PATTERNS OF WHO HIV DRUG RESISTANCE EARLY WARNING INDICATOR PERFORMANCE ACROSS ART PROGRAMS IN SUB-SAHARAN AFRICA: A SYSTEMATIC REVIEW

Human immunodeficiency virus drug resistance (HIVDR) remains a major threat to the long-term success of antiretroviral therapy (ART) programs, particularly in Sub-Saharan Africa, where the HIV burden remains high and ART coverage continues to expand. In many low-resource settings, limited access to routine HIVDR testing increases reliance on program-level monitoring to identify conditions associated with HIVDR emergence. The World Health Organization (WHO) developed HIVDR Early Warning Indicators (EWIs) to monitor ART program performance and identify vulnerabilities linked to increased HIVDR risk. The objective is to systematically review evidence on the performance of WHO HIVDR EWIs across ART programs in Sub-Saharan Africa and identify recurring program and health system challenges associated with poor EWI performance. A systematic review was conducted in accordance with a PROSPERO-registered protocol. Electronic database searches were conducted in PubMed, Scopus, and Google Scholar for studies published between 1 January 2013 and 31 December 2023. Eligible studies included surveillance studies, operational research, program evaluations, and facility- or program-level assessments reporting WHO HIVDR EWI outcomes in Sub-Saharan Africa. Country-level observations from WHO multi-country HIVDR reports were also included. Study screening, eligibility assessment, and data extraction were conducted systematically using Covidence. Two reviewers independently screened titles, abstracts, and full-text articles and extracted data using standardized tools. Disagreements were resolved through discussion and consultation with a third reviewer. Findings were synthesized narratively due to heterogeneity in study designs, EWI frameworks, and reporting approaches. A total of 13 studies met the inclusion criteria, representing 37 country-level observations across 25 countries in Sub-Saharan Africa. Retention in care met WHO-recommended targets in 14 of 37 observations (37.8%), while 22 (59.5%) failed to meet targets. Adherence/on-time ARV pick-up performed the poorest, with only 1 of 31 observations (3.2%) meeting targets and 30 (96.8%) failing. Viral load suppression was assessed in only five observations, of which one (20.0%) met targets and two (40.0%) failed to meet targets. No observation assessing viral load testing coverage/completion met the WHO-recommended targets (0/3; 0%), while all three (100%) failed to meet targets. ARV stock continuity met targets in only 3 of 26 observations (11.5%), compared with 23 (88.5%) that failed to meet targets. In contrast, prescribing and dispensing practices consistently performed well, meeting WHO-recommended targets in 35 of 36 observations (97.2%). Reported challenges evolved over time. Studies conducted between 2004 and 2010 primarily reported challenges with adherence, retention, stock-outs, and routine monitoring. Between 2011 and 2015, laboratory, viral load monitoring, workforce, and information systems challenges became more prominent. Studies conducted between 2016 and 2023 reported broader systems-level challenges related to data integration, laboratory capacity, supply chain management, patient follow-up, and program sustainability. Although substantial progress was made in ART scale-up and in implementing standardized treatment practices across Sub-Saharan Africa, as reflected in consistently strong prescribing and dispensing performance, critical program and health-system weaknesses persisted. Poor performance in adherence monitoring, treatment continuity, ARV stock continuity, viral load monitoring, and patient follow-up systems was reported across multiple countries and reporting periods, suggesting that ART scale-up was not consistently matched by equivalent system strengthening. Reported challenges evolved from early ART access and continuity-of-care constraints to broader laboratory, information-system, and program sustainability challenges, yet poor EWI performance persisted across successive reporting periods.