Exploratory Age-stratified Analysis of Risk-taking Behaviors and Trial Participation Outcomes in the Thai Phase III HIV Vaccine Trial

Transcription

1 RV RV 144 Exploratory Age-stratified Analysis of Risk-taking Behaviors and Trial Participation Outcomes in the Thai Phase III HIV Vaccine Trial J Kaewkungwal, P Pitisuttithum, S Nitayapan, D. Stablein, Chiu, M Benenson, J Kim, M Robb, N Michael, S Rerks-Ngarm for MOPH TAVEG J Phase III Prime-Boost HIV Vaccine Trial AIDS Vaccine Conference October 29, 2010

2 Background Trial RV144: A Phase III Trial of Aventis Pasteur Live Recombinant ALVAC-HIV (vcp1521) Priming With VaxGen gp120 B/E (AIDSVAX B/E) Boosting in HIVuninfected Thai Adults Clinical Trials.gov: NCT Official final results announcement: September

3 Background Final Analyses: RV144 Trial revealed modest protection from HIV infection in Modified I Intentto-Treat analysis. ITT mitt PP N (# subjects) 16,402 16,395 12,542 Person years 52,985 52,985 36,720 Vaccine/Placebo (event #) 56 / / / 50 Vaccine efficacy 26.4% 31.2% 26.2% 2-sided p value % confidence interval -4.0, , , 51.9 Includes 5 vaccine and 2 placebo recipients who were HIV positive at baseline Decreased event numbers, lower precision

4 Background Post-hoc analyses: Different protection levels were observed among different age-groups (mitt population). Age-stratified groups < >26 N (# subjects) 4,543 7,341 4,511 Person years 14,574 23,659 14,753 Vaccine/Placebo (infections #) 12 / / / 23 Vaccine/Placebo (incidence %) 0.163/ / /0.314 Vaccine efficacy -7.1% 49.0% 18.7% 95% confidence interval -143, , ,55.7 Caveat: Sample size of was not powered for subgroup analyses; plus low incidence (125 events) requires cautious interpretation.

5 Background Post-hoc analyses: Examining baseline risk, the incidence rates appeared to be different by risk category N Vaccine Placebo Treatment Effect End points PY Rate % N End points PY Rate % Efficacy 95% CI Low 3, , % Medium 2, , % High 1, , % Note: 1. VE for each risk category was statistically similar; 2. Study was not powered to perform subgroup analysis. -8.5, , , 46.3 Research Question: Is it possible that the distribution of risk categories was different among age groups and therefore the differences in efficacy by age group?

6 Specific Objective Background To explore age-stratified analysis of risk-taking behavioral markers, and trial participation outcomes.

7 Methodology A standard questionnaire was used to assess risk behaviors at baseline and during scheduled followup visit intervals (every 6-month).

8 Methodology Baseline HIV infection risk was classified into 3 levels. High risk volunteer: categorized themselves as high risk, or reported high risk behaviors, e.g needle sharing, multiple sex partners, sex work, STD symptoms Low risk volunteer: perceived their risk as low, and in previous 6 months reported 0-1 sex partners and no sex with CSWs casual partners, same gender partner, HIV infected partner, IDU partner or a partner with multiple partners, reported no STD symptoms or incarceration within 6 months of study entry. Moderate risk volunteer: were neither low nor high risk.

9 Methodology Selected adverse events - AEs that were classified in MedDRA preferred term as Injury were used as a marker of risk-taking behavior. Within the Injury AEs, road accident was particularly evaluated Comparisons of each characteristics and risk behavior factor against its counterpart were performed for the three age-groups (< 20, 21-25, > 26) using chi-square tests. All analyses were based on mitt population.

10 Age-stratified subgroups Total Age-group - N (%) Results: Baseline Characteristics < >26 4,543 (27.7%) 7,341 (44.8%) 4,511 (27.5%) % male * 64.5% 62.3% 56.8% % married * 33.5% 52.3% 64.7% % education above secondary school * % labour or factory work * % SW or Entertainment business work 73.3% 66.7% 51.4% 62.0% 80.9% 87.7% 3.4% 3.6% 3.1% * p-value < 0.01

11 Results: Baseline HIV infection risk Each age-group had similar baseline risk levels. Age-stratified groups < >26 Total Total Age-group - N (%) 4,543 (27.7%) 7,341 (44.8%) 4,511 (27.5%) 16,395 (100%) % High 24.6% 24.5% % Moderate 27.4% 28.2% 22.7% 29.8% 24.1% 28.4% % Low 48.0% 47.3% 47.5% 47.5%

12 Results: HIV infection risk changes overtime Each age-group had similar proportions of risk changes overtime, and had similar experiences in ever having high risk categorization. Age-stratified groups Total Age-group - N (%) < ,543 (27.7%) 7,341 (44.8%) % Always High 14.5% 14.2% % Always moderate 7.3% 8.1% % Always Low 4.2% 4.4% >26 4,511 (27.5%) 15.4% 7.6% 4.1% Total 16,395 (100%) 14.6% 7.7% 4.3% % Risk Changes 74.1% 73.3% % Ever High 57.4% 55.7% 72.9% 55.2% 73.4% 56.0%

13 Results: Risk-taking behavioral markers-injury Overall Adverse Events (injury and road accidents) in each subgroup were similar. Proportions of injury and deaths distributed equally to age-group size. Age-stratified groups < Total Age-group - N (%) % with at least one injury AE % among all 2389 road accident cases 4,543 (27.7%) 28.4% 7,341 (44.8%) 29.1% 31.4% % of road accidents 14.9% 14.6% % among all 160 dead volunteers 44.8% 28.8% 43.8% >26 4,511 (27.5%) 32.5% 14.2% 26.8% 27.5% Total 16,395 (100%) 5,090 (31.0%) 2,389 (14.6%) 2,389 (100%) 160 (100%)

14 Results: Trial participation outcomes as drop out Proportions of dropouts and infections among different baseline risk of the age-stratified groups appeared to be different. Age-stratified subgroups Total Age-group - N (%) % drop out * % per-protocol * % Infected among High-risk group % infected among Moderate-risk group * % infected among Low-risk group < ,543 (27.7%) 7.5% 74.1% 7,341 (44.8%) 8.1% 75.1% 1.01% 1.15% 0.47% 0.56% 0.17% 1.05% * p-value < 0.05 >26 4,511 (27.5%) 6.2% 81.2% 1.40% 0.81% 0.84% Total 16,395 (100%) 7.4% 76.5% 1.18% 0.60% 0.75%

15 Conclusion The post-hoc analyses of the trial suggested the possibility of disparate efficacy by age-groups; in which age group appeared to have statistically significant protection levels at 49% ( %) But characteristics and risk taking patterns of this age-group were found not to be different from other age-groups.

16 Conclusion With no behavioral support as well as the fact that the sample size was not powered for subgroup analyses, it was not possible in this study to conclude that trial participants were heterogeneous or age was an effect modifier. 15 October 20, 2009

17 Lesson Learned A participant s risk taking activity and participation outcomes explored in this study could be used as baseline information for design and analyses of future trials in the general population: The trial enrolled participants aged from the general population; their baselinehiv risk behaviors across agegroups were found equally distributed (24% high, 28% moderate, 48% low)

18 Lesson Learned Tendencies of lower proportions of dropping out and more complete vaccination among older age (> 26) group. Over the course of the 3.5-year follow-up, about 56% of trial participants in all age groups were ever classified in the high risk category.

19 Acknowledgements RV144 volunteers and community members Ministry of Public Health, Thailand Faculty of Tropical Medicine, Mahidol University AFRIMS US and Thai Components Division of AIDS, National Institute of Allergy and Infectious Diseases, NIH Henry M. Jackson Foundation for the Advancement of Military Medicine U.S. Military HIV Research Program, Walter Reed Army Institute of Research U.S. Army Medical Research and Materiel Command Global Solutions for Infectious Diseases sanofi pasteur

20 Thank you for your attention This work was supported in part by a cooperative agreement (W81XWH ) between the Henry M. Jackson Foundation for the Advancement of Military Medicine and the U.S. Department of Defense (DOD) and by an Interagency Agreement (Y1- AI ) between the US Army Medical Research and Materiel Command and the National Institute of Allergy and Infectious Diseases. The views expressed are those of the authors and should not be construed to represent the positions of the U.S. Army or DoD.

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