Overall there was no statistically significant protective effect of daily isoniazid for 6 months in the prevention of tuberculosis. In the TST-positive subjects, where reactivation is likely to be the more important pathogenetic mechanism, there was some protection and some reduction in mortality, although this was not statistically significant. The small number of individuals in this subgroup made the power to detect a statistically significant difference in this subgroup low. Other influences that may have diluted the efficacy of isoniazid include a high rate of transmission of new infection and rapid progression to disease or insufficient duration of isoniazid in subjects with relatively advanced immunosuppression. The rate of drug resistance observed in subjects who received isoniazid and subsequently developed tuberculosis was low.

Background The number of youth and adolescents (10–24 years) with HIV infection has increased substantially presenting unique challenges to effective health service delivery. Methods We examined routinely collected patient-level data for antiretroviral treatment (ART)-naive HIV-infected patients, aged 10–24 years, enrolled in care during 2006–2011 at 109 ICAP-supported health facilities in three provinces in Kenya. Loss to follow-up (LTF) was defined as having no clinic visit for 12 months prior to ART initiation (pre-ART) and 6 months for ART patients. Competing risk and Kaplan–Meier estimators were used to calculate LTF and death rates. Sub-distributional and Cox proportional-hazards models were used to identify potential predictors of death and LTF. Results Overall 22 832 patients were enrolled in care at 10–24 years of age, 69.5% were aged 20–24 years, and 82% were female. Median CD4+ cell count was 332 cells/μl (interquartile range 153–561); 70.8% were WHO stage I/II. Young adolescents (10–14 years) had more advanced WHO stage and lower median CD4+ cell count compared to youth (15–24 years) at enrollment (284 vs. 340 cells/μl; P <0.0001). Cumulative incidence of LTF and death at 24 months for pre-ART patients was 46.1% [95% confidence interval (CI) 45.4–46.8%) and 2.1% (95% CI 1.9–2.3%), respectively. For those on ART, 32.2% (95% CI 31.1–33.3%) were LTF and 3.9% (95% CI 1.7–2.3%) died within 24 months. LTF among pre-ART and ART patients was twice as high among youth compared to young adolescents. Conclusion LTF of young people with HIV in this Kenyan cohort was high and notably greater among youth compared to young adolescents. Novel strategies targeting these populations are urgently needed to improve retention.

HIV infection has now been consistently identified as the major cause of death in young Africans in both urban and rural areas. In Africa, several studies have defined the clinical presentation of HIV disease but there have only been a limited number of autopsy studies. Because of the scarcity of autopsy data and the possibility of differing type and frequency of opportunistic infections between different geographic locations we set out to study consecutive new adult medical admissions to a tertiary referral hospital in Nairobi and perform autopsies on a sample of HIV-1-positive and HIV-1-negative patients who died in the hospital ward. Basic demographic data were collected on all patients admitted to two acute medical wards over an 11-month period. Final outcome and final clinical diagnoses were recorded at discharge or death. An autopsy examination was requested if the patient died in the ward. Autopsy examination was performed in 75 HIV-1-positive (40 men, 35 women) and 47 HIV-1-negative (28 men, 19 women) adults who died in the hospital. This represented 48.4% of all HIV-1-positive deaths and 33.3% of all HIV-1-negative deaths. Tuberculosis (TB) and bacterial and interstitial bronchopneumonia accounted for 96% of the major pathology in patients found to be HIV-1-positive at autopsy. TB was present in half the HIV-1-positive autopsy patients and was disseminated in over 80% of cases. Meningeal involvement was present in 26% of those with disseminated TB. By contrast, TB was much less common in the HIV-1-negative patients at autopsy in whom bacterial bronchopneumonia and malignancies were the most common pathologies. The type pathology found in the HIV-1-positive autopsy patients was not different than that found in other areas in Africa so far studied.

To test the hypothesis that antituberculous drug disposition is altered in patients with AIDS, we studied the steady-state pharmacokinetics of isoniazid (300 mg/d), rifampin (600 mg/d), and pyrazinamide (1,500 mg/d) in 29 adults (14 patients infected with human immunodeficiency virus [HIV] and 15 non-HIV-infected patients) with tuberculosis in Nairobi, Kenya. Intestinal integrity was assessed with xylose. Neither HIV infection nor diarrhea accounted for the interpatient variability in the area-under-the-plasma concentration vs. time curve (AUC), the maximum concentration, or the terminal half-life (t1/2) of isoniazid, rifampin, and pyrazinamide. No significant association between HIV infection or diarrhea and pharmacokinetics was seen for any of the compounds. In addition, neither the AUC nor the t1/2 of any of these drugs reflected interpatient differences in CD4 lymphocyte counts. Xylose absorption was uniformly low. We did not demonstrate that HIV infection, diarrhea, or CD4 lymphocyte counts contributed significantly to the variability in pharmacokinetics of isoniazid, rifampin, and pyrazinamide in TB patients in Nairobi.