3.1: Identification 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 final meta-analysis as the 46 studies were excluded with limitations in methodology (Figure 1).
3.2: Characteristics of included studies
A total of forty studies (8, 10, 12-14, 16-49) that surveyed HIV associated neurocognitive disorders in 14107 HIV/AIDS patients were integrated in the current systematic review and meta-analysis study. Of the forty included studies; eleven were from Europe (8, 14, 20, 22, 23, 26, 27, 39, 40, 43), twenty one were from Africa(10, 13, 17, 19, 24, 29, 30, 34, 36-38, 44-49), and six were from Asia(16, 25, 33, 35, 42) (fazel) and two from United States of America (USA) (28, 40). Most of the included studies (28)(8, 10, 12-14, 16-19, 22, 24, 25, 27, 29, 30, 33-39, 44-49) were cross-sectional in design whereas the remaining ten and two were cohort(8, 20, 22, 23, 26, 28, 40, 42, 43) and case control(29, 62) respectively. Regarding tools used for the assessment of HIV associated neurocognitive disorders, half of the included studies (twenty) used International HIV Dementia Scale (IHDS)(8, 10, 12-14, 16, 19, 24, 34-36, 38, 42, 43, 45, 47-49, 62) . Frascati criteria, global dementia scale (GDS) and Montreal Cognitive Assessment (MoCA) were also used to assess HIV associated neurocognitive disorders in three(25, 30, 46), three(29, 37) (Yechoor et al.2016 ) and three (18, 22) (Chan et al.2016) studies respectively. HIV associated neurocognitive disorders were assessed on a total of 14107 HIV/AIDS patients (Table 1).
3.3: Quality of Included Studies
Using the modified version of Newcastle Ottawa quality assessment scale, we assessed the quality of forty studies (8, 10, 12-14, 16-49). 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 (I2 =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) was found to be 50.015% (95% CI: 43.339, 56.691) whereas in Africa (10, 13, 17, 19, 24, 29, 30, 34, 36-38, 44-49), Asia (16, 25, 33, 35, 42) (fazel) and United States of America (USA) (28, 40) the average prevalence of HAND were 49.566% (95% CI: 41.342, 57.791) with (I2= 96.6%, p-value <0.001), 52.032 % (95% CI: 34.46, 69.604) with (I2 =98%, p-value<0.001) and 50.407% (95%CI: 45.555, 55.258) (I2 =100%, P<0.001) respectively (Table 2). The average estimate of HIV associated neurocognitive disorders in studies which used International HIV Dementia Scale (IHDS) (8, 10, 12-14, 16, 19, 24, 34-36, 38, 42, 43, 45, 47-49, 62) (Webb et al.2016) was 36.883% (95%CI: 21.196, 52.571) & 59.956% (95%CI: 49.985, 69.928) at a cutoff points of IHDS< 9.5 & IHDS<10 respectively. The estimated average of HAND in studies used the global dementia scale (GDS)(29, 37) (Yechoor et al.2016 ) was 40.766% (95%CI: 31.995, 49.537). The estimated average of HAND in cross-sectional (8, 10, 12-14, 16-19, 22, 24, 25, 27, 29, 30, 33-39, 44-49) cohort (8, 20, 22, 23, 26, 28, 40, 42, 43) and case control (29, 62) studies was 49.52% (95% CI: 43.490, 55.545) (I2= 48.6%, P=1.00) , 54.087% (95% CI: 45.087, 63.087) (I2= 96%%, P<0.001) and 44.45% (95% CI: 25.144, 63.756) (I2= 94.8%, P<0.001) respectively(Table 2).
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 influential study outweighing the average estimate.
3.6: Publication bias
The eggers test of publication bias had been runned and its p-value is not significant; (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).
3.7: Associated factors of HIV associated neurocognitive disorders among HIV/AIDS patients
Among the forty studies, only fifteen studies described the factors related with HIV associated neurocognitive disorders (8, 10, 12, 14, 17, 19, 20, 24, 25, 33, 34, 45-48). The most frequently reported sociodemographic variable as associated factor of HIV associated neurocognitive disorders were low level of education(12, 14, 17, 20, 29, 45, 46) and older age (8, 14, 19, 45, 48) Among clinical and HIV related variables late clinical stage of the illness (19, 20, 24, 48) and CD4 count of 500 cells/dl or less (8, 17, 45) were the most commonly described factor for HIV associated neurocognitive disorders. In addition, from psychological variables comorbidity of depression increases the risk of HIV associated neurocognitive disorders (14, 20, 34). Moreover, clinical and HIV related variables such as impairment in the activity of daily living(19), duration of HIV infection > 5 years (25), poor medication adherence (45), co-morbid medical illness, highest prior VL >100,000 copies/ml(8), history of neurological disease(20), use of benzodiazepines(33), body mass index< 16 kg/m2 (24), plasma HIV-1 RNA load between 1.7log10 and 3log10 copies/ml(48), having co-morbid opportunistic infection(19) and psychological variables like negative life events, high stress score index (score>10) (10), generalized anxiety symptoms (20), and substance use (19, 48) were related to HIV associated neurocognitive disorders (Table 4).
3.7. 1 Association between old age and HIV associated neurocognitive disorders among HIV/AIDS patients
Older age was reported as the risk factor for HIV associated neurocognitive disorders by five studies (8, 14, 19, 45, 48).
3.7.2 Association between depression and HIV associated neurocognitive disorders among HIV/AIDS patients
As reported with three studies (14, 20, 34) that assessed HIV associated neurocognitive disorders, depression increases the risk of HIV associated neurocognitive disorders.
3.7.3 Association between advanced stages of AIDS and HIV associated neurocognitive disorders among HIV/AIDS patients
Advanced clinical stages of the illness (stage III and stage IV AIDS) (19, 20, 24, 48) were also associated factor for HIV associated neurocognitive disorders.