OBJECTIVES : This review estimates prevalence of pretreatment (PDR) and acquired (ADR) HIV drug resistance in SA and Botswana and evaluates the impact of drug resistance on effectiveness of treatment.

METHODS : Using the PICOS model, multiple databases were searched for publications from 2014-2019 addressing HIV drug resistance in SA and Botswana.

RESULTS : 42 data sources met the inclusion criteria for review, only 3 of which related to Botswana. Estimated prevalence of PDR among patients living in SA and Botswana is 7.4%. The rate has increased over the years and is largely driven by Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI) resistance. About 6% of patients can have decreased susceptibility to first-generation NNRTI drugs even before treatment initiation. Most (76%) of those who fail NNRTI-based treatment have ADR to this class, prompting the introduction of integrase inhibitors and second-generation NNRTIs. INSTIs are currently recommended as a first-line treatment option but are not yet popularized in SA and Botswana. The rate of PI resistance among patients failing NNRTI is low (2%), suggesting changes in preferred options for second-line treatment are not yet necessary. Drug resistance levels among patients failing protease inhibitor (PI)-based regimens are lower than in those failing NNRTI, confirming viral variability in response to changes in drug pressure. Most patients failing PI do not demonstrate resistance to this class, indicating that in many cases inability to achieve suppression is caused by suboptimal adherence rather than resistance. The rate of resistance to third-line drugs is 23% to darunavir and 33% to etravirine. Drug resistance impacts response to treatment. Predictors of resistance is very limited and inconsistent across available studies.

CONCLUSIONS : Resistance of HIV to therapies is a concern and increasing resistance rates in SA and Botswana suggest that introduction of new drugs, particularly first-line drugs, may be helpful in treatment failure prevention.