Risk compensation after HIV-1 vaccination may accelerate viral adaptation and reduce cost-effectiveness: a modeling study

Abstract

Pathogen populations can evolve in response to selective pressure from vaccine-induced immune responses. For HIV, models predict that viral adaptation, either via strain replacement or selection on de novo mutation, may rapidly reduce the effectiveness of an HIV vaccine. We hypothesized that behavioral risk compensation after vaccination may accelerate the transmission of vaccine resistant strains, increasing the rate of viral adaptation and leading to a more rapid decline in vaccine effectiveness. To test our hypothesis, we modeled: (a) the impact of risk compensation on rates of HIV adaptation via strain replacement in response to a partially effective vaccine; and (b) the combined impact of risk compensation and viral adaptation on vaccine-mediated epidemic control. We used an agent-based epidemic model that was calibrated to HIV-1 trends in South Africa, and includes demographics, sexual network structure and behavior, and within-host disease dynamics. Our model predicts that risk compensation can increase the rate of HIV viral adaptation in response to a vaccine. In combination, risk compensation and viral adaptation can, under certain scenarios, reverse initial declines in prevalence due to vaccination, and result in HIV prevalence at 15 years equal to or greater than prevalence without a vaccine.

Figure 1

HIV-1 prevalence following introduction of a partially effective vaccine in the year 2018 (dashed vertical line), with 50% overall vaccine efficacy and 70% vaccine coverage (note that 50% overall efficacy can result from weighted combinations of efficacy and resistant strain frequency). Model scenarios shown include variation in the proportion of vaccine-sensitive virus at vaccine rollout (83% or 100%) and variation in the reduction in condom use among vaccinated individuals (from 0 to 30% reduction). The mean and 95% credible interval of 64 replicates of each scenario are shown. The black line shows the model scenario without a vaccine.

Figure 2

Percent of HIV-1 infections averted via vaccination over the first 15 years after vaccine rollout, in model scenarios that include variation in the proportion of vaccine-sensitive virus at vaccine rollout (83% or 100%) and variation in the reduction in condom use among vaccinated individuals (from 0 to 30% reduction), with 50% overall vaccine efficacy and 70% vaccine coverage.

Figure 3

Frequencies of HIV genotypes that are either sensitive or resistant to vaccine induced immune responses, following introduction of a partially effective vaccine (here shown as years from vaccine rollout). The plot shows the mean and 95% credible interval of 64 replicates for each scenario (no vaccine, vaccine with risk compensation, and vaccine without risk compensation). The vaccine scenarios include a vaccine with 60% vaccine efficacy, 83.3% vaccine sensitive virus at vaccine rollout, and 70% population vaccine coverage (50% overall vaccine efficacy at rollout). Risk compensation is modeled as a 30% reduction in condom use among vaccinated individuals.

Figure 4

HIV-1 incidence of vaccine-sensitive and vaccine-resistant viral strains following introduction of a partially effective vaccine in the year 2018 (dashed vertical line), with 50% overall vaccine efficacy and 70% vaccine coverage. Model scenarios include variation in the reduction in condom use among vaccinated individuals (from 0 to 30% reduction). The mean and 95% credible interval of 64 replicates of each scenario are shown. Black line shows total incidence (incidence from sensitive and resistant viruses combined).

Figure 5

Heatmap of HIV-1 infections averted within 5, 10, and 15 years after vaccine rollout, for multiple combinations of vaccine coverage, risk compensation in vaccinated individuals, and the population frequency of the vaccine resistant virus, relative to a counterfactual model scenario with no vaccine. Overall vaccine efficacy is 50% at vaccine rollout. Perverse vaccine outcomes can occur in scenarios with higher initial frequencies of resistant virus and higher rates of risk compensation (decreased condom use), at all levels of vaccine coverage.