The cost-effectiveness and value of information of three influenza vaccination dosing strategies for individuals with human immunodeficiency virus

Abstract

Background: Influenza vaccine immunogenicity is diminished in patients living with HIV/AIDS. We evaluated the cost-effectiveness and expected value of perfect information (EVPI) of three alternative influenza vaccine dosing strategies intended to increase immunogenicity in those patients.

Methods: A randomized, multi-centered, controlled, vaccine trial was conducted at 12 CIHR Canadian HIV Trials Network sites. Three dosing strategies with seasonal, inactivated trivalent, non-adjuvanted intramuscular vaccine were used in HIV infected adults: two standard doses over 28 days (Strategy A), two double doses over 28 days (Strategy B) and a single standard dose of influenza vaccine (Strategy C), administered prior to the 2008 influenza season. The comparator in our analysis was practice in the previous year, in which 82.8% of HIV/AIDS received standard-dose vaccination (Strategy D). A Markov cohort model was developed to estimate the monthly probability of Influenza-like Illness (ILI) over one influenza season. Costs and quality-adjusted life years, extrapolated to the lifetime of the hypothetical study cohorts, were estimated in calculating incremental cost-effectiveness ratios (ICER) and EVPI in conducting further research.

Results: 298 patients with median CD4 of 470 cells/µl and 76% with viral load suppression were randomized. Strategy C was the most cost-effective strategy for the overall trial population and for suppressed and unsuppressed individuals. Mean ICERs for Strategy A for unsuppressed patients could also be considered cost-effective. The level of uncertainty regarding the decision to implement strategy A versus C for unsuppressed individuals was high. The maximum acceptable cost of reducing decision uncertainty in implementing strategy A for individuals with unsuppressed pVL was $418,000--below the cost of conducting a larger-scale trial.

Conclusion: Our results do not support a policy to implement increased antigen dose or booster dosing strategies with seasonal, inactivated trivalent, non-adjuvanted intramuscular vaccine for individuals with HIV in Canada.

Trial registration: ClinicalTrials.gov NCT00764998.

Figure 1. Decision analytic model.

All nodes following vaccine response are repeated each month throughout the initial 12 months of the model duration; therefore patients not suffering fatal ILI or death due to other causes may transition from HIV viral load suppression to non-suppression, and subsequently face differential risk of ILI at each month. The probability of ILI is summed across each of the three strains of influenza assessed in CTN-237.

Figure 2. Monthly distribution of the probability of ILI.

Weekly influenza surveillance report form CDC . 2008–2009 influenza season, week 39 ending October 3, 2009. Data shows only seasonal influenza and pandemic strain, 2009 influenza A (H1N1) virus, has been omitted.

Figure 3. Mean of the probabilities of ILI and 95% credibility interval for each strategy by baseline pVL.

Strategy A: single standard dose+single standard dose booster; Strategy B: double dose+double dose booster; Strategy C: single standard dose+no booster; Strategy D: standard of care.

Figure 4. Cost-effectiveness acceptability curves.