Studies of heterosexual discordant couples observed no transmission in patients treated with ART and with viral load below 400 copies/ml, but data were compatible with one transmission per 79 person-years. Further studies are needed to better define the risk of HIV transmission from patients on ART.

Summary This systematic review examines the incidence of Immune Reconstitution Disease (IRD) in HIV-1 infected patients starting antiretroviral combination therapy (ART). We analysed 13103 patients from 54 cohort studies; 1685 patients developed IRD. Pooled incidences with 95% credibility intervals (CrI) were calculated using Bayesian methods. In patients with previously diagnosed AIDS-defining conditions the incidence was 37.7% (95% CrI 26.6–49.4%) for CMV retinitis, 19.5% (6.7–44.8%) for cryptococcal meningitis, 15.7% (9.7–24.5%) for tuberculosis, 16.7% (2.3–50.7%) for progressive multifocal leukencephalopathy and 6.4% (1.2–24.7%) for Kaposi’s sarcoma. The incidence of any type of IRD, based on studies of unselected patients starting ART, was 16.1% (11.1–22.9%). Lethality was 4.5% (2.1–8.6%) for any type of IRD, 3.2% (0.7–9.2%) for tuberculosis and 20.8% (5.0–52.7%) for cryptococcal meningitis. Meta-regression analyses showed that the incidence is largely determined by the CD4 cell count at the start of ART, with a high risk in patients starting below 50 cells/μl. Many of the IRD events might therefore be prevented with earlier initiation of ART.

Background: Diarrhea affects a large proportion of children with severe acute malnutrition (SAM). However, its etiology and clinical consequences remain unclear.Objective: We investigated diarrhea, enteropathogens, and systemic and intestinal inflammation for their interrelation and their associations with mortality in children with SAM.Design: Intestinal pathogens (n = 15), cytokines (n = 29), fecal calprotectin, and the short-chain fatty acids (SCFAs) butyrate and propionate were determined in children aged 6–59 mo (n = 79) hospitalized in Malawi for complicated SAM. The relation between variables, diarrhea, and death was assessed with partial least squares (PLS) path modeling.Results: Fatal subjects (n = 14; 18%) were younger (mean ± SD age: 17 ± 11 compared with 25 ± 11 mo; P = 0.01) with higher prevalence of diarrhea (46% compared with 18%, P = 0.03). Intestinal pathogens Shigella (36%), Giardia (33%), and Campylobacter (30%) predominated, but their presence was not associated with death or diarrhea. Calprotectin was significantly higher in children who died [median (IQR): 1360 mg/kg feces (2443–535 mg/kg feces) compared with 698 mg/kg feces (1438–244 mg/kg feces), P = 0.03]. Butyrate [median (IQR): 31 ng/mL (112–22 ng/mL) compared with 2036 ng/mL (5800–149 ng/mL), P = 0.02] and propionate [median (IQR): 167 ng/mL (831–131 ng/mL) compared with 3174 ng/mL (5819–357 ng/mL), P = 0.04] were lower in those who died. Mortality was directly related to high systemic inflammation (path coefficient = 0.49), whereas diarrhea, high calprotectin, and low SCFA production related to death indirectly via their more direct association with systemic inflammation.Conclusions: Diarrhea, high intestinal inflammation, low concentrations of fecal SCFAs, and high systemic inflammation are significantly related to mortality in SAM. However, these relations were not mediated by the presence of intestinal pathogens. These findings offer an important understanding of inflammatory changes in SAM, which may lead to improved therapies. This trial was registered at www.controlled-trials.com as ISRCTN13916953.