Duration of efficacy of treatment of latent tuberculosis infection in HIV-infected adults.

BACKGROUND: Treatment of latent infection is needed to protect HIV-infected individuals against tuberculosis. A previous report addressed short-term efficacy of three regimens in HIV-infected adults. We now report on long-term efficacy of the study regimens. METHODS: Three daily self-administered regimens were compared in a randomized placebo-controlled trial in 2736 purified protein derivative (PPD)-positive and anergic HIV-infected adults. PPD-positive subjects were treated with isoniazid (INH) for 6 months (6H), INH plus rifampicin for 3 months (3HR), INH plus rifampicin and pyrazinamide for 3 months (3HRZ), or placebo for 6 months. Anergic subjects were randomized to 6H or placebo. RESULTS: 6H initially protected against tuberculosis in PPD-positive individuals; however, benefit was lost within the first year of treatment. Sustained benefit was observed in persons receiving 3HR and 3HRZ. In a Cox regression analysis, the adjusted relative risk for tuberculosis compared with placebo was 0.67 [95% confidence interval (CI), 0.42-1.07] for 6H, 0.49 (95% CI, 0.29-0.82) for 3HR, and 0.41 (95% CI, 0.22-0.76) for 3HRZ. When the rifampicin-containing regimens were combined, the adjusted relative risk for tuberculosis compared with placebo was 0.46 (95% CI, 0.29-0.71). Among anergic subjects, a modest degree of protection with 6H was present (adjusted relative risk, 0.61; 95% CI, 0.32-1.16). Treatment of latent tuberculosis infection had no effect on mortality. CONCLUSION: Six months of INH provided short-term protection against tuberculosis in PPD-positive HIV-infected adults. Three month regimens including INH plus rifampicin or INH, rifampicin and pyrazinamide provided sustained protection for up to 3 years.

Comparison of three composite compliance indices in a trial of self-administered preventive therapy for tuberculosis in HIV-infected Ugandan adults. Uganda-Case Western Reserve University Research Collaboration.

Compliance with tuberculosis preventive therapy in a randomized placebo-controlled trial in 2736 HIV-infected Ugandans was measured using urinary isoniazid metabolite testing, clinic attendance, and self-report. Overall, 77% of urine tests were positive, subjects kept 85% of their scheduled visits while on therapy, and 69% reportedly never forgot to take their medication. Different strategies were used for constructing three composite compliance indices in active arms: (1) an unweighted index of the summed scores on scaled compliance measures; (2) a weighted index using weights obtained from a survey of experts on tuberculosis; and (3) a statistically weighted index using principal components analysis. Composite indices were evaluated for reliability, validity, and practical utility. Understanding of the regimen, study arm, subsequent follow-up, tuberculosis status, and urine spot-check result were associated with composite compliance scores. The unweighted index in this study performed as well as the weighted indices.

Tuberculosis knowledge, attitudes and health-seeking behaviour in rural Uganda.

OBJECTIVES: To assess tuberculosis (TB) knowledge, attitudes and health-seeking behaviour to inform the design of communication and social mobilisation interventions. SETTING: Iganga/Mayuge Demographic Surveillance Site, Uganda. DESIGN: Between June and July 2008, 18 focus group discussions and 12 key informant interviews were conducted, including parents of infants and adolescents and key informant interviews with community leaders, traditional healers and patients with TB. RESULTS: People viewed TB as contagious, but not necessarily an airborne pathogen. Popular TB aetiologies included sharing utensils, heavy labour, smoking, bewitchment and hereditary transmission. TB patients were perceived to seek care late or to avoid care. Combining care from traditional healers and the biomedical system was common. Poverty, drug stock-outs, fear of human immunodeficiency virus (HIV) testing and length of TB treatment negatively affect health-seeking behaviour. Stigma and avoidance of persons with TB often reflects an assumption of HIV co-infection. CONCLUSION: The community's concerns about pill burden, quality of care, financial barriers, TB aetiology, stigma and preference for pluralistic care need to be addressed to improve early detection. Health education messages should emphasise the curability of TB, the feasibility of treatment and the engagement of traditional healers as partners in identifying cases and facilitating adherence to treatment.

Severity of human immunodeficiency virus infection is associated with decreased phase angle, fat mass and body cell mass in adults with pulmonary tuberculosis infection in Uganda.

Although coinfection with tuberculosis and human immunodeficiency virus (HIV) is emerging as a major problem in many developing countries, nutritional status has not been well characterized in adults with tuberculosis and HIV infection. We compared nutritional status between 261 HIV-positive and 278 HIV-negative adults with pulmonary tuberculosis in Kampala, Uganda, using anthropometry and bioelectrical impedance analysis. Among 163 HIV-positive and 199 HIV-negative men, intracellular water-to-extracellular water (ICW:ECW) ratio was 1.48 +/- 0.26 and 1.59 +/- 0.48 (P = 0.006) and phase angle was 5.42 +/- 1.05 and 5.76 +/- 1.30 (P = 0.009), respectively. Among 98 HIV-positive and 79 HIV-negative women, ICW:ECW was 1.19 +/- 0.16 and 1.23 +/- 0.15 (P = 0.11) and phase angle was 5.35 +/- 1.27 and 5.43 +/- 0.93 (P = 0.61), respectively. There were no significant differences in BMI, body cell mass, fat mass or fat-free mass between HIV-positive and HIV-negative adults. Among HIV-positive subjects, BMI, ICW:ECW, body cell mass, fat mass and phase angle were significantly lower among those with CD4(+) lymphocytes < or = 200 cells/microL compared with those who had > 200 cells/microL. In sub-Saharan Africa, coinfection with pulmonary tuberculosis and HIV is associated with smaller body cell mass and intracellular water, but not fat-free mass, and by large differences in ICW:ECW and phase angle alpha.

Effects of combination therapy with low dose fluconazole and flucytosine against cryptococcal; meningitis (CM) in patients in Uganda

From January through July 1994; 58 AIDS patients were enrolled at Mulago Hospital; Makerere Medical School. Of these 58 patients; 30 were assigned to a primary therapy with fluconazole (FLCZ) at a dose of 200mg/day for 2 months and flucytosine (5FC; 150/mg/Kg) for 2 weeks and 28 were assigned to month therapy with FLCZ at the same doze. All the patients who survived for 2 months continued to administrate FLCZ at a doze of 200mg three times per week as a maintenance therapy for 4 months. Fifty patients were evaluated for the survival rate at the end of the therapy for six months. The combination therapy prevented the early death of these patients; while half of patients who received monotherapy died within the first two weeks. The survival rate (32) of 25 patients receiving the combination therapy was significantly higher than that (12) of 25 patients receiving the monotherapy at the end of therapy for 6 months (P0.05). No serious adverse reactions were observed. These data suggest the combination therapy with low dose FLCZ and short course 5FC is cost-effective and safe regimen against CM in AIDS patients in developing countries

Effects of combination therapy with low dose fluconazole and flucytosine against cryptococcal; meningitis (CM) in patients in Uganda

From January through July 1994; 58 AIDS patients were enrolled at Mulago Hospital; Makerere Medical School. Of these 58 patients; 30 were assigned to a primary therapy with fluconazole (FLCZ) at a dose of 200mg/day for 2 months and flucytosine (5FC; 150/mg/Kg) for 2 weeks and 28 were assigned to month therapy with FLCZ at the same doze. All the patients who survived for 2 months continued to administrate FLCZ at a doze of 200mg three times per week as a maintenance therapy for 4 months. Fifty patients were evaluated for the survival rate at the end of the therapy for six months. The combination therapy prevented the early death of these patients; while half of patients who received monotherapy dided within the first two weeks. The survival rate (32) of 25 patients receiving the combination therapy was significantly higher than that (12) of 25 patients receiving the monotherapy at the end of therapy for 6 months (P0.05). No serious adverse reactions were observed. These data suggest the combination therapy with low dose FLCZ and short course 5FC is cost-effective and safe regimen against CM in AIDS patients in developing countries