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Updated assessment of risks and benefits of dolutegravir versus efavirenz in new antiretroviral treatment initiators in sub-Saharan Africa: modelling to inform treatment guidelines.
Lancet HIV. 2020 03; 7(3):e193-e200.LH

Abstract

BACKGROUND

The integrase inhibitor dolutegravir is being considered in several countries in sub-Saharan Africa instead of efavirenz for people initiating antiretroviral therapy (ART) because of superior tolerability and a lower risk of resistance emergence. WHO requested updated modelling results for its 2019 Antiretroviral Guidelines update, which was restricted to the choice of dolutegravir or efavirenz in new ART initiators. In response to this request, we modelled the risks and benefits of alternative policies for initial first-line ART regimens.

METHODS

We updated an existing individual-based model of HIV transmission and progression in adults to consider information on the risk of neural tube defects in women taking dolutegravir at time of conception, as well as the effects of dolutegravir on weight gain. The model accounted for drug resistance in determining viral suppression, with consequences for clinical outcomes and mother-to-child transmission. We sampled distributions of parameters to create various epidemic setting scenarios, which reflected the diversity of epidemic and programmatic situations in sub-Saharan Africa. For each setting scenario, we considered the situation in 2018 and compared ART initiation policies of an efavirenz-based regimen in women intending pregnancy, and a dolutegravir-based regimen in others, and a dolutegravir-based regimen, including in women intending pregnancy. We considered predicted outcomes over a 20-year period from 2019 to 2039, used a 3% discount rate, and a cost-effectiveness threshold of US$500 per disability-adjusted life-year (DALY) averted.

FINDINGS

Considering updated information on risks and benefits, a policy of ART initiation with a dolutegravir-based regimen rather than an efavirenz-based regimen, including in women intending pregnancy, is predicted to bring population health benefits (10 990 DALYs averted per year) and to be cost-saving (by $2·9 million per year), leading to a reduction in the overall population burden of disease of 16 735 net DALYs per year for a country with an adult population size of 10 million. The policy involving ART initiation with a dolutegravir-based regimen in women intending pregnancy was cost-effective in 87% of our setting scenarios and this finding was robust in various sensitivity analyses, including around the potential negative effects of weight gain.

INTERPRETATION

In the context of a range of modelled setting scenarios in sub-Saharan Africa, we found that a policy of ART initiation with a dolutegravir-based regimen, including in women intending pregnancy, was predicted to bring population health benefits and be cost-effective, supporting WHO's strong recommendation for dolutegravir as a preferred drug for ART initiators.

FUNDING

Bill & Melinda Gates Foundation.

Authors+Show Affiliations

Institute for Global Health, University College London, London, UK. Electronic address: andrew.phillips@ucl.ac.uk.Institute for Global Health, University College London, London, UK.Ezintsha, Wits Reproductive Health and HIV Institute, University of the Witwatersrand, Johannesburg, South Africa.School of Medicine, University of California San Francisco, San Francisco, CA, USA.Chelsea and Westminster Hospital, London, UK; London School of Hygiene & Tropical Medicine, London, UK.Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.Ezintsha, Wits Reproductive Health and HIV Institute, University of the Witwatersrand, Johannesburg, South Africa; University Medical Center Utrecht, Utrecht, Netherlands.Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.Africa Health Research Institute, Mtubatuba, South Africa.Department of Medicine, Division of Infectious Diseases, University of Pittsburgh, Pittsburgh, PN, USA.Institute for Global Health, University College London, London, UK.Ministry of Health, Lilongwe, Malawi.Ministry of Health and Child Care, Harare, Zimbabwe.Ministry of Health and Child Care, Harare, Zimbabwe.Clinton Health Access Initiative, New York, NY, USA.Centers for Disease Control and Prevention, Atlanta, GA, USA.Centers for Disease Control and Prevention, Atlanta, GA, USA.Centre for Infectious Disease Epidemiology and Research, University of Cape Town, Cape Town, South Africa; WHO, Geneva, Switzerland.Office of HIV/AIDS, Global Health Bureau, United States Agency for International Development, Arlington, VA, USA.Cambridge Institute of Immunology and Infectious Diseases, University of Cambridge, Cambridge, UK.Department of Global Health, University of Washington, Seattle, WA, USA.Centre for Health Economics, University of York, York, UK.Elizabeth Glaser Paediatric Health Foundation, Washington, DC, USA.HIV/AIDS Unit, Geneva University Hospital, University of Geneva, Geneva, Switzerland.WHO, Geneva, Switzerland.

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32035041

Citation

Phillips, Andrew N., et al. "Updated Assessment of Risks and Benefits of Dolutegravir Versus Efavirenz in New Antiretroviral Treatment Initiators in sub-Saharan Africa: Modelling to Inform Treatment Guidelines." The Lancet. HIV, vol. 7, no. 3, 2020, pp. e193-e200.
Phillips AN, Bansi-Matharu L, Venter F, et al. Updated assessment of risks and benefits of dolutegravir versus efavirenz in new antiretroviral treatment initiators in sub-Saharan Africa: modelling to inform treatment guidelines. Lancet HIV. 2020;7(3):e193-e200.
Phillips, A. N., Bansi-Matharu, L., Venter, F., Havlir, D., Pozniak, A., Kuritzkes, D. R., Wensing, A., Lundgren, J. D., Pillay, D., Mellors, J., Cambiano, V., Jahn, A., Apollo, T., Mugurungi, O., Ripin, D., Da Silva, J., Raizes, E., Ford, N., Siberry, G. K., ... Bertagnolio, S. (2020). Updated assessment of risks and benefits of dolutegravir versus efavirenz in new antiretroviral treatment initiators in sub-Saharan Africa: modelling to inform treatment guidelines. The Lancet. HIV, 7(3), e193-e200. https://doi.org/10.1016/S2352-3018(19)30400-X
Phillips AN, et al. Updated Assessment of Risks and Benefits of Dolutegravir Versus Efavirenz in New Antiretroviral Treatment Initiators in sub-Saharan Africa: Modelling to Inform Treatment Guidelines. Lancet HIV. 2020;7(3):e193-e200. PubMed PMID: 32035041.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Updated assessment of risks and benefits of dolutegravir versus efavirenz in new antiretroviral treatment initiators in sub-Saharan Africa: modelling to inform treatment guidelines. AU - Phillips,Andrew N, AU - Bansi-Matharu,Loveleen, AU - Venter,Francois, AU - Havlir,Diane, AU - Pozniak,Anton, AU - Kuritzkes,Daniel R, AU - Wensing,Annemarie, AU - Lundgren,Jens D, AU - Pillay,Deenan, AU - Mellors,John, AU - Cambiano,Valentina, AU - Jahn,Andreas, AU - Apollo,Tsitsi, AU - Mugurungi,Owen, AU - Ripin,David, AU - Da Silva,Juliana, AU - Raizes,Elliot, AU - Ford,Nathan, AU - Siberry,George K, AU - Gupta,Ravindra K, AU - Barnabas,Ruanne, AU - Revill,Paul, AU - Cohn,Jennifer, AU - Calmy,Alexandra, AU - Bertagnolio,Silvia, Y1 - 2020/02/05/ PY - 2019/08/17/received PY - 2019/11/08/revised PY - 2019/11/25/accepted PY - 2020/2/9/pubmed PY - 2020/8/29/medline PY - 2020/2/9/entrez SP - e193 EP - e200 JF - The lancet. HIV JO - Lancet HIV VL - 7 IS - 3 N2 - BACKGROUND: The integrase inhibitor dolutegravir is being considered in several countries in sub-Saharan Africa instead of efavirenz for people initiating antiretroviral therapy (ART) because of superior tolerability and a lower risk of resistance emergence. WHO requested updated modelling results for its 2019 Antiretroviral Guidelines update, which was restricted to the choice of dolutegravir or efavirenz in new ART initiators. In response to this request, we modelled the risks and benefits of alternative policies for initial first-line ART regimens. METHODS: We updated an existing individual-based model of HIV transmission and progression in adults to consider information on the risk of neural tube defects in women taking dolutegravir at time of conception, as well as the effects of dolutegravir on weight gain. The model accounted for drug resistance in determining viral suppression, with consequences for clinical outcomes and mother-to-child transmission. We sampled distributions of parameters to create various epidemic setting scenarios, which reflected the diversity of epidemic and programmatic situations in sub-Saharan Africa. For each setting scenario, we considered the situation in 2018 and compared ART initiation policies of an efavirenz-based regimen in women intending pregnancy, and a dolutegravir-based regimen in others, and a dolutegravir-based regimen, including in women intending pregnancy. We considered predicted outcomes over a 20-year period from 2019 to 2039, used a 3% discount rate, and a cost-effectiveness threshold of US$500 per disability-adjusted life-year (DALY) averted. FINDINGS: Considering updated information on risks and benefits, a policy of ART initiation with a dolutegravir-based regimen rather than an efavirenz-based regimen, including in women intending pregnancy, is predicted to bring population health benefits (10 990 DALYs averted per year) and to be cost-saving (by $2·9 million per year), leading to a reduction in the overall population burden of disease of 16 735 net DALYs per year for a country with an adult population size of 10 million. The policy involving ART initiation with a dolutegravir-based regimen in women intending pregnancy was cost-effective in 87% of our setting scenarios and this finding was robust in various sensitivity analyses, including around the potential negative effects of weight gain. INTERPRETATION: In the context of a range of modelled setting scenarios in sub-Saharan Africa, we found that a policy of ART initiation with a dolutegravir-based regimen, including in women intending pregnancy, was predicted to bring population health benefits and be cost-effective, supporting WHO's strong recommendation for dolutegravir as a preferred drug for ART initiators. FUNDING: Bill & Melinda Gates Foundation. SN - 2352-3018 UR - https://www.unboundmedicine.com/medline/citation/32035041/Updated_assessment_of_risks_and_benefits_of_dolutegravir_versus_efavirenz_in_new_antiretroviral_treatment_initiators_in_sub_Saharan_Africa:_modelling_to_inform_treatment_guidelines_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S2352-3018(19)30400-X DB - PRIME DP - Unbound Medicine ER -