To our knowledge, this is one of the few primary studies in the sub-Saharan Africa region, conducted using an integrated system of data collection (WHO stepstools and document review), to examine the predictors of metabolic syndrome among relatively larger number PLHIVs using a strong case-control study design, under one centralized clinical laboratory biochemistry unit.. Whereas, previous studies have examined the associated risk factors of MS using crossectional study approaches among a little number of individuals by employing nonstandard tools. Overall, the study concluded that the age, education, occupation, ART status, WHO-staging, physical activity state, previous history of blood sugar measured, raised BMI, raised WC, elevated fasting blood glucose, elevated triglycerides, and low HDL-cholesterols were found to be an independent predictor of metabolic syndrome. While, education, occupation, ART status, WHO-staging, and physical activity variables were found to be indirect predictors of MS, the rest of the variables were determined as the direct predictors of the syndrome.
It had several limitations, which were emerged from the nature use of a case-control study design, potentially liable for several biases, such as: selection biases, recall bias, information bias and social desirability biases, along with the other problems associated with the current study contexts like the absence of complete matching of it with an important variable (i.e. sex, age, and self-rated wealth), a strict adherence to the ATP III standardized criteria, and the variability’s of the studies used for comparison purposes.
As it has been stated above, the odds MS was more likely increased among older age groups than a younger age. Although not consistent on the age groups, but a marked disturbance in the MS with aging has also been reported by several epidemiological studies done worldwide[15, 18, 21, 23, 25, 29, 35, 40, 41]. The observed comparability among the studies might be because, regardless of the difference in the target population, age is a common non-modifiable risk factor that equally likely predisposes all to such health mater. In the reverse, Bosho, et al (2018 )[42], Lívia D. Akl et al.(2017)[43], Tesfaye DY, et al (2014)[35], and Kaduk et al [44]studies were reported that age is not an independent predictors of MS. The differences across studies might be due to the variation on the studies approaches employed; the differences in the standard criteria used the differences in the target population, along with the time differences. In spite of the observed variances, overall the result might highlighted that succeeding with the advance of ART, the PLHIVs started to have prolonged lifetimes and consequently leads them to be a victim to the identified risk factors; which are likely to inflict an equal impact on PLHIVs as they do in the general population. Notably, this may implicates, with the advance of age of individuals, there will be an inevitable degeneration of organ functions that could potentially imposes a reduction on the quality of the intrinsic physiologic metabolic process, which eventually leads anyone to be at risk of developing either of the risk markers of MS. And hence, looking forward intervention actions aimed at reducing the chronic health problems in general and the syndrome in advance for those PLHIVs aged with the virus will be a vital aspect. Additionally, inconsistent with our finding, while several studies [15, 26, 35, 40, 45-48] noted the direct link of sex with MS incidence, some other studies were also found a similar link of the place of residence with MS[40, 41].
As well, the relation between education and the risk of MS is worth further discussion. The current study result indicated that those PLHIVs with completed secondary schooling education were less likely to develop MS compared to those with no formal education. Correlating with our result, Bosho, et al (2018 ) [42], Kaduka et al (2012)[44] studies designated that engagement in formal education resulted in 75% increment in the odds of MS (AOR = 0.25, 95% CI [0.072–0.879]). This might confirm that education is a key to open any locked secrets of life in the world that enable everybody to have a standardized and healthy lifestyle or behaviour, which eventually renders them to be safe from such chronic disease that is highly dependent on individuals habits. Inconsistent with our finding, Lívia D. Akl et al. (2017) [43] revealed the absence of a significant association between education and the syndrome.
Notably, our finding also pinpointed that the odds of MS was less likely among un-employed but worked as a home-maker and able to work than those employed in the government institution. Inconsistent with this result, Mashinya et al (2015) [41] study stated that the high unemployment rate was a direct predictor of the syndrome. This unlikeness may be due to the difference in the design used by the former and the later studies. This could be justified due to similar details discussed overhead. As per Mashinya et al (2015) [41] study report, the high unemployment rate might be precipitated with stigma emerged from the viral infection, which may predispose the PLHIVs to high levels of stress; which eventually leads them to develop MS. However, in our view, the observed inverse association may not be out of the domains of differences income earned between the employed and un-employed PLHIVs. This means that, in our country contexts, the unemployed individuals are often earning a lower income that they cannot able to purchase any goods necessary for them to lead a qualified life that it might spontaneously help them to be protected from such high-quality lifestyle-related health problem. Overall, the finding implicated that apart from the actions aimed at design of occupations among HIV infected people might so play an essential part by easing stress-related with unemployment.in indirectly, but still the planning of awareness creation intervention to all, regardless of their employment status may correspondingly play an essential role in the prevention of the risk of acquisition of MS.
Also, our study as well showed that compared with ART naïve a group, the risk of MS was less likely in the ART exposed PLHIVs. It was consistent with several previous studies [26, 35, 40, 49]. Correlating with our finding, G.T. Bune et al. (2019)[37] revealed the existence of higher magnitude of MS among PLWHs participants. As well, Todowede et al. (2019,)[45] meta-study highlighted that the relative risks to estimate for MS among PLHIVs than un-infected population was twofold having with the existed a higher estimated predictive interval for the infected population; this signifies, regardless of the ART status, the risk of acquiring MS among PLHIVs is higher than the general population. This implicates, HIV infection alone is the risk factor that contributed for the incidence of MS. Overall, the finding may accentuate the significances of those traditional risk markers. Nonetheless, still the finding may suggested the significance of further cohort study to be initiated to distinguish the explicit effect of HIV infection and ART exposure on the acquisition of MS in these target population. On the other hand, inconsistent with our finding, quite a lot of studies from developing countries [15, 21, 26, 35, 40, 41, 45, 47, 50] were shown the presence of a direct strong association between ART exposure and MS incidences. With this regards, for instance, G.T. Bune et al. (2019)[37] a comparative crossectional finding revealed that ART has no significant association with the occurrence of MS. This might attribute to the differences in the target population’s socio-economic and demographic characteristics, the study approaches, and standard criteria employed by the current and previous studies. And, the implementation of the consolidated guidelines to accelerate the attainment of strategic global and the Ethiopian national HIV goals for 2016–2021 and the Sustainable Development Goals[38], could be taken as an explanation for the variability’s visualized in between the former and the current study.
Furthermore, specific with the ART regimen and in the contrary to our report, a few other studies besides notified the existence of significant differences across ART-regimen [15, 21, 26]. In this respects, still studies have shown inconsistencies’ amongst each other about the definite ART regimen there were no consistencies in between. While few studies have agreeable output on the second line regimen, (primarily the protease inhibitors (PI)) as a predictor for the incidence of MS[21, 35, 51], however, few other studies were disclosed that the first-line ART regimen, mainly of the Nucleoside Reverse Transcriptase Inhibitors (NRTIs) and the Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) as predictor of MS incidence[15, 26, 35, 42, 51]. In relation to this regimen, studies were further revealed that in patients using Stavudine (d4T)[42, 52, 53] alone, and NRTI as a whole [42, 54] would became risky to acquire dyslipidemia than MS. On the other hands, Tesfaye, D. Y. et al. (2014) [35], Alvarez et al. (2010) [55], Mondey et al.(2007) [56], and Jacobson et al.(2006) [57] studies have shown that this regimen has no association with the incidence of the syndrome. Overall, the finding shown the existence of contradicted knowledge regarding the typical influences of specific ART regimen with the incidence of MS arose from the drug combination given together as one time dose . Also, it might also dictate the direct impact of exposure to any ART regimens on lipid metabolism, endothelial and adipocyte cell function, and mitochondria dysfunction [42, 58], along with the link of the treatment with the incidences of each traits [42, 59] of MS, might be the possible reason for the differences encountered. This implicates to initiates further studies with strong design to differentiate the specific effects each drug regimen with MS incidence.
On top of that, with regards to the HIV/AIDS-related factors, this study was revealed that the odds of MS much times higher in those PLHIVs with more than or equal to three WHO staging, compared with less than three WHO staging. Inconsistent with our finding, van Oosterhout JJ, et al.(2012) reported as it had no association with MS. This may dictate the direct relationship of the WHO staging with the immune reconstruction induced inflammatory process, that could the potential to triggers the release of an inflammatory markers, which are responsible for to facilitate the onset of different intrinsic metabolites, which renders anyone to experience each MS traits first followed by overall MS, could be the possible attribute.
As per the self-reported lifestyle associated factors, although the following factors such as alcohol consumption, smoking habits, ‘Khat chewing habits, frequency of consumption of fruit and vegetable, and fat and oil showed no significant association with the presence of MS; however, physical activity was found to be indirect predictors of MS. Studies with this respects are inconsistent with some reporting significant association for smoking habits[41, 50, 60], alcohol consumption [41, 50, 61], and physical activity [41, 62] while others and results of the same study reported no association for ‘Khat chewing habits[42], alcohol use[35, 42], physical activity [35, 42, 61], smoking habits [15, 35, 42, 61, 62]. This might be partly explained due to the lower number of individuals grouped under each category that might affect the analysis. Another possible justification the nature of the data relies on self-reporting, which is liable to response bias. With regards to diet, unrelated to our finding, Jantarapakde, et al (2014) study astonishingly discovered the presence of a direct association between food insecurity (OR 1.8, 95%CI 1.0-3.3, p = 0.05)[40]. This could be justified partly due to the time variation, and inconsistent approaches employed by the former and the latter studies.
In the contexts of MS related risks, the current finding notified that raised BMI and WC were directly associated with the incidence of MS. Correlating with our finding, and regardless of the standard criteria employed, several studies were reported similar [45, 61, 63]. For instance, Bosho, et al (2018 ) [42] study shown that the odds of MS in patients with BMI > 25 kg/m2 was 13.4 times higher (AOR = 13.39, 95% CI [3.943–45.525]); as well, Hirgo, et al (2016) likewise pinpointed the presence of significant association with BMI >25 kg/m2 (p = 0.003) and raised central obesity(p = <0.0001) with the incidence of MS and criteria. In the reverse, while Tesfaye DY, et al (2014)[35] and Jantarapakde et al (2014) [40] studies were disclosed the presence of an indirect association in between BMI score and MS incidence; whereas Bosho, et al (2018) [42] and Bajaj, et al (2013)[64] studies were revealed the existed indirect relationship in between WC MS. The mismatch may be emerged from the different standard criteria used across studies, the time variation, study approaches, the environmental variations, and the dissimilarity in the socioeconomic, cultural and behavioral characteristics of the target populations.
On top of that, our finding shown that the previous history of blood sugar measured and raised fasting plasma glucose (>/=110mg/dl) were variable significantly associated MS occurrence. Correlating with this finding, studies pinpointed that diabetes and or impaired fasting glucose were the most common traits that predict the incidence of MS among PLHIVs [45, 65, 66]. On the other hands, Bajaj, et al (2013) was reported as they had no any significant associated with MS[64]. Moreover, with regards of hypertension and or elevated blood pressure measures, correlating with our study result, even if Bajaj, et al (2013) [64] study disclosed as they don’t have association with the incidence of MS, on the other hand several other literatures from developing countries were indicated in the reverse, and prevails that these variables were identified as a common traits and a significant predictor of MS among those PLHIVs[45, 65, 66] [42]. As regards, as Bosho, et al (2018) [42] describes, more of the raised BP measure was the most common feature of abnormalities MS, than impaired fasting plasma glucose commonly seen among PLHIVs. All in all, though our result supported that only diabetes predicts MS, but this doesn’t guarantee to conclude that it is the only predictors. Thus, this demands a longitudinal study further to be initiated; so as to understand which of the subcomponent is contributes to the development of MS.
As well, the current study result also shown that elevated triglyceride cholesterol (TGL_c >/=150 mg/dl), and lower levels of high density lipoprotein cholesterol (HDL_c <50 mg/dl for female and <40 mg/dl for men) were found to be an independent and a direct predictors of MS. With regards, the finding from Bosho, et al (2018) [42] study done in Jimma Zone, Southwest Ethiopia pinpointed that, lower level of HDL_c than elevated triglycerides as the most common predictor of MS. Inline, Hirgo, A, T et al (2016) [18] study also supported, regardless of the diagnostic criteria, the low HDL_c was the only significantly associated variable with MS (P<0.005), primarily in females than males(P<0.005). Further, in relation with the above contexts, while Jantarapakde et al (2014) [40] study noted that an overall fat redistribution (i.e. resulted either from “lipoatrophy and or hypertrophy”, which is collectively called as “lipodystrophy”) was a significant predictor of MS (OR 1.8, 95%CI 1.0-3.0, p = 0.032), largely in the ART exposed groups (P<0.005). Paradoxically, Bosho, et al (2018) [42], Jantarapakde et al (2014) [40], along with Tesfaye DY, et al (2014)[35] were designated that elevated total cholesterol (TC>200mg/dl) was the most common direct predictors of all lipid profiles that predicts MS incidence. On the other hand, while Bosho, et al (2018) [42] study shown that low-density lipoprotein cholesterol (LDL_c) was the common lipid profile predicts MS occurrence in those target groups, Bajaj, et al (2013) study was disclosed that none of the above components were significantly associated with the syndrome[64]. The discrepancies observed in between the former and the current studies might be an attribute of the expiations given before, along with the differences observed by the studies on the application of standard diagnostic criteria and the cut of point of each of the biochemical profiles to be decided.
In light of these drawbacks, to increase the generalizability of the findings of this study, a much larger number of sample sizes than required were included in the analysis. The consideration of more than the minimum sample size required has increased the power of the study. On top of that, to see the result of chance, we besides computed the 95% CI as a measure of association between exposure and outcome variables. The confidence interval for most of the variables used in the current study was not wide enough suggesting the adequacy of the sample size. Furthermore, the predictors identified in those health care institutions of the current study can represent HIV- infected people found in the zone. This is because the PLHIVs flows in those health institutions represent the majority of them residing in the Gedio zone. Therefore, the findings of this study can be generalized to the study area and other similar settings in particular.
Finally, this study was funded with Addis Ababa University, college of Medicine and school of Health science, in collaboration with DIlla University College of medicine and health science, for the partial fulfillment of Ph.D in Public health. All the above funding organizations have no role in conducting this study as whole on preparing the manuscript, except the financial delivery and the supporting supervision.