USING DISCRETE EVENT SIMULATION TO IMPROVE OUTCOMES IN U.S. AIDS DRUG ASSISTANCE PROGRAMS

Purpose: U.S. AIDS Drug Assistance Programs (ADAPs) provide antiretroviral therapy (ART) to HIV-infected patients with no other access to treatment.  Many ADAPs cannot meet demand and limit program eligibility.  We sought to identify an ADAP eligibility criterion that would minimize mortality while containing costs.
Methods: We developed a Discrete Event Simulation (DES) model of ADAP.  The model simulated the clinical progression of HIV infected patients and tracked capacity utilization of a simulated ADAP.  When demand exceeded capacity, the model maintained a wait-list for care.  Massachusetts ADAP administrative data informed patient demographics (mean age 45 years, CD4 count 181/µl, 78% male), applicant arrival rate (approximately 80/month), and program attrition (0.017/person month).  Published reports of ART efficacy, incidence of opportunistic infections, and HIV-related mortality informed disease progression parameters. Outcomes included incidence of death and first opportunistic infection or death/1,000 person months, and time to starting ART.  We first simulated an ADAP with as-needed capacity.  We then simulated a fixed capacity program facing 10% excess demand and compared outcomes under two policies: 1) first-come first-served (FCFS) eligibility for all with CD4 count ≤350/µl, and 2) CD4 count prioritized eligibility for those with CD4 count below a defined threshold.  To define the optimal CD4 count eligibility threshold, we repeated the simulation, altering the threshold until we found the value that minimized mortality.  Sensitivity analyses varied patient arrival, CD4 count at entry, and ART efficacy.
Results: Compared to FCFS eligibility, CD4-prioritized eligibility resulted in fewer deaths, lower incidence of first opportunistic infection or death, and shorter time to starting ART for patients with CD4 count ≤200/µl (Table). 

Program	Deaths/1000 person months	First OI or death/1000 person months	Median months wait to Starting ART (IQR) CD4 at presentation (cells/µl)  ≤100         101-200     201-350
As needed capacity	2.50	4.56	-	-	-
Capacity capped
FCFS CD4 ≤ 350/µl	3.27	6.98	3 (1-3)	3 (2-3)	3 (2-3)
Prioritize CD4 ≤250/µl	2.77	5.55	0 (0-1)	0 (0-1)	4 (0-12)

In sensitivity analyses, CD4-prioritized eligibility consistently resulted in lower morbidity and mortality than FCFS eligibility.  As demand increased and/or the population had more advanced HIV infection, the benefit of CD4-prioritized eligibility increased. 
Conclusions: Discrete Event Simulation is useful for planning resource allocation policies.  With fixed capacity and excess demand, AIDS treatment programs can minimize morbidity and mortality by prioritizing patients with lower CD4 cell-counts rather than choosing a first-come first-served approach.