A total of 873 articles were found from PubMed (n=187), Google Scholar (n=134), Web of Science (n=21), Scopus (n=13), and Ethiopian Universities’ online repository library (University of Gondar and Addis Ababa University) (n=33). A total of 331 articles have remained after duplicate studies were removed. Then, 302 articles were removed based on the unmatched title and abstracts. Finally, 18 articles were included (Figure 1).
Characteristics of studies
Studies found through databases search were done between 2005 and 2016. Eight of the studies were conducted in the Amhara region, whereas five in Addis Ababa (13, 21-24), three in Oromia (18, 25, 26), one in Tigray (14), and one in SNNPR (27). Three studies were done by case-control study design (24, 28, 29), four studies by cross-sectional (14, 30-32), and eleven by cohort study design (13, 15-18, 21-23, 25-27). Ten studies were done on adult population (13, 16, 17, 21, 23-25, 28, 29, 32), six on children (15, 18, 22, 26, 27, 31), and two on all age group (14, 30) (Table 1).
The funnel plot for HIV treatment failure is shown below (Figure 2). Egger’s regression test of the p-value for overall HIV treatment failure is 0.226.
HIV treatment failure based on the definition of HAART failure
A total of 4,738 participants in nine studies were used to estimate the pooled prevalence of HIV treatment failure based on the definition of HAART failure. The pooled prevalence of HIV treatment failure was 15.9% (95% CI: 11.6%-20.1%) (Figure 3).
Immunological and Virological definition of HIV treatment failure
A total of 5,899 study participants in 13 studies were involved to determine HIV treatment failure based on the immunological definition. Of which, 10.2% (95% CI: 6.9%-13.6%) developed immunological failure. Regarding virological failure, the pooled prevalence from six studies with a total of 2,406 participants was 5.6% (95% CI: 2.9%-8.3%) (Figure 4).
Clinical definition of HIV treatment failure
A total of 4,497 study participants in 9 studies were found to estimate the clinical failure, in which the pooled prevalence was 6.3% (95% CI: 4.6%-8.0%) (Figure 5).
Subgroup analysis was employed based on region, age of the study participants, and study design. Lower prevalence of HIV treatment failure based on the definition of HAART, immunological, and virological failure was 13.7%in Amhara, 6.5% in Tigray, and 1.5% in Addis Ababa, respectively (Table 2).
In the sensitivity analysis, the overall HIV treatment failure based on the definition of HAART failure was observed high (17.3%) and low (15.2%) when Ayalew MB et al 2016 and Sisay C et al/2017 was omitted respectively. The minimum pooled prevalence of HIV treatment failure based on immunological definition (9.3%), virological definition (4.4%), and clinical definition (5.5%) when Yayehirad AM et al/2013, Hailu GG et al /2015, and Yassin S /2016 omitted, respectively. And the maximum pooled prevalence of HIV treatment failure based on immunological definition (10.8%) and virological failure (6.5%) Ayalew MB et al/2016 and Yimer YT/2015 was dropped from the analysis, respectively (Table 3).
Associated factors of HIV treatment failure
HIV treatment failure is attributed to socio-demographic, clinical, drug, and health system-related factors.
Based on a single study report, children’s age between 6 and 9 years (AOR = 0.26; 95% CI: 0.09-0.72) was protective towards HIV treatment failure as compared to 10-15 years old children (18). Another study showed children less than three years old were high risk (AHR=1.85; 95% CI: 1.24-2.76) for HIV treatment failure as compared to 5-15 years old children (22).
One study which was done on the adult population (29) showed that those aged <35 years were high risk (AOR=2.5; 95% CI: 1.3-4.8) to develop HIV treatment failure as compared to their counterparts.
From a single study, male adult patients (AOR=4.6; 95% CI: 1.7-12.3) (14), and patients in the formal educational level (AOR = 5.15; 95% CI: 1.5-17.3) (28) were at higher risk for HIV treatment failure.
Babo YD et al/2017 (AOR=4.9; 95% CI: 1.5-16) and Yayehirad MA et al/2013 (AOR=1.7; 95% CI: 1.1-2.7) (16, 28) found that the odds of being unemployed is more likely to develop HIV treatment failure.
Report from one study showed that lower baseline body mass index (BMI) (AOR = 2.8; 95% CI: 1.01-7.5) (28) and patients who had height for age in the third percentile or less (AHR= 3.3; 95% CI: 1.0-10.6) (22) were more likely to expose to HIV treatment failure. On the other hand, weight change per 1 kg increase (AHR=0.9, 95% CI: 0.9-0.9) (17), and <50 kg weight at baseline (AHR=0.58, 95% CI:0.38-0.89) (13) were less likely to expose to HIV treatment failure.
One study showed (16), being in ambulatory functional status was at high risk (AOR=2.9, 95%CI: 1.2-7.5) to develop HIV treatment failure than being in working functional status.
Another study (15) showed that those children who did not know their HIV status were at high risk (AHR=4.4, 95% CI: 1.8-11.3) to develop HIV treatment failure.
The pooled effects of CD4 cell count <200 cells/mm3 (AOR=7.2; 95% CI: 2.5-12.0), ≤ 100 cells/ mm3 (AOR=2.1; 95% CI: 1.4-2.8) and <50 cells/mm3 (AOR=3.3; 95% CI: 1.4-5.3) as compared to those with >200, >100, and > 50 cells/mm3 on HIV treatment failure were estimated, respectively (Figure 6).
The pooled effect of being on WHO clinical stage III/IV found to be at higher risk (AOR=1.9; 95% CI: 1.3-2.6) to HIV treatment failure as compared to stage II/I. The pooled effect of the presence of opportunistic infections (TB, diarrhea, pneumonia, other OIs) are more likely (AOR=1.8; 95% CI: 1.2-2.4) to expose patients to HIV treatment failure (Figure 7).
Stavudine based regimen (AOR = 3.5; 95% CI: 1.3-10.6) (28), ART drug substitution (AHR=1.7; 95% CI:1.1-2.7) (22), substitution of original regimen (AOR=3.3; 95% CI=1.6-6.7) (31), absence of PMTCT prophylaxis (AOR=1.4; 95% CI: 1.2-2.5) (31), and using faith healing medicine (AOR=8.1, 95% CI: 3.1-21.5) (30) were reported predictors of HIV treatment failure. Another study (30) showed that patients who didn’t have consultation were positively associated (AOR=4.9,95% CI:1.5-15.8) with HIV treatment failure.
The pooled effect (AOR) of poor HAART adherence to HIV treatment failure was 8.1 (95% CI: 4.3-11.8) (Figure 8).