Guidelines on long-acting injectable cabotegravir for HIV prevention: web annex E: predicted effects of introduction of long-acting injectable cabotegravir pre-exposure prophylaxis in sub-Saharan Africa: a modelling study

GUIDELINES ON LONG-ACTING INJECTABLE CABOTEGRAVIR FOR HIV PREVENTION WEB ANNEX E. PREDICTED EFFECTS OF INTRODUCTION OF LONG- ACTING INJECTABLE CABOTEGRAVIR PRE-EXPOSURE PROPHYLAXIS IN SUB-SAHARAN AFRICA: A MODELLING STUDY Guidelines on long-acting injectable cabotegravir for HIV prevention. Web Annex E. Predicted effects of introduction of long-acting injectable cabotegravir pre-exposure prophylaxis in sub-Saharan Africa: a modelling study ISBN 978-92-4-005415-8 (electronic version) © World Health Organization 2022 Some rights reserved. This work is available under the Creative Commons Attribution- NonCommercial-ShareAlike 3.0 IGO licence (CC BY-NC-SA 3.0 IGO; https://creativecommons.org/licenses/ by-nc-sa/3.0/igo). Under the terms of this licence, you may copy, redistribute and adapt the work for non-commercial purposes, provided the work is appropriately cited, as indicated below. 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The responsibility for the interpretation and use of the material lies with the reader. In no event shall WHO be liable for damages arising from its use. This publication forms part of the WHO guideline entitled Guidelines on long-acting injectable cabotegravir for HIV prevention. It is being made publicly available for transparency purposes and information, in accordance with the WHO handbook for guideline development, 2nd edition (2014). Design and layout by 400 Communications Limited. 1 HIV Modelling Consortium Working Group on Modelling Integrase Inhibitor Drug Resistance in Relation to Injectable Long-acting Cabotegravir Use in Sub-Saharan Africa Abstract Background: Long-acting injectable cabotegravir (CAB-LA) is an HIV integrase inhibitor that has demonstrated high efficacy as HIV pre-exposure prophylaxis (PrEP) and is now under consideration as a new option for HIV prevention in sub-Saharan Africa. There is concern, however, that this could lead to increases in integrase inhibitor resistant virus undermining current treatment programmes that rely on dolutegravir. We used an individual-based model of HIV transmission and effects of ART to jointly model the positive and negative effects of CAB-LA introduction in settings in sub-Saharan Africa. Methods: We simulated 1000 “setting-scenarios” reflecting both variability and uncertainty about HIV epidemics in sub-Saharan Africa. PrEP use is assumed to be risk-informed and to be used only in 3-month periods of having condomless sex. For people who initiate on CAB-LA after being infected with HIV or seroconvert while on CAB-LA, or for those with high cabotegravir concentrations due to being in the early tail period after stopping CAB-LA, we consider the risk of integrase inhibitor resistance emergence. We projected the outcomes of a policy of no CAB-LA introduction and CAB- LA introduction in 2022 over 50 years. We considered in 50% of setting-scenarios that RNA-based HIV testing, rather than regular antibody-based HIV testing, be used to allow higher sensitivity and to reduce resistance risk. For cost–effectiveness analysis we assumed the cost of CAB-LA to be the same as for oral PrEP (US$ 116 per year), a cost–effectiveness threshold of US$ 500 per DALY averted, and a discount rate of 3% per year. Results: As modelled, CAB-LA PrEP introduction leads 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) on PrEP compared with 1.5% (28%) without CAB-LA introduction over 20 years, due to the relative preference for injectable PrEP. Given our assumption that PrEP use is risk-informed and there is high use of PrEP in those at risk, there is a predicted reduction in HIV incidence of 29% (90% range across setting-scenarios 6–52%) over the same period. In people initiating ART, the proportion with integrase inhibitor resistance (including to dolutegravir) is projected to be in 20 years’ time only 1.7% (0–7.2%) without CAB-LA introduction but 13.1% (1.9–29.7%) with CAB-LA introduction. CAB-LA PrEP introduction is predicted to lower the proportion of all people on ART with VL < 1000 copies/mL by 0.9% (-2.6 – +0.5%) at 20 years. For an adult population of 10 million, an overall decrease in numbers of deaths of approximately 4540 HIV-related deaths per year (-13 000 – -300) over 50 years is predicted, with little discernible benefit of using RNA-based testing. HIV-related deaths are averted with CAB-LA introduction in 97% of setting-scenarios. Over the 50-year time horizon, overall HIV programme costs are predicted to be lower if CAB-LA is introduced rather than not (total mean discounted annual HIV programme costs per year over 50 years US$ 151.3 million vs. US$ 150.7 million), assuming use of standard antibody testing. Introduction of CAB-LA is cost- effective under an assumed threshold of US$ 500 per DALY averted in 82% of setting-scenarios at the fully-loaded PrEP cost of US$ 116 per year and in 52% of setting-scenarios if the annual cost of CAB-LA is US$ 224, and cost-effective in 87% of setting-scenarios if the annual cost of CAB-LA is US$ 86. Interpretation: Despite leading to increases in integrase inhibitor drug resistance, CAB-LA introduction is likely to have net benefits in terms of reduction in HIV-related deaths in addition to reductions in incidence. It is predicted to be cost-effective if delivered at the same cost as oral PrEP. Web Annex E. Predicted effects of introduction of long-acting injectable cabotegravir pre-exposure prophylaxis in sub-Saharan Africa: a modelling study ISBN 978-92-4-005415-8 For more information, contact: World Health Organization Department of Global HIV, Hepatitis and Sexually Transmitted Infections Programmes 20, avenue Appia 1211 Geneva 27 Switzerland Email: hiv-aids@who.int