Efficacy and safety of once-daily nevirapine- or efavirenz-based antiretroviral therapy in HIV-associated tuberculosis: a randomized clinical trial.

BACKGROUND: Nevirapine (NVP) can be safely and effectively administered once-daily but has not been assessed in human immunodeficiency virus (HIV)-infected patients with tuberculosis (TB). We studied the safety and efficacy of once-daily NVP, compared with efavirenz (EFV; standard therapy); both drugs were administered in combination with 2 nucleoside reverse-transcriptase inhibitors. METHODS: An open-label, noninferiority, randomized controlled clinical trial was conducted at 3 sites in southern India. HIV-infected patients with TB were treated with a standard short-course anti-TB regimen (2EHRZ(3)/4RH(3); [2 months of Ethambutol, Isoniazid, Rifampicin, Pyrazinamide / 4 months of Isoniazid and Rifampicin] thrice weekly) and randomized to receive once-daily EFV at a dose of 600 mg or NVP at a dose of 400 mg (after 14 days of 200 mg administered once daily) with didanosine 250/400 mg and lamivudine 300 mg after 2 months. Sputum smears and mycobacterial cultures were performed every month. CD4+ cell count, viral load, and liver function test results were monitored periodically. Primary outcome was a composite of death, virological failure, default, or serious adverse event (SAE) at 24 weeks. Both intent-to-treat and per protocol analyses were done, and planned interim analyses were performed. RESULTS: A total of 116 patients (75% [87 patients] of whom had pulmonary TB), with a mean age of 36 years, a median CD4+ cell count of 84 cells/mm(3), and a median viral load of 310 000 copies/mL, were randomized. At 24 weeks, 50 of 59 patients in the EFV group and 37 of 57 patients in the NVP group had virological suppression (P = .024). There were no deaths, 1 SAE, and 5 treatment failures in the EFV arm, compared with 5 deaths, 2 SAEs, and 10 treatment failures in the NVP arm. The trial was halted by the data and safety monitoring board at the second interim analysis. Favorable TB treatment outcomes were observed in 93% of the patients in the EFV arm and 84% of the patients in the NVP arm (P = .058). CONCLUSIONS: Compared with a regimen of didanosine, lamivudine, and EFV, a regimen of once-daily didanosine, lamivudine, and NVP was inferior and was associated with more frequent virologic failure and death. Clinical Trials Registration. NCT00332306.

Long term follow up of HIV-infected patients with tuberculosis treated with 6-month intermittent short course chemotherapy.

BACKGROUND: Tuberculosis occurs in 60%-70% of HIV-positive persons in India. The outcome of HIV-positive patients treated with 6-month intermittent short course antituberculosis regimens in India is not well described. METHODS: This was a prospective observational feasibility study of 71 patients with HIV and tuberculosis who were treated with category I regimen of the Revised National Tuberculosis Control Programme (ethambutol, isoniazid, rifampicin and pyrazinamide thrice weekly for the initial 2 months followed by rifampicin and isoniazid thrice weekly for the next 4 months). Sputum was examined by smear and culture for Mycobacterium tuberculosis every month up to 24 months. Chest X-ray, CD4 cell count and viral load were done prior to and at the end of treatment. None of the patients received antiretroviral therapy. RESULTS: We present here the treatment response of patients with sputum culture-positive pulmonary tuberculosis to category I regimen. By efficacy analysis, among 43 patients treated with category I regimen, sputum smear conversion was observed in 79% and culture conversion in 82% at the second month. A favourable response was seen in 72% of patients. The mean (SD) CD4% fell from 12.6 (5.9) to 8.9 (4.9) (p < 0.001) with no significant change in mean (SD) CD4 cell count (169 [126] to 174 [158]; ns) at the end of treatment. Viral load change from 1.8 x 10(5) at baseline to 1.3 x 10(5) at the end of treatment was not statistically significant. Thirty-one patients, who completed the full course of treatment, were declared cured and were followed up for 24 months. Twelve had recurrent tuberculosis (39%); 16 of 43 (37%) patients had died by the end of 24 months, two-thirds due to causes other than tuberculosis. CONCLUSION: Though the early bacteriological response to intermittent short course antituberculosis regimen was satisfactory, the overall outcome was adversely affected by the high mortality (during and after completion of treatment) and recurrence rate among HIV-infected patients with tuberculosis. Immune status deteriorated in spite of antituberculosis treatment, highlighting the need for antiretroviral treatment in addition to antituberculosis treatment to improve the long term outcome. The results of this pilot study need to be confirmed by larger studies.

Percentages, Process, and Patterns of HIV Disclosure Among the Spouses of HIV-Infected Men in South India.

Most studies have described the outcome of HIV status disclosure rather than the process of disclosure. Hence, a study was conducted among 201 women who accompanied their spouses and children to 3 hospitals at Chennai and Vellore, Tamil Nadu, India, during January to June 2007. Majority of the respondents were sero-positive (69%) and marriage was the only risk factor for them. Of 201 women, 49% did not know the reason for their husbands' HIV infection. Confidentiality of the patient was often breached during disclosure as family members were drawn into the process without consulting the patient. Only for 117 (50%) respondents, HIV diagnosis was disclosed directly by the health providers. There was a considerable delay for men in disclosing their HIV status to their spouses. Apart from the spouses, 122 (61%) shared their diagnosis with other family members. Disgrace to self and family (54%), fear of discrimination (27%), and fear of rejection (9%) were reported for nondisclosure.