Cost-effectiveness of tuberculosis screening and isoniazid treatment in the TB/HIV in Rio (THRio) Study.

OBJECTIVE: To estimate the incremental cost-effectiveness of tuberculosis (TB) screening and isoniazid preventive therapy (IPT) among human immunodeficiency virus (HIV) infected adults in Rio de Janeiro, Brazil. DESIGN: We used decision analysis, populated by data from a cluster-randomized trial, to project the costs (in 2010 USD) and effectiveness (in disability-adjusted life years [DALYs] averted) of training health care workers to implement the tuberculin skin test (TST), followed by IPT for TST-positive patients with no evidence of active TB. This intervention was compared to a baseline of usual care. We used time horizons of 1 year for the intervention and 20 years for disease outcomes, with all future DALYs and medical costs discounted at 3% per year. RESULTS: Providing this intervention to 100 people would avert 1.14 discounted DALYs (1.57 undiscounted DALYs). The median estimated incremental cost-effectiveness ratio was $2273 (IQR $1779-$3135) per DALY averted, less than Brazil's 2010 per capita gross domestic product (GDP) of $11,700. Results were most sensitive to the cost of providing the training. CONCLUSION: Training health care workers to screen HIV-infected adults with TST and provide IPT to those with latent tuberculous infection can be considered cost-effective relative to the Brazilian GDP per capita.

The cost-effectiveness of DOTS in urban Brazil.

SETTING: Rio de Janeiro, Brazil, is a middle-income setting with an estimated 1% adult human immunodeficiency virus (HIV) seroprevalence. OBJECTIVE: To examine the cost-effectiveness of DOTS in Rio de Janeiro. DESIGN: Cost-effectiveness analysis based on cost data and an epidemiological model based on programmatic outcomes from the Health Department in Rio de Janeiro, cost data from the retail market sector and epidemiological data from published studies. RESULTS: The 10-year cost of a tuberculosis program treating a population of 262 000 based on self-administered therapy (SAT) was estimated to be $580 271 compared to $1047 886 for DOTS. The largest portion of the DOTS budget was for staff costs and costs incurred by patients, both at 28%. For SAT, the largest percentage of the budget was allocated to medication costs, at 34%. Upgrading from SAT to DOTS averted 1558 cases of tuberculosis (TB, uncertainty range [UR] 1418-1704) and 143 TB deaths (UR 131-155). The incremental cost effectiveness ratio (ICER) for DOTS was $300 per case averted (UR $289-$312) and $3270 per death averted (UR $3123-$3435). In terms of disability adjusted life years (DALYs), DOTS saved 5426 DALYs (UR 4908-5961). The ICER for DOTS was $86 per DALY saved (UR $74-$100). CONCLUSIONS: DOTS is a highly cost-effective intervention in Brazil.

Costs of HIV medical care in the era of highly active antiretroviral therapy.

OBJECTIVES: In the USA, Medicaid is the principal payer of the health care costs of patients with HIV infection. We wished to determine how the costs to Medicaid of patients in Maryland infected with HIV have changed in the setting of highly active antiretroviral treatment. DESIGN: Observational cohort study. METHODS: Analysis of combined economic and clinical data of patients from the Johns Hopkins HIV Service, the provider of primary and sub-specialty care for a majority of HIV-infected patients in the Baltimore metropolitan region. All patients were enrolled in Medicaid and received care longitudinally in Maryland from 1 January 1995 through 31 December 1997. Monthly Medicaid payments were calculated for all inpatient and outpatient services by fiscal year, CD4 cell count, and use of protease inhibitors. RESULTS: For inpatients with a CD4 cell count < or = 50 x 10(6) cells/l, the total health care average monthly payments remained unchanged ($2629 in 1995, $2585 in 1997). Total mean monthly payments increased for those with a CD4 cell count > 50 x 10(6) cells/l (CD4 cell count 50-200 x 10(6) cells/l, $1172 in 1995 and $1615 in 1997, P < 0.05; CD4 cell count 201-500 x 10(6) cells/l, $1078 in 1995 and $1305 in 1997, P < 0.05). However, when data were stratified according to use of a protease inhibitor-containing regimen (used during approximately 50% of follow-up time in 1996-1997) it was found that hospital inpatient payments decreased significantly in all CD4 strata for patients on a protease inhibitor-containing regimen whereas pharmacy payments increased significantly. Inpatient payments associated with treating opportunistic illness were lower in 1996-1997 for patients receiving protease inhibitor therapy compared with those not receiving protease inhibitors. On balance, total health care payments tended to be slightly lower for patients receiving a protease inhibitor regimen. CONCLUSION: Although protease inhibitor-containing antiretroviral regimens are being used by only about half of our Medicaid-insured patients, when they are used, there are significantly lower hospital inpatient and community care costs, as well as lower costs associated with the treatment of opportunistic illness. Even with the concurrent increase in their pharmacy costs, total health care costs were stable or slightly lower for these patients. We believe this is a favorable result suggesting a good clinical value being achieved without an increase in costs.

Tuberculosis vaccination versus isoniazid preventive therapy: a decision analysis to determine the preferred strategy of tuberculosis prevention in HIV-infected adults in the developing world.

SETTING: The developing world. OBJECTIVE: To compare the strategy of TB vaccination with that of tuberculin skin-testing in conjunction with isoniazid (INH) in preventing tuberculosis in HIV-infected persons. For any clinical scenarios in which immunization would be more effective than INH preventive therapy, to determine the minimum necessary vaccine safety and effectiveness required. DESIGN: Decision analysis. A hypothetical cohort of 10000 HIV-infected persons, 65% of whom were tuberculin positive, living in the developing world, was studied. Probability estimates were based on BCG vaccine for the baseline analysis, and it was assumed that the vaccine cannot protect if given after infection. RESULTS: Under the probability estimates and assumptions of the analysis, tuberculin skin testing/INH preventive therapy would prevent 458 more cases of TB and 45 more deaths due to TB than TB vaccination. One- and two-way sensitivity analyses revealed no thresholds at which TB vaccination would be the preferred strategy. Vaccine safety did not impact the outcome of the analysis. Three-way sensitivity analysis revealed that if the prevalence of anergy were 35% and the risk of progression to active TB among anergic persons 12.2 cases per 100 person-years, a vaccine would have to be at least 87% effective to be preferred over INH preventive therapy. CONCLUSIONS: Under the conditions of the analysis, which did not account for cost or logistics, tuberculin skin testing/INH preventive therapy would be more effective than TB vaccination in preventing TB among HIV-infected persons. The hypothesized TB vaccine would prevent more TB than INH preventive therapy only in areas where the prevalence of anergy and risk of active TB if anergic were high, and vaccine effectiveness exceeded 87%.

Cost-utility analysis of prophylactic treatment with oral ganciclovir for cytomegalovirus retinitis.

OBJECTIVE: Cytomegalovirus (CMV) retinitis is a relatively common opportunistic infection in late-stage HIV disease, causing significant morbidity and mortality. Prophylactic use of oral ganciclovir has recently been shown to decrease the incidence of CMV retinitis but is relatively expensive and may not be very well tolerated by many patients. We performed a decision analysis to assess the cost-effectiveness of prophylactic oral ganciclovir therapy. METHODS: A decision analysis using a Markov approach compared absence of prophylaxis and prophylaxis with oral ganciclovir. Estimates of effectiveness of prophylaxis and costs of illness were obtained from published literature. Drug costs were based on national average wholesale prices. All health care costs were based on 1996 U.S. dollars. Sensitivity analyses were done over ranges of estimates of cost and effectiveness. RESULTS: Using our baseline estimates of cost and effectiveness, use of oral ganciclovir prophylaxis in patients with CD4 counts <50 cells/mm3 would be associated with average lifetime health care costs of $104,746, compared with $90,985 for no prophylaxis. Using oral ganciclovir, the average quality-adjusted life-years (QALYs) would be 2.05, and the CMV retinitis-free life-years would be 1.64, compared with 1.87 and 1.27, respectively, for no prophylaxis. The incremental cost-utility of oral ganciclovir is $76,676 per year of life saved and $37,542 per year of additional CMV retinitis-free life. Oral ganciclovir would become more cost-effective relative to no prophylaxis if the probability of CMV retinitis while taking oral ganciclovir declined. Oral ganciclovir would be less cost-effective if the cost of treating CMV retinitis declines, if our estimates of quality of life are low, or if the overall incidence of CMV retinitis declines. CONCLUSIONS: Oral ganciclovir is a less cost-effective approach than several other interventions used for HIV-disease prophylaxis. It would potentially become cost-effective if it is possible to target oral ganciclovir prophylaxis to patients who are most likely to benefit.

Costs to Medicaid of advancing immunosuppression in an urban HIV-infected patient population in Maryland.

Human immunodeficiency virus (HIV) infection is increasingly an urban disease in the United States, and Medicaid is the principal payer of the health care costs of patients with HIV. We wished to determine the costs to Medicaid of patients in Maryland infected with HIV as immunosuppression progresses, and to determine how costs varied by demographic characteristics of the patient. We analyzed combined economic and clinical data in patients from the Johns Hopkins HIV Service, the provider of primary and specialty care for a majority of HIV-infected patients in the Baltimore metropolitan region. All patients were enrolled in Medicaid and received care longitudinally in Maryland from July 1992 to June 1995. Monthly Medicaid payments were calculated for all inpatient and outpatient services by sex, race, age, use of injecting drugs, CD4+ count (>500, 201-500, 51-200, < or =50 cells/mm3), several opportunistic diseases, and death. Lifetime costs were also calculated by use of a Markov simulation. During 13,174 person-months of follow-up in 606 patients, a total of $18,223,700 in Medicaid payments was made. Mean monthly payments ranged from $2,436 (SE $171) for patients with CD4+ counts < or =50 cells/mm3 to $1,015 (SE $177) for patients with CD4+ counts >500 cells/mm3. Mean monthly inpatient costs ranged from $1,355 (SE $131) for CD4+ counts < or =50 cells/mm3 and $617 (SE $164) for CD4- counts >500 cells/mm3. For those with CD4+ counts < or =50 cells/mm3, outpatient pharmacy costs averaged $515 (SE $57) monthly, second only to inpatient costs. In bivariate analysis, costs were significantly higher (p = .013) in men (mean $1696; SE $126) than in women (mean $1,208; SE $101), though the difference was not significant with multivariate adjustment. Cytomegalovirus retinitis was the most costly opportunistic disease, with mean monthly costs of $7,825 (SE $1,141) within the 6 mo after diagnosis. Within 6 mo of death, mean monthly costs are $4,600 (SE $424). Lifetime costs for treating an HIV-infected patient who presents with a CD4+ count >500 cells/mm3 are $133,500 over 8.3 years of life. We concluded that in the clinic where the analysis was done, average costs to Medicaid of treating patients increase more than two-fold as the CD4+ count declines from >500 cells/mm3 to < or =50 cells/mm3. Interventions that decrease hospitalization, opportunistic disease, and the costs of terminal care may be most likely to decrease overall costs. Demographic patient characteristics do not affect costs significantly when access to care is comparable.

Prevention of opportunistic infections in the era of improved antiretroviral therapy.

Patients with advanced human immunodeficiency virus (HIV) infection who are severely immunosuppressed develop a variety of opportunistic infections that have a significant impact on their well-being, quality of life, health-care costs, and survival. The risk for development of opportunistic infections depends on exposure to potential pathogens, the virulence of the pathogens, the degree of host immunity, and the use of antimicrobial prophylaxis. Many studies have confirmed the benefits of prophylaxis in severely immunosuppressed patients. Factors that affect the use of prophylaxis for prevention of opportunistic infections in HIV-infected patients include the prevalence and potential severity of the disease, ease of treatment if infection occurs, the cost-effectiveness of the prophylactic regimen, and the potential for increased survival, drug toxicity, drug interactions, and emergence of resistance with the regimen. The United States Public Health Service and the Infectious Diseases Society of America (USPHS/IDSA) have established disease-specific recommendations for use of prophylaxis for opportunistic infections in HIV-infected patients. These guidelines identify regimens that are strongly recommended as standards of care, regimens that should be seriously considered in selected patients, and regimens that are not routinely indicated but may be considered in selected patients. Although further study is needed, advances in antiretroviral therapy may have an important impact on the recommendations for prophylaxis and may eventually allow discontinuation of these regimens in patients who regain functional immunity.

Cost-effectiveness of directly observed versus self-administered therapy for tuberculosis.

Decision analysis was used to compare three alternative strategies for a 6-mo course of treatment for tuberculosis: directly observed drug therapy (DOT), self-administered fixed-dose combination drug therapy, and self-administered conventional individual drug therapy. Estimates of effectiveness were obtained from the published literature. Estimates of costs were obtained from the literature and the Baltimore City Health Department. Both DOT and fixed-dose combination therapy were less costly and more effective than conventional therapy, although DOT was most cost-effective. In total, the average cost per patient treated was $13,925 for DOT, $13,959 for fixed-dose combination therapy, and $15,003 for conventional therapy. Per 1,000 patients treated, 31 relapses and three deaths could be expected for DOT, 96 relapses and eight deaths for fixed-dose combination therapy, and 133 relapses and 13 deaths for conventional therapy. The marginal cost-effectiveness of DOT relative to fixed-dose combination therapy was most sensitive to variability in the direct cost of DOT and less sensitive to relapse rates for DOT and fixed-dose combination therapy. The inferior cost-effectiveness of conventional therapy was not sensitive to plausible variability in cost or effectiveness. Both DOT and fixed-dose combination therapy were cost-effective relative to conventional therapy, although DOT is probably most cost-effective.

The impact of prophylaxis on outcome and resource utilization in Pneumocystis carinii pneumonia.

STUDY OBJECTIVE: Pneumocystis carinii pneumonia (PCP) is a major late complication of HIV infection associated with morbidity and mortality. Because chemoprophylaxis is highly effective, cases of PCP can be viewed as failures in the management of HIV disease. METHODS: We reviewed demographic, clinical, and cost data for all cases of confirmed HIV-related PCP at The Johns Hopkins Hospital in 1991 to determine consequences of missed prophylaxis. We also analyzed hospital discharge data for Maryland in 1991 to assess hospital charges, length of stay, and outcome for all patients with a principal diagnosis of HIV-related PCP. RESULTS: Pneumocystis carinii pneumonia was diagnosed in 79 patients. Of the 79 patients, 61 (77%) did not receive prophylaxis, including 26 who were not previously known to have HIV infection, 17 who did not have prophylaxis prescribed, and 18 who had prophylaxis prescribed, but were not compliant with the regimen. Patients not taking prophylaxis accounted for all 12 deaths ascribed to PCP. This group also accounted for 85% of the hospital days, 100% of the ICU days, and 89% of the inpatient charges. The total hospital charges were $849,540. Extrapolation of these figures for the state of Maryland suggest that the failure to receive prophylaxis in 1991 resulted in 62 patient deaths and a cost of approximately $4.7 million. CONCLUSION: Patients who developed PCP despite prophylaxis had a better outcome and used fewer resources than patients not receiving preventive therapy. This study emphasizes the impact of PCP prophylaxis on the morbidity, mortality, and economics of HIV health care.

Effectiveness of supervised, intermittent therapy for tuberculosis in HIV-infected patients.

OBJECTIVE: To evaluate the effectiveness of supervised therapy for tuberculosis (TB) in patients with HIV infection. DESIGN: Retrospective, chart review. PATIENTS: Patients with TB and HIV infection. SETTING: Urban, public TB clinic. MAIN MEASURES AND RESULTS: A total of 107 patients with TB and HIV infection were studied. Most were men (78%), African American (91%), uninsured or on Medicaid (88%), and 67% were injecting drug users. TB was diagnosed before AIDS in 31% of subjects, at the time of AIDS in 32%, and after AIDS in 37%. Clinical features varied by stage of HIV disease. Sixteen patients received no therapy and died before TB was diagnosed, 10 died during the first 8 weeks of treatment. Seventy-eight patients received > 8 weeks therapy, of whom 48 (62%) were given directly observed therapy twice weekly and 30 (38%) received self-administered daily therapy. Patients who received directly observed therapy were more likely to complete 6 months of therapy (96 versus 76%, P = 0.02) and more likely to survive after therapy ended (85 versus 57%, P = 0.01). By logistic regression, directly observed therapy, AIDS diagnosed before TB, and age were significantly associated with survival outcome. CONCLUSION: Directly observed therapy for TB in patients with HIV infection is highly effective and associated with better adherence to therapy and survival.

Zidovudine therapy and health resource utilization in AIDS.

We wished to determine whether antiretroviral therapy with zidovudine first received when a person is diagnosed with AIDS was associated with diminished or increased direct health resource utilization. As a measure of health resource utilization, we examined all Medicaid-administered health care charges to adult Maryland residents diagnosed with AIDS from 1987 to 1989 who were part of the Human Immunodeficiency Virus Information System. We specifically compared those persons who first received zidovudine therapy either prior to or within 60 days of diagnosis of AIDS (n = 101) with those who never received zidovudine therapy (n = 279). Median survival time after diagnosis of AIDS in those who received zidovudine was 605 days and in those who did not receive zidovudine 235 days. After diagnosis of AIDS, median per-person lifetime direct health care charges to Medicaid were $66,200 in those who received zidovudine and $31,300 in those who did not receive zidovudine. The median incremental charge per year of life gained in zidovudine users was $34,600 compared with nonusers. Adjusting by proportional hazards regression for age, gender, race/ethnicity, HIV transmission risk group, AIDS-defining diagnosis, and length of follow-up, lifetime Medicaid charges were higher in zidovudine receivers. Compared with patients who did not receive zidovudine, patients who first received zidovudine at the time AIDS was diagnosed incurred higher cumulative lifetime charges, associated principally with longer survival time. The rate of resource utilization was not decreased by zidovudine use.

Health effects and exposure assessment of aerosolized pentamidine handlers.

Nurses administering aerosolized pentamidine (AP) were studied to determine any effect AP may be having on their health. Exposure was determined by each nurse's self-report of treatment given as recorded in a daily log and personal and area pentamidine sampling. Outcome measures were self-reported symptoms recorded in a daily log and peak expiratory flow rates (PEFR) and cross-shift and cross-week pulmonary function tests (PFTs). Results revealed no dose-response effect of pentamidine exposure on cross-shift and cross-week PFTs. However, declines in cross-shift PEFRs, diffusion capacities, and increased symptom complaints were observed for a subset of the study population. This suggested that outcomes were modulated by host factors (history of hay fever and allergy) as well as exposure doses. Treatment both efficacy in containing fugitive AP aerosol was also corroborated as a means of minimizing worker exposure.