BACKGROUND. Cytotoxic T lymphocyte–mediated (CTL-mediated) severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), are rare but life-threatening adverse reactions commonly induced by drugs. Although high levels of CTL-associated cytokines, chemokines, or cytotoxic proteins, including TNF-α and granulysin, were observed in SJS-TEN patients in recent studies, the optimal treatment for these diseases remains controversial. We aimed to evaluate the efficacy, safety, and therapeutic mechanism of a TNF-α antagonist in CTL-mediated SCARs. METHODS. We enrolled 96 patients with SJS-TEN in a randomized trial to compare the effects of the TNF-α antagonist etanercept versus traditional corticosteroids. RESULTS. Etanercept improved clinical outcomes in patients with SJS-TEN. Etanercept decreased the SCORTEN-based predicted mortality rate (predicted and observed rates, 17.7% and 8.3%, respectively). Compared with corticosteroids, etanercept further reduced the skin-healing time in moderate-to-severe SJS-TEN patients (median time for skin healing was 14 and 19 days for etanercept and corticosteroids, respectively; P = 0.010), with a lower incidence of gastrointestinal hemorrhage in all SJS-TEN patients (2.6% for etanercept and 18.2% for corticosteroids; P = 0.03). In the therapeutic mechanism study, etanercept decreased the TNF-α and granulysin secretions in blister fluids and plasma (45.7%–62.5% decrease after treatment; all P < 0.05) and increased the Treg population (2-fold percentage increase after treatment; P = 0.002), which was related to mortality in severe SJS-TEN. CONCLUSIONS. The anti–TNF-α biologic agent etanercept serves as an effective alternative for the treatment of CTL-mediated SCARs. TRIAL REGISTRATION. ClinicalTrials.gov NCT01276314. FUNDING. Ministry of Science and Technology of Taiwan.

(See the editorial commentary by Levine and Farag, on pages 349-351 .) Background. Few studies describe patterns of human immunodeficiency virus (HIV) co-infections in African hospitals in the antiretroviral therapy (ART) era. Methods. We enrolled consecutive admitted patients aged ≥13 years with oral temperature of ≥38.0°C during 1 year in Moshi, Tanzania. A standardized clinical history and physical examination was done and hospital outcome recorded. HIV antibody testing, aerobic and mycobacterial blood cultures, and malaria film were performed. HIV-infected patients also received serum cryptococcal antigen testing and CD4⁺ T lymphocyte count (CD4 cell count). Results. Of 403 patients enrolled, the median age was 38 years (range, 14–96 years), 217 (53.8%) were female, and 157 (39.0%) were HIV-infected. Of HIV-infected patients, the median CD4 cell count was 98 cells/μL (range, 1–1,105 cells/ μL), 20 (12.7%) were receiving ART, and 29 (18.5%) were receiving trimethoprim-sulfamethoxazole prophylaxis. There were 112 (27.7%) patients who had evidence of invasive disease, including 26 (23.2%) with Salmonella serotype Typhi infection, 24 (21.4%) with Streptococcus pneumoniae infection, 17 (15.2%) with Cryptococcus neoformans infection, 12 (10.7%) with Mycobacterium tuberculosis complex infection, 8 (7.1%) with Plasmodium falciparum infection, and 7 (6.3%) with Escherichia coli infection. HIV infection was associated with M. tuberculosis and C. neoformans bloodstream infection but not with E. coli, S. pneumoniae, or P. falciparum infection. HIV infection appeared to be protective against Salmonella. Typhi bloodstream infection (odds ratio, .12; P = .001). Conclusions. While Salmonella Typhi and S. pneumoniae were the most common causes of invasive infection overall, M. tuberculosis and C. neoformans were the leading causes of bloodstream infection among HIV-infected inpatients in Tanzania in the ART era. We demonstrate a protective effect of HIV against Salmonella. Typhi bloodstream infection in this setting. HIV co-infections continue to account for a large proportion of febrile admissions in Tanzania.

Data on weight gain and the progression to overweight/obesity in HIV-infected persons during initial combination antiretroviral therapy (cART) are limited, and comparisons to the general population are inconclusive. Weight and body mass index (BMI) changes were studied in HIV-infected adults who remained on initial cART for 12 consecutive months and in an HIV-uninfected cohort receiving care at Duke University Medical Center between 1998 and 2008. Overweight/obesity was defined as BMI ≥25 kg/m ² . Variables were analyzed by Chi-square and Student's t -tests. Ninety-two HIV-infected persons (median age 38.2 years) met inclusion criteria. Weight and BMI increased during 12 months of cART (80.0 to 84.4 kg, p <0.0001; 26.4 to 27.9 kg/m ² , p <0.0001; respectively). Weight gain was greater in HIV-infected females compared to males (8.6 vs. 3.6 kg, p =0.04), in persons treated with protease inhibitor (PI)-based cART compared to non-PI-based cART (9.0 vs. 2.7 kg, p =0.001), and in persons with a pretreatment CD4 count <200 cells/mm ³ compared to ≥200 cells/mm ³ (8.9 vs. 0.3 kg, p <0.0001). Overweight/obesity prevalence increased from 52% to 66% during 12 months of initial cART, a 27% relative increase ( p =0.002). HIV-infected persons had a lower prevalence of pretreatment overweight/obesity compared to 94 age-matched control subjects (52% vs. 91%, p 0.9) during 12 months in the control cohort. Management should anticipate excess weight gain during the first year of cART in persons who are female, have a pretreatment CD4 <200 cells/mm ³ , or will initiate PI-based cART.

Summary: Objective  To describe the contribution of paediatric HIV and of HIV co‐infections to admissions to a hospital in Moshi, Tanzania, using contemporary laboratory methods.Methods  During 1 year, we enrolled consecutively admitted patients aged ≥2 months and <13 years with current or recent fever. All patients underwent standardized clinical history taking, a physical examination and HIV antibody testing; standard aerobic blood cultures and malaria film were also done, and hospital outcome was recorded. Early infant HIV diagnosis by HIV‐1 RNA PCR was performed on those aged <18 months. HIV‐infected patients also received serum cryptococcal antigen testing and had their CD4‐positive T‐lymphocyte count and percent determined.Results  A total of 467 patients were enrolled whose median age was 2 years (range 2 months–13 years); Of those patients, 57.2% were female and 12.2% were HIV‐infected. Admission clinical diagnosis of HIV disease was made in 10.7% and of malaria in 60.4%. Of blood cultures, 5.8% grew pathogens; of these 25.9% were Salmonella enterica (including 6 Salmonella Typhi) and 22.2%Streptococcus pneumoniae. Plasmodium falciparum was identified on blood film of 1.3%. HIV infection was associated with S. pneumoniae (odds ratio 25.7, 95% CI 2.8, 234.0) bloodstream infection (BSI), but there was no evidence of an association with Escherichia coli or P. falciparum; Salmonella Typhi BSI occurred only among HIV‐uninfected participants. The sensitivity and specificity of an admission clinical diagnosis of malaria were 100% and 40.3%; and for an admission diagnosis of bloodstream infection, they were 9.1% and 86.4%, respectively.Conclusion  Streptococcus pneumoniae is a leading cause of bloodstream infection among paediatric admissions in Tanzania and is closely associated with HIV infection. Malaria was over‐diagnosed clinically, whereas invasive bacterial disease was underestimated. HIV and HIV co‐infections contribute to a substantial proportion of paediatric febrile admissions, underscoring the value of routine HIV testing.