Analyses methodology.

<p>Pipeline workflow for intervention bundle prioritization. a, Creation of efficient frontier for all combinations of 15 interventions and filtering out 8 interventions that were never found on the frontier. b, For the remaining 7 interventions, completion of 100 probabilistic runs varying intervention costs and effects and filtering out intervention bundles that were never found on the frontier. c, Completion of a full probabilistic analyses (run N = 1000) varying intervention cost and effect as well as 96 input variables. All analysis was run for a 20-year simulation.</p

Betting on the fastest horse: Using computer simulation to design a combination HIV intervention for future projects in Maharashtra, India

<div><p>Objective</p><p>To inform the design of a combination intervention strategy targeting HIV-infected unhealthy alcohol users in Maharashtra, India, that could be tested in future randomized control trials.</p><p>Methods</p><p>Using probabilistic compartmental simulation modeling we compared intervention strategies targeting HIV-infected unhealthy alcohol users on antiretroviral therapy (ART) in Maharashtra, India. We tested interventions targeting four behaviors (unhealthy alcohol consumption, risky sexual behavior, depression and antiretroviral adherence), in three formats (individual, group based, community) and two durations (shorter versus longer). A total of 5,386 possible intervention combinations were tested across the population for a 20-year time horizon and intervention bundles were narrowed down based on incremental cost-effectiveness analysis using a two-step probabilistic uncertainty analysis approach.</p><p>Results</p><p>Taking into account uncertainty in transmission variables and intervention cost and effectiveness values, we were able to reduce the number of possible intervention combinations to be used in a randomized control trial from over 5,000 to less than 5. The most robust intervention bundle identified was a combination of three interventions: long individual alcohol counseling; weekly Short Message Service (SMS) adherence counseling; and brief sex risk group counseling.</p><p>Conclusions</p><p>In addition to guiding policy design, simulation modeling of HIV transmission can be used as a preparatory step to trial design, offering a method for intervention pre-selection at a reduced cost.</p></div

Efficient frontier for HIV interventions during a 20-year simulation of HIV epidemic in Maharashtra, India.

<p>a, Graphical representation efficient frontier for all permutations of 12 interventions (4096 total combinations). Blue circles represent packages of interventions on the frontier, red represent packages off the frontier. b, focused graphical representation of efficient frontier for the lower end of discounted cost (0.888–0.898 Billion USD). c, Interventions contained within each efficient frontier package.</p

Clinical trial interventions and associated costs and effects considered in HIV transmission simulation model.

<p>Uniform distributions were used for all costs and lognormal distribution for all effects in probabilistic analyses. Intervention costs were derived from India-specific sources.[<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0184179#pone.0184179.ref035" target="_blank">35</a>,<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0184179#pone.0184179.ref049" target="_blank">49</a>–<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0184179#pone.0184179.ref051" target="_blank">51</a>] Cost in 2012 USD.</p

India transmission model inputs.

<p>India transmission model inputs.</p

Final probabilistic analysis of top 32 intervention bundles.

<p>a, Percentage of runs in which each bundle was identified on the efficient frontier across 1000 probabilistic runs using the 32 bundles identified in the previous analysis step. b, bundle ranking comparison between intervention-only probabilistic and the full probabilistic analysis. c, intervention bundle details corresponding to panel a. *Bundle 0 represents runs with no intervention.</p