High Virologic Suppression and Favorable Profiles of Two‐Drug Antiretroviral Regimens in Africa: A Systematic Review of Current Evidence

HIV remains a major public health challenge, with Africa bearing over two‐thirds of the global burden. While three‐drug antiretroviral therapy (ART) is the standard of care, emerging evidence suggests that two‐drug regimens (2DRs) may offer comparable efficacy with reduced toxicity and cost. However, data on their use in African populations are limited. This systematic review assessed outcomes of 2DRs compared to other ART regimens among adults in Africa, following PRISMA guidelines. A comprehensive search of PubMed, Scopus, Web of Science, Embase, and African Journals Online was conducted for English‐language studies published from 2015 onwards. Eligible studies included adult HIV patients in Africa comparing 2DRs with other ART regimens, reporting outcomes such as viral suppression, drug resistance, adherence, safety, and toxicity. Five randomized, open‐label phase III trials were included, all conducted across multiple countries with African sites. Four (80%) were non‐inferiority trials involving virologically suppressed or ART‐naïve adults. Regimens included dolutegravir‐based (40%) and long‐acting injectable cabotegravir+rilpivirine (CAB+RPV) (60%). Virological suppression (<50 copies/mL) was achieved in 80% of studies over 24–144 weeks, with stable or improved CD4+ counts in 60%. Injection‐site reactions occurred in 40% of trials; adverse effects with dolutegravir ranged from 6 to 20%, while CAB + RPV showed high adherence (97–98%) but injection‐site reactions (75–86%). Non‐inferiority was confirmed in 60% of studies, with strong patient preference for injectables reported in 40%. Limitations included short follow‐up, lack of blinding (80%), and potential selection bias (40%). Two‐drug ART regimens appear effective and well‐tolerated in African settings, warranting further high‐quality, long‐term studies.