Mai T. Pho

Efficacy of a Six-Month versus a 36-Month Regimen for Prevention of Tuberculosis in HIV-Infected Persons in India: A Randomized Clinical Trial

Background The optimal duration of preventive therapy for tuberculosis (TB) among HIV-infected persons in TB-endemic countries is unknown. Methods An open-label randomized clinical trial was performed and analyzed for equivalence. Seven hundred and twelve HIV-infected, ART-naïve patients without active TB were randomized to receive either ethambutol 800 mg and isoniazid 300 mg daily for six-months (6EH) or isoniazid 300 mg daily for 36-months (36H). Drugs were dispensed fortnightly and adherence checked by home visits. Patients had chest radiograph, sputum smear and culture performed every six months, in addition to investigations if they developed symptoms. The primary endpoint was incident TB while secondary endpoints were all-cause mortality and adverse events. Survival analysis was performed on the modified intent to treat population (m-ITT) and rates compared. Findings Tuberculosis developed in 22 (6.4%) of 344 subjects in the 6EH arm and 13 (3.8%) of 339 subjects in the 36H arm with incidence rates of 2.4/100py (95%CI- 1.4–3.5) and 1.6/100py (95% CI-0.8–3.0) with an adjusted rate ratio (aIRR) of 1.6 (0.8–3.2). Among TST-positive subjects, the aIRR of 6EH was 1.7 (0.6–4.3) compared to 36H, p = 0.8. All-cause mortality and toxicity were similar in the two arms. Among 15 patients with confirmed TB, 4 isolates were resistant to isoniazid and 2 were multidrug-resistant. Interpretation Both regimens were similarly effective in preventing TB, when compared to historical incidence rates. However, there was a trend to lower TB incidence with 36H. There was no increase in isoniazid resistance compared to the expected rate in HIV-infected patients. The trial is registered at ClinicalTrials.gov, NCT00351702.

The cost-effectiveness of tuberculosis preventive therapy for HIV-infected individuals in southern India: a trial-based analysis.

Background Regimens for isoniazid-based preventive therapy (IPT) for tuberculosis (TB) in HIV-infected individuals have not been widely adopted given concerns regarding efficacy, adherence and drug resistance. Further, the cost-effectiveness of IPT has not been studied in India. Methods We used an HIV/TB model to project TB incidence, life expectancy, cost and incremental cost-effectiveness of six months of isoniazid plus ethambutol (6EH), thirty-six months of isoniazid (36H) and no IPT for HIV-infected patients in India. Model input parameters included a median CD4 count of 324 cells/mm3, and a rate ratio of developing TB of 0.35 for 6EH and 0.22 for 36H at three years as compared to no IPT. Results of 6EH and 36H were also compared to six months of isoniazid (6H), three months of isoniazid plus rifampin (3RH) and three months of isoniazid plus rifapentine (3RPTH). Results Projected TB incidence decreased in the 6EH and 36H regimens by 51% and 62% respectively at three-year follow-up compared to no IPT. Without IPT, projected life expectancy was 136.1 months at a lifetime per person cost of

Valuing cure: Bridging cost-effectiveness and coverage decisions for hepatitis C therapy

5,630. 6EH increased life expectancy by 0.8 months at an additional per person cost of

Clinical impact of treatment timing for chronic hepatitis C infection: a decision model

100 (incremental cost-effectiveness ratio (ICER) of

Topical gentian violet compared with nystatin oral suspension for the treatment of oropharyngeal candidiasis in HIV-1-infected participants.

1,490/year of life saved (YLS)). 36H further increased life expectancy by 0.2 months with an additional per person cost of

Cost Effectiveness and Cost Containment in the Era of Interferon-Free Therapies to Treat Hepatitis C Virus Genotype 1

55 (ICER of

Cost-effectiveness of meglumine antimoniate versus miltefosine caregiver DOT for the treatment of pediatric cutaneous leishmaniasis

3,120/YLS). The projected clinical impact of 6EH was comparable to 6H and 3RH; however when compared to these other options, 6EH was no longer cost-effective given the high cost of ethambutol. Results were sensitive to baseline CD4 count and adherence. Conclusions Three, six and thirty-six-month regimens of isoniazid-based therapy are effective in preventing TB. Three months of isoniazid plus rifampin and six-months of isoniazid are similarly cost-effective in India, and should be considered part of HIV care.

Expanded HIV Testing and Linkage to Care: Conventional vs. Point-of-Care Testing and Assignment of Patient Notification and Linkage to Care to an HIV Care Program

The development of direct-acting antiviral agents (DAAs) has revolutionized the treatment of hepatitis C infection. High rates of sustained virologic response (SVR) achieved by DAAs as compared to interferon-based dual therapy will have a profound impact on morbidity and mortality among those individuals able to access and complete treatment.(1, 2) Regimens free of interferon and its punishing adverse effects are now available for genotype 2 and 3 infections, and the most recent treatment guidelines released by the American Association for the Study of Liver Diseases and the Infectious Diseases Society for American have endorsed the off-label combination of sofosbuvir (SOF) plus simeprevir (SMV) as first line therapy for genotype 1 infections in patients who are interferon-ineligible. Enthusiasm for the new wave of hepatitis C therapeutics has been hindered to no small extent by the accompanying price tag of DAAs. Based on wholesale acquisition costs for sofosbuvir and simeprevir, overall costs for a treatment course has reached

Right Buttock Rash for Thirty Years in a Patient from China

100,000–

The Cost-Effectiveness of Sofosbuvir-Based Regimens for Treatment of Hepatitis C Virus Genotype 2 or 3 Infection

250,000 per person.(3) This pricing has provoked outrage from hepatitis C advocates and the community in general.(4, 5) The controversy has given rise to larger questions; How much should hepatitis medications cost? What is a reasonable price to pay to avoid the use of interferon? If costs are non-negotiable, how should expensive but highly efficacious drugs be evaluated by payers? In this issue of Hepatology, Hagan et al. begin to address these questions through a cost-effectiveness analysis of currently available therapies for HCV genotype 1 infection. The authors compare 12 weeks of sofosbuvir plus simeprevir (SOF/SMV) to 24 weeks of sofosbuvir plus ribavirin (SOF/RBV) in genotype 1, interferon-ineligible patients.(6) Their analysis excludes patients who have failed prior therapy with protease inhibitors, as well as those with decompensated cirrhosis. The baseline assumptions for SOF/SMV included a higher SVR rate, as well as a lower cost as compared to SOF/RBV. With these assumptions, it is not surprising that the authors found that treatment with SOF/SMV “dominated” treatment with SOF/RBV, i.e. resulted in greater health benefit at lower cost. The authors compared the cost per SVR attained for each strategy, and found that SOF/SMV resulted in a “cost saving” of