Objectives: To determine the long-term incidence of tuberculosis (TB) and associated risk factors among individuals receiving HAART in South Africa. Design: Prospective cohort study. Methods: Microbiologically or histologically confirmed incident TB was identified in a hospital-based cohort of 346 patients receiving HAART between 1996 and 2005 in Cape Town. Results: The TB incidence density rate was 3.5/100 person-years in the first year and significantly decreased during follow-up, reaching 1.01/100 person-years in the fifth year (P = 0.002 for trend). TB incidence during the study was highest among patients with baseline CD4 cell counts < 100 cells/μl and those with World Health Organization (WHO) clinical stage 3 or 4 disease (5.71 and 3.88/100 person-years, respectively). Risk of TB was independently associated with CD4 cell count < 100 cells/μl (adjusted risk ratio [ARR], 2.38; 95% confidence interval (CI), 1.01–5.60; P = 0.04), WHO stage 3 or 4 disease (ARR, 3.60; 95% CI, 1.32–9.80; P = 0.01) and age < 33 years (ARR, 2.86; 95% CI, 1.29–6.34; P = 0.01). Risk of TB was not independently associated with plasma viral load, previous history of TB, low socioeconomic status or sex. Despite similar virological responses to HAART, blood CD4 cell count increases were much smaller among patients who developed TB than among those who remained free of TB. Conclusions: Incidence of TB continues to decrease during the first 5 years of HAART and so HAART may contribute more to TB control in low-income countries than was previously estimated from short-term follow-up. Patients with advanced pretreatment immunodeficiency had persistently increased risk of TB during HAART; this may reflect limited capacity for immune restoration among such patients.

To determine adherence of an indigent African HIV-infected cohort initiating antiretroviral therapy (ART); to identify predictors of incomplete adherence (< 95%) and virologic failure (> 400 HIV RNA copies/ml). Prospective monitoring of adherence in a poor HIV-positive cohort, attending a public sector hospital and receiving ART through phase III studies. Adherence to ART was determined over 48 weeks by counting tablet-returns. Logistic regression models including age, WHO HIV stage, home language, socio-economic status, complexity and type of regimen were fitted to determine predictors of incomplete adherence and virologic failure at 48 weeks. 289 patients were recruited between January 1996 and May 2001. Median (mean) adherence of the cohort was 93.5% (87.2%). Three times daily dosing [risk ratio (RR), 3.07; 95% confidence interval (CI), 1.40-6.74], speaking English (RR, 0.41; 95% CI, 0.21-0.80) and age (RR, 0.97; 95% CI, 0.94-0.99) were independent predictors of incomplete adherence. Socio-economic status, sex and HIV stage did not predict adherence. Independent predictors of virologic failure included baseline viral load (RR, 2.57; 95% CI, 1.57-4.22) and three times daily dosing (RR, 2.64; 95% CI, 1.23-5.66), incomplete adherence (RR, 1.92; 95% CI, 1.10-3.57), age (RR, 0.96; 95% CI, 0.92-0.99) and dual nucleoside therapy (RR, 2.69; 95% CI, 1.17-6.15). The proportion of individuals achieving viral suppression matched results from the developing world. Speaking the same language as site staff and simplified dosing frequency were beneficial. Socio-economic status had no impact on adherence and should not be used as a limitation to ART access.

Data from Kwazulu Natal, South Africa, suggest that almost all patients with extensively drug-resistant (XDR) tuberculosis are HIV-positive, with a fatal outcome. Since, there are few data for the treatment-related outcomes of XDR tuberculosis in settings with a high HIV prevalence, we investigated the associations of these diseases in such settings to formulate recommendations for control programmes. In a retrospective cohort study, we analysed the case records of patients (>16 years old) with XDR tuberculosis (culture-proven at diagnosis) between August, 2002, and February, 2008, at four designated provincial treatment facilities in South Africa. We used Cox proportional hazards regression models to assess risk factors associated with the outcomes-mortality and culture conversion. 195 of 227 patients were analysed. 21 died before initiation of any treatment, and 174 patients (82 with HIV infection) were treated. 62 (36%) of these patients died during follow-up. The number of deaths was not significantly different in patients with or without HIV infection: 34 (41%) of 82 versus 28 (30%) of 92 (p=0.13). Treatment with moxifloxacin (hazard ratio 0.11, 95% CI 0.01-0.82; p=0.03), previous culture-proven multidrug-resistant tuberculosis (5.21, 1.93-14.1; p=0.001), and number of drugs used in a regimen (0.59, 0.45-0.78, p<0.0001) were independent predictors of death. Fewer deaths occurred in patients with HIV infection given highly active antiretroviral therapy than in those who were not (0.38, 0.18-0.80; p=0.01). 33 (19%) of 174 patients showed culture conversion, of which 23 (70%) converted within 6 months of initiation of treatment. In South Africa, patients with XDR tuberculosis, a substantial proportion of whom are not infected with HIV, have poor management outcomes. Nevertheless, survival in patients with HIV infection is better than previously reported. The priorities for the country are still prevention of XDR tuberculosis, and early detection and management of multidrug-resistant and XDR tuberculosis through strengthened programmes and laboratory capacity. South African Medical Research Council, European Union Framework 7 program, and European Developing Countries Clinical Trials Partnership.

To assess the prevalence and risk factors for faecal carriage of fluoroquinolone-resistant, extended-spectrum β-lactamase (ESBL)-producing, Escherichia coli (MDR E. coli) among residents in nursing homes in Northern Ireland. Between January 2004 and May 2006, retrospective histories of hospital admissions, antimicrobial treatment and co-morbidities were collected. Faecal samples were cultured for MDR E. coli. These isolates and their ESBL genes were typed by a reference laboratory. Of the 294 patients included in the study, faecal samples from 119 (40.5%) grew MDR E. coli. The proportion of carriers in the different homes ranged from 0% to 75%. Epidemic strain A belonging to the ST131, O25:H4 lineage with the CTX-M-15 enzyme accounted for 58 (49%) of all isolates; its proportion varied from 0% to 100% among homes. Fifty-one percent of carriers had no history of recent hospital admission and only 13.5% had a known history of ESBL E. coli colonization or infection. In a multivariate logistic regression model, days of fluoroquinolone use [odds ratio (OR) = 1.33, 95% confidence interval (CI) 1.04–1.69, P = 0.02] and a history of urinary tract infection (OR = 2.56, 95% CI 1.37–4.78, P = 0.003) were the only variables independently associated with the risk of carrying MDR E. coli. The high level of faecal carriage of MDR E. coli in nursing home residents demonstrates their importance as a reservoir population. Public health measures to combat spread of these organisms should address the needs of this group.