We are going to follow the Preferred Reporting Items for the Systematic Reviews and Meta-analysis Protocols (PRISMA-P) 2015 guideline (additional file1) . We will systematically review observational studies reporting on morbidity and mortality in the ART era in Sub-Saharan Africa.
Participants included in eligible studies will be adult patients,18 years or older infected with HIV during the antiretroviral therapy.
The antiretroviral therapy (ART) used to treat people with HIV infection in Sub-Saharan Africa from 2008 to 2018.
The reasons for hospitalization and the causes of mortality among people with HIV infection, dying in the antiretroviral era will be described and that will help clinicians and patients living with HIV to have comprehensive information and find strategies to improve treatment outcomes.
- Studies reporting on morbidity and mortality in the antiretroviral era in Sub-Saharan Africa.
- Studies conducted in the period of 2008 to 2018.
- Studies reporting on Adult males or females aged 18 years or older.
- Peer-reviewed English language publications
- Observational studies on Sub-Saharan Africa.
- Studies reporting on morbidity or mortality in Pregnant women infected with HIV
- Studies reporting on morbidity or mortality in women infected with HIV in the post-partum period.
Search Strategy for identifying relevant studies
To identify relevant studies, we will search in the following database: Medline, Pub Med, CINAHL. Studies published in English from January 2008 to December 2018 in Sub-Saharan Africa. The choice from 2008 to 2018 because we want to compare the time the ART was available for everyone and the time it was not available for everyone.
The search strategy will be based on a combination of relevant terms.
Find below the main search strategy conducted in PubMed in Table1.
Table 1: Search strategy in PubMed
(Morbidity OR Opportunistic infection related HIV) [MeSH Terms]
(Mortality OR Death) [MeSH Terms]
(ART OR Antiretroviral therapy) [MeSH Terms]
(Sub-Saharan Africa) [Title/Abstract]
#1 AND #2 AND #3 AND #4
We will adapt this search strategy for a possible extension to other databases and it will be adapted as we progress through the review. We will also contact experts in the field to identify additional eligible studies and we will manually search reference lists from relevant studies.
Data collection and analysis
Two reviewers will follow the inclusion criteria for selecting studies, articles will be identified and screened by their titles and abstracts eligibility. The full texts of articles will be retrieved. The process of literature selection and reasons for exclusion and inclusion will be documented by a PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis) flow diagram (figure 1) .
Data extraction and management
Data will be extracted in accordance with the methods outlined in the Cochrane Handbook for systematic reviews of interventions and the data extraction form will be designed and it will be collected in the following order:
- First author-name
- Years of publication,
- Geographical location
- Sample size
- Participants (age, sex)
- Study design
If there are disagreements between the two review authors, it will be resolved through discussion and by consulting a third author. For managing missing data, we will contact the corresponding author of the respective studies to obtain the required details.
Data analysis and synthesis.
We will systematically review observational studies that examined morbidity and mortality in antiretroviral therapy in Sub-Saharan Africa. All statistical analyses will be carried out using Stata statistical software version 14 (Stata Corporation, College Station, Texas, USA). Statistical heterogeneity among the included studies will be assessed by the X2 test on Cochrane’s Q statistic. Significant heterogeneity will be indicated if P-value is less than 0.1. Heterogeneity will be quantified by using the I-squared values. Values of 25, 50, and 75% for I-squared will be represented low, medium, and high heterogeneity, respectively . If substantial heterogeneity is detected, a subgroup will be performed to investigate the possible sources of heterogeneity using the following grouping variables: gender (male, female).
A qualitative narrative synthesis of the findings will be performed, R software will be used to synthesis the data, we will capture information into a spreadsheet about the most causes of hospitalization and death related to HIV in the antiretroviral treatment, Graphic displays such as Bar chart or multiple bar chart component will be used to visually compare the prevalence of comorbidities across the study region. This will also enable to provide any form of patterns in the comorbidities.
A subgroup analysis will be conducted following Gender (male vs female) The heterogeneity between subgroups will be detected by using the X2 test on Cochrane’s Q statistic.