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.
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