Risks and benefits of dolutegravir-based antiretroviral drug regimens in sub-Saharan Africa: a modelling study

TY - JOUR

T1 - Risks and benefits of dolutegravir-based antiretroviral drug regimens in sub-Saharan Africa

T2 - a modelling study

AU - Phillips, Andrew N

AU - Venter, Francois

AU - Havlir, Diane

AU - Pozniak, Anton

AU - Kuritzkes, Daniel

AU - Wensing, Annemarie

AU - Lundgren, Jens D

AU - De Luca, Andrea

AU - Pillay, Deenan

AU - Mellors, John

AU - Cambiano, Valentina

AU - Bansi-Matharu, Loveleen

AU - Nakagawa, Fumiyo

AU - Kalua, Thokozani

AU - Jahn, Andreas

AU - Apollo, Tsitsi

AU - Mugurungi, Owen

AU - Clayden, Polly

AU - Gupta, Ravindra K

AU - Barnabas, Ruanne

AU - Revill, Paul

AU - Cohn, Jennifer

AU - Bertagnolio, Silvia

AU - Calmy, Alexandra

N1 - Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

PY - 2019/2

Y1 - 2019/2

N2 - BACKGROUND: The integrase inhibitor dolutegravir could have a major role in future antiretroviral therapy (ART) regimens in sub-Saharan Africa because of its high potency and barrier to resistance, good tolerability, and low cost, but there is uncertainty over appropriate policies for use relating to the potential for drug resistance spread and a possible increased risk of neural tube defects in infants if used in women at the time of conception. We used an existing individual-based model of HIV transmission, progression, and the effect of ART with the aim of informing policy makers on approaches to the use of dolutegravir that are likely to lead to the highest population health gains.METHODS: We used an existing individual-based model of HIV transmission and progression in adults, which takes into account the effects of drug resistance and differential drug potency in determining viral suppression and clinical outcomes to compare predicted outcomes of alternative ART regimen policies. We calculated disability adjusted life-years (DALYs) for each policy, assuming that a woman having a child with a neural tube defect incurs an extra DALY per year for the remainder of the time horizon and accounting for mother-to-child transmission. We used a 20 year time horizon, a 3% discount rate, and a cost-effectiveness threshold of US$500 per DALY averted.FINDINGS: The greatest number of DALYs is predicted to be averted with use of a policy in which tenofovir, lamivudine, and dolutegravir is used in all people on ART, including switching to tenofovir, lamivudine, and dolutegravir in those currently on ART, regardless of current viral load suppression and intention to have (more) children. This result was consistent in several sensitivity analyses. We predict that this policy would be cost-saving.INTERPRETATION: Using a standard DALY framework to compare health outcomes from a public health perspective, the benefits of transition to tenofovir, lamivudine, and dolutegravir for all substantially outweighed the risks.FUNDING: Bill & Melinda Gates Foundation.

AB - BACKGROUND: The integrase inhibitor dolutegravir could have a major role in future antiretroviral therapy (ART) regimens in sub-Saharan Africa because of its high potency and barrier to resistance, good tolerability, and low cost, but there is uncertainty over appropriate policies for use relating to the potential for drug resistance spread and a possible increased risk of neural tube defects in infants if used in women at the time of conception. We used an existing individual-based model of HIV transmission, progression, and the effect of ART with the aim of informing policy makers on approaches to the use of dolutegravir that are likely to lead to the highest population health gains.METHODS: We used an existing individual-based model of HIV transmission and progression in adults, which takes into account the effects of drug resistance and differential drug potency in determining viral suppression and clinical outcomes to compare predicted outcomes of alternative ART regimen policies. We calculated disability adjusted life-years (DALYs) for each policy, assuming that a woman having a child with a neural tube defect incurs an extra DALY per year for the remainder of the time horizon and accounting for mother-to-child transmission. We used a 20 year time horizon, a 3% discount rate, and a cost-effectiveness threshold of US$500 per DALY averted.FINDINGS: The greatest number of DALYs is predicted to be averted with use of a policy in which tenofovir, lamivudine, and dolutegravir is used in all people on ART, including switching to tenofovir, lamivudine, and dolutegravir in those currently on ART, regardless of current viral load suppression and intention to have (more) children. This result was consistent in several sensitivity analyses. We predict that this policy would be cost-saving.INTERPRETATION: Using a standard DALY framework to compare health outcomes from a public health perspective, the benefits of transition to tenofovir, lamivudine, and dolutegravir for all substantially outweighed the risks.FUNDING: Bill & Melinda Gates Foundation.

KW - Adolescent

KW - Adult

KW - Africa South of the Sahara

KW - Antiretroviral Therapy, Highly Active/methods

KW - Developmental Disabilities/chemically induced

KW - Drug Resistance, Viral

KW - Female

KW - HIV Infections/drug therapy

KW - HIV Integrase Inhibitors/adverse effects

KW - Heterocyclic Compounds, 3-Ring/adverse effects

KW - Humans

KW - Male

KW - Middle Aged

KW - Pregnancy

KW - Risk Assessment

KW - Sustained Virologic Response

KW - Treatment Outcome

KW - Viral Load

KW - Young Adult

U2 - 10.1016/S2352-3018(18)30317-5

DO - 10.1016/S2352-3018(18)30317-5

M3 - Journal article

C2 - 30503325

SN - 2352-3018

VL - 6

SP - e116-e127

JO - The Lancet HIV

JF - The Lancet HIV

IS - 2

ER -