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 - Funding Information:
We thank Elliot Raizes, Marco Vitoria, Nathan Ford, Meg Doherty, George Siberry, David Ripin, Lisa Nelson, Juliana da Silva, Carolyn Amole, Geoff Garnett, and Peter Ehrenkranz for their helpful advice. Our computing resource was legion@ucl. JDL is supported by Danish National Research Foundation. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the authors’ institutions.
Publisher Copyright:
© 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license
PY - 2019/2/1
Y1 - 2019/2/1
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
UR - http://www.scopus.com/inward/record.url?scp=85060946095&partnerID=8YFLogxK
U2 - 10.1016/S2352-3018(18)30317-5
DO - 10.1016/S2352-3018(18)30317-5
M3 - Article
C2 - 30503325
AN - SCOPUS:85060946095
SN - 0140-6736
VL - 6
SP - e116-e127
JO - The Lancet HIV
JF - The Lancet HIV
IS - 2
ER -