. 2023 Apr;10(4):e254-e265.

doi: 10.1016/S2352-3018(22)00365-4. Epub 2023 Jan 12.

Predicted effects of the introduction of long-acting injectable cabotegravir pre-exposure prophylaxis in sub-Saharan Africa: a modelling study

Jennifer Smith¹, Loveleen Bansi-Matharu¹, Valentina Cambiano¹, Dobromir Dimitrov², Anna Bershteyn³, David van de Vijver⁴, Katharine Kripke⁵, Paul Revill⁶, Marie-Claude Boily⁷, Gesine Meyer-Rath⁸, Isaac Taramusi⁹, Jens D Lundgren¹⁰, Joep J van Oosterhout¹¹, Daniel Kuritzkes¹², Robin Schaefer¹³, Mark J Siedner¹⁴, Jonathan Schapiro¹⁵, Sinead Delany-Moretlwe¹⁶, Raphael J Landovitz¹⁷, Charles Flexner¹⁸, Michael Jordan¹⁹, Francois Venter²⁰, Mopo Radebe²¹, David Ripin²², Sarah Jenkins²², Danielle Resar²², Carolyn Amole²², Maryam Shahmanesh²³, Ravindra K Gupta²⁴, Elliot Raizes²⁵, Cheryl Johnson¹³, Seth Inzaule¹³, Robert Shafer²⁶, Mitchell Warren²⁷, Sarah Stansfield²⁸, Roger Paredes²⁹, Andrew N Phillips³⁰; HIV Modelling Consortium

Affiliations

¹ Institute for Global Health, University College London, London, UK.
² Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
³ Department of Population Health, New York University Grossman School of Medicine, New York, NY, USA.
⁴ Department of Viroscience, Erasmus Medical Centre, Rotterdam, Netherlands.
⁵ Avenir Health, Takoma Park, MD, USA.
⁶ Centre for Health Economics, University of York, York, UK.
⁷ MRC Centre for Global Infectious Disease Analysis, School of Public Health, Imperial College London, London, UK.
⁸ Health Economics and Epidemiology Research Office (HE2RO), Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
⁹ National AIDS Council, Harare, Zimbabwe.
¹⁰ Department of Clinical Medicine, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
¹¹ Partners in Hope, Lilongwe, Malawi; Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
¹² Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA, USA; Department of Medicine, Harvard Medical School, Boston, MA, USA.
¹³ Global HIV, Hepatitis, and STIs Programmes, WHO, Geneva, Switzerland.
¹⁴ Department of Medicine, Harvard Medical School, Boston, MA, USA; Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA; Clinical Research Department, Africa Health Research Institute, Mtubatuba, South Africa.
¹⁵ National Hemophilia Center, Sheba Medical Center, Ramat Gan, Israel.
¹⁶ Wits RHI, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
¹⁷ Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA; Center for Clinical AIDS Research and Education, University of California, Los Angeles, CA, USA.
¹⁸ Johns Hopkins University School of Medicine and Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
¹⁹ Tufts Medical Center, Tufts University School of Medicine, Boston, MA, USA.
²⁰ Ezintsha, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
²¹ Regional Office for Africa, WHO, Gauteng, South Africa.
²² Infectious Diseases Program, Clinton Health Access Initiative, New York, NY, USA.
²³ Institute for Global Health, University College London, London, UK; Clinical Research Department, Africa Health Research Institute, Mtubatuba, South Africa.
²⁴ Clinical Research Department, Africa Health Research Institute, Mtubatuba, South Africa; Department of Medicine, University of Cambridge, Cambridge, UK.
²⁵ US Department of Health and Human Services, Centers for Disease Control, Atlanta, GA, USA.
²⁶ Department of Medicine, Stanford University, Palo Alto, CA, USA.
²⁷ AVAC, New York, NY, USA.
²⁸ Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
²⁹ Department of Infectious Diseases, Irsi Caixa Institut de Recerca de la SIDA, Barcelona, Spain.
³⁰ Institute for Global Health, University College London, London, UK. Electronic address: andrew.phillips@ucl.ac.uk.

PMID: 36642087
PMCID: PMC10065903
DOI: 10.1016/S2352-3018(22)00365-4

Predicted effects of the introduction of long-acting injectable cabotegravir pre-exposure prophylaxis in sub-Saharan Africa: a modelling study

Jennifer Smith et al. Lancet HIV. 2023 Apr.

. 2023 Apr;10(4):e254-e265.

doi: 10.1016/S2352-3018(22)00365-4. Epub 2023 Jan 12.

Authors

Affiliations

¹ Institute for Global Health, University College London, London, UK.
² Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
³ Department of Population Health, New York University Grossman School of Medicine, New York, NY, USA.
⁴ Department of Viroscience, Erasmus Medical Centre, Rotterdam, Netherlands.
⁵ Avenir Health, Takoma Park, MD, USA.
⁶ Centre for Health Economics, University of York, York, UK.
⁷ MRC Centre for Global Infectious Disease Analysis, School of Public Health, Imperial College London, London, UK.
⁸ Health Economics and Epidemiology Research Office (HE2RO), Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
⁹ National AIDS Council, Harare, Zimbabwe.
¹⁰ Department of Clinical Medicine, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
¹¹ Partners in Hope, Lilongwe, Malawi; Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
¹² Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA, USA; Department of Medicine, Harvard Medical School, Boston, MA, USA.
¹³ Global HIV, Hepatitis, and STIs Programmes, WHO, Geneva, Switzerland.
¹⁴ Department of Medicine, Harvard Medical School, Boston, MA, USA; Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA; Clinical Research Department, Africa Health Research Institute, Mtubatuba, South Africa.
¹⁵ National Hemophilia Center, Sheba Medical Center, Ramat Gan, Israel.
¹⁶ Wits RHI, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
¹⁷ Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA; Center for Clinical AIDS Research and Education, University of California, Los Angeles, CA, USA.
¹⁸ Johns Hopkins University School of Medicine and Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
¹⁹ Tufts Medical Center, Tufts University School of Medicine, Boston, MA, USA.
²⁰ Ezintsha, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
²¹ Regional Office for Africa, WHO, Gauteng, South Africa.
²² Infectious Diseases Program, Clinton Health Access Initiative, New York, NY, USA.
²³ Institute for Global Health, University College London, London, UK; Clinical Research Department, Africa Health Research Institute, Mtubatuba, South Africa.
²⁴ Clinical Research Department, Africa Health Research Institute, Mtubatuba, South Africa; Department of Medicine, University of Cambridge, Cambridge, UK.
²⁵ US Department of Health and Human Services, Centers for Disease Control, Atlanta, GA, USA.
²⁶ Department of Medicine, Stanford University, Palo Alto, CA, USA.
²⁷ AVAC, New York, NY, USA.
²⁸ Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
²⁹ Department of Infectious Diseases, Irsi Caixa Institut de Recerca de la SIDA, Barcelona, Spain.
³⁰ Institute for Global Health, University College London, London, UK. Electronic address: andrew.phillips@ucl.ac.uk.

PMID: 36642087
PMCID: PMC10065903
DOI: 10.1016/S2352-3018(22)00365-4

Abstract

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.

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Conflict of interest statement

AB received funding for their institution from The Bill & Melinda Gates Foundation, The National Institute of Mental Health, The National Institute of Allergy and Infectious Diseases (NIAID), and personal funding from Gates Ventures. M-CB received funding for their institution from the HIV Prevention Trials Network Modelling Centre—funded by the US National Institutes of Health (NIH; UM1AI068617) through the HIV Prevention Trials Network Statistical and Data Management Center. DvdV received funding for their institution from ViiV, Gilead Sciences, and the NIH. SD-M received funding for their institution from NIAID. DD received funding for their institution from NIH. JSc received personal funding from Abbvie, Merck, Gilead Sciences, GlaxoSmithKline, ViiV, Pfizer, Moderna, and Teva. KK received funding for their employer from the United States Agency for International Development (USAID). RJL received personal funding for lectures and scientific advisory board membership from Cepheid, Gilead Sciences, and Merck. MS received funding for their institution from the Gates Foundation, NIH, Wellcome Trust, and National Institute for Health and Social Research (NIHR). GM-R received funding for their institution from the Gates Foundation, USAID, the NIH, and the Foundation for Innovative New Diagnostics. MW received funding for their institution from the Gates Foundation and received personal funds for attending meetings and consulting from the Global Fund to Fight AIDS, Tuberculosis, and Malaria, USAID, and the Overseas Development Institute. RSh received personal funding for advisory board participation and presentations for ViiV, Gilead Sciences, Vir and GlaxoSmithKline, and Gilead Sciences. RP received funding for their institution from Gilead, ViiV, and Merck and personally from Gilead, ViiV, Merck, Lilly, and Theratechnologies. SS received funding for their institution from the NIH. VC received funding for their institution from Unitaid, NIHR, USAID, the Medical Research Council, the Gates Foundation, and UK Research and Innovation, and personal funds from WHO. ANP received funding for their institution from the Gates Foundation, Wellcome Trust, and NIH and personal funding from the Gates Foundation and Ashfield. FV receives grants from the Gates Foundation, the South African MRC, NIH, Unitaid, Foundation for Innovative New Diagnostics, Children’s Investment Fund Foundation, USAID, ViiV, and Merck, receives drug donations from Gilead, ViiV, Merck, and Johnson & Johnson, and does commercial drug studies for Merck; individually, he receives honoraria for educational talks and advisory board membership for Gilead, ViiV, Mylan and Viatris, Merck, Adcock-Ingram, Aspen, Abbott, Roche, Johnson & Johnson, Sanofi, and Virology Education. CF received personal consulting payments from Gilead Sciences, Janssen Pharmaceuticals, Merck, ViiV, Virology Education, the International Antiviral Society-USA, and Navigen and is co-inventor on two issued patents related to long-acting delivery of antiretroviral drugs. DK received payment to their institution from the NIH and personal payments from AbbVie, Gilead, GlaxoSmithKline, Janssen, Merck, ViiV, Sidley Austin LLP. All other authors declare no competing interests declare.

Figures

**Figure 1:. Key outcomes across 50 years according to whether or not cabotegravir-PrEP was introduced (across all 1000 setting-scenarios)**
ART=antiretroviral therapy. PrEP= pre-exposure prophylaxis.

See this image and copyright information in PMC

Comment in

Long-acting PrEP: new opportunities with some drawbacks.
Xiridou M, Hoornenborg E. Xiridou M, et al. Lancet HIV. 2023 Apr;10(4):e213-e215. doi: 10.1016/S2352-3018(22)00397-6. Epub 2023 Jan 12. Lancet HIV. 2023. PMID: 36642088 No abstract available.

References

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Predicted effects of the introduction of long-acting injectable cabotegravir pre-exposure prophylaxis in sub-Saharan Africa: a modelling study

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Predicted effects of the introduction of long-acting injectable cabotegravir pre-exposure prophylaxis in sub-Saharan Africa: a modelling study

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