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

Adolescent Adult Africa South of the Sahara Antiretroviral Therapy, Highly Active / methods Developmental Disabilities / chemically induced Drug Resistance, Viral Female HIV Infections / drug therapy HIV Integrase Inhibitors / adverse effects Heterocyclic Compounds, 3-Ring / adverse effects Humans Male Middle Aged Oxazines Piperazines Pregnancy Pyridones Risk Assessment Sustained Virologic Response Treatment Outcome Viral Load Young Adult

Journal

The lancet. HIV

ISSN: 2352-3018

Titre abrégé: Lancet HIV

Pays: Netherlands

ID NLM: 101645355

Informations de publication

Date de publication:
Feb 2019

Historique:

received: 07 09 2018

revised: 15 10 2018

accepted: 24 10 2018

pubmed: 7 12 2018

medline: 18 5 2019

entrez: 4 12 2018

Statut: ppublish

Résumé

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. 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. 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. 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. Bill & Melinda Gates Foundation.

Sections du résumé

BACKGROUND BACKGROUND

METHODS 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 RESULTS

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 CONCLUSIONS

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 BACKGROUND

Bill & Melinda Gates Foundation.

Identifiants

DOI: 10.1016/S2352-3018(18)30317-5 PMID: 30503325 PMC: PMC6361866

pubmed: 30503325

pii: S2352-3018(18)30317-5

doi: 10.1016/S2352-3018(18)30317-5

pmc: PMC6361866

pii:

doi:

Substances chimiques

HIV Integrase Inhibitors 0

Heterocyclic Compounds, 3-Ring 0

Oxazines 0

Piperazines 0

Pyridones 0

dolutegravir DKO1W9H7M1

Types de publication

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

Langues

eng

Sous-ensembles de citation

Pagination

e116-e127

Subventions

Organisme : World Health Organization

ID : 001

Pays : International

Organisme : NIAID NIH HHS

ID : P30 AI027757

Pays : United States

Commentaires et corrections

Type : CommentIn

Informations de copyright

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