1. A cost-effectiveness evaluation of preventive interventions for HIV-TB in Sub-Saharan Africa (Tanzania): Relevance for neurological infections Lucie Jean-Gilles Casey Quinn Corinne Camilleri-Ferrante

2. Outline Background on HIV-Tuberculosis (TB) in Sub- Saharan Africa and neurological implications Prevention & treatments for HIV-TB Cost-effectiveness study for HIV-TB in Tanzania Implication of results and relevance to neuro-TB Conclusion and future directions

3. Background Burden of TB closely linked to HIV epidemic in SSA (80% of global co-infection cases)  HIV increases risk for Mycobacterium tuberculosis infection and for latent TB progression into active disease (30-50 fold higher) Microscopic view of T. Bacilli

4. Estimated global incidence of TB (2007) http://www.who.int/tb/publications/global_report/2009/pdf/chapter1.pdf

5. Estimated global distribution of HIV prevalence in new TB cases (2007)

6. Background HIV-infected TB (prevalence 30-75% of ~7% Tanzania HIV prevalence) = high annual death incidence (↑ death risk <200 CD4+ lymphocytes/mm 3 ) and ↑ opportunistic infections  TB accelerates HIV progression Although 1/3 TB deaths are HIV associated and 7% mortality rate in 1.4 million HIV population of Tanzania in 2009, central nervous system TB kills & disables more than any other form of TB

7. Neurological implications Meningeal TB most lethal (~30% of cases) and disabling despite anti-TB chemotherapy  common and serious clinical problem in high HIV-TB prevalent SSA Diagnosis & treatment of meningeal TB difficult  HIV co-infection increases management difficulties Worldwide use of highly active anti-retroviral therapy (HAART) (↓ opportunistic infections)  significantly reduced incidence of neurological complications in AIDS patients and TB/HIV/AIDS progression and mortality

8. Meningeal Tuberculosis T.S. Ramachandran (2008)Tuberculous Meningitis. Medscape

9. Neurological implications (cont.) Survival improvement and decrease in HIV-TB by HAART can be complicated by immune reconstitution inflammatory syndrome (IRIS) (transient worsening of disease i. e. neurological symptoms due to meningitis) and drug toxicity when: 1) <200 CD4+ lymphocytes/mm 3 (high HIV viral load) 2) HAART initiated within 2 months of anti-TB Rx regimen However, HAART overall clinical and mortality benefits on HIV and HIV-TB outweighs adverse effects

10. HAART & Anti-TB therapy in Tanzania Anti-TB drugs widely available (isoniazid, rifampicin, pyrazinamide) in Tanzania High unmet need  only 3-6% of HIV +ve population have access to HAART in Tanzania; no specific treatment for neurological HIV-TB Contributing factors to problem: Systematic: high cost, lack of availability, distribution logistics, int’l programme sustainability and health care system support Priority setting: Lack of cost-effectiveness evidence of HAART on HIV-TB  strong economic case needed for prioritisation of TB preventive interventions in HIV population

11. Are HAART & Anti-TB therapies worth prioritising for HIV-TB in Tanzania?

12. Aims of Study Cost-effectiveness of HAART as an adjunctive therapy to, or following, anti-TB regimen for HIV-TB from health care system perspective in low-resource setting Tanzania Relevance of results for HIV-TB neurological intervention measures

13. Methodology Decision analysis model using transition probabilities sourced from Schiffer & Sterling (2007) study: “Timing of Antiretroviral Therapy Initiation in Tuberculosis Patients with AIDS: A Decision Analysis” Data obtained from primary source studies where patients received standard rifamycin-based anti-TB therapy for 6 months with or without HAART Analysis ran under 3 conditions: 1) Early HAART + Anti-TB 2) Deferred HAART + Anti-TB 3) No HAART (Anti-TB only)

14. Methodology

16. TreeAge Pro ®  Probabilistic micro-simulation for parameter sampling distributions (transition probabilities & costs) Markov modelling- Monte Carlo and Monte- Carlo PSA micro-simulations (n= 1000)

17. Results

18. Kernel Densities of Costs using Monte-Carlo Simulation

19. Results Kernel Densities of Life-Years using Mont-Carlo Simulation

20. Results Scatter plots of Costs and Life-Years using Monte-Carlo Simulation

21. Results

23. Cost-Effectiveness Acceptability Curves of Treatment Options

24. Discussion More sensitivity analysis to be undertaken for this model: Difference between Early HAART and Deferred HAART (life-years)  not statistically significant and may influence results. More consideration for transition probabilities and effect to be sensitive to our definitions (i.e. death due to drug toxicity). This analysis only considered pulmonary TB in HIV patients, however extra-pulmonary TB-related neurological conditions (i.e. meningeal TB) in particular are of interest in this study. Next steps are: - To infer rates of meningeal TB from these results - To analyze a more complicated decision model or Markov model that accommodates meningeal TB. Inclusion of meningeal TB, its costs and mortality/morbidity in Tanzania  conducting a cost-effectiveness analysis will provide essential information for priority setting of this disease burden in Low- Income Countries like Tanzania.

25. Conclusion Although previous analysis found that Early HAART was preferred to Deferred HAART for HIV +ve TB patients  incremental effect of Early HAART on mortality due to disease (HIV and TB) and drug toxicity is not statistically significant. Early HAART does not appear to be cost-effective relative to Deferred HAART. However, adjunctive treatment with HAART (early & deferred) are effective and cost-effective relative to treatment only using standard TB therapy. Expanding this HIV-TB model to meningeal TB in the Tanzanian setting will help determine cost-effective strategies to help significantly reduce risk of TB-related morbidity and mortality in its HIV population.

26. Thank you!