RESUMEN
Background: Tuberculosis (TB) is an infectious morbidity that commonly occurs in people living with HIV (PWH) and increases the progression of HIV disease, as well as the risk of death. Simple markers of progression are much needed to identify those at highest risk for poor outcome. This study aimed to assess how baseline severity of anaemia and associated inflammatory profiles impact death and the incidence of TB in a cohort of PWH who received TB preventive therapy (TPT). Methods: This study is a secondary posthoc analysis of the AIDS Clinical Trials Group A5274 REMEMBER clinical trial (NCT0138008), an open-label randomised clinical trial of antiretroviral-naïve PWH with CD4 <50 cells/µL, performed from October 31, 2011 to June 9, 2014, from 18 outpatient research clinics in 10 low- and middle-income countries (Malawi, South Africa, Haiti, Kenya, Zambia, India, Brazil, Zimbabwe, Peru, and Uganda) who initiated antiretroviral therapy and either isoniazid TPT or 4-drug empiric TB therapy. Plasma concentrations of several soluble inflammatory biomarkers were measured prior to the commencement of antiretroviral and anti-TB therapies, and participants were followed up for at least 48 weeks. Incident TB or death during this period were primary outcomes. We performed multidimensional analyses, logistic regression analyses, survival curves, and Bayesian network analyses to delineate associations between anaemia, laboratory parameters, and clinical outcomes. Findings: Of all 269 participants, 76.2% (n = 205) were anaemic, and 31.2% (n = 84) had severe anaemia. PWH with moderate/severe anaemia exhibited a pronounced systemic pro-inflammatory profile compared to those with mild or without anaemia, hallmarked by a substantial increase in IL-6 plasma concentrations. Moderate/severe anaemia was also associated with incident TB incidence (aOR: 3.59, 95% CI: 1.32-9.76, p = 0.012) and death (aOR: 3.63, 95% CI: 1.07-12.33, p = 0.039). Interpretation: Our findings suggest that PWH with moderate/severe anaemia display a distinct pro-inflammatory profile. The presence of moderate/severe anaemia pre-ART was independently associated with the development of TB and death. PWH with anaemia should be monitored closely to minimise the occurrence of unfavourable outcomes. Funding: National Institutes of Health.
RESUMEN
OBJECTIVE: Type 2 diabetes is increasingly common in HIV-infected individuals. The objective of this study was to compare the glycemic effectiveness of oral diabetic medications among patients with and without HIV infection. RESEARCH DESIGN AND METHODS: A longitudinal cohort study was conducted among HIV-infected and uninfected veterans with type 2 diabetes initiating diabetic medications between 1999 and 2010. Generalized estimating equations were used to compare changes in hemoglobin A1c (HbA1c) through the year after medication initiation, adjusting for baseline HbA1c level and clinical covariates. A subanalysis using propensity scores was conducted to account for confounding by indication. RESULTS: A total of 2,454 HIV-infected patients and 8,892 HIV-uninfected patients initiated diabetic medications during the study period. The most commonly prescribed medication was metformin (n = 5,647, 50%), followed by a sulfonylurea (n = 5,554, 49%) and a thiazolidinedione (n = 145, 1%). After adjustment for potential confounders, there was no significant difference in the change in HbA1c level among the three groups of new users. HIV infection was not significantly associated with glycemic response (P = 0.24). Black and Hispanic patients had a poorer response to therapy compared with white patients, with a relative increase in HbA1c level of 0.16% (95% CI 0.08, 0.24) [1.7 mmol/mol (0.9, 2.6)] (P < 0.001) and 0.25% (0.11, 0.39) [2.7 mmol/mol (1.2, 4.3)] (P = 0.001), respectively. CONCLUSIONS: We found that glycemic response was independent of the initial class of diabetic medication prescribed among HIV-uninfected and HIV-infected adults with type 2 diabetes. The mechanisms leading to poorer response among black and Hispanic patients, who make up a substantial proportion of those with HIV infection and type 2 diabetes, require further investigation.