1. Cost-effectiveness of different starting criteria of antiretroviral therapy in Mexico. Caro Y., Colchero A., Valencia A., Bautista-Arredondo S., Sierra J.

2. Background  Optimal time for antiretroviral (ARV) therapy initiation for asymptomatic HIV infected individuals remains controversial, especially in developing countries.  Previous studies agree on initiation of ARV in CD4 counts<200 cells/mm 3. Few of them focus on asymptomatic patients.  Results indicate higher survival in early initiation, however this decision implies higher financial burden.  In Mexico there are no cost effectiveness studies on this topic. Studies to assess the costs and effects of different criteria to start ARV in Mexico are needed to guide optimal resource allocation.

3. Mexican Guidelines (currently under revision)

4. Initiating ARV with CD4>350 *DHHS. Guidelines for the use of ARV agents in HIV-1 infected adults and adolescents, Dec 2007

5. Objective To develop a cost-effectiveness model to compare different CD4 counts levels for treatment initiation in asymptomatic HIV infected patients in Mexico.

6. Methods A Markov model was developed to simulate a cohort of HIV positive patients with starting CD4 points of therapy between 200 and 500cells/mm 3. Disease progression for treated individual was modeled as a function of time on therapy. We assumed different probabilities of viral suppression by adherence level and time on treatment.

7. Natural History ARV survive die acute chronic survive die survive die survive die acute chronic ARV No ARV suppressed non suppressed (*) survive die Model

8. Main assumptions Only first line treatment is available. Viral suppression is defined as VL<50copies/ml CD4 reaches a plateau according CD4 count at ARV initiation. High adherence (>95%) in 77% of patients. Non suppressed patients continue treatment but disease progression is 50% lower for 5 years.

9. CD4 and VL distributions from cohorts of asymptomatic patients without prior treatment in INCMNSZ. (National Institute of Medical Sciences and Nutrition) Changes in CD4 and VL, supression by adherence, probabilities of OD and mortality from previous studies. Costs data were extracted from local sources. We estimated the cost per year lived for each simulated alternative. Data modeling

10. Mean: 292.2cel/mm 3 (sd:188.38) n=195 Source:National Institute of Medical Sciences and Nutrition

11. Treatment initiation criteria CD4 count for treatment initiation is randomly selected from a uniform distribution Unif(200,500).  Each patient has a random CD4 count for treatment initiation. Treat if AIDS defining condition is present regardless of CD4 cell count.

12. Base case results * All costs are in 2007 US dollars. Discounted costs

13. Sensitivity analysis * p-value<0.01 CD4 200-300 vs No ARV ** p-value<0.01 CD4 200-300 vs CD4 400-500 *** p-value<0.01 CD4 300-400 vs CD4 400-500 ScenarioStrategy Mean Effectiveness Mean Cost ICER No ARV3.214,431- 200-30011.21*52,0115,948 300-40011.4357,166 Weakly dominated 400-50011.53**57,60117,467 No ARV 4.816,418- 200-3009.96*40,0766,535 300-400 11.92*** 53,5186,858 400-50012.99**63,8239,631 No ARV3.224,430- 200-30010.89*49,7115,904 300-40010.6649,844 Weakly dominated 400-50011.25**55,40315,443 Base Case CD4 at baseline 500cell/mm 3 50% of patients with high adherence

14. Comparison with other studies

15. Conclusions In Mexico, starting therapy early may lead better survival benefits but at a higher cost. Results could be overestimated due to uncertainty in the parameters used. However, sensitivity analysis showed similar conclusions.

16. Discussion Improvement in VCT services with earlier detection could lead to higher benefits from ARVs. Costs could be overestimated. Using median costs could lead to lower ICERs. Including second-line therapy could increase benefits but at a higher cost. Future models should incorporate adverse effects to treatment, drug resistance and disease transmission to fully assess all risk and benefits of early versus late treatment initiation. Results of this study can help decision makers select cost effective strategies for treatment initiation.