What leads to treatment failure among people living with HIV: first systematic review from the middle east and North Africa.

backgroundWhile antiretroviral therapy (ART) has significantly improved human immunodeficiency virus (HIV) outcomes globally, some individuals experience treatment failure (TF). Data on TF rates and determinants in the Middle East and North Africa (MENA) region are limited.

methodsFor the first time, a systematic review following PRISMA guidelines was conducted to synthesize evidence on TF from MENA countries. Electronic databases were searched from inception to May 2025. Studies reporting quantitative TF data among people living with HIV (PLWH) on ART in MENA were included. Failure was evaluated on the basis of virological, immunological, and/or clinical criteria. The protocol was registered in PROSPERO with the ID CRD420251050407.

resultsForty-one studies representing 24,019 individuals in 12 countries between 2003 and 2025 were included. The majority were from Morocco, Turkey, Oman, Iran, and Ethiopia. Standard first-line ART includes two nucleoside reverse transcriptase inhibitors with a nonnucleoside reverse transcriptase inhibitor or protease inhibitor. Virological failure rates range widely from 21.5 to 85.6% on the basis of different viral load thresholds. The prevalence of drug resistance varied from 48 to 86%. Factors associated with a greater risk of failure included younger age, male sex, higher baseline viral load, lower CD4 count, poor adherence, receiving care outside major cities, age > 40, unemployment, sexual transmission, and antituberculosis therapy coadministration.

conclusionsThis comprehensive review is the first to provide insights into patterns of ART responses across the MENA region over 20 years. Research has revealed wide variation in reported virological failure rates, mainly due to factors such as high baseline viral load, low CD4 count, and reduced adherence to medications, highlighting the urgent need for standardized outcome definitions and more stringent viral suppression thresholds to monitor rates properly and evaluate interventions. Notably, this robust study encompassing over two decades is the most extensive examination of ART responses in MENA to date, offering novel population-level insights with important implications for optimizing first-line regimens, targeting healthcare resources, informing regional collaborative strategies, and establishing modifiable risk factors to guide future research aimed improving HIV care and clinical outcomes across this underrepresented region. Prospective research standardizing outcomes is needed to elucidate modifiable causes of TF and how addressing barriers with optimized strategies can bolster HIV outcomes in MENA. Policymakers must coordinate multilevel efforts prioritizing expanded access to care, enhanced adherence support, optimized regimens including integrase inhibitors as first-line therapy, standardized monitoring, and regional collaborations to strengthen HIV treatment outcomes across the MENA region.