Cost‐effectiveness of broadly neutralizing antibody prophylaxis for HIV‐exposed infants in sub‐Saharan African settings

Abstract

Introduction Infant HIV prophylaxis with broadly neutralizing anti‐HIV antibodies (bNAbs) could provide long‐acting protection against vertical transmission. We sought to estimate the potential clinical impact and cost‐effectiveness of hypothetical bNAb prophylaxis programmes for children known to be HIV exposed at birth in three sub‐Saharan African settings. Methods We conducted a cost‐effectiveness analysis using the CEPAC‐Pediatric model, simulating cohorts of infants from birth through death in Côte d'Ivoire, South Africa and Zimbabwe. These settings were selected to reflect a broad range of HIV care cascade characteristics, antenatal HIV prevalence and budgetary constraints. We modelled strategies targeting bNAbs to only WHO‐designated “high‐risk” HIV‐exposed infants (HR‐HIVE) or to all HIV‐exposed infants (HIVE). We compared four prophylaxis approaches within each target population: standard of care oral antiretroviral prophylaxis (SOC), and SOC plus bNAbs at birth (1‐dose), at birth and 3 months (2‐doses), or every 3 months throughout breastfeeding (Extended). Base‐case model inputs included bNAb efficacy (60%/dose), effect duration (3 months/dose) and costs ($60/dose), based on published literature. Outcomes included paediatric HIV incidence and incremental cost‐effectiveness ratios (ICERs) calculated from discounted life expectancy and lifetime HIV‐related costs. Results The model projects that bNAbs would reduce absolute infant HIV incidence by 0.3–2.2% (9.6–34.9% relative reduction), varying by country, prophylaxis approach and target population. In all three settings, HR‐HIVE–1‐dose would be cost‐saving compared to SOC. Using a 50% GDP per capita ICER threshold, HIVE‐Extended would be cost‐effective in all three settings with ICERs of $497/YLS in Côte d'Ivoire, $464/YLS in South Africa and $455/YLS in Zimbabwe. In all three settings, bNAb strategies would remain cost‐effective at costs up to $200/dose if efficacy is ≥30%. If the bNAb effect duration were reduced to 1 month, the cost‐effective strategy would become HR‐HIVE–1‐dose in Côte d'Ivoire and Zimbabwe and HR‐HIVE–2‐doses in South Africa. Findings regarding the cost‐effectiveness of bNAb implementation strategies remained robust in sensitivity analyses regarding breastfeeding duration, maternal engagement in postpartum care, early infant diagnosis uptake and antiretroviral treatment costs. Conclusions At current efficacy and cost estimates, bNAb prophylaxis for HIV‐exposed children in sub‐Saharan African settings would be a cost‐effective intervention to reduce vertical HIV transmission.

Antibody interventions in HIV: broadly neutralizing mAbs in children

“…Currently, bNAbs are not commercially available, making the production cost study-specific and expensive. One cost-effectiveness study has been performed evaluating bNAbs for PVT [43], but to the best of our knowledge, no study to date has evaluated the cost-effectiveness of strategies involving bNAbs as a treatment strategy. As more potent and broader-acting agents become available, and potential agents with longer half-lives, feasibility considerations will continue to evolve for the field as a whole.…”

The role of economic evaluations in advancing HIV multipurpose prevention technologies in early-stage development

“…However, there are use case examples for how these evaluations are leveraged for internal decision making ( 2 , 23 ) and to mitigate the risks ( 23 ) and high costs of late-stage development ( 23 ). In this context, they can provide valuable insights into clinical trial design ( 23 , 24 ), into target populations or other drivers that improve value for money ( 25 , 26 ) and can guide decisions on what data need to be collected at the next phase of development ( 27 ) so that uncertainty is reduced when introduction decisions are made by policy makers and payers. Importantly, these early analyses can inform product developers' decisions on how to improve a product's eventual value for money, helping refine the target product profile as well as informing which product to prioritise across a given portfolio, focusing resources on those most promising products for further development and those most appropriate for a future programme ( Figure 1 ).…”

“…Linked model outputs include estimates of efficacy, dosing regimen, pharmacokinetics, among others. These outputs can guide clinical development and help reframe value propositions once new data are collected during the different stages of clinical trials, providing an iterative framework for decision making ( 35 , 36 ), future trial design ( 25 ), and the preparation of strategies for reimbursement and pricing ( 2 , 29 , 32 , 37 – 39 ). Though researchers often emphasize the uncertainty that comes with modelling early in the development process as a limitation of early economic modelling ( 2 , 22 – 24 , 28 – 32 ), the framing and communication of this uncertainty becomes the objective of these analyses and future evidence generation will revolve around addressing this uncertainty.…”

“…For example, in the context of novel products for HIV prevention, Dugdale et al selected three countries with a range of HIV epidemic characteristics to model cost effectiveness of novel HIV broadly neutralizing antibodies (bnAbs) for infant prophylaxis ( 25 ). Alongside a base case, bnAbs were modelled using sensitivity analysis across a range of varying parameters (e.g., efficacy, cost, different implementation strategies, different target populations) to determine parameter space of likely market feasibility ( 25 ).…”

Cost-effectiveness of broadly neutralizing antibodies for infant HIV prophylaxis in settings with high HIV burdens: a simulation modeling study

“…Our previous modeling work found that offering a bNAb to infants with known HIV exposure at birth would be cost-effective in Côte d’Ivoire, South Africa, and Zimbabwe. 11 However, the potential long-term, population-level clinical benefits and cost-effectiveness of a universal infant bNAb prophylaxis program in high HIV burden settings have not yet been studied. Here, we extend our prior modeling work to include infants born to mothers with unrecognized HIV infection or mothers at risk for acute HIV acquisition postpartum.…”