Prevalence of metabolic syndrome among people living with human immunodeficiency virus in sub-Saharan Africa: a systematic review and meta-analysis

Metabolic syndrome (MetS) poses a significant clinical challenge for individuals living with HIV (PLHIV). In sub-Saharan Africa (SSA), this condition is becoming a growing concern, owing to lifestyle changes and an increasingly aging population. Several SSA countries have reported on the prevalence of MetS. However, these estimates may be outdated because numerous recent studies have updated MetS prevalence among PLHIV in these countries. Moreover, prior research has focused on various study designs to report the pooled prevalence, which is a methodological limitation. Therefore, this systematic review and meta-analysis aimed to determine the pooled estimates of MetS in PLHIV in SSA by addressing these gaps. We systematically searched Google Scholar, Science Direct, Scopus, Web of Sciences, EMBASE, and PubMed/Medline for the prevalence of MetS and its subcomponents among people with HIV in sub-Saharan Africa. The estimated pooled prevalence was presented using a forest plot. Egger’s and Begg’s rank regression tests were used to assess evidence of publication bias. Twenty-five studies fulfilled the inclusion criteria after review of the updated PRISMA guidelines. The pooled prevalence of MetS was 21.01% [95% CI: (16.50, 25.51)] and 23.42% [95% CI: (19.16, 27.08)] to the National Cholesterol Education Program Adult Treatment Panel III (NCEP/ATP III) and International Diabetes Federation (IDF) criteria, respectively. Low levels of high-density lipoprotein cholesterol (Low HDL) at 47.25% [95% CI: 34.17, 60.33)] were the highest reported individual subcomponent, followed by abdominal obesity at 38.44% [95% CI: (28.81, 48.88)]. The prevalence of MetS is high in sub-Saharan Africa. Low HDL levels and increased waist circumference/abdominal obesity were the most prevalent components of MetS. Therefore, early screening for MetS components and lifestyle modifications is required. Policymakers should develop strategies to prevent MetS before an epidemic occurs. PROSPERO: CRD42023445294.


Search strategy
We used different electronic biomedical databases and indexing services such as Google Scholar, Science Direct, Scopus, Web of Sciences, EMBASE, and PubMed/MEDLINE to search for relevant articles.Potentially applicable studies were manually searched for using a list of references from the retrieved studies.The search was limited to articles published in English.The search terms used for this systematic review and meta-analysis were 'prevalence, ' 'Epidemiology, ' 'magnitude, ' 'burden, ' 'metabolic syndrome, ' 'metabolic disease, ' 'metabolic disorder, ' 'HIV/ AIDS, ' ' Africa' and 'Sub-Saharan Africa.' Studies relevant to MetS prevalence were considered.The search strategy involved using keywords with "Medical Subjects Headings (MeSH)" and "All fields" by connecting "AND" and "OR" as necessary.The search was conducted between February 15th and March 12, 2023, by three authors (YSA, GAK, and MMK) who thoroughly examined various sources and databases following a rigorous methodology.The search strategy details are provided in a separate file (Supplementary Table S2).

Eligibility criteria (inclusion and exclusion criteria)
The following criteria were used to include studies: (1) study type, both observational and experimental; (2)  study period, studies published from database inception until December 2022; (3) study area, studies conducted in sub-Saharan Africa; (4) population, people living with HIV aged 18 years; and (5) Published in the English Language.Case reports, case series, review articles, and letters to editors, articles reported other than NCEP-ATP III and IDF criteria were excluded.

Data extraction
Endnote citation manager for Windows Version X8 (Thomson Reuters, Philadelphia, PA, USA) was used to import the retrieved studies, and duplicates were removed.Four independent reviewers screened all the articles for the eligibility criteria.Reviewers began by screening the abstracts and titles, followed by full-text screening.
Disagreements were resolved by inviting a fifth investigator to participate.Microsoft Excel with a standardized extraction format was used by two investigators for the data extraction.The Excel spreadsheet included the first author's name, sample size, publication year, country, study design, impaired fasting glucose, elevated blood pressure, high triglyceride (TG), low level of high-density lipoprotein (low HDL), and prevalence of MetS according to the criteria of (

Statistical analysis
STATA version 14.2 Statistical software (StataCorp, College Station, Texas, USA) was used for the analysis, and heterogeneity was checked across studies by computing the I 2 statistical test.We assumed no, low, medium, and high heterogeneity across the studies if the I 2 values were 0%, 25%, 50%, and 75%, respectively.A random effects model was used to analyze the pooled estimated prevalence with 95% confidence intervals (CI) using the "metaprop" command, since significant heterogeneity was detected between studies.Funnel plots for visual inspection and Egger's and Begg's rank tests were used to assess the evidence of publication bias.A forest plot was used to report the estimated pooled prevalence of MetS and its subcomponents.

Outcome measurement
This study aimed to gather and analyze data from various studies conducted across sub-Saharan Africa to determine the pooled prevalence of MetS among people living with HIV in SSA, according to the NCEP ATP III and IDF criteria.The researchers used a systematic approach to identify relevant studies and extract relevant data.They then employed statistical methods to combine data from different studies and estimate the overall prevalence of MetS among people living with HIV in SSA.
These criteria are considered a subset of the following medical conditions or disorders: 1. Hypertension: systolic blood pressure > 130 mmHg or Diastolic blood pressure > 85 mmHg or pharmacologic Hypertension treatment 2. Abdominal obesity: Waist circumference of > 102 cm for men and > 88 cm for women 3. Dyslipidemia: Triglyceride (TG) 150 mg/dl or pharmacologic treatment 4. Hyperglycaemia: Fasting glucose > 100 mg/dl or pharmacologic treatment Dyslipidemia (Low HDL) 5. High-density lipoprotein cholesterol (HDL): < 40 mg/dl for men and < 50 mg/dl for women or pharmacologic treatment In the case of NCEP-ATP III, three of the aforementioned criteria are utilized as diagnostic variables Similarly, in the IDF criteria, abdominal obesity (defined as waist circumferences of 94 cm for men and 80 cm for women) in combination with two of the aforementioned criteria listed above are considered 19,20 .

Search results
A total of 1112 articles were initially identified using different biomedical databases, and 969 duplicates were excluded.Of the remaining 143 studies, 114 were excluded after reviewing their abstracts and titles.The full texts of the remaining 29 studies were downloaded and assessed to fulfil the required criteria.We again excluded seven studies (N = 4, different outcomes of Interest and N = 3, inconsistent results).Using citation search, we found three articles that met all inclusion criteria.Finally, 25 studies that met the inclusion criteria were included in this review using the search strategy, and duplicates were excluded using the endnote citation manager.Figure 1 illustrates the process of literature review, screening, and eligibility assessment of the study articles, and Supplementary Table S3 illustrates the details of the exclusion criteria.

Characteristics of included studies
Among the 25 included studies, eight were from Ethiopia [21][22][23][24][25][26][27][28] , six were from South Africa [29][30][31][32][33][34] , three were from Nigeria [35][36][37] , two were from Kenya 38,39 , two were from Zambia 40,41 , and one each was from Cameroon 42 , Uganda 43 , Botswana 44 , and Zimbabwe 40 .The included study sample sizes ranged from 79 45 to 1108 41 , with a total of 8602 people living with HIV/AIDS.Observational and experimental studies were conducted before July 2023, were conducted.The estimated pooled prevalence of MetS was assessed according to NCEP/ATP III and IDF criteria.Table 1 summarizes the baseline characteristics of the included studies.All the articles had a cross-sectional design and were facility-based.More than ten studies have been published since 2018.Nineteen studies defined MetS according to the NCEP/ATP III criteria, and 18 studies used the IDF criteria.

Publication bias
Funnel plots and Egger and Begg rank statistical tests at a 5% significance level were used to evaluate the presence of publication bias.The funnel plot showed symmetry (Supplementary Fig. S4) for pooled estimates using the NCEP-ATP III, and the Egger and Begg rank tests were not statistically significant (P-value = 0.258 and P-value = 0.225, respectively).Additionally, the funnel plot was almost symmetric (Supplementary Fig. S5) for IDF pooled estimates, and the Egger and Begg rank tests did not provide statistical evidence for the presence of publication bias (P-value = 0.863 and P-value = 0.158, respectively).

Sensitivity analysis
By excluding each study individually, a leave-out-one sensitivity analysis was used to determine the effect of a single study on the pooled prevalence of MetS among people living with HIV in sub-Saharan Africa.According www.nature.com/scientificreports/ to our findings, no single study had a significant impact on the pooled prevalence of MetS among people living with HIV in sub-Saharan Africa using the NCEP-ATP III and IDF (Figs. 9 and 10).

Discussion
The review found that among people living with HIV in sub-Saharan Africa, the prevalence of metabolic syndrome (MetS) was 21.01% according to NCEP/ATPIII criteria and 23.42% based on IDF criteria.Common components of MetS in this population included low HDL levels, increased waist circumference, and elevated blood pressure.This review is consistent with a similar review that found a high estimated pooled prevalence of MetS according to IDF criteria 17 .The use of a similar case definition for MetS might be attributed to the similarity of the studies.Likewise, the pooled prevalence in this study based on the NCEP/ATP III was comparable with reports from a global systematic review (20.6%) 49 and sub-Saharan Africa (19.9%) 17 .This suggests that the findings of this study are consistent with those of previous research on MetS in PLHIV.These findings highlight the need for routine screening and management of MetS in PLHIV in SSA to reduce the risk of cardiovascular disease and other related complications.Further research is needed to understand the underlying mechanisms and risk factors associated with MetS and to inform targeted interventions to prevent and manage MetS in this vulnerable population.
In the present review, Low HDL (47%) was a common subcomponent of MetS, which is comparable to reports from Brazil 50 and Italy 51 .Low HDL-C reflects an atherogenic dyslipidemia phenotype.Atherogenic dyslipidemia is a central lipoprotein associated with the development of MetS 52 .Atherogenic dyslipidemia can inhibit insulin metabolism through apoptosis and dysfunction of pancreatic beta cells [53][54][55] .Although the relationship between HDL function and MetS is not well established, it is likely that the relationship between HDL and insulin resistance also affects the development of MetS.Low HDL is mainly a result of apoA-I dysfunction (low levels of HDL in the blood) and systematic low-grade inflammation 56 .The second highest individual component of MetS was increased blood pressure/hypertension (30%).This finding was supported by studies from a systematic review and meta-analysis 57 .Antiretroviral therapy for PLHIV is commonly associated with hypertension (30%).The other MetS sub-component observed to be prevalent in this study was increased waist circumference (38%).This finding is consistent with that of a previous review 58 .The justification for the high prevalence of low HDL raised blood pressure/hypertension and increased waist circumference as individual components of MetS among PLHIV in sub-Saharan Africa might be due to the use of HAART.HAART has been shown to increase lipid levels and may not return to normal levels, leading to a high prevalence of low HDL levels.Additionally, the use of HAART in PLHIV is commonly associated with hypertension, resulting in a high prevalence of elevated

Strength and limitation of the study
This review adhered to the PRISMA guidelines and conducted a thorough literature search across multiple databases to identify relevant studies.Although the meta-analytical methods applied in this study were robust, the findings must be interpreted with caution because of the limitations of the study.Heterogeneity was observed among the studies included in the meta-analysis.In addition, the study only included data from ten countries, which restricts the representativeness of the findings.

Conclusion
The prevalence of MetS among PLHIV in sub-Saharan Africa is relatively high.Our review revealed that one in five study participants had MetS.Low high-density lipoprotein (HDL) levels, increased waist circumference, and increased BP pressure were more common in this review.We recommend early screening and appropriate interventions, including lifestyle modifications and pharmacological treatment, may be essential to prevent and manage MetS in PLHIV.Routine follow-up clinical and biochemical monitoring is also recommended.Additionally, creating awareness among PLHIV about MetS prevention, diagnosis, and treatment to prevent further complications is crucial.Promoting regular physical exercise, developing legislation for health promotion, and fighting obesity must be developed as a policy to address the modifiable risk factors of MetS among PLHIV.Furthermore, implementing novel interventions, such as integrated care plans for PLHIV in the region that can help strengthen the overburdened health system that also deals with other communicable diseases, can be an essential action.

Figure 2 .
Figure 2. Forest plot depicting the overall pooled prevalence estimate of MetS among PLHIV in sub-Saharan Africa using NCEP/ATP III criteria.

Figure 3 .
Figure 3. Forest plot depicting the overall pooled prevalence estimate of MetS among PLHIV in sub-Saharan Africa using the IDF criteria.

Figure 4 .
Figure 4. Forest plot depicting the overall pooled prevalence estimate of hyperglycemia among PLHIV in sub-Saharan Africa in 2023.

Figure 5 .
Figure 5. Forest plot depicting the overall pooled prevalence estimate of raised blood pressure among PLHIV in sub-Saharan Africa in 2023.

Figure 6 .
Figure 6.Forest plot depicting the overall pooled prevalence estimate of elevated triglyceride among PLHIV in sub-Saharan Africa in 2023.

Figure 7 .
Figure 7. Forest plot depicting the overall pooled prevalence estimate of LDL-C among PLHIV in sub-Saharan Africa 2023.

Figure 8 .
Figure 8. Forest plot depicting the overall pooled prevalence estimate of abdominal obesity among PLHIV in sub-Saharan Africa in 2023.

Figure 9 .
Figure 9. Sensitivity analysis for single study effect of estimated pooled prevalence based on NCEP/ATP III 2023.
National Cholesterol Education Program and Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in adults (Adults Treatment Panel III)) and IDF (International Diabetes Federation).According to the PICO statement: Population: People living with HIV in SSA; Intervention: Exploring MetS; Comparison: Studies reporting MetS among people living with HIV outside SSA; Outcome: Proportion of MetS.

Identification of studies via databases and registers Identification of studies via other methods Identification Screening Included
Figure 1.PRISMA flow diagram of the selection process of studies on MetS prevalence among PLHIV in sub-Saharan Africa in 2023.Vol.:(0123456789) Scientific Reports | (2024) 14:11709 | https://doi.org/10.1038/s41598-024-62497-y

Table 1 .
Baseline characteristics of the included studies for the prevalence metabolic syndrome among people living with HIV in sub-Saharan Africa 2023.