Targeting and vaccine durability are key for population-level impact and cost-effectiveness of a pox-protein HIV vaccine regimen in South Africa

Abstract

Background: RV144 is to date the only HIV vaccine trial to demonstrate efficacy, albeit rapidly waning over time. The HVTN 702 trial is currently evaluating in South Africa a similar vaccine formulation to that of RV144 for subtype C HIV with additional boosters (pox-protein regimen). Using a detailed stochastic individual-based network model of disease transmission calibrated to the HIV epidemic, we investigate population-level impact and maximum cost of an HIV vaccine to remain cost-effective. Methods: Consistent with the original pox-protein regimen, we model a primary series of five vaccinations meeting the goal of 50% cumulative efficacy 24 months after the first dose and include two-yearly boosters that maintain durable efficacy over 10 years. We simulate vaccination programs in South Africa starting in 2027 under various vaccine targeting and HIV treatment and prevention assumptions. Results: Our analysis shows that this partially effective vaccine could prevent, at catch-up vaccination with 60% coverage, up to 941,000 (15.6%) new infections between 2027 and 2047 assuming current trends of antiretroviral treatment. An impact of up to 697,000 (11.5%) infections prevented could be achieved by targeting age cohorts of highest incidence. Economic evaluation indicates that, if treatment scale-up was achieved, vaccination could be cost-effective at a total cost of less than $385 and $62 per 10-year series (cost-effectiveness thresholds of $5,691 and $750). Conclusions: While a partially effective, rapidly waning vaccine could help to prevent HIV infections, it will not eliminate HIV as a public health priority in sub-Saharan Africa. Vaccination is expected to be most effective under targeted delivery to age groups of highest HIV incidence. Awaiting results of trial, the introduction of vaccination should go in parallel with continued innovation in HIV prevention, including studies to determine the costs of delivery and feasibility and further research into products with greater efficacy and durability.

Competing biomedical HIV prevention strategies: potential cost‐effectiveness of HIV vaccines and PrEP in Seattle, WA

“…Parameter uncertainty was evaluated in a sensitivity analysis . One‐way sensitivity analyses evaluated the effect of uncertainty from individual parameters.…”

The future of a partially effective HIV vaccine: assessing limitations at the population level

“…The parameters, model input values, sources, projections, and sensitivities of the epidemic projection without vaccine, used as the reference group for comparison, have been described previously (Bershteyn et al 2012, 2013; Klein et al 2014; Selinger et al 2019). A detailed model description, default parameters, user tutorials, model installer, and source code are available for download at http://idmod.org/software.…”

“…To allow for maximum hypothetical impact of a vaccine, we assume proportion of HIV-positive adults diagnosed of about 85% and future ART coverage of about 60% [consistent with the current guidelines assumed in the HIV/TB Investment Case Report for South Africa (South African National AIDS Council 2016), see also (Johnson et al 2017b)] and no use of oral PrEP. Variations on these assumptions, explored elsewhere (Selinger et al 2017, 2019), only further diminish the impact of the vaccine.…”

“…The protocol was later revised to include a boost at month 18, but this was not considered at the time of this modeling effort. Time-dependent vaccine efficacy was interpreted as a per exposure reduction in the probability of acquisition parameterized by an impulse and exponential decay model (Selinger et al 2019). where is the efficacy increase of immunization with ALVAC-HIV-C, is efficacy increase after ALVAC-HIV-C + gp120 immunization, is the efficacy decay rate per month, and d is the delay between immunization and initiation of protective effect in months.…”

“…Adolescent vaccination would require further licensure procedures and potentially delay vaccination scale-up and was therefore excluded. The impact of age- and gender-dependent targeting for this vaccine regimen was explored elsewhere (Selinger et al 2019).…”