Cost-effectiveness of public-health policy options in the presence of pretreatment NNRTI drug resistance in sub-Saharan Africa: a modelling study

Abstract

SummaryBackgroundThere is concern over increasing prevalence of non-nucleoside reverse-transcriptase inhibitor (NNRTI) resistance in people initiating antiretroviral therapy (ART) in low-income and middle-income countries. We assessed the effectiveness and cost-effectiveness of alternative public health responses in countries in sub-Saharan Africa where the prevalence of pretreatment drug resistance to NNRTIs is high.MethodsThe HIV Synthesis Model is an individual-based simulation model of sexual HIV transmission, progression, and the effect of ART in adults, which is based on extensive published data sources and considers specific drugs and resistance mutations. We used this model to generate multiple setting scenarios mimicking those in sub-Saharan Africa and considered the prevalence of pretreatment NNRTI drug resistance in 2017. We then compared effectiveness and cost-effectiveness of alternative policy options. We took a 20 year time horizon, used a cost effectiveness threshold of US$500 per DALY averted, and discounted DALYs and costs at 3% per year.FindingsA transition to use of a dolutegravir as a first-line regimen in all new ART initiators is the option predicted to produce the most health benefits, resulting in a reduction of about 1 death per year per 100 people on ART over the next 20 years in a situation in which more than 10% of ART initiators have NNRTI resistance. The negative effect on population health of postponing the transition to dolutegravir increases substantially with higher prevalence of HIV drug resistance to NNRTI in ART initiators. Because of the reduced risk of resistance acquisition with dolutegravir-based regimens and reduced use of expensive second-line boosted protease inhibitor regimens, this policy option is also predicted to lead to a reduction of overall programme cost.InterpretationA future transition from first-line regimens containing efavirenz to regimens containing dolutegravir formulations in adult ART initiators is predicted to be effective and cost-effective in low-income settings in sub-Saharan Africa at any prevalence of pre-ART NNRTI resistance. The urgency of the transition will depend largely on the country-specific prevalence of NNRTI resistance.FundingBill & Melinda Gates Foundation, World Health Organization.

Effectiveness of dolutegravir‐based regimens as either first‐line or switch antiretroviral therapy: data from the Icona cohort

“…Despite the differences in healthcare setting and HIV epidemiology, our data might add reassuring information in the light of the forthcoming broad use of DTG‐based first‐line therapies in middle‐ and low‐income countries after the recent update of WHO guidelines recommendations . Although DTG rollout in resource‐limited countries is predicted to be not only effective but also cost‐effective, particularly in view of the increasing prevalence of pretreatment NNRTI resistance , several questions on DTG safety remain to be addressed, particularly in special sub‐populations as severely immunocompromised patients and pregnant women . In this latter group, surveillance data from Botswana cohort have recently reported potential risk of neural tube defects in infants born to women who were taking DTG at the time of conception , leading to the release of a safety alert on DTG use in pregnancy .…”

90‐90‐90 by 2020? Estimation and projection of the adult HIV epidemic and ART programme in Zimbabwe – 2017 to 2020

“…Adherence counselling and efforts to increase testing have, and are currently taking place but continued effort in these areas is needed to ensure transmitted drug resistance does not become an issue that is unable to be effectively addressed. WHO guidelines have changed the national first line ART regimen in new initiators to be dolutegravir, rather than efavirenz, containing in countries with pre‐ART NNRTI resistance >10% 20, and it is predicted this change would be both effective and cost‐effective 21. The Zimbabwe treatment guidelines have not yet incorporated this change 16.…”

Strengthening the scale‐up and uptake of effective interventions for sex workers for population impact in Zimbabwe

“…The HIV Synthesis model has been used to assess (potential) effectiveness and/or cost effectiveness of a range of interventions in SSA, including HIV self‐testing , a vaccine , a cure , ART monitoring and drug resistance testing . It is an individual‐based model of HIV transmission, progression and the effect of ART in adults.…”