The World Health Organization recommends drug resistance surveillance in people initiating antiretroviral therapy (ART). If high levels of pre-ART non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance are identified, options for ART program response must be considered. One possible option is to transition from efavirenz to dolutegravir, which is associated with a lower rate of resistance acquisition and greater tolerability.
We used an individual-based model of HIV transmission and the effect of ART which considers specific drugs and resistance mutations (HIV Synthesis Model). Multiple potential epidemics/ART programs (setting scenarios) were generated through simulation, informed by data from sub-Saharan Africa. Parameters relating to ART adherence and interruption rate, ART monitoring strategy, and switch rate to a 2nd-line regimen after 1st-line failure were varied randomly within bounds reflecting data from the region. For each setting scenario, if the pre-ART resistance in 2016 was >10% we compared outcomes of potential policy options (Table) over 2016-2036 (20 yr time horizon). Costs of all aspects of HIV testing and care included, dolutegravir cost $44, efavirenz $38, cost effectiveness threshold $500, health systems perspective, 3% discount rate.
In over 2000 setting scenarios median HIV prevalence was 8% (5%-95% 5-17), 62% of HIV+ people were on ART (90% range 44-76), and 20% of ART initiators had prior drug exposure (90% range 9-34). Of ART initiators without / with prior ARV exposure the % with NNRTI resistance in majority virus was 9% (2-20) / 16% (5-34). As shown in the Table, a policy of transitioning from efavirenz to dolutegravir for all on 1st-line ART was predicted to lead to improved health outcomes and was cost effective (incremental cost effectiveness ratio (ICER) $80 per disability adjusted life year (DALY) averted). Conclusions were consistent in sensitivity analyses including a dolutegravir cost of $80/year. Updated results will be presented considering a wider range of policy options and extended sensitivity analyses.
A future transition from efavirenz to dolutegravir may be cost effective in low income settings in sub-Saharan Africa. The level of pre-ART NNRTI drug resistance will be just one factor to consider when estimating the potential impact of this transition. Further studies, such as stepped-wedge trials, should be conducted to understand the real-life impact of such a transition.