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 Outline Background on HIV-Tuberculosis (TB) in SubSaharan 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 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 Estimated global incidence of TB (2007) http://www.who.int/tb/publications/global_report/2009/pdf/chapter1.pdf Estimated global distribution of HIV prevalence in new TB cases (2007) http://www.who.int/tb/publications/global_report/2009/pdf/chapter1.pdf Background HIV-infected TB (prevalence 30-75% of ~7% Tanzania HIV prevalence) = high annual death incidence (↑ death risk <200 CD4+ lymphocytes/mm3) 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 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 Meningeal Tuberculosis T.S. Ramachandran (2008)Tuberculous Meningitis. Medscape 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/mm3 (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 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 Are HAART & Anti-TB therapies worth prioritising for HIV-TB in Tanzania? 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 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 Deferred HAART + Anti-TB No HAART (Anti-TB only) 2) 3) Methodology Methodology Methodology Pro ® Probabilistic micro-simulation for parameter sampling distributions (transition probabilities & costs) • TreeAge • Markov modelling- Monte Carlo and MonteCarlo PSA micro-simulations (n= 1000) Results Cost ($) No HAART Early HAART Deferred HAART Life-Years Cost/LY ($) 361 0.720 502 13 0.026 19 1,687 0.906 1,864 181 0.042 201 1,198 0.862 1,390 109 0.034 129 Results Kernel Densities of Costs using Monte-Carlo Simulation Results Kernel Densities of Life-Years using Mont-Carlo Simulation Results Scatter plots of Costs and Life-Years using Monte-Carlo Simulation Results Cost per life- Incremental Cost Cost Life-year year 361 0.720 501 Deferred HAART 1,198 0.862 1,389 5,888 Early HAART 1,687 0.906 1,862 11,095 No HAART Incremental Cost per Life - Year = Cost HAART per Life-Year Cost - NoHAART LY HAART LY NoHAART Results Mean Std. Dev. Lower 95% Upper 95% C(def) - C(none) 837 110 621 1,052 LY(def) - LY(none) 0.142 0.043 0.058 0.226 C(early) - C(none) 1,326 182 969 1,684 LY(early) - LY(none) 0.186 0.050 0.088 0.284 C(early) - C(def) 490 208 LY(early) - LY(def) 0.044 0.054 -0.062 0.151 Incr. C/E (Def vs. None) 6,716 4,980 -3,045 16,477 Incr. C/E (Early vs. None) 7,738 2,828 2,196 13,280 Incr. C/E (Early vs. Def) -9,655 442,866 83 -877,672 897 858,362 Results Cost-Effectiveness Acceptability Curves of Treatment Options 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 LowIncome Countries like Tanzania. 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. Thank you!