Predicted effects of the introduction of long-acting injectable cabotegravir pre-exposure prophylaxis in sub-Saharan Africa: a modelling study
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Predicted effects of the introduction of long-acting injectable cabotegravir pre-exposure prophylaxis in sub-Saharan Africa : a modelling study. / Smith, Jennifer; Bansi-Matharu, Loveleen; Cambiano, Valentina; Dimitrov, Dobromir; Bershteyn, Anna; van de Vijver, David; Kripke, Katharine; Revill, Paul; Boily, Marie-Claude; Meyer-Rath, Gesine; Taramusi, Isaac; Lundgren, Jens D; van Oosterhout, Joep J; Kuritzkes, Daniel; Schaefer, Robin; Siedner, Mark J; Schapiro, Jonathan; Delany-Moretlwe, Sinead; Landovitz, Raphael J; Flexner, Charles; Jordan, Michael; Venter, Francois; Radebe, Mopo; Ripin, David; Jenkins, Sarah; Resar, Danielle; Amole, Carolyn; Shahmanesh, Maryam; Gupta, Ravindra K; Raizes, Elliot; Johnson, Cheryl; Inzaule, Seth; Shafer, Robert; Warren, Mitchell; Stansfield, Sarah; Paredes, Roger; Phillips, Andrew N; HIV Modelling Consortium.
In: The lancet. HIV, Vol. 10, No. 4, 2023, p. e254-e265.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Predicted effects of the introduction of long-acting injectable cabotegravir pre-exposure prophylaxis in sub-Saharan Africa
T2 - a modelling study
AU - Smith, Jennifer
AU - Bansi-Matharu, Loveleen
AU - Cambiano, Valentina
AU - Dimitrov, Dobromir
AU - Bershteyn, Anna
AU - van de Vijver, David
AU - Kripke, Katharine
AU - Revill, Paul
AU - Boily, Marie-Claude
AU - Meyer-Rath, Gesine
AU - Taramusi, Isaac
AU - Lundgren, Jens D
AU - van Oosterhout, Joep J
AU - Kuritzkes, Daniel
AU - Schaefer, Robin
AU - Siedner, Mark J
AU - Schapiro, Jonathan
AU - Delany-Moretlwe, Sinead
AU - Landovitz, Raphael J
AU - Flexner, Charles
AU - Jordan, Michael
AU - Venter, Francois
AU - Radebe, Mopo
AU - Ripin, David
AU - Jenkins, Sarah
AU - Resar, Danielle
AU - Amole, Carolyn
AU - Shahmanesh, Maryam
AU - Gupta, Ravindra K
AU - Raizes, Elliot
AU - Johnson, Cheryl
AU - Inzaule, Seth
AU - Shafer, Robert
AU - Warren, Mitchell
AU - Stansfield, Sarah
AU - Paredes, Roger
AU - Phillips, Andrew N
AU - HIV Modelling Consortium
N1 - Copyright © 2023 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 - 2023
Y1 - 2023
N2 - BACKGROUND: Long-acting injectable cabotegravir pre-exposure prophylaxis (PrEP) is recommended by WHO as an additional option for HIV prevention in sub-Saharan Africa, but there is concern that its introduction could lead to an increase in integrase-inhibitor resistance undermining treatment programmes that rely on dolutegravir. We aimed to project the health benefits and risks of cabotegravir-PrEP introduction in settings in sub-Saharan Africa.METHODS: With HIV Synthesis, an individual-based HIV model, we simulated 1000 setting-scenarios reflecting both variability and uncertainty about HIV epidemics in sub-Saharan Africa and compared outcomes for each with and without cabotegravir-PrEP introduction. PrEP use is assumed to be risk-informed and to be used only in 3-month periods (the time step for the model) when having condomless sex. We consider three groups at risk of integrase-inhibitor resistance emergence: people who start cabotegravir-PrEP after (unknowingly) being infected with HIV, those who seroconvert while on PrEP, and those with HIV who have residual cabotegravir drugs concentrations during the early tail period after recently stopping PrEP. We projected the outcomes of policies of cabotegravir-PrEP introduction and of no introduction in 2022 across 50 years. In 50% of setting-scenarios we considered that more sensitive nucleic-acid-based HIV diagnostic testing (NAT), rather than regular antibody-based HIV rapid testing, might be used to reduce resistance risk. For cost-effectiveness analysis we assumed in our base case a cost of cabotegravir-PrEP drug to be similar to oral PrEP, resulting in a total annual cost of USD$144 per year ($114 per year and $264 per year considered in sensitivity analyses), a cost-effectiveness threshold of $500 per disability-adjusted life years averted, and a discount rate of 3% per year.FINDINGS: Reflecting our assumptions on the appeal of cabotegravir-PrEP, its introduction is predicted to lead to a substantial increase in PrEP use with approximately 2·6% of the adult population (and 46% of those with a current indication for PrEP) receiving PrEP compared with 1·5% (28%) without cabotegravir-PrEP introduction across 20 years. As a result, HIV incidence is expected to be lower by 29% (90% range across setting-scenarios 6-52%) across the same period compared with no introduction of cabotegravir-PrEP. In people initiating antiretroviral therapy, the proportion with integrase-inhibitor resistance after 20 years is projected to be 1·7% (0-6·4%) without cabotegravir-PrEP introduction but 13·1% (4·1-30·9%) with. Cabotegravir-PrEP introduction is predicted to lower the proportion of all people on antiretroviral therapy with viral loads less than 1000 copies per mL by 0·9% (-2·5% to 0·3%) at 20 years. For an adult population of 10 million an overall decrease in number of AIDS deaths of about 4540 per year (-13 000 to -300) across 50 years is predicted, with little discernible benefit with NAT when compared with standard antibody-based rapid testing. AIDS deaths are predicted to be averted with cabotegravir-PrEP introduction in 99% of setting-scenarios. Across the 50-year time horizon, overall HIV programme costs are predicted to be similar regardless of whether cabotegravir-PrEP is introduced (total mean discounted annual HIV programme costs per year across 50 years is $151·3 million vs $150·7 million), assuming the use of standard antibody testing. With antibody-based rapid HIV testing, the introduction of cabotegravir-PrEP is predicted to be cost-effective under an assumed threshold of $500 per disability-adjusted life year averted in 82% of setting-scenarios at the cost of $144 per year, in 52% at $264, and in 87% at $114.INTERPRETATION: Despite leading to increases in integrase-inhibitor drug resistance, cabotegravir-PrEP introduction is likely to reduce AIDS deaths in addition to HIV incidence. Long-acting cabotegravir-PrEP is predicted to be cost-effective if delivered at similar cost to oral PrEP with antibody-based rapid HIV testing.FUNDING: Bill & Melinda Gates Foundation, National Institute of Allergy and Infectious Diseases of the National Institutes of Health.
AB - BACKGROUND: Long-acting injectable cabotegravir pre-exposure prophylaxis (PrEP) is recommended by WHO as an additional option for HIV prevention in sub-Saharan Africa, but there is concern that its introduction could lead to an increase in integrase-inhibitor resistance undermining treatment programmes that rely on dolutegravir. We aimed to project the health benefits and risks of cabotegravir-PrEP introduction in settings in sub-Saharan Africa.METHODS: With HIV Synthesis, an individual-based HIV model, we simulated 1000 setting-scenarios reflecting both variability and uncertainty about HIV epidemics in sub-Saharan Africa and compared outcomes for each with and without cabotegravir-PrEP introduction. PrEP use is assumed to be risk-informed and to be used only in 3-month periods (the time step for the model) when having condomless sex. We consider three groups at risk of integrase-inhibitor resistance emergence: people who start cabotegravir-PrEP after (unknowingly) being infected with HIV, those who seroconvert while on PrEP, and those with HIV who have residual cabotegravir drugs concentrations during the early tail period after recently stopping PrEP. We projected the outcomes of policies of cabotegravir-PrEP introduction and of no introduction in 2022 across 50 years. In 50% of setting-scenarios we considered that more sensitive nucleic-acid-based HIV diagnostic testing (NAT), rather than regular antibody-based HIV rapid testing, might be used to reduce resistance risk. For cost-effectiveness analysis we assumed in our base case a cost of cabotegravir-PrEP drug to be similar to oral PrEP, resulting in a total annual cost of USD$144 per year ($114 per year and $264 per year considered in sensitivity analyses), a cost-effectiveness threshold of $500 per disability-adjusted life years averted, and a discount rate of 3% per year.FINDINGS: Reflecting our assumptions on the appeal of cabotegravir-PrEP, its introduction is predicted to lead to a substantial increase in PrEP use with approximately 2·6% of the adult population (and 46% of those with a current indication for PrEP) receiving PrEP compared with 1·5% (28%) without cabotegravir-PrEP introduction across 20 years. As a result, HIV incidence is expected to be lower by 29% (90% range across setting-scenarios 6-52%) across the same period compared with no introduction of cabotegravir-PrEP. In people initiating antiretroviral therapy, the proportion with integrase-inhibitor resistance after 20 years is projected to be 1·7% (0-6·4%) without cabotegravir-PrEP introduction but 13·1% (4·1-30·9%) with. Cabotegravir-PrEP introduction is predicted to lower the proportion of all people on antiretroviral therapy with viral loads less than 1000 copies per mL by 0·9% (-2·5% to 0·3%) at 20 years. For an adult population of 10 million an overall decrease in number of AIDS deaths of about 4540 per year (-13 000 to -300) across 50 years is predicted, with little discernible benefit with NAT when compared with standard antibody-based rapid testing. AIDS deaths are predicted to be averted with cabotegravir-PrEP introduction in 99% of setting-scenarios. Across the 50-year time horizon, overall HIV programme costs are predicted to be similar regardless of whether cabotegravir-PrEP is introduced (total mean discounted annual HIV programme costs per year across 50 years is $151·3 million vs $150·7 million), assuming the use of standard antibody testing. With antibody-based rapid HIV testing, the introduction of cabotegravir-PrEP is predicted to be cost-effective under an assumed threshold of $500 per disability-adjusted life year averted in 82% of setting-scenarios at the cost of $144 per year, in 52% at $264, and in 87% at $114.INTERPRETATION: Despite leading to increases in integrase-inhibitor drug resistance, cabotegravir-PrEP introduction is likely to reduce AIDS deaths in addition to HIV incidence. Long-acting cabotegravir-PrEP is predicted to be cost-effective if delivered at similar cost to oral PrEP with antibody-based rapid HIV testing.FUNDING: Bill & Melinda Gates Foundation, National Institute of Allergy and Infectious Diseases of the National Institutes of Health.
KW - Adult
KW - Humans
KW - HIV Infections/drug therapy
KW - Pre-Exposure Prophylaxis/methods
KW - Acquired Immunodeficiency Syndrome/drug therapy
KW - Cost-Benefit Analysis
KW - HIV Integrase Inhibitors/pharmacology
KW - Integrases/therapeutic use
KW - Anti-HIV Agents
U2 - 10.1016/S2352-3018(22)00365-4
DO - 10.1016/S2352-3018(22)00365-4
M3 - Journal article
C2 - 36642087
VL - 10
SP - e254-e265
JO - The Lancet HIV
JF - The Lancet HIV
SN - 2352-3018
IS - 4
ER -
ID: 387089513