Securing accelerated access to long-acting injectable cabotegravir for HIV prevention in low- and middle-income countries.

INTRODUCTION: Reductions in HIV acquisition have slowed, and the global community is significantly off track from global goals. Oral pre-exposure prophylaxis (PrEP) alone cannot address the diverse needs of the millions of people at risk of HIV acquisition. Long-acting injectable cabotegravir (CAB-LA) received United States Food and Drug Administration approval for HIV prevention in December 2021. When studied, CAB-LA demonstrated high effectiveness, provides months of protection versus daily use, is preferred by some users and has the potential to achieve commodity cost reduction. These factors position CAB-LA to catalyse transformation in HIV prevention. Significant work must be undertaken to ensure at-scale uptake in low- and middle-income countries. Leveraging decades of product introduction experience, Clinton Health Access Initiative (CHAI) has developed an innovative roadmap to support equitable CAB-LA introduction, comprising tightly executed market-shaping, product development, regulatory, and programmatic and implementation action. DISCUSSION: Proven models exist (e.g. long-acting reversible contraceptives, paediatric tuberculosis treatment and antiretrovirals (ARVs), such as paediatric dolutegravir and tenofovir disoproxil fumarate, lamivudine, and dolutegravir) for partnership-driven, accelerated, impactful product introduction. Based on learnings from these models and needs in the prevention space, CHAI developed a roadmap to maximize the near-term impact of CAB-LA and accelerate the development of, access to and impact of quality-assured, low-cost generic CAB-LA. This roadmap is intended to inform introduction planning and investment decision-making across a range of stakeholders, including donors, governments, manufacturers and other partners working in the HIV prevention space. Elements include (1) ensuring coordination and alignment across partners, and avoiding redundancy experienced during oral PrEP introduction; (2) preparing national programmes and providing support to maximize impact, including the development of national policies, guidelines and introduction plans; system strengthening; quantification and procurement; and addressing evidence needs, among other areas; (3) supporting community engagement, ensuring that demand generation and delivery approaches are person-centred and community-led; (4) incentivizing generic product development through, for example, milestone-based commercialization incentives and product development cost-sharing; and (5) expediting regulatory reviews. CONCLUSIONS: Accelerating access to affordable, generic CAB-LA can transform progress towards HIV epidemic control. This vision of impact at scale in prevention is achievable, if informed by results-backed approaches to introduction.

Cost-effectiveness of the dual prevention pill for contraception and HIV pre-exposure prophylaxis.

Introduction: Women in sub-Saharan Africa (SSA) experience the world's highest rates of both HIV infection and unintended pregnancy. The Dual Prevention Pill (DPP) is a novel multipurpose prevention technology (MPT) that co-formulates HIV pre-exposure prophylaxis (PrEP) and combined hormonal oral contraception into a single daily pill. As a dual indication product, the DPP may be preferred by women facing these overlapping health risks. However, most SSA countries face severe healthcare resource constraints. Research is needed to assess whether, in what populations, and in what use cases the DPP would be cost-effective. Methods: We augmented an agent-based SSA HIV model with maternal health parameters including unintended pregnancy, abortion, and maternal mortality. Based on a previous market analysis, we assumed a primary DPP user population of current oral contraceptive users ages 25-49, and alternative user populations in different risk groups (age 15-24, sex workers, HIV-serodiscordant couples) and baseline product use profiles (unmet need for contraception, oral PrEP use, condom use). In three geographies (western Kenya, Zimbabwe, South Africa), we estimated HIV infections averted, pregnancies averted, disability-adjusted life-years (DALYs) averted, and the incremental cost-effectiveness ratio (ICER) over a 30-year time horizon, assuming equivalent adherence to the DPP as to oral contraceptives, higher adherence, or lower adherence. Results: The DPP is likely to be a cost-effective alternative to oral PrEP among users in need of contraception. Among women not already using PrEP, the DPP is likely to be cost-saving in sex workers and serodiscordant couples. The DPP is unlikely to be cost-effective in oral contraceptive users in the general population. Switching from oral contraception to the DPP could be net harmful in some settings and populations if it were to substantially reduces adherence to oral contraception. Results were robust to a range of time horizons or discount rates. Conclusion: The DPP has the potential to be cost-effective and cost-saving in populations at substantial HIV risk. Outcomes are sensitive to adherence, implying that effective counseling and decision-making tools for users considering the DPP will be essential. More research is needed to understand real-life adherence patterns and ensure health benefits achieved from contraception alone are not lost.

Applying mathematical modelling to estimate the impact of COVID-19-related VMMC service disruptions on new HIV infections in Zimbabwe.

BACKGROUND: The COVID-19 pandemic has overwhelmed health systems with knock on effects on diagnosis, treatment, and care. To mitigate the impact, the government of Zimbabwe enforced a strict lockdown beginning 30 March 2020 which ran intermittently until early 2021. In this period, the Ministry of Health and Childcare strategically prioritized delivery of services leading to partial and full suspension of services considered non-essential, including HIV prevention. As a result, Voluntary Medical Male Circumcision (VMMC) services were disrupted leading to an 80% decline in circumcisions conducted in 2020. Given the efficacy of VMMC, we quantified the potential effects of VMMC service disruption on new HIV infections in Zimbabwe. METHODS: We applied the GOALS model to evaluate the impact of COVID-19-related disruptions on reducing new HIV infections over 30-years. GOALS is an HIV simulation model that estimates number of new HIV infections based on sexual behaviours of population groups. The model is parameterized based on national surveys and HIV program data. We hypothesized three coverage scenarios by 2030: scenario I - pre-COVID trajectory: 80% VMMC coverage; Scenario II - marginal COVID-19 impact: 60% VMMC coverage, and scenario III - severe COVID-19 impact: 45% VMMC coverage. VMMC coverage between 2020 and 2030 was linearly interpolated to attain the estimated coverage and then held constant from 2030 to 2050, and discounted outcomes at 3%. RESULTS: Compared to the baseline scenario I, in scenario II, we estimated that the disruption of VMMC services would generate an average of 200 (176-224) additional new infections per year and 7,200 new HIV infections over the next 30 years. For scenario III, we estimated an average of 413 (389-437) additional new HIV infections per year and 15,000 new HIV infections over the next 30 years. The disruption of VMMC services could generate additional future HIV treatment costs ranging from $27 million to $55 million dollars across scenarios II and III, respectively. CONCLUSION: COVID-19 disruptions destabilized delivery of VMMC services which could contribute to an additional 7,200 new infections over the next 30 years. Unless mitigated, these disruptions could derail the national goals of reducing new infections by 2030.

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

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.