South Africa has observed a decline in overall HIV drug resistance, according to national surveillance data, signaling the effectiveness of current antiretroviral treatment (ART) strategies. However, the increasing prevalence of integrase strand transfer inhibitor (INSTI) resistance necessitates ongoing vigilance. The National Institute for Communicable Diseases (NICD) and the National Health Laboratory Service (NHLS) have been conducting nationally representative HIV drug resistance surveys since 2019, utilizing remnant HIV viral load samples from public health facilities.
Declining Overall Drug Resistance
The surveys, which test drug levels as a proxy for treatment exposure, reveal a promising trend. The prevalence of any drug resistance has decreased from 72% in 2019 to 54% in 2023. A similar decline was observed in non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance, dropping from 71% to 51% during the same period. Protease inhibitor (PI) resistance has remained stable, ranging from 2.2% to 4.1%.
"The observed HIVDR levels in this survey are similar to those observed before the roll-out of DTG; however, the overall prevalence of resistance appears to be declining in recent years," the NICD reported. This decline is likely driven by less frequent NRTI and NNRTI resistance observations.
Increasing INSTI Resistance
Despite the overall positive trend, INSTI resistance, while still low, has steadily increased from 0.2% in 2021 to 2.3% in 2023. Among samples with confirmed INSTI exposure, the prevalence of INSTI resistance increased from 2.7% in 2021 to 11.1% in 2022, with a slight decrease to 10.5% in 2023. This underscores the need for continued monitoring to track the development of INSTI resistance, particularly in patients with detectable dolutegravir (DTG) levels.
Treatment Adherence Challenges
A significant finding across all surveys is that drug levels were detected in less than 60% of specimens with a viral load >1,000 copies/mL, with a notable drop to 37% in 2023. This indicates that treatment failure is often due to sub-optimal treatment adherence. The proportion of samples with detectable protease inhibitor levels remained stable (4%-7%). As per changing treatment guidelines, the proportion of specimens with detectable efavirenz levels decreased from 43% in 2019 to 12% in 2023. In contrast, the proportion of specimens with detectable dolutegravir increased from 7% in 2021 to 18% in 2023.
Implications for Treatment Strategies
The observed trends have important implications for HIV treatment strategies in South Africa. The decline in overall drug resistance suggests that current strategies are effective. However, the persistence of NNRTI resistance in a substantial proportion of patients with detectable drug levels indicates that the DTG roll-out was not fully implemented by May-June 2023, despite treatment guidelines recommending the unconditional switch to TLD for most patients by May 2022.
The low prevalence of PI and INSTI resistance aligns with the high genetic barrier of lopinavir/ritonavir (LPV/r) and DTG, as well as the recent introduction of DTG at a large scale. However, the confirmation of INSTI resistance levels of around 10% in the 2022 and 2023 surveys underscores the need for continued monitoring.
Future Directions
The NICD emphasizes the importance of regular surveillance efforts to continuously monitor the possible development of DTG resistance in the population. They also suggest that drug level testing could be used to triage specimens for HIVDR testing. Further investigation is needed to address the increase in patients without any detectable drug levels, and investments could be made to improve adherence interventions.
Despite the national representativeness of the survey, the NICD cautions that results should be interpreted cautiously, given the limitations of obtaining accurate treatment regimen information. Sub-analyses should also be interpreted cautiously, as the study was not powered to compare results among different age groups or by province. Additionally, over-sampling of patients taking NNRTI-based regimens may have occurred due to potentially higher viral suppression among patients receiving DTG-based regimens.
