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Background: We assessed risk factors for viremia and drug resistance among long-term recipients of antiretroviral therapy (ART) in South Africa., Methods: In 2008, we conducted a cross-sectional study among patients receiving ART for 12 months or more. Genotypic resistance testing was performed on individuals with a viral load higher than 400 RNA copies/ml. Multiple logistic regression analysis was used to assess associations., Results: Of 998 participants, 75% were women with a median age of 41 years. Most (64%) had been on treatment for more than 3 years. The prevalence of viremia was 14% (n = 139): 12% (102/883) on first-line [i.e. nonnucleoside reverse-transcriptase inhibitor (NNRTI)-based regimen] and 33% (37/115) on second-line (i.e. protease inhibitor (PI)-based regimen) ART. Of viremic patients, 78% had drug resistance mutations. For NRTIs, NNRTIs and PIs, the prevalence of mutations was 64, 81 and 2%, respectively, among first-line failures and 29, 54 and 6%, respectively, among second-line failures. M184V/I, K103N and V106A/M were the most common mutations. Significant risk factors associated with viremia on first-line regimen included concurrent tuberculosis treatment [odds ratio (OR) 6.4, 95% confidence interval (CI) 2.2-18.8, P < 0.01] and a recent history of poor adherence (OR 2.7, 1.3-5.6, P = 0.01). Among second-line failures, attending a public clinic (OR 4.6, 95% CI 1.8-11.3, P < 0.01) and not having a refrigerator at home (OR 6.7, 95% CI 1.2-37.5, P = 0.03) were risk factors for virological failure., Conclusion: Risk factors for viral failure were line regimen dependent. Second-line ART recipients had a higher rate of viremia, albeit with infrequent PI drug resistance mutations. Measures to maintain effective virologic suppression should include increased adherence counseling, attention to concomitant tuberculosis treatment and heat-stable formulations of second-line ART regimens.

Objective: To ascertain the immediate and underlying causes of death in adults who died in hospital with a premortem diagnosis of tuberculosis., Design: Causes of death were assessed independently by internists and pathologists in 50 adults admitted to two Soweto hospitals who died 24 h or more after admission. Detailed record reviews and complete autopsies, including HIV tests when not performed premortem, were performed. In addition, a variety of postmortem microbiological tests were performed., Results: Forty-seven patients had HIV infection; all were antiretroviral naive. Their median age was 34.5 years, median CD4 cell count was 48 cells/microl and median length of hospitalization before death was 6 days. Autopsy confirmed the premortem diagnosis of tuberculosis in 37 HIV-infected patients (79%), whereas 10 (21%) did not demonstrate tuberculosis. Bronchopneumonia and cytomegalovirus pneumonitis were the leading pathologies in these 10 patients. In 47 HIV-infected cadavers immediate or contributory causes of death were: extensive pulmonary tuberculosis, 32 (68%); disseminated tuberculosis, 28 (60%); bacterial pneumonia, 13 (26%); cytomegalovirus pneumonitis in seven (15%); cytomegalovirus DNA was found in 31 (66%) and Pneumocystis pneumonia was found in five cadavers (11%). The lung, followed by lymph nodes, liver and kidney, were the commonest sites of tuberculosis. Mycobacterium tuberculosis was cultured from 19 spleens, one of which was multidrug resistant, and Salmonella spp. was cultured from 11 splenic specimens., Conclusion: We demonstrated disseminated, extensive tuberculosis associated with advanced HIV disease. Severe bacterial infections, including salmonellosis, were the leading co-morbidity, suggesting that hospitalized HIV-infected adults in whom tuberculosis is suspected may benefit from broad-spectrum antibiotic therapy.