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

Andrew N. Phillips, Valentina Cambiano, Fumiyo Nakagawa, Paul Revill, Michael R. Jordan, Timothy B. Hallett, Meg Caroline Doherty, Andrea De Luca, Jens D. Lundgren, Mutsa Mhangara, Tsitsi Apollo, John Mellors, Brooke Nichols, Urvi Parikh, Deenan Pillay, Tobias Rinke de Wit, Kim Sigaloff, Diane Havlir, Daniel R. Kuritzkes, Anton PozniakDavid van de Vijver, Marco Vitoria, Mark A. Wainberg, Elliot Raizes, Silvia Bertagnolio

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
JournalThe Lancet HIV
DOIs
StateAccepted/In press - Jan 1 2017
Externally publishedYes

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Reverse Transcriptase Inhibitors
Africa South of the Sahara
Public Policy
Health Policy
Drug Resistance
Cost-Benefit Analysis
Public Health
efavirenz
HIV
Therapeutics
Costs and Cost Analysis
Health Transition
Information Storage and Retrieval
Insurance Benefits
Protease Inhibitors
Mutation
dolutegravir

ASJC Scopus subject areas

  • Epidemiology
  • Immunology
  • Infectious Diseases
  • Virology

Cite this

Cost-effectiveness of public-health policy options in the presence of pretreatment NNRTI drug resistance in sub-Saharan Africa : A modelling study. / Phillips, Andrew N.; Cambiano, Valentina; Nakagawa, Fumiyo; Revill, Paul; Jordan, Michael R.; Hallett, Timothy B.; Doherty, Meg Caroline; De Luca, Andrea; Lundgren, Jens D.; Mhangara, Mutsa; Apollo, Tsitsi; Mellors, John; Nichols, Brooke; Parikh, Urvi; Pillay, Deenan; Rinke de Wit, Tobias; Sigaloff, Kim; Havlir, Diane; Kuritzkes, Daniel R.; Pozniak, Anton; van de Vijver, David; Vitoria, Marco; Wainberg, Mark A.; Raizes, Elliot; Bertagnolio, Silvia.

In: The Lancet HIV, 01.01.2017.

Research output: Contribution to journalArticle

Phillips, AN, Cambiano, V, Nakagawa, F, Revill, P, Jordan, MR, Hallett, TB, Doherty, MC, De Luca, A, Lundgren, JD, Mhangara, M, Apollo, T, Mellors, J, Nichols, B, Parikh, U, Pillay, D, Rinke de Wit, T, Sigaloff, K, Havlir, D, Kuritzkes, DR, Pozniak, A, van de Vijver, D, Vitoria, M, Wainberg, MA, Raizes, E & Bertagnolio, S 2017, 'Cost-effectiveness of public-health policy options in the presence of pretreatment NNRTI drug resistance in sub-Saharan Africa: A modelling study', The Lancet HIV. https://doi.org/10.1016/S2352-3018(17)30190-X
Phillips, Andrew N. ; Cambiano, Valentina ; Nakagawa, Fumiyo ; Revill, Paul ; Jordan, Michael R. ; Hallett, Timothy B. ; Doherty, Meg Caroline ; De Luca, Andrea ; Lundgren, Jens D. ; Mhangara, Mutsa ; Apollo, Tsitsi ; Mellors, John ; Nichols, Brooke ; Parikh, Urvi ; Pillay, Deenan ; Rinke de Wit, Tobias ; Sigaloff, Kim ; Havlir, Diane ; Kuritzkes, Daniel R. ; Pozniak, Anton ; van de Vijver, David ; Vitoria, Marco ; Wainberg, Mark A. ; Raizes, Elliot ; Bertagnolio, Silvia. / Cost-effectiveness of public-health policy options in the presence of pretreatment NNRTI drug resistance in sub-Saharan Africa : A modelling study. In: The Lancet HIV. 2017.
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T1 - Cost-effectiveness of public-health policy options in the presence of pretreatment NNRTI drug resistance in sub-Saharan Africa

T2 - A modelling study

AU - Phillips, Andrew N.

AU - Cambiano, Valentina

AU - Nakagawa, Fumiyo

AU - Revill, Paul

AU - Jordan, Michael R.

AU - Hallett, Timothy B.

AU - Doherty, Meg Caroline

AU - De Luca, Andrea

AU - Lundgren, Jens D.

AU - Mhangara, Mutsa

AU - Apollo, Tsitsi

AU - Mellors, John

AU - Nichols, Brooke

AU - Parikh, Urvi

AU - Pillay, Deenan

AU - Rinke de Wit, Tobias

AU - Sigaloff, Kim

AU - Havlir, Diane

AU - Kuritzkes, Daniel R.

AU - Pozniak, Anton

AU - van de Vijver, David

AU - Vitoria, Marco

AU - Wainberg, Mark A.

AU - Raizes, Elliot

AU - Bertagnolio, Silvia

PY - 2017/1/1

Y1 - 2017/1/1

N2 - 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.

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