15]. Effective programming requires robust data from well designed studies to determine the association between, and mechanisms linking, food insecurity and HIV outcomes in order to develop and differentiate between potential interventions.
We examined the longitudinal associations between food insecurity and HIV treatment response in a cohort of HIV-infected individuals receiving ART in rural Uganda. We hypothesized that food insecurity is associated with worse ART adherence, and poorer virologic and immunologic outcomes, and that the association between food insecurity and biologic treatment outcomes is explained by ART nonadherence .
Participants and study design
Participants were from the Uganda AIDS Rural Treatment Outcomes (UARTO) study, a prospective cohort initiated in July 2005 in Mbarara town (population 65 000) within the rural Mbarara District in south-western Uganda. Participants were eligible if they were initiating ART, were 18 years or older, and lived within 20 km of the Mbarara Immune Suppression Syndrome Clinic. All UARTO participants from August 2007 were enrolled into a sub-study examining the impact of food insecurity on HIV health outcomes and followed until July 2010. We conducted quarterly assessments using standardized instruments administered in Runyankole by a native speaker and performed phlebotomy for plasma HIV RNA levels and CD4+ T-cell counts. Informed consent was obtained from all participants. We obtained ethical approval from institutional review boards at the University of California at San Francisco, Partners Healthcare, and Mbarara University of Science and Technology.
We measured food insecurity, the primary explanatory variable, with the Household Food Insecurity Access Scale (HFIAS), a nine-item scale based on validation studies in eight countries [17–19]. Cronbach's alpha in the baseline sample was 0.91. A dichotomous variable for being food secure versus food insecure was created from a standard algorithm .
The primary outcomes were the following:
1. ART nonadherence: ART adherence was measured quarterly using the visual analog scale (VAS) [20,21]. Participants marked the amount of each antiretroviral drug taken over the previous 7 days, on a scale ranging from 0 to 100% [22,23]. ART nonadherence was defined as less than 90% adherence (compared to ≥90% adherence), averaging across all drugs in the patient's regimen, based on previous literature showing that adherence below 90% is associated with increased progression to AIDS and death [24,25].
2. Incomplete viral load suppression was defined as HIV-1 viral load above 400 copies/ml. HIV-1 viral load determinations were made at the Mulago University-Johns Hopkins University (MUJHU) Laboratory in Kampala using the Roche Cobas Amplicor HIV 1 Monitor version 1.5 with a lower limit of quantification of 400 copies/ml.
3. Low CD4+ T-cell count (also processed at MUJHU) was defined as CD4+ cell count below 350 cells/μl, the threshold for ART initiation recommended by the WHO  at the time of analysis and associated with greater survival on ART  (dichotomous).
We selected covariates based on prior literature and our conceptual framework showing hypothesized links between food insecurity and HIV health outcomes . Baseline socio-demographic and clinical covariates included age, sex, marital status, education, ART status at baseline, and pre-ART CD4+ cell count measured in 100 cell increments. Time-varying variables included employment, household asset index , positive screen for heavy drinking as measured by the three-item consumption subset of the Alcohol Use Disorders Identification Test (AUDIT-C) , and tobacco use in the past 30 days.
We used generalized estimating equations (GEE) to separately model the marginal expectation of the primary outcomes as a function of food insecurity and time. All analyses were conducted using PROC GLMMIX in SAS version 9.2 (SAS Institute, Inc., Cary, North Carolina, USA). For each outcome, covariates with a P ≤ 0.2 in bivariate analysis were included in adjusted models. To evaluate the hypothesis that ART adherence is a potential mechanism through which food insecurity is adversely associated with virologic and immunologic outcomes, we added time-varying ART adherence to the adjusted models for incomplete viral load suppression, and added both ART adherence and viral load suppression to the adjusted models for low CD4+ cell count. We then reassessed the magnitude and statistical significance of the estimates of the relationship between food insecurity and these two outcomes.
We implemented sensitivity analyses to test the robustness of our results to alternate model specifications, including using categorical food insecurity (mild, moderate, and severe food insecurity versus food secure) as our primary explanatory variable, introducing a 3-month lag for the explanatory variables, and including duration of ART as a covariate in models restricted to those on ART for at least 1 year duration.
The study included 438 participants followed for a median of 33.0 months [interquartile range (IQR) 21.9–35.7]. The majority (99%) were on non-nucleoside reverse transcriptase inhibitor-based regimens throughout the study, and the proportion on one-pill fixed-dose combination ART increased from 7.3% in 2007 to 22.1% in 2010. At baseline, 78% of participants were food insecure (Table S1, http://links.lww.com/QAD/A388). Half of these – or 39% of all participants – were severely food insecure. Median pre-ART CD4+ cell count was 137 cells/μl and median pre-ART viral load was 109 615 copies/ml. During follow-up, 28.6% of all participants reported adherence under 90% during at least one visit and 63.9% of participants had incomplete viral suppression during at least one visit.
Associations between food insecurity and HIV-related outcomes
Food insecurity was associated with 67% higher odds of ART nonadherence in unadjusted models, and 56% greater odds of ART nonadherence in adjusted models [adjusted odds ratio (AOR) 1.56, 95% confidence interval (CI) 1.10–2.20, P < 0.01; Table 1]. Evaluated at the mean of other covariates averaged over the course of follow-up, 7.0% of those with any food insecurity were nonadherent compared with 4.6% of those with no food insecurity, a 52% relative difference. Food insecurity was also associated with 30% higher odds of incomplete viral suppression in unadjusted analyses, and with 52% higher odds of incomplete viral suppression in adjusted analyses (AOR 1.52, 95% CI 1.18–1.96, P < 0.01; Table 1). Evaluated at the mean of other covariates averaged over the course of follow-up, 11.0% of those with any food insecurity were not suppressed compared with 7.5% of those with no food insecurity, a 47% relative difference.
Food insecurity was associated with 22% higher odds of having a CD4+ cell count less than 350 cells/μl in unadjusted analyses, and 47% greater odds of low CD4+ cell count in adjusted analyses (AOR 1.47, 95% CI 1.24–1.74, P < 0.001; Table 2). Of those with any food insecurity, 69.9% had CD4+ cell count below 350 cells/μl during follow-up versus 61.3% of those with no food insecurity, a 13% relative difference.
Adjusting for adherence as a potential pathway variable
In regression models of virologic suppression including ART adherence, adherence below 90% was associated with over two times higher odds of incomplete viral suppression, and food insecurity was no longer significantly associated with incomplete viral suppression (AOR 0.96, 95% CI 0.68–1.35, P = 0.80; Table 1). In adjusted models for low CD4+ cell count, including time-varying ART adherence and viral load suppression at CD4+ determination, ART adherence below 90% was associated with 58% higher odds of CD4+ cell count below 350 cells/μl. The association between food insecurity and low CD4+ cell count retained statistical significance (AOR 1.47, 95% CI 1.21–1.77, P < 0.001; Table 2). Sensitivity analyses did not significantly alter the main results (Table S2, http://links.lww.com/QAD/A388).
In this longitudinal study in rural Uganda, food insecurity was common and associated with poor ART adherence and worse biologic treatment outcomes. Low ART adherence was an important mechanism through which food insecurity appeared to negatively influence virologic outcomes. Although intervention studies are needed to confirm that improved food security is causally connected with improved HIV treatment outcomes, these findings provide further support that alleviating food insecurity may improve biologic treatment response and thereby reduce morbidity and mortality among HIV-infected populations.
Our work is consistent with qualitative and cross-sectional studies showing that food insecurity is associated with ART nonadherence, incomplete viral load suppression, and low CD4+ cell counts [9,30–33]. Whereas ART adherence was an important mediator of virologic outcomes, consistent with our previously published conceptual framework , this was not the case for CD4+ cell counts. This may be because CD4+ cell responses also relate to nutritional pathways and to pretreatment CD4+ cell counts, which may be negatively affected by food insecurity if food-insecure individuals present late to care .
Responding to the evidence of adverse impacts of food insecurity on the HIV/AIDS epidemic, international organizations have called for the implementation of food and nutrition support and counseling as part of the essential HIV/AIDS package [12,35]. A few small intervention studies have demonstrated that food supplementation at the clinic can lead to improved ART adherence, food security, BMI, and clinic attendance [36–38], but these need to be confirmed in larger studies measuring treatment responses. To address food insecurity and its negative consequences including poor ART adherence, broader interventions beyond short-term food supplementation should be considered to address upstream drivers of food insecurity and all of the pathways through which food insecurity negatively affects health. Global institutions such as WHO , Joint United Nations Programme on HIV/AIDS , World Bank , American Dietetic Association , and the International Fund for Agricultural Development  have begun to shift attention to longer-range food security strategies such as livelihood enhancement [44–46]. Studies are needed to evaluate the impacts of different types of food security interventions on immunologic and virologic outcomes, in specific contexts and of varying duration , to better understand which mitigation strategies are most acceptable and cost-effective in specific contexts.
Although we used a self-reported measure of ART adherence, which may incompletely capture the variance in adherence behavior, VAS was strongly associated with both incomplete viral suppression and low CD4+ cell counts, thereby supporting its construct validity. Participants in our study had very good ART adherence and virologic responses, which may limit generalizability to other populations. It is possible that food insecurity is a consequence rather than a cause of worse HIV treatment health outcomes. Yet, the finding that food insecurity contributed to worse immunologic outcomes even in lagged covariate models, coupled with evidence from other studies , suggests that food insecurity may be causally related to poor outcomes. Intervention studies will be needed to fully understand the extent to which improved food security is causally related to better HIV treatment responses, and to determine which aspects of food insecurity are most important to address to improve HIV treatment outcomes.
In summary, we found that food insecurity is highly prevalent among HIV-infected individuals in rural Uganda, and is associated with worse ART adherence and worse virologic and immunologic outcomes. Our study further supports the need to foster integration of resources and systems responding to the parallel epidemics of food insecurity and HIV/AIDS.
We thank the Uganda AIDS Rural Treatment Outcomes study participants who made this study possible by sharing their experiences; Annet Kembabazi, Annet Kawuma, and Dr Nneka Emenyonu for providing study coordination and administrative support; and Dr Nozmo Mukiibi, Dr Jude K. Senkungu, and Dr Jessica Haberer for providing invaluable input on all aspects of study design and implementation.
Financial disclosure: The study was funded by the National Institutes of Health (R01 MH054907, K23 MH079713, and P30 AI027793) and the Meyer Family Foundation. The authors acknowledge the following additional sources of salary support: Burke Family Foundation (S.D.W.), AHRQ T32HS00046 (K.P.), NIH K23MH096620 (A.C.T.), and NIH K24MH087227 (D.R.B.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Conflicts of interest
There are no conflicts of interest.
1. Radimer KL, Olson CM, Greene JC, Campbell CC, Habicht JP. Understanding hunger and developing indicators to assess it in women and children
. J Nutr Educ
2. Bukusuba J, Kikafunda J, Whitehead R. Food security status in households of people living with HIV/AIDS (PLWHA) in a Ugandan urban setting
. Br J Nutr
3. Tsai AC, Bangsberg DR, Emenyonu N, Senkungu JK, Martin JN, Weiser SD. The social context of food insecurity among persons living with HIV/AIDS in rural Uganda
. Soc Sci Med
4. Weiser S, Tsai AC, Gupta R, Frongillo EA, Kawuma A, Senkugu J, et al. Food insecurity is associated with morbidity and patterns of healthcare utilization among HIV-infected individuals in rural Uganda
5. Tsai AC, Bangsberg DR, Frongillo EA, Hunt PW, Muzoora C, Martin JN, et al. Food insecurity, depression and the modifying role of social support among people living with HIV/AIDS in rural Uganda
. Soc Sci Med
6. Vogenthaler NS, Hadley C, Rodriguez AE, Valverde EE, del Rio C, Metsch LR. Depressive symptoms and food insufficiency among HIV-infected crack users in Atlanta and Miami
. AIDS Behav
7. Weiser SD, Hatcher A, Frongillo EA, Guzman D, Riley ED, Bangsberg DR, et al. Food insecurity is associated with greater acute care utilization among HIV-infected homeless and marginally housed individuals in San Francisco
. J Gen Intern Med
8. Weiser SD, Frongillo EA, Ragland K, Hogg RS, Riley ED, Bangsberg DR. Food insecurity is associated with incomplete HIV RNA suppression among homeless and marginally housed HIV-infected individuals in San Francisco
. J Gen Intern Med
9. Weiser SD, Tuller DM, Frongillo EA, Senkungu J, Mukiibi N, Bangsberg DR. Food insecurity as a barrier to sustained antiretroviral therapy adherence in Uganda
. PLoS One
10. Thompson MA, Mugavero MJ, Amico KR, Cargill VA, Chang LW, Gross R, et al. Guidelines for improving entry into and retention in care and antiretroviral adherence for persons with HIV: evidence-based recommendations from an International Association of Physicians in AIDS Care Panel
. Ann Intern Med
11. Bärnighausen T, Chaiyachati K, Chimbindi N, Peoples A, Haberer J, Newell ML. Interventions to increase antiretroviral adherence in sub-Saharan Africa: a systematic review of evaluation studies
. Lancet Infect Dis
13. PEPFAR. Report on Food and Nutrition for People Living with HIV/AIDS (Report to Congress mandated by House Report 109–265, accompanying H.R. 3057). Washington DC: Department of State. Office of the United States Global AIDS Coordinator; 2006. http://pdf.usaid.gov/pdf_docs/PCAAB509.pdf
. [Accessed 16 June 2013]
16. Weiser SD, Young SL, Cohen CR, Kushel MB, Tsai AC, Tien PC, et al. Conceptual framework for understanding the bidirectional links between food insecurity and HIV/AIDS
. Am J Clin Nutr
17. Coates J, Swindale A, Bilinsky P. Household Food Insecurity Access Scale (HFIAS) for measurement of food access: indicator guide.
Washington, D.C:Food and Nutrition Technical Assistance Project, Academy for Educational Development; 2006.
18. Frongillo EA, Nanama S. Development and validation of an experience-based measure of household food insecurity within and across seasons in Northern Burkina Faso
. J Nutr
19. Swindale A, Bilinsky P. Development of a universally applicable household food insecurity measurement tool: process, current status, and outstanding issues
. J Nutr
20. Giordano TP, Guzman D, Clark R, Charlebois ED, Bangsberg DR. Measuring adherence to antiretroviral therapy in a diverse population using a visual analogue scale
. HIV Clin Trials
21. Oyugi JH, Byakika-Tusiime J, Charlebois ED, Kityo C, Mugerwa R, Mugyenyi P, et al. Multiple validated measures of adherence indicate high levels of adherence to generic HIV antiretroviral therapy in a resource-limited setting
. J Acquir Immune Defic Syndr
22. Simoni JM, Kurth AE, Pearson CR, Pantalone DW, Merrill JO, Frick PA. Self-report measures of antiretroviral therapy adherence: a review with recommendations for HIV research and clinical management
. AIDS Behav
23. Walsh JC, Mandalia S, Gazzard BG. Responses to a 1 month self-report on adherence to antiretroviral therapy are consistent with electronic data and virological treatment outcome
24. Garcia de Olalla P, Knobel H, Carmona A, Guelar A, Lopez-Colomes JL, Cayla JA. Impact of adherence and highly active antiretroviral therapy on survival in HIV-infected patients
. J Acquir Immune Defic Syndr
25. Bangsberg DR, Perry S, Charlebois ED, Clark RA, Roberston M, Zolopa AR, et al. Nonadherence to highly active antiretroviral therapy predicts progression to AIDS
27. Kitahata MM, Gange SJ, Abraham AG, Merriman B, Saag MS, Justice AC, et al. Effect of early versus deferred antiretroviral therapy for HIV on survival
. N Engl J Med
28. Filmer D, Pritchett LH. Estimating wealth effects without expenditure data: or tears: an application to educational enrollments in states of India
29. Bush K, Kivlahan DR, McDonell MB, Fihn SD, Bradley KA. The AUDIT alcohol consumption questions (AUDIT-C): an effective brief screening test for problem drinking. Ambulatory Care Quality Improvement Project (ACQUIP). Alcohol Use Disorders Identification Test
. Arch Intern Med
30. Au JT, Kayitenkore K, Shutes E, Karita E, Peters PJ, Tichacek A, et al. Access to adequate nutrition is a major potential obstacle to antiretroviral adherence among HIV-infected individuals in Rwanda
31. Kalofonos IA. ‘All I Eat Is ARVs’
. Med Anthropol Q
32. Nagata JM, Magerenge RO, Young SL, Oguta JO, Weiser SD, Cohen CR. Social determinants, lived experiences, and consequences of household food insecurity among persons living with HIV/AIDS on the shore of Lake Victoria, Kenya
. AIDS Care
33. Hardon A, Akurut D, Comoro C, Ekezie C, Irunde H, Gerrits T, et al. Hunger, waiting time and transport costs: time to confront challenges to ART adherence in Africa
. AIDS Care
34. Drain PK, Losina E, Parker G, Giddy J, Ross D, Katz JN, et al. Risk factors for late-stage HIV disease presentation at initial HIV diagnosis in Durban, South Africa
. PloS One
35. World Food Programme. WFP HIV and AIDS Policy. Executive Board Second Regular Session: Rome, 8–11 November 2010. In Policy Issues: World Food Programme; 2010.
36. Cantrell RA, Sinkala M, Megazinni K, Lawson-Marriott S, Washington S, Chi BH, et al. A pilot study of food supplementation to improve adherence to antiretroviral therapy among food-insecure adults in Lusaka, Zambia
. J Acquir Immune Defic Syndr
37. Serrano C, Laporte R, Ide M, Nouhou Y, de Truchis P, Rouveix E, et al. Family nutritional support improves survival, immune restoration and adherence in HIV patients receiving ART in developing country
. Asia Pac J Clin Nutr
38. Ivers LC, Chang Y, Gregory Jerome J, Freedberg KA. Food assistance is associated with improved body mass index, food security and attendance at clinic in an HIV program in central Haiti: a prospective observational cohort study
. AIDS Res Ther
39. Koh HK, Oppenheimer SC, Massin-Short SB, Emmons KM, Geller AC, Viswanath K. Translating research evidence into practice to reduce health disparities: a social determinants approach
. Am J Public Health
2010; 100 (Suppl 1):S72–S80.
40. UNAIDSUNAIDS expanded business case: enhancing social protection
. Geneva:Joint United Nations Programme on HIV/AIDS (UNAIDS); 2010.
41. World BankHIV/AIDS, nutrition, and food security: what we can do: a synthesis of international guidance
. Washington, DC:World Bank; 2007.
42. American Diatetic AssociationPosition of the American Diatetic Association: food insecurity in the United States
. J Am Diet Assoc
44. Yager JE, Kadiyala S, Weiser SD. HIV/AIDS, food supplementation and livelihood programs in Uganda: a way forward?
. PloS One
45. Frega R, Duffy F, Rawat R, Grede N. Food insecurity in the context of HIV/AIDS: a framework for a new era of programming
. Food Nutr Bull
46. Pandit J, Sirotin N, Tittle R, Onjolo E, Bukusi E, Cohen C. Shamba Maisha: a pilot study assessing impacts of a micro-irrigation intervention on the health and economic wellbeing of HIV patients
. BMC Public Health
47. McMahon JH, Wanke CA, Elliott JH, Skinner S, Tang AM. Repeated assessments of food security predict CD4 change in the setting of antiretroviral therapy
. J Acquir Immune Defic Syndr