Examining the production costs of antiretroviral drugs.

OBJECTIVES: To present direct manufacturing costs and price calculations of individual antiretroviral drugs, enabling those responsible for their procurement to have a better understanding of the cost structure of their production, and to indicate the prices at which these antiretroviral drugs could be offered in developing country markets. METHODS: Direct manufacturing costs and factory prices for selected first and second-line antiretroviral drugs were calculated based on cost structure data from a state-owned company in Brazil. Prices for the active pharmaceutical ingredients (API) were taken from a recent survey by the World Health Organization (WHO). The calculated prices for antiretroviral drugs are compared with quoted prices offered by privately-owned, for-profit manufacturers. RESULTS: The API represents the largest component of direct manufacturing costs (55-99%), while other inputs, such as salaries, equipment costs, and scale of production, have a minimal impact. The calculated prices for most of the antiretroviral drugs studied fall within the lower quartile of the range of quoted prices in developing country markets. The exceptions are those drugs, primarily for second-line therapy, for which the API is either under patent, in short supply, or in limited use in developing countries (e.g. abacavir, lopinavir/ritonavir, nelfinavir, saquinavir). CONCLUSION: The availability of data on the cost of antiretroviral drug production and calculation of factory prices under a sustainable business model provide benchmarks that bulk purchasers of antiretroviral drugs could use to negotiate lower prices. While truly significant price decreases for antiretroviral drugs will depend largely on the future evolution of API prices, the present study demonstrates that for several antiretroviral drugs price reduction is currently possible. Whether or not these reductions materialize will depend on the magnitude of indirect cost and profit added by each supplier over the direct production costs. The ability to achieve price reductions in line with production costs will have critical implications for sustainable treatment for HIV/AIDS in the developing world.

Expanding tuberculosis case detection by screening household contacts.

OBJECTIVES: Tuberculosis (TB) case detection remains low in many countries, compromising the efficacy of TB control efforts. Current global TB control policy emphasizes case finding through sputum smear microscopy for patients who self-report to primary health centers. Our objective was to assess the feasibility and yield of a simple active case finding strategy in a high incidence population in northern Lima, Peru. METHODS: We implemented this pilot strategy in one health center's catchment area. Health workers visited household contacts of new TB case subjects to identify symptomatic individuals and collect sputum for screening. Neighboring households were screened in the same manner. Secondary analyses measured risk of TB by (1) sputum smear status of the index case subject, (2) compliance with testing, and (3) risk factors for disease detected through active contact tracing in contrast to self-report. RESULTS: The TB prevalence detected through combined active and passive case finding among 1,094 household contacts was 0.91% (914 per 100,000), much higher than with passive case finding alone (0.18%; 183 per 100,000; p=0.02). Among 2,258 neighbors, the combined strategy detected a TB prevalence of 0.22% (221 per 100,000) in contrast to 0.08% (80 per 100,000) detected through passive case finding alone (p=0.25). Risk factors for being diagnosed through active case finding in contrast with self-report included age >55 years (odds ratio [OR]=5.5; 95% confidence interval [CI] 1.2, 22.8) and female gender (OR=3.9; 95% CI 0.99, 22.3). CONCLUSIONS: Risk of active TB among symptomatic household contacts of active case subjects in this community is very high. Results suggest that contact tracing in such settings may be a powerful means of improving case detection rates for active TB disease.

Community-based treatment of multidrug-resistant tuberculosis in Lima, Peru: 7 years of experience.

Programs implementing community-based directly observed therapy (DOT) have demonstrated success in the treatment of patients with tuberculosis. However, given complexities in the management and treatment of patients infected with multidrug-resistant tuberculosis (MDR-TB), the utilization of community-based DOT to treat MDR-TB patients has only recently been successfully attempted. We describe the first such program and highlight the crucial components and most critical challenges to creating a successful community-based MDR-TB treatment program.

Community-based therapy for multidrug-resistant tuberculosis in Lima, Peru.

BACKGROUND: Despite the prevalence of multidrug-resistant tuberculosis in nearly all low-income countries surveyed, effective therapy has been deemed too expensive and considered not to be feasible outside referral centers. We evaluated the results of community-based therapy for multidrug-resistant tuberculosis in a poor section of Lima, Peru. METHODS: We describe the first 75 patients to receive ambulatory treatment with individualized regimens for chronic multidrug-resistant tuberculosis in northern Lima. We conducted a retrospective review of the charts of all patients enrolled in the program between August 1, 1996, and February 1, 1999, and identified predictors of poor outcomes. RESULTS: The infecting strains of Mycobacterium tuberculosis were resistant to a median of six drugs. Among the 66 patients who completed four or more months of therapy, 83 percent (55) were probably cured at the completion of treatment. Five of these 66 patients (8 percent) died while receiving therapy. Only one patient continued to have positive cultures after six months of treatment. All patients in whom treatment failed or who died had extensive bilateral pulmonary disease. In a multiple Cox proportional-hazards regression model, the predictors of the time to treatment failure or death were a low hematocrit (hazard ratio, 4.09; 95 percent confidence interval, 1.35 to 12.36) and a low body-mass index (hazard ratio, 3.23; 95 percent confidence interval, 0.90 to 11.53). Inclusion of pyrazinamide and ethambutol in the regimen (when susceptibility was confirmed) was associated with a favorable outcome (hazard ratio for treatment failure or death, 0.30; 95 percent confidence interval, 0.11 to 0.83). CONCLUSIONS: Community-based outpatient treatment of multidrug-resistant tuberculosis can yield high cure rates even in resource-poor settings. Early initiation of appropriate therapy can preserve susceptibility to first-line drugs and improve treatment outcomes.