Under Nutrition and Its Determinants Among Adults Receiving Antiretroviral Therapy in Ethiopia: A Systematic Review and Meta-analysis

: Under nutrition and human immune deficiency virus/HIV have a vicious cycle. This study aimed to assess the pooled prevalence of under nutrition and determinants among adults receiving antiretroviral therapy in Ethiopia. Google scholar, PubMed, Cochrane library and web of science data bases were searched. Studies were assessed using risk of bias assessment tool. The heterogeneity of study was assessed using I2 test statistics. Data were pooled and a random effect meta-analysis model was fitted to provide the prevalence of under nutrition. Twenty-one studies that satisfy the eligibility criteria were included. The pooled prevalence of under nutrition among adults receiving ART was 27.4% (95% CI: 24.4-31.4). The pooled analysis showed that lack of RUTF was more likely to lead to under nutrition [AOR=2.34 (95%CI: 1.85- 3.85)]. Also under nutrition was more likely among adults receiving ART with WHO clinical stage four [AOR=2.01 (95%CI: 1.91- 3.82). The pooled prevalence of under nutrition was high and Lack of RUTF as well as WHO clinical stage 4 showed significant associations with under nutrition. This finding has implication to develop policy to improve under nutrition and to continue RUTF supplement program as an integral part of HIV/AIDS continuum of care.


Introduction
Under nutrition is a serious problem especially among HIV positive clients receiving antiretroviral therapy. Micronutrient deficiencies may also increase viral load in the blood and affect immune functions. HIV infection in nutritionally deprived individuals intensifies the nutritional deficits and further enhances cellular oxidative stress. This affects the functions of transcription factors as NF-kB and contributes to HIV replication and progression and malnutrition could hasten the development of AIDS in an HIV-infected person [41].
Malnutrition is considered to be the most common cause of immunodeficiency worldwide [31]. Malnutrition, immune system, and infectious diseases are interlocked in a complex negative cascade [29]. Every type of immunological deficiency induced by malnutrition can be included under the NAIDS umbrella. Malnutrition and HIV form a vicious cycle and ultimately aim at reducing the immunity of the patient. In both malnutrition and HIV there is reduced CD4 and CD8 T-lymphocyte numbers [32]. The world's highest HIV infection rates are found in Sub-Saharan Africa, where adult prevalence in most countries exceeds 25% [30]. A complex Therapy in Ethiopia: A Systematic Review and Meta-analysis and negatively reinforcing relationship exists between infection with Human Immune Deficiency Virus (HIV) and malnutrition. HIV-induced immune impairment and its resulting opportunistic infections (OIs) can lead to malnutrition and nutritional deficits, can, in turn, hasten the progression of HIV infection and reduce chances of survival. The determinants of under nutrition among patients receiving antiretroviral therapy are poorly understood in Ethiopia, despite a high prevalence of food-insecurity that overlaps with a generalized HIV/AIDS epidemic [8]. Therefore, this study aimed to assess under nutrition and determinants of under nutrition among adults receiving antiretroviral therapy in Ethiopia.

Study Design and Setting
A systematic review and meta-analysis, which aimed to estimate the overall prevalence of under nutrition and its determinants was conducted in Ethiopia.

Eligibility Criteria
Studies were selected by considering, if conducted in Ethiopia [2], reported in English Language [3], only involved clients on ART [4], reported under nutrition and its determinants [5] and published or unpublished [3].

Search Methods
Search was done exhaustively by 4 (TM, DD, TM and LG) authors. Both published and unpublished articles were searched from Google scholar, PubMed, Science direct, web of science, Cochrane library and National electronic data bases. Articles were searched using both full title (under nutrition and determinants among adult clients on antiretroviral therapy in Ethiopia) and key words (under nutrition, determinants, clients on ART, Ethiopia). And then all studies were imported in to End Note reference management software. Each of the original studies was assessed using tool for assessing risk of bias. The heterogeneity of study was assessed using i 2 test statistics. Data were pooled and a random effect meta-analysis model was fitted to provide the prevalence of under nutrition and its determinants among clients using ART in Ethiopia.

Out Come Measures
Under nutrition and determinants was the outcome of this study. All data were extracted independently by 4 (TM, DD, TM and LG) authors. Deviation in data extraction was resolved by discussion.

Quality Assessment for Studies
Authors assessed the risk of bias for included studies using the tool of risk of bias assessment for observational studies. This tool includes 10 items. The first 4 items assess external validity while the rest 6 internal validity. All items of the tool were categorized as low risk of bias, higher risk and not clear. The quality of the study was determined by summing the score given for each item. The summary assessment risk of bias for each study was categorized according to the number of high risk of bias: low (>/=2), moderate (3)(4), and high (>/=5) [3].

Data Processing and Analysis
After extraction data were exported to R statistical software for meta-analysis. The double arcsine was applied to estimate the weighted average prevalence. Consistency of studies was checked via I 2 test. A random effect meta-analysis was performed and subgroup analyses were conducted.

Search Results
The study was conducted in 14 th March to 30 th April 2020. The flow chart diagram is under figure 1. Three hundred nineteen (319) studies were searched, then 6 were excluded due to duplication, 292 does not fulfill the criteria and 21 were included in this systematic review since met the criteria.

Description of Included Studies
Description was in table 1 below. It includes studies between 2009 and 2020 and respondents were clients on ART. The number of each study participants varied from lowest (234) to highest (1062). Furthermore, 9 studies conducted in SNNP region followed by 8 in Oromiya, 3 in Amhara, 2 in AA and 1 in Tigray. More over under nutrition ranged from 12.3 (lowest prevalence) [35] to 43 (highest prevalence) [2] ( Figure 1).

Risk of Bias Assessment
Of the total studies included, 21 (95.5%) of the studies had a low risk and 1 (4.5%) had a high risk of bias.

Under Nutrition and Its Determinants among Clients on ART in Ethiopia
Findings from this systematic review showed that the pooled prevalence of under nutrition among adults on Antiretroviral Therapy was 27.4% (95% CI: 24.4-31.4). The highest percentage of under nutrition (43%) was reported from Jimma Town, whereas the lowest proportion of under nutrition (12.3%) was reported from Dilla University referral hospital. Under nutrition among adults on Antiretroviral Therapy is higher in the Northern part (33.3%) as compared to Central parts of Ethiopia (27.78%) and Southern parts of Ethiopia (18.9%). Of 21 studies, seven studies [7,42,14,13,2,12,1] showed that WHO clinical stage 3&4 was associated with under nutrition, Five studies [2,7,8,14,17] showed that lack of RUTF was associated with under nutrition and four studies [23,13,43,12] showed CD4 <350 was associated with under nutrition. Four studies, showed association between duration on ART with under nutrition. Of this 4 studies 2 Studies [27,14] showed association between long duration on ART (>12month) and under nutrition. However, another 2 studies [9,26] showed that association between short duration on ART (<12month) and under nutrition. Under nutrition is more likely among clients who are at clinical stage 4 (OR: 2.01, 95%CI:

Discussion
This review aimed to estimate the pooled prevalence of under nutrition among adult receiving antiretroviral therapy in Ethiopia. According to this meta-analysis, the pooled proportion of under nutrition among adults receiving antiretroviral therapy was 27.4% (95% CI: 24.4%, 31.4%). This is consistent with a national study in Tanzania [10] while, a much higher pooled proportion than some other studies. For example a study conducted Sub-Saharan Africa countries showed that the pooled proportion of under nutrition among adults receiving antiretroviral therapy was 10.3% (95% CI: 7.4%, 14.1%) [30], also it is higher as compared to study conducted in Zimbabwe 7.1% [21] and Nepal (18.3% (95%CI: 14.3%, 22.6%) [33]. The above disparities could be due to the difference in socio-demographic, socio-economic, cultural and feeding pattern-related characteristics.
The subgroup analyses showed 33 [21] While a study conducted in Sub-Saharan Africa showed that the pooled prevalence of HIV-related malnutrition was higher among women residing in rural areas [30]. And a study conducted in Nepal showed that age, being male, being married, smoking, hemoglobin level and on ART duration were significantly associated with body mass index score [33].

Conclusions
Findings from this systematic review showed that the pooled prevalence of under nutrition among adults on Antiretroviral Therapy was high (27.4%). Under nutrition is more likely among clients who are at clinical stage 4. Furthermore, WHO clinical stage 3 and 4, lack of RUTF, CD4 <350, ART Interruption, Presence of opportunistic infection like tuberculosis, house hold food insecurity, inadequate diversified diet, low meal frequency, lack of nutritional support, Smoking Habit, lack of formal education, Functional status bedridden, Intestinal Parasite were associated with under nutrition among clients on antiretroviral therapy. This finding has implication for Ethiopian Federal Ministry of Health to develop policy for improving under nutrition among clients on antiretroviral therapy.