METHODS AND ANALYSIS: This review will be conducted in accordance with the preferred reporting items for systematic review and meta-analyses protocols. Primary outcomes will include: (1) proportion of eligible patients initiating antiretroviral therapy (ART); (2) proportion of those on ART with <1000 copies/mL; (3) rate of all-cause mortality among ART recipients. Secondary outcomes will include: (1) proportion receiving Pneumocystis jiroveci pneumonia prophylaxis; (2) proportion with >90% ART adherence (based on any measure reported); (3) proportion screened for non-communicable diseases (specifically cervical cancer, diabetes, hypertension and mental ill health); (iv) proportion screened for tuberculosis. A search of five electronic bibliographical databases (Embase, Medline, PsychINFO, Web of Science and CINAHL) and reference lists of included articles will be conducted to identify relevant articles reporting HIV clinical outcomes. Searches will be limited to LMIC. No age, publication date, study-design or language limits will be applied. Authors of relevant studies will be contacted for clarification. Two reviewers will independently screen citations and abstracts, identify full text articles for inclusion, extract data and appraise the quality and bias of included studies. Outcome data will be pooled to generate aggregative proportions of primary and secondary outcomes. Descriptive statistics and a narrative synthesis will be presented. Heterogeneity and sensitivity assessments will be conducted to aid interpretation of results.
ETHICS AND DISSEMINATION: The results of this review will be disseminated through a peer-reviewed scientific manuscript and at international scientific conferences. Results will inform quality improvement strategies, replication of identified good practices, potential policy changes, and future research.
PROSPERO REGISTRATION NUMBER: CRD42016040053.
DESIGN: Prospective studies of HIV-infected individuals in Europe and the US included in the HIV-CAUSAL Collaboration.
METHODS: Antiretroviral therapy-naive and AIDS-free individuals were followed from the time they started an NRTI, efavirenz or nevirapine, classified as following one or both types of regimens at baseline, and censored when they started an ineligible drug or at 6 months if their regimen was not yet complete. We estimated the 'intention-to-treat' effect for nevirapine versus efavirenz regimens on clinical, immunologic, and virologic outcomes. Our models included baseline covariates and adjusted for potential bias introduced by censoring via inverse probability weighting.
RESULTS: A total of 15 336 individuals initiated an efavirenz regimen (274 deaths, 774 AIDS-defining illnesses) and 8129 individuals initiated a nevirapine regimen (203 deaths, 441 AIDS-defining illnesses). The intention-to-treat hazard ratios [95% confidence interval (CI)] for nevirapine versus efavirenz regimens were 1.59 (1.27, 1.98) for death and 1.28 (1.09, 1.50) for AIDS-defining illness. Individuals on nevirapine regimens experienced a smaller 12-month increase in CD4 cell count by 11.49 cells/μl and were 52% more likely to have virologic failure at 12 months as those on efavirenz regimens.
CONCLUSIONS: Our intention-to-treat estimates are consistent with a lower mortality, a lower incidence of AIDS-defining illness, a larger 12-month increase in CD4 cell count, and a smaller risk of virologic failure at 12 months for efavirenz compared with nevirapine.