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

Abstract

Background: There 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.

Methods: The 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.

Findings: A 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.

Interpretation: A 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.

Funding: Bill & Melinda Gates Foundation, World Health Organization.

Figure 1

Predicted mean outcomes for 2018–38 according to policy option for setting scenarios where more than 10% of initiators have NNRTI resistance in 2017 (mean over all 3 month periods in 20 years; n=2915) Data are mean differences in percentage relative to no change in policy (95% CI; 90% range). Option 1: no change. Option 2: drug resistance tests for ART initiators with previous antiretroviral exposure. Option 3: drug resistance tests for all ART initiators. Option 4: first-line dolutegravir for people with previous ART exposure. Option 5: first-line dolutegravir for all ART initiators. (A) Mean percent with viral load <1000 copies per mL 1 year from ART initiation. (B) Mean percent of ART initiators with NNRTI resistance (NNRTI pretreatment drug resistance). (C) Mean percent of people with viral load less than 1000 copies per mL at any time after start of ART. (D) Mean mortality in people on ART. (E) Mean incidence of HIV infection. ART=antiretroviral therapy. NNRTI=non-nucleoside reverse transcriptase inhibitor.

Figure 2

Mean annual cost for 2018–38 according to policy option for setting scenarios where more than 10% of ART initiators have NNRTI resistance in 2017 Option 1: no change. Option 2: drug resistance tests for ART initiators with previous antiretroviral exposure. Option 3: drug resistance tests for all ART initiators. Option 4: first-line dolutegravir for people with previous ART exposure. Option 5: first-line dolutegravir for all ART initiators. 95% CIs are generally narrow (appendix, p 13). ART=antiretroviral therapy. NNRTI=non-nucleoside reverse transcriptase inhibitor.

Figure 3

Increment in discounted cost and discounted DALYs averted for each policy option relative to no change (option 1) in setting scenarios where more than 10% of all ART initiators have NNRTI pretreatment drug resistance in 2017 DALYs are for the whole adult population, so this takes into account reductions in new HIV infections associated with increased levels of viral suppression. First-line dolutegravir in all ART initiators is the most cost-effective policy in 90% of the 2815 setting scenarios, using a cost-effectiveness threshold of $500 per DALY averted where more than 10% of ART initiators have NNRTI pretreatment drug resistance in 2017. Incremental net DALYs shows the reduction in population burden of disease, measured in DALYs, per year of each policy compared with no change. The policy that reduces population burden of disease the most (ie, all ART initiators receive first-line dolutegravir) is cost-effective. Option 1: no change. Option 2: drug resistance tests for ART initiators with previous antiretroviral exposure (2857 net DALYs averted). Option 3: drug resistance tests for all ART initiators (22 249). Option 4: first-line dolutegravir for people with previous ART exposure (9190). Option 5: first-line dolutegravir for all ART initiators (50 669). DALYs=disability-adjusted life-years. ART=antiretroviral therapy. NNRTI=non-nucleoside reverse transcriptase inhibitor. *Discounted at 3% per annum.

Figure 4

Reductions in mortality and cost associated with use of dolutegravir in ART initiators rather than efavirenz (A) Difference in mortality (per 1000 people on ART per year) for 2018–38 when using dolutegravir in ART initiators versus continuing with efavirenz-based ART, according to proportion of all ART initiators with NNRTI resistance in 2017. 95% CIs are narrower than +/– 0·1. (B) Percentage reduction in annual costs for the policy of using dolutegravir in ART initiators versus continuing with efavirenz-based ART, according to proportion of all ART initiators with NNRTI resistance in 2017. 95% CIs are narrower than +/– 0·4. ART=antiretroviral therapy. NNRTI=non-nucleoside reverse transcriptase inhibitor.