Mortality and its Predictors among children on Antiretroviral treatment in Ethiopia: A systematic review and Meta –analysis

Background: It is well known that antiretroviral therapy (ART) decrease the progress of acquired immune deficiency syndrome (AIDS) related morbidity and mortality and helps the progress towards achieving the United Nations Program on HIV/ AIDS(UNAIDS) treatment goals. Despite this, mortality in Ethiopia becomes public health concern, and variance is observed across studies. With this gap, there is no pooled estimate. Thus, the goal of this study was to assess the pooled mortality and its predictors among antiretroviral treated HIV/AIDS patients.Methods: PubMed, Scopus and Google Scholar databases were used to search articles. The quality of studies was assessed using the Newcastle Ottawa quality assessment scale. The funnel plot and Egger's test were performed to confirm the presence of publication bias. Heterogeneity across studies was evaluated using the I2 statistic. The pooled incidence rate and its predictors were estimated using a weighted inverse variance random-effects model. Subgroup analysis and sensitivity analysis were also performed. Results: In this review, 12 studies with the cohort size of 4,935 were included. The overall incidence of mortality rate was 6.02 (95% CI: 3.7, 8.2) per 100 person-years. A higher incidence of mortality was observed (12.51% (95%CI: 0.32, 24.7)) in south nation nationality and Peoples (SNNP) on subgroup analysis. Being advanced world health organization(WHO) clinical stage (AHR:5.34( 95% CI: 3.1,9.2.6)), lower CD4 cell count (AHR :2.46 (95 %CI: 1.8, 3.2)), anemia (AHR :2.76 (95% CI: 1.9,3.9)), and nutritional status (AHR :1.9 (95%CI: 1.3, 2.6)) were major predictors of mortality. In contrast, cotrimoxazole preventive therapy (CPT) (AHR: 0.34, (95% CI 0.05, 0.63)) reduced mortality.Conclusions: In Ethiopia, the incidence of mortality was high. Lower CD4 cell count, anemia, WHO clinical staging (III/IV), and undernutrition were the contributing factors. But cotrimoxazole preventive therapy had a high effect on mortality reduction. Therefore, an earlier management would be started before advancing signs of acquired immune deficiency syndrome (AIDS) regardless of WHO staging, CD4 cell level, and nutritional status.

[1]  A. Gelagay,et al.  Survival and predictors among preterm neonates admitted at University of Gondar comprehensive specialized hospital neonatal intensive care unit, Northwest Ethiopia , 2019, Italian Journal of Pediatrics.

[2]  Getachew Arage,et al.  Survival rate of HIV-infected children after initiation of the antiretroviral therapy and its predictors in Ethiopia: A facility-based retrospective cohort , 2019, SAGE open medicine.

[3]  R. Heffron,et al.  Global and national guidance for the use of pre-exposure prophylaxis during peri-conception, pregnancy and breastfeeding. , 2018, Sexual health.

[4]  S. Hebo,et al.  Survival time and its predictors among HIV-infected children after antiretroviral therapy in public health facilities of Arba Minch town, Gamo Gofa Zone, Southern Ethiopia , 2018 .

[5]  Kendalem Asmare Atalell,et al.  Survival and predictors of mortality among children co-infected with tuberculosis and human immunodeficiency virus at University of Gondar Comprehensive Specialized Hospital, Northwest Ethiopia. A retrospective follow-up study , 2018, PloS one.

[6]  Shimelash Bitew,et al.  Predictors on mortality of human immunodeficiency virus infected children after initiation of antiretroviral treatment in Wolaita zone health facilities, Ethiopia: Retrospective cohort study , 2017 .

[7]  S. Vermund,et al.  Mortality in Children with Human Immunodeficiency Virus Initiating Treatment: A Six‐Cohort Study in Latin America , 2017, The Journal of pediatrics.

[8]  Lamessa Dube,et al.  Determinants of Survival among HIV PositiveChildren on Antiretroviral Therapy in Publichospitals, Addis Ababa, Ethiopia , 2017 .

[9]  N. Bajaj,et al.  Predictors of poor outcome in neonates with respiratory distress , 2016 .

[10]  G. Ameni,et al.  Survival and predictors of mortality among human immunodeficiency virus patients on anti-retroviral treatment at Jinka Hospital, South Omo, Ethiopia: a six years retrospective cohort study , 2016, Epidemiology and health.

[11]  Dumessa Edessa,et al.  Early Mortality among HIV-positive Children Initiated Anti-retroviral Therapy in Eastern Ethiopia: A Retrospective Cohort Study , 2016 .

[12]  E. Zandonade,et al.  Mortality in children and adolescents vertically infected by HIV receiving care at a referral hospital in Vitoria, Brazil , 2015, BMC Infectious Diseases.

[13]  W. Fawzi,et al.  Nutritional Status and Other Baseline Predictors of Mortality among HIV-Infected Children Initiating Antiretroviral Therapy in Tanzania , 2015, Journal of the International Association of Providers of AIDS Care.

[14]  S. Biadgilign,et al.  Predictors of early mortality in a cohort of HIV-infected children receiving high active antiretroviral treatment in public hospitals in Ethiopia , 2015, AIDS care.

[15]  A. Tshefu,et al.  Antiretroviral Treatment Program Retention among HIV-Infected Children in the Democratic Republic of Congo , 2014, PloS one.

[16]  J. Tappero,et al.  Protective efficacy of prolonged co-trimoxazole prophylaxis in HIV-exposed children up to age 4 years for the prevention of malaria in Uganda: a randomised controlled open-label trial. , 2014, The Lancet. Global health.

[17]  Shimelash Bitew.  Assessment of the effect of malnutrition on survival of HIV infected children after initiation of antiretroviral treatment in Wolaita zone health facilities, SNNPR, Ethiopia , 2014 .

[18]  N. Ford,et al.  Task Shifting for the Delivery of Pediatric Antiretroviral Treatment: A Systematic Review , 2014, Journal of acquired immune deficiency syndromes.

[19]  A. Desta,et al.  Factors Affecting Survival of HIV Positive Children Taking AntiretroviralTherapy at Adama Referral Hospital and Medical College, Ethiopia , 2014 .

[20]  Berhe Weldearegawi,et al.  Predictors of mortality among HIV infected children on anti-retroviral therapy in Mekelle Hospital, Northern Ethiopia: a retrospective cohort study , 2013, BMC Public Health.

[21]  L. Picker,et al.  CD4+ T‐cell depletion in HIV infection: mechanisms of immunological failure , 2013, Immunological reviews.

[22]  T. Ayele,et al.  Predictors of mortality among children on Antiretroviral Therapy at a referral hospital, Northwest Ethiopia: A retrospective follow up study , 2012, BMC Pediatrics.

[23]  A. Amare,et al.  The pattern and predictors of mortality of HIV/AIDS patients with neurologic manifestation in Ethiopia: a retrospective study , 2012, AIDS Research and Therapy.

[24]  T. Girma,et al.  Immunologic and clinical outcomes of children on HAART: A retrospective cohort analysis at Jimma University Specialized Hospital , 2011 .

[25]  M. Egger,et al.  Early Mortality and Loss to Follow-up in HIV-Infected Children Starting Antiretroviral Therapy in Southern Africa , 2010, Journal of acquired immune deficiency syndromes.

[26]  B. Richardson,et al.  Predictors of mortality in HIV-1 infected children on antiretroviral therapy in Kenya: a prospective cohort , 2010, BMC pediatrics.

[27]  W. Fawzi,et al.  Patterns and predictors of CD4 T-cell counts among children born to HIV-infected women in Tanzania. , 2009, Journal of tropical pediatrics.

[28]  Victor Segalen Bordeaux,et al.  Low Risk of Death, but Substantial Program Attrition, in Pediatric HIV Treatment Cohorts in Sub-Saharan Africa , 2008, Journal of acquired immune deficiency syndromes.

[29]  F. Dabis,et al.  Cohort profile: the paediatric antiretroviral treatment programmes in lower-income countries (KIDS-ART-LINC) collaboration. , 2008, International journal of epidemiology.

[30]  C. Giaquinto,et al.  Use of total lymphocyte count for informing when to start antiretroviral therapy in HIV-infected children: a meta-analysis of longitudinal data , 2005, The Lancet.