The Impact of Scaling up Dolutegravir on Antiretroviral Resistance in South Africa

Abstract Background Rising resistance of HIV-1 to non-nucleoside reverse transcriptase inhibitors (NNRTIs) threatens the success of the global scale-up of antiretroviral therapy (ART). The switch to WHO-recommended dolutegravir (DTG)-based regimens could reduce this threat due to DTG’s high genetic barrier to resistance. We used mathematical modelling to examine the impact of the scale-up of DTG-based ART on NNRTI pre-treatment drug resistance (PDR) in South Africa, 2019-2040. Methods and results We adapted the MARISA (Modelling Antiretroviral drug Resistance In South Africa) model, an epidemiological model of the transmission of NNRTI resistance in South Africa. We modelled the introduction of DTG in 2019 under two scenarios: DTG as first-line regimen for ART-initiators, or DTG for all patients, including patients on suppressive NNRTI-based ART. Due to safety concerns related to DTG during pregnancy, we assessed the impact of prescribing DTG to all men and in addition to i) women beyond reproductive age, ii) women beyond reproductive age or using contraception, and iii) all women. The model projections show that, compared to the continuation of NNRTI-based ART, introducing DTG would lead to a reduction in NNRTI resistance in all scenarios if both ART initiators are started on a DTG-based regimens and those on NNRTI-based regimens are rapidly switched to DTG. NNRTI resistance would continue to increase if DTG-based ART was restricted to men. When given to all men and women, DTG-based ART could reduce the level of NNRTI resistance from 58.5% (without DTG) to 14.8% (with universal DTG) in 2040. If all men and women beyond reproductive age or on contraception are started on or switched to DTG-based ART, NNRTI resistance would reach 35.1% in 2040. Conclusions Our model shows the potential benefit of scaling up DTG-based regimens for halting the rise of NNRTI resistance. Starting or switching all men and women to DTG would lead to a sustained decline in resistance levels whereas using DTG-based ART in all men, or in men and women beyond childbearing age, would slow down the increase in levels of NNRTI resistance.