Worldwide Prevalence of HIV Associated Neurocognitive Disorders (HAND) and its associated factors: A systematic review and meta- analysis

Background: HIV associated neurocognitive disorders are common in people living with HIV/AIDS and affects adherence of patients to prescription, activities of daily living and quality of life of patients. However, there is a lack of summative evidence in the area. The present meta-analysis was therefore employed to address this gap. Methods: we used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines during our electronic search in Psych-Info, EMBASE, Scopus and PubMed. The retrieved articles were stored with endnote reference manager and data was extracted using Meta-XL version 5.3. The quality of studies were evaluated with modied Newcastle–Ottawa Scale (NOS). A random-effect model and STATA-16 were used to compute the average estimate of HAND. Heterogeneity was weighed with I 2 statistics. A sensitivity analysis and subgroup analysis were employed. The existence /nonexistence of a publication bias were checked with the eye ball test and eggers test of publication bias. Results: The average prevalence of HAND was 50.41% (95% CI: 45.56, 55.26). The average estimate of HAND in Europe was found to be 50.015% whereas in Africa, Asia and United States of America (USA) it was 49.566%, 52.032 %, 50.407% respectively. The prevalence of HAND in studies which used HIV Dementia Scale (IHDS) was 36.883% & 59.956% at a cutoff points of IHDS< 9.5 & IHDS <10 respectively. In addition the estimated average of HAND with the global dementia scale (GDS) was 40.766%. The prevalence of HAND in cross-sectional, cohort and case control studies was 49.52%, 54.087% and 44.45% in that order. Sociodemographic variables such as low level of education and older age, clinical and HIV related variables such as advanced stage of the illness and CD4 count of 500 cells/dl or less and psychological variables such as comorbidity of depression increases the risk of HAND. Conclusion: The average prevalence of HAND was high (more than half of participants) and factors such as low level of education, older age, advanced stage of the illness and comorbidity


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2.2: Eligibility criteria's During our study of a systematic review ad meta-analysis on HIV-associated neurocognitive disorder in people living with HIV AIDS, we have set the following inclusion and exclusion criteria's based on the PICO criteria : (1) the primary inclusion criteria was the design of the study. In this context all observational studies (case control, cross-sectional ad cohort) were eligible for analysis. (2) The next criteria for inclusion to analysis were the study should assessed prevalence OR associated factors of HIV-associated neurocognitive disorder in people living with HIV AIDS. We excluded studies 1) that assessed neurocognitive disorder in samples other than people living with HIV/AIDS. 2) That assessed neurocognitive disorder in individuals that had a history of depression or other forms of mental illness or those taking a psychotropic medication. 3) Studies which are letters to the editor with non-original data content, earlier reviews, case studies, studies involving non-human subjects, articles published in a language other than English language were also excluded from the analysis. After all relevant articles were searched in the mentioned data bases; they were stored in an endnote reference manager. Two of the authors (MN and YZ) individually screened the titles and abstracts of articles stored in an endnote reference manager using the eligibility criteria's. Next to that, the above two authors carefully read the full length of articles which passed the initial screening and decided independently articles suitable for inclusion in the nal meta-analysis. Any disagreement in between them regarding eligibility criteria was resolved by agreement and with a third reviewer (WY).

2.3: Data extraction and quality assessment techniques
Once the articles for inclusion to the nal analysis were settled, the previously mentioned two authors (MN and YZ) extracted all the necessary data individualistically using an identical data extraction form. The forty nal incorporated studies were extracted using the data extraction template as suggested by PRISMA guidelines (55), using Meta-XL version 5.3 (56) and the result was summarized in a table presentation. The contents of the data extraction template were author name, year of publication, country where the study was done, study design, studied sample population, assessment tool for HIV associated neurocognitive disorders, number of cases with HIV associated neurocognitive disorders, prevalence of HIV associated neurocognitive disorders, sampling technique employed to recruit participants, and response rate of the study.
The quality of forty included studies (8,10,(12)(13)(14) had been evaluated using modi ed Newcastle-Ottawa Scale (NOS) (57) as gold standard. Representativeness of sample and sample size, statistical quality, comparability among participants and ascertainment of cases were the components of this quality assessment scale. Based on this scale studies with a quality score of 7 to 10 were categorized as very good/good, score of 5 to 6 were categorized as having satisfactory quality, and a score less than 5 was take as unsatisfactory quality.

2.4: Data analysis and synthesis
The random-effect model was used to compute the average estimate of HIV associated neurocognitive disorders and its associated factors with 95% CIs (58). The STATA-16 Meta-prop package (59) was employed to nd the average estimate of HIV associated neurocognitive disorders. Heterogeneity among the forty involved studies (8,10,(12)(13)(14) was weighed with Q and I 2 statistics (60). An I 2 numerical value of more than 50% imply a signi cant degree of heterogeneity among forty studies (60). As there existed a potential heterogeneity during analysis, we further conducted a sensitivity analysis to identify an in uential study outweighing the study nding. Additionally, we did a subgroup analysis regarding the country of the study, study design and the assessment tools used to screen HIV associated neurocognitive disorders. The presence /absence of a publication bias was done visually with the eye ball test (61) and eggers test of publication bias.

3.1: Identi cation of studies
Our electronic search in Psych-Info, EMBASE, Scopus and PubMed gave to a total of 10231 articles. Additionally 12 articles were retrieved by looking for reference list of earlier articles. Thus, a total of 10243 articles were retrieved during the overall searching process, of which 39 were removed as they were duplicates. During the initial stage of screening, most of the articles (10118) were excluded merely by looking at their title or abstract. The lasting 86 articles were completely inspected for suitability of inclusion to the study but only 40 articles were suited for nal meta-analysis as the 46 studies were excluded with limitations in methodology ( Figure 1).

3.3: Quality of Included Studies
Using the modi ed version of Newcastle Ottawa quality assessment scale, we assessed the quality of forty studies (8, 10, 12-14, . This scale divides the quality score of 40 studies in to three; 7 to 10 categorized as very good/good, 5 to 6 categorized as having satisfactory quality and a score less than 5 as unsatisfactory quality. Among the forty included studies; the majority (twenty nine) had scored from 7 to 10 so that good quality scores on the scale. Of the remaining eleven studies, seven had a satisfactory quality and remaining four of the studies had unsatisfactory quality.

3.4: The prevalence of HIV associated neurocognitive disorders among HIV/AIDS patients
Forty studies that evaluated HIV associated neurocognitive disorders in HIV/AIDS had been included to determine the average prevalence of HIV associated neurocognitive disorders. The reported prevalence of HIV associated neurocognitive disorders included in the meta-analysis differs from 7.3% in United Kingdom (27) to 88% in Kenya (34). The average prevalence of HIV associated neurocognitive disorders using the random effect model was 50.41% (95% CI: 45.56, 55.26). This average prevalence of HIV associated neurocognitive disorders has been affected by substantial heterogeneity (I 2 =100%, p-value ≤ 0.001) from the difference among forty included studies ( Figure 2).

3.4: Subgroup analysis of the prevalence of HIV associated neurocognitive disorders among HIV/AIDS patients
Since the average estimate of HIV associated neurocognitive disorders was predisposed to a considerable heterogeneity, we employed a subgroup analysis based on country where the study was done, the assessment tool used to screen HIV associated neurocognitive disorders and study design. The average estimate of HIV associated neurocognitive disorders in Europe (8,14,20,22,23,26,27,39,40,43)

3.5: Sensitivity analysis
In addition to a subgroup analysis, we did a sensitivity analysis to know whether one or more of the individual studies outweighed the overall estimate of HIV associated neurocognitive disorders. The result however reported that the average estimate of HIV associated neurocognitive disorders ranges from 46.92638% (95% CI: 46.889656, 46.963104) to 50.478935% (95% CI: 50.439026, 50.518841) when each studies were omitted from the analysis (Table 3). This implies that there was no single in uential study outweighing the average estimate.

3.6: Publication bias
The eggers test of publication bias had been runned and its p-value is not signi cant; (P-value=0.55) suggesting that there was no publication bias for the prevalence HIV associated neurocognitive disorders. Additionally, a graphical inspection from a funnel plot for a Logit event rate of occurrence of HIV associated neurocognitive disorders in HIV AIDS patients alongside its standard error suggests an accommodating evidence for the nonexistence of a publication bias (Figure 3).
The average worldwide prevalence of HIV associated neurocognitive disorders in this study was 50.41% (95% CI: 45.56, 55.26). This was higher than the result of a meta-analysis that assessed 16 studies in sub-Sahara Africa where the prevalence of HAND was 30.39% (Neurocognitive impairment in HIV-1-infected adults in Sub-Saharan Africa: a systematic review and meta-analysis).
This review and meta-analysis has its own strengths and limitations. Its strength begins with the use of a prespeci ed search strategy that minimizes reviewer's bias. The second strength was that the data extraction and quality assessment of the study was done by independent reviewers that also further minimize reviewer's bias. The implementation of subgroup analysis and sensitivity analysis to detect the source of heterogeneity was strength. On the contrary, the limitations of the present study rise from the existence of heterogeneity that might affect the conclusion of the study ndings. Another limitation is that inclusion of few numbers of studies in the subgroup analysis might minimize validity of estimate.

Conclusion And Recommendation
This systematic review and meta-analysis study reported a high prevalence of HIV associated neurocognitive