Weiser SD, Gupta R, Tsai AC, Frongillo EA, Grede N, Kumbakumba E, et al. Changes in Food Insecurity, Nutritional Status, and Physical Health Status After Antiretroviral Therapy Initiation in Rural Uganda. J Acquir Immune Defic Syndr. 2012 Oct 1;61(2):179-186.
To investigate duration of antiretroviral therapy (ART) is associated with improvements in food security and nutritional status and the extent to which associations are mediated by improved physical health status.
Regional referral clinic in western Uganda.
Prospective cohort study.
Adults initiating ART who lived within 20 kilometers of the clinic.
Household food insecurity, measured by the Household Food Insecurity Access Scale (HFIAS);1-3 nutritional status, with body-mass index (BMI) calculated from measurements of weight and height as well as mid-upper arm circumference (MUAC); physical health-related quality of life, measured with the Medical Outcomes Study-HIV Health Survey Physical Health Summary (PHS);4-6 and social support, measured with a modified version of the Duke-UNC Functional Social Support Questionnaire.7 The primary predictor variable was duration of ART, constructed as a series of variables for each 3-month period subsequent to ART initiation.
Participants were recruited from the Uganda AIDS Rural Treatment Outcomes (UARTOs) study, a prospective cohort of HIV-infected adults initiating ART free of charge at the Mbarara Regional Referral Hospital Immune Suppression Syndrome (ISS) Clinic in Mbarara, Uganda. Baseline socio-demographic and clinical covariates were selected for adjusted models based on prior literature and theory, including gender, marital status, employment status, educational attainment, household wealth, number of persons in the participant's household, distance to the clinic in hours of travel time, and CD4 cell count measured as a continuous variable in 50-cell increments.
Investigators conducted quarterly assessments using standardized interviewer-administered instruments, detailed anthropometric measurements for nutritional status, and plasma HIV RNA levels and CD4+ T-cell counts. In their questionnaires, investigators collected information about socio-demographic and clinical characteristics, including food insecurity and physical health-related quality of life. All surveys were translated and back translated into the local language (Runyankole) and administered by a native Runyankole speaker.
Data were analyzed with STATA statistical software, version 11.0. Researchers fit multiple linear regression models pooled over observation periods with HFIAS score, BMI, mid-upper arm circumference, and PHS as the linear dependent variables and cluster-correlated robust estimates of variance to account for within-person dependence of observations over time. Estimates were adjusted for potential confounding by socio-demographic and clinical variables measured at baseline. A Wald-type F-test was used to assess the joint statistical significance of the time indicator variables. A test for linear trend in the time indicator variables was performed by refitting the adjusted model with duration of ART specified as a continuous variable. Researchers also included concurrent PHS in the models as a time-dependent variable and then reassessed the estimates and statistical significance of the time indicator variables.
A total of 259 participants was eligible for inclusion. Of this group, 29 participants were excluded because of having incomplete data on any primary outcome of interest, with a remaining sample of 228 individuals included in the current analysis. Of the 228 individuals included in the analysis, eight died and 28 were lost to follow-up. By the time of this analysis, depending on their date of enrollment, participants had been monitored for three months to three years after ART initiation, with a median follow-up time of 1.8 years.
Most (n=161, 71%) participants were women. At baseline, the mean age was 34.4 years (standard deviation [SD] 8.7 years), 53 (23%) participants had completed secondary education, and 101 (44%) participants were married. The mean baseline CD4 count was 185.1 cells/µL (SD = 122.4 cells/µL), and median CD4 count at ART initiation was 161 cells/µL. The mean HFIAS score was 8.8, with 185 participants (81%) categorized as food insecure, 74 (33%) as moderately food insecure, and 97 (43%) as severely food insecure. At baseline, 14% had a BMI <18.5 kg/m2, and 11% had MUAC consistent with malnutrition (<22 cm for women, <23 cm for men).
Food insecurity decreased steadily over time after ART initiation. In adjusted analyses, the mean HFIAS score at nearly every time point was lower than the preceding time point, beginning with the second quarter (beta regression coefficient ??] = -1.7, 95% confidence interval [CI] -2.8 to -0.6] and ending with the final quarter (? = -6.5, 95% CI -10.4 to -2.7). F-tests for the joint statistical significance of the time indicator variables and for a linear trend in them were also statistically significant (p< 0.001). Of the 86 individuals who were severely food insecure at baseline and provided at least one-year of follow-up data, only 36 (42%) remained severely food insecure after one year on ART.
At baseline, the mean PHS was 43.1 (SD = 11.9). This increased subsequent to ART initiation. After statistical adjustment for baseline socio-demographic and clinical variables, the mean PHS was greater at every time point, beginning with the first quarter (? = 5.2, 95% CI 3.1 to 7.4) and ending with the last quarter (? = 11.9, 95% CI 3.1 to 20.6). F-tests for the joint statistical significance of the time indicator variables and for a linear trend in them were statistically significant (p< 0.001).
Nutritional status improved with time following ART initiation. In adjusted analysis, BMI increased at nearly every time point, beginning with the second quarter (? = 0.7, 95% CI 0.2 to 1.1) and ending with the last quarter (? = 5.3, 95% CI 0.1 to 10.5). Similarly, MUAC increased at nearly every time point, beginning with the second quarter (? = 0.9, 95% CI 0.4 to 1.4) and ending with the last quarter (? = 1.4, 95% CI 0.1 to 2.7). F-tests for the joint statistical significance of time indicator variables and for a linear trend in them for both nutritional outcomes were also statistically significant (p< 0.001).
Improvements in physical health status partially explained the decreases in food insecurity over time. When PHS was added to the regression models examining trends in food insecurity over time, the time indicator variables were no longer statistically significant as a group (p = 0.37) and the magnitude of the regression coefficients decreased substantially . At 24 months on ART, for example, adjusting only for clinical and socio-demographic covariates, ? was -2.72 (95% CI -4.21 to -1.22), but by adjusting additionally for PHS, ? was -1.49 (95% CI -3.08 to 0.94). Conversely, when social support was added to the regression models examining trends in food security over time, the time indicator variables were still statistically significant as a group, and the regression coefficients were not attenuated, suggesting no mediation.
The authors conclude that that among HIV-infected individuals in rural Uganda, food insecurity declined and nutritional status improved continuously subsequent to initiation of ART. Changes in food insecurity, but not nutritional status, were largely explained by improvements in physical health status.
Although this observational study was conducted very well, the evidence from it has a moderate risk of bias. Participants were not randomized and there was no control arm. However, the study included a cohort that completed the baseline assessment and follow-up assessments, loss to follow-up was fairly low and the researchers conducted statistical tests to control for potential confounders in the analysis.
HIV infection has been associated with food insecurity and malnutrition since the earliest days of the epidemic. Patients not receiving ART are often too sick to work or obtain food, and a range of social and cultural factors (e.g. stigma, lack of family or social support) can make it even more difficult to maintain sufficient caloric and micronutrient intake. The situation is exacerbated in settings where resources are limited and/or food prices are high. As ART becomes more accessible throughout the world, patients will at least have a better chance to keep healthy. The challenge for patients then becomes to maintain nearly perfect lifelong ART adherence.
This study's findings further support the rationale for early ART initiation in resource-poor settings, coupled with measures to improve food and nutrition security.
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