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

Bohdan Nosyk, Behnam Sharif, Huiying Sun, Curtis Cooper, Aslam H Anis, CIHR Canadian HIV Trials Network Influenza Vaccine Research Group, Curtis Cooper, Jeff Cohen, Brian Conway, Guy Boivin, David Haase, Marianne Harris, Don Kilby, Marina Klein, Anurag Markanday, Anita Rachlis, Stephen Shafran, Marek Smieja, Sharon Walmsley, Anona Thorne, Joel Singer, Wendy Zubyk, Isabelle Seguin, Edward Mills, Scott Halperin, Bohdan Nosyk, Behnam Sharif, Huiying Sun, Curtis Cooper, Aslam H Anis, CIHR Canadian HIV Trials Network Influenza Vaccine Research Group, Curtis Cooper, Jeff Cohen, Brian Conway, Guy Boivin, David Haase, Marianne Harris, Don Kilby, Marina Klein, Anurag Markanday, Anita Rachlis, Stephen Shafran, Marek Smieja, Sharon Walmsley, Anona Thorne, Joel Singer, Wendy Zubyk, Isabelle Seguin, Edward Mills, Scott Halperin

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.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. Decision analytic model.
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…
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…
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.
Figure 4. Cost-effectiveness acceptability curves.

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