HIV/AIDS is among the primary public health challenges that have affected the world’s social, economic, and political system in the recent past. During the last three decades, millions of people died due to HIV infection. In the year 2012, more than 1.6 million AIDS deaths were recorded [
The introduction of antiretroviral therapy (ART) significantly improved the survival of HIV patients [
Even though the benefit of ART for people living with HIV/AIDS in terms of improving quality of life and reducing morbidity and mortality is well established, there is a regional variation in the extent of its benefit. A significant number of mortalities in HIV patients were also recorded within a few years of starting ART. This early mortality is higher in resource constrained settings. A high rate of early mortality was reported from a number of sub-Saharan African ART programs [
Studies conducted on mortality and its predictors among HIV patients who had started ART were searched on PubMed and Google Scholar databases. Additional articles were also obtained from the reference lists of retrieved articles and manual Google search. Retrospective cohort studies conducted on adult HIV patients in Ethiopia and written in English language were included. No restriction was applied on the year of publication. The following search terms were used in different combinations: mortality/death/survival, HIV, ART/HAART, predictor/determinant/factors, and Ethiopia.
Studies were included in this review if they assess mortality and factors associated with it among HIV infected patients taking antiretroviral treatment in Ethiopia. Studies which were conducted on pediatric populations and those studies which include HIV patients who did not start ART were excluded.
Included studies were critically appraised by using the “STROBE Checklist” [
Relevant information was obtained from the 17 studies by using a data extraction form. Author, year of publication, study area, study subjects, sample size, study design, median follow-up period, mortality incidence density/100 person-years (PY), mortality during the full follow-up period and at 3, 6, and 12 months, and factors affecting mortality with respective odds ratio (OR) were recorded in data abstraction format.
A total of 217 articles were obtained from database (PubMed and Google Scholar) search, out of which 132 were duplicates. After screening the titles and abstracts of 85 studies, 69 were excluded. Two additional articles were obtained from reference lists of retrieved articles and one article was found to be of no importance after its full text was assessed. Finally, 17 articles were selected to be included in this review. The details of the article selection process are indicated in Figure
Article selection process.
After evaluation of each study against STROBE Checklist [
All of the studies included in this review were retrospective cohort studies conducted on adult HIV patients. A total of 19321 (range = 272–4210) study participants were included in the 17 studies reviewed. The detailed description of individual study characteristics is shown in Table
Individual study characteristics.
Sr. number | Author, year of publication | Study area | Study subjects | Study design | Sample size |
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(1) | Hambisa MT et al., 2013 | Nekemte Referral Hospital, East Wollega | Adult HIV patients (age > 14) | Retrospective cohort study | 416 |
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(2) | Tsehaineh B. et al., unpublished | JUSH, SW Ethiopia | Adult HIV patients | Retrospective cohort study | 832 |
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(3) | Setegn et al., 2015 | Goba Hospital, Bale Zone | Adult HIV patients (age >15) | Retrospective cohort study | 2036 |
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(4) | Biadgilign S. et al., 2012 | Hiwot Fana, Jugal and Dil Chora Hospitals, Eastern Ethiopia | Adult HIV patients | Retrospective cohort study | 1537 |
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(5) | Kassa A. et al., 2012 | Zewditu Memorial Hospital | Adult HIV patients (aged 15 or more) | Retrospective cohort study | 4210 |
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(6) | Seyoum D. et al., 2017 | JUSH | Adult HIV patients (age ≥ 18) | Retrospective cohort study | 456 |
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(7) | Damtew B. et al., 2015 | Kharamara Hospital, Jijiga Town, Eastern Ethiopia | Adult HIV patients (age ≥ 15) | Retrospective cohort study | 784 |
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(8) | Alemu AW and Sebastian MS, 2010 | Shashemene and Assela Hospitals, Arsi Zone | Adult HIV patients (age ≥ 15) | Retrospective cohort study | 272 |
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(9) | Ayalew et al., 2014 | Boru Meda and Dessie Referral Hospitals and Kombolcha Health Center | Adult HIV patients (age ≥ 15) | Retrospective cohort study | 654 |
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(10) | Ahunie MA and Ebrahim EA, 2017 | Debre Tabor General Hospital and Woreta Health Center | Adult HIV patients (age ≥ 15) | Retrospective cohort study | 698 |
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(11) | Abebe N et al., 2014 | Debremarkos Referral Hospital, NW Ethiopia | Adult HIV patients (age ≥15) | Retrospective cohort study | 640 |
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(12) | Tadesse K et al., 2014 | Aksum Hospital | Adult HIV patients (age ≥ 15) | Retrospective cohort study | 520 |
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(13) | Bedru A. and worku A, unpublished | Zewditu Hospital | Adult HIV patients (age ≥14) | Retrospective cohort study | 1070 |
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(14) | Mengesha S et al., 2014 | Zewditu Memorial Hospital | Adult HIV patients (age ≥14) | Retrospective cohort study | 416 |
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(15) | Moshago T et al., 2012 | Mizan Aman Hospital | Adult HIV patients | Retrospective cohort study | 2655 |
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(16) | Sapa et al., 2016 | Dilla Hospital | Adult HIV patients (age ≥15) | Retrospective cohort study | 1391 |
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(17) | Kebebew K and wencheko E, 2012 | Armed Forces Teaching and General Hospital | Adult HIV patients (age >15) | Retrospective cohort study | 734 |
The included studies followed up patients for a median of 25–60 months with an average of 38.8 months of follow-up. As indicated in Table
Mortality indicators.
Sr. number | Author, year of publication | Median follow-up period | Death, |
Mortality incidence density/100 PY | Mean survival time (95% CI) | Mortality at each period | ||
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First 3 months | First 6 months | First 12 months | ||||||
(1) | Hambisa MT et al., 2013 | 47 months | 30 (7.2%) | 1.89 | NR | NR | 17 (56.7%) | 21 (70%) |
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(2) | Tsehaineh B. et al., unpublished | 40 months | 144 (17.3%) | NR | 63.7 months (61.1–66.3) | 70 (48.6%) | 99 (68.8%) | NR |
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(3) | Setegn et al., 2015 | NR | 120 (5.9%) | 2.03 | 34.9 months (33.8–35.9) | NR | NR | 78 (65%) |
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(4) | Biadgilign S. et al., 2012 | NR | 86 (5.6%) | 2.03 | NR | NR | NR | 63 (73.3%) |
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(5) | Kassa A. et al., 2012 | NR | 291 (6.9%) | 2.8 | NR | NR | 166 (57%) | NR |
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(6) | Seyoum D. et al., 2017 | NR | 66 (14.5%) | 5.3 | 34 months (22.8–42.0) | NR | NR | 40 (60.6%) |
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(7) | Damtew B. et al., 2015 | 60 months | 87 (11.1) | 5.15 | 20.7 months | 49 (56.3%) | NR | NR |
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(8) | Alemu AW and Sebastian MS, 2010 | 28 (10.3%) | 7 | NR | NR | NR | NR | |
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(9) | Ayalew et al., 2014 | NR | 92 (14.1%) | NR | 41.8 months (40.61–43.00) | NR | NR | NR |
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(10) | Ahunie MA and Ebrahim EA | NR | 35 (5.0%) | 1.5 | NR | NR | NR | NR |
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(11) | Abebe N et al., 2014 | NR | 261 (40.8%) | 10.74 | NR | NR | NR | NR |
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(12) | Tadesse K et al., 2014 | 32 months | 46 (8.9%) | 3.2 | NR | NR | NR | 27 (59%) |
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(13) | Bedru A. and worku A, unpublished | 34 months | 360 (33.6%) | NR | NR | 200 (55.6%) | NR | NR |
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(14) | Mengesha S et al., 2014 | 34 months | 37 (9%) | 3.8 | 39 months | 22 (59.5%) | NR | NR |
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(15) | Moshago T et al., 2012 | NR | 159 (5.9%) | 0.2 | 89 months | NR | NR | NR |
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(16) | Sapa et al., 2016 | 25 months | 128 (9.2%) | 3.5 | NR | 33 (26%) | NR | 66 (52%) |
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(17) | Kebebew K and wencheko E, 2012 | 38.5 months | 86 (11.7%) | NR | NR | 28 (32.6%) | 43 (50%) | 86 (100%) |
NR: not reported.
Among the demographic and clinical characteristics mentioned as a predictor for death in the reviewed studies, the most frequently mentioned were advanced stage disease (stage III and stage IV), nonworking functional status (bedridden and ambulatory), low CD4 count, low hemoglobin level, TB coinfection, poor adherence to ART, older age, lower weight, and lower baseline BMI. A detailed description of factors that predict mortality is indicated in Table
Predictors of mortality.
Sr. number | Author, year of publication | Predictor variable | AHR | 95% CI (upper limit, lower limit) |
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(1) | Hambisa MT et al., 2013 | Age ≥ 40 | 3.055 | 1.292–7.223 |
Baseline hemoglobin level | 0.523 | 0.335–0.816 | ||
Poor ART adherence | 27.848 | 8.928–86.863 | ||
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(2) | Tsehaineh B. et al., unpublished | Old age | 1.03 | 1.01–1.051 |
CD4 count at baseline | 0.994 | 0.992–0.996 | ||
Weight at baseline | 0.902 | 0.816–0.996 | ||
Bedridden functional status | 6.904 | 4.005–11.902 | ||
Ambulatory functional status | 2.877 | 1.899–4.360 | ||
Coinfection with TB | 1.906 | 1.305–2.784 | ||
Substance use | 1.42 | 1.016–1.985 | ||
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(3) | Setegn et al., 2015 | Male | 2.67 | 1.74–4.10 |
Bedridden clients | 4.4 | 1.55–12.36 | ||
TB coinfected at ART initiation | 4.51 | 2.86–7.11 | ||
Primary education | 0.28 | 0.11–0.70 | ||
Secondary education | 0.34 | 0.154–0.728 | ||
WHO stage 1 | 0.16 | 0.08–0.33 | ||
WHO stage 2 | 0.34 | 0.16–0.73 | ||
WHO stage 3 | 0.24 | 0.13–0.43 | ||
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(4) | Biadgilign S. et al., 2012 | WHO stage IV | 3.19 | 1.51–6.76 |
Bedridden | 4.09 | 2.12–7.90 | ||
>10% weight loss from baseline | 4.93 | 1.20–20.41 | ||
CD4 | 0.40 | 0.17–0.93 | ||
Education | 2.79 | 1.26–6.16 | ||
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(5) | Kassa A. et al., 2012 | CD4 < 50 cells/ |
1.80 | 1.17–2.83 |
WHO stage III | 1.46 | 1.03–2.08 | ||
WHO stage IV | 2.72 | 1.91–3.88 | ||
Those who developed TB after ART | 1.60 | 1.19–2.15 | ||
Ambulatory functional status | 1.44 | 1.07–1.93 | ||
Bedridden functional status | 2.95 | 2.10–4.13 | ||
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(6) | Seyoum D. et al., 2017 | Age > 35 | 3.8 | 1.6–9.1 |
Baseline weight | 0.93 | 0.90–0.97 | ||
Baseline WHO stage IV | 6.2 | 2.2–14.2 | ||
Low adherence to ART | 4.2 | 2.5–7.1 | ||
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(7) | Damtew B. et al., 2015 | Single marital status | 2.31 | 1.18–4.50 |
Bedridden functional status | 5.91 | 2.87–12.16 | ||
Advanced WHO stage | 7.36 | 3.17–17.12 | ||
BMI < 18.5 kg/m2 | 2.20 | 1.18–4.09 | ||
CD4 count < 50 cells/ |
2.70 | 1.26–5.80 | ||
Severe anemia | 4.57 | 2.30–9.10 | ||
TB coinfection | 2.30 | 1.28–4.11 | ||
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(8) | Alemu AW and Sebastian MS, 2010 | Hemoglobin < 10 g/dL | 2.56 | 1.11–5.88 |
WHO stage IV | 5.13 | 2.33–11.33 | ||
Not on cotrimoxazole prophylaxis | 7.14 | 2.7–20.00 | ||
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(9) | Ayalew et al., 2014 | Age 30–40 | 0.49 | 0.28–0.85 |
Rural residency | 1.74 | 1.11–2.74 | ||
CD4 count | 0.998 | 0.996–0.999 | ||
Weight | 0.968 | 0.943–0.993 | ||
Not working functional status | 3.62 | 1.96–6.68 | ||
Lymphocyte count | 0.969 | 0.945–0.994 | ||
WHO stage IV | 2.38 | 1.21–4.63 | ||
TB positive | 1.87 | 1.03–3.40 | ||
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(10) | Ahunie MA and Ebrahim EA | Ambulatory functional status | 4.2 | 1.7–10.7 |
Bedridden functional status | 6.5 | 2.0–20.7 | ||
Poor antiretroviral drug adherence | 5.1 | 1.6–16.3 | ||
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(11) | Abebe N et al., 2014 | Baseline hemoglobin < 10 g/mm3 | 1.86 | 1.39–2.64 |
Ambulatory functional status | 2.72 | 1.90–3.90 | ||
Bedridden functional status | 2.38 | 1.32–4.27 | ||
WHO stages III and IV | 2.16 | 1.10–4.25 | ||
Poor adherence | 2.16 | 1.03–4.56 | ||
Fair adherence | 1.88 | 1.08–3.29 | ||
Unexplained chronic diarrhea | 1.53 | 1.09–2.15 | ||
Not on TB prophylaxis | 3.98 | 1.87–8.44 | ||
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(12) | Tadesse K et al., 2014 | Hemoglobin level < 11 mg/dl | 1.9 | 1.01–3.52 |
CD4 cell count < 50 cells/ |
2.1 | 1.13–3.89 | ||
Male gender | 1.9 | 1.01–3.52 | ||
Weight < 40 kg | 2.3 | 1.24–4.55 | ||
Primary and lower level of education | 2.6 | 1.29–5.55 | ||
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(13) | Bedru A. and worku A, unpublished | Poor ART adherence | 3.92 | 3.13–4.90 |
Advanced WHO staging | 2.47 | 1.58–3.81 | ||
Being unemployed | 1.87 | 1.49–2.34 | ||
Moderate anemia | 1.86 | 1.35–2.56 | ||
Low CD4 count | 1.85 | 1.35–2.52 | ||
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(14) | Mengesha S et al., 2014 | WHO clinical stage | 2.99 | 1.26–5.31 |
Anemia | 5.54 | 2.58–11.86 | ||
Having past TB coinfection | 4.13 | 1.79–9.51 | ||
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(15) | Moshago T et al., 2012 | WHO clinical stage IV | 4.5 | 1.36–14.88 |
WHO clinical stage III | 3.2 | 1.06–10.24 | ||
History of TB coinfection | 1.25 | 1.03–1.53 | ||
Bedridden functional status | 2.63 | 2.05–3.37 | ||
Ambulatory functional status | 1.56 | 1.31–1.86 | ||
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(16) | Sapa et al., 2016 | BMI < 18.5 kg/m2 | 3.12 | 1.39–7.76 |
CD4 cell count < 50 cells/mm3 | 4.55 | 1.19–8.44 | ||
Drug addiction | 2.03 | 1.11–4.56 | ||
WHO stages III and IV | 11.25 | 8.67–17.96 | ||
Severe anemia | 5.14 | 3.12–9.65 | ||
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(17) | Kebebew K and Wencheko E, 2012 | CD4 cell count at baseline | 0.78 | 0.64–0.95 |
Employment status | 2.31 | 1.25–4.28 | ||
Ambulatory functional status | 2.01 | 1.02–3.98 | ||
Bedridden functional status | 3.36 | 1.73–6.50 | ||
WHO clinical stage III | 7.05 | 1.68–29.66 | ||
WHO clinical stage IV | 12.64 | 3.00–53.20 | ||
TB coinfection | 1.73 | 1.04–2.89 | ||
Presence of opportunistic infections | 8.99 | 1.24–65.09 |
Patients who started ART after they developed advanced stage disease are 1.4–11.2 times more likely to die than patients who started ART while they are in stage I or II. Patients who are bedridden and ambulatory are 2.4–6.9 and 1.4–4.2 times more likely to die than those who have a working functional status, respectively. Some studies express the effect of CD4 count as a continuous variable and demonstrated that the risk of death decreases by 1%–22% as the CD4 at initiation of ART rises by one unit. Other studies reported that CD4 < 50 cells/microliter at ART initiation increases the risk of death by 1.8–4.5 times. Lower hemoglobin level has 1.9–5.5 times increased risk of death. TB-HIV coinfection increases the risk of mortality 1.3–4.5-fold.
Most of the studies (82%) included in the current review reported that 5–15% of the patients died within the respective follow-up periods. These rates of mortality were higher than what was reported in Uganda (4.5%) [
All of the studies which reported death rates at different points of follow-up indicated that more than half (50%–68.8%) of the deaths occurred within 6 months of initiating ART. This indicated that most of the deaths in HIV patients occur early in the course of treatment. The reports that compare early mortality in HIV patients of low income and high income countries indicated that patients starting ART in resource constrained settings have increased mortality rates in the first months of therapy compared to those in developed countries [
Many factors were found as a determinant of death. Among these, advanced stage disease, nonworking (bedridden and ambulatory) functional status, lower baseline CD4 count, lower baseline weight, lower baseline hemoglobin, TB coinfection, and poor adherence were frequently mentioned.
WHO clinical stage of the disease is the most important predictor of mortality reported by many of the studies included in this review. Many other studies conducted outside Ethiopia also reported the same result [
Furthermore, the risk of death is higher for patients with low baseline CD4 count. The CD4 count is a reflection of the patients’ immune status, so when it becomes low, the risk of developing opportunistic infections will increase, which may finally lead to death. Low CD4 count at initiation of ART was mentioned as the main predictor of death in HIV patients in various studies [
Presence of TB coinfection is another important risk factor for death in HIV patients. According to Suchindran et al., the risk of death in TB-HIV coinfected individuals is double as compared to HIV infected individuals without TB [
Medication adherence is very important to get the full benefit of antiretroviral drugs. Nonadherence to ART will result in treatment failure by increasing the chance of mutation that could lead to a drug resistant virus and finally death. Even though a self-reported adherence assessment method was used in all of the reviewed studies, which is not as such reliable to measure adherence, some of the studies revealed that poor adherence is significantly associated with mortality. Those who did not have proper adherence to their ART medication were 2.2–27.8 times at greater risk of death than those who adhered to their medication. This was also reported in different studies conducted in various parts of the world [
Age of patients was found to affect survival in HIV patients who are on ART. Four of the studies included in this review found significant association between age and death due to HIV after starting ART. Other studies also confirmed that most of the patients of older age were more likely to die [
In addition to the above factors, lower level of education, male sex, substance abuse, and unemployment were also mentioned as a significant predictor of mortality by some of the studies included in this review. Another study also reported negative influence of low level of education on mortality among ART users [
Even though the inclusion of many homogeneous studies is the strength of this review, there are also some limitations that should be considered in the interpretation of the result of this study. The retrospective nature of the included studies limits the cause and effect relation between death and the different factors reported in the individual studies. Mortality might also be underestimated, since individuals dying at home without being reported were considered as lost to follow-up. On the other hand, HIV-related mortality might also be overestimated since the exact cause of death was not determined and every recorded death in HIV patients was considered as HIV-related.
5%–40.8% of HIV patients in Ethiopia die in 2–5 years of initiating antiretroviral treatment. Most of the deaths in HIV patients occur early in the course of treatment. The main predictors for death were advanced stage disease, nonworking (bedridden and ambulatory) functional status, lower baseline CD4 count, lower baseline hemoglobin, TB coinfection, lower baseline weight, and poor treatment adherence. Special emphasis and closer follow-up should be given for patients with such characteristics.
Acquired immune deficiency syndrome
Antiretroviral therapy
Body mass index
Highly active antiretroviral therapy
Human immunodeficiency virus
Person-years
Tuberculosis.
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
The author declares that he has no conflicts of interest.
The author would like to express his thanks to the University of Gondar for granting him Internet access.