Rapidly improving ARDS differs clinically and biologically from persistent ARDS.

BACKGROUND: Rapidly improving acute respiratory distress syndrome (RIARDS) is an increasingly appreciated subgroup of ARDS in which hypoxemia improves within 24 h after initiation of mechanical ventilation. Detailed clinical and biological features of RIARDS have not been clearly defined, and it is unknown whether RIARDS is associated with the hypoinflammatory or hyperinflammatory phenotype of ARDS. The purpose of this study was to define the clinical and biological features of RIARDS and its association with inflammatory subphenotypes. METHODS: We analyzed data from 215 patients who met Berlin criteria for ARDS (endotracheally intubated) and were enrolled in a prospective observational cohort conducted at two sites, one tertiary care center and one urban safety net hospital. RIARDS was defined according to previous studies as improvement of hypoxemia defined as (i) PaO2:FiO2 > 300 or (ii) SpO2: FiO2 > 315 on the day following diagnosis of ARDS (day 2) or (iii) unassisted breathing by day 2 and for the next 48 h (defined as absence of endotracheal intubation on day 2 through day 4). Plasma biomarkers were measured on samples collected on the day of study enrollment, and ARDS phenotypes were allocated as previously described. RESULTS: RIARDS accounted for 21% of all ARDS participants. Patients with RIARDS had better clinical outcomes compared to those with persistent ARDS, with lower hospital mortality (13% vs. 57%; p value < 0.001) and more ICU-free days (median 24 vs. 0; p value < 0.001). Plasma levels of interleukin-6, interleukin-8, and plasminogen activator inhibitor-1 were significantly lower among patients with RIARDS. The hypoinflammatory phenotype of ARDS was more common among patients with RIARDS (78% vs. 51% in persistent ARDS; p value = 0.001). CONCLUSIONS: This study identifies a high prevalence of RIARDS in a multicenter observational cohort and confirms the more benign clinical course of these patients. We report the novel finding that RIARDS is characterized by lower concentrations of plasma biomarkers of inflammation compared to persistent ARDS, and that hypoinflammatory ARDS is more prevalent among patients with RIARDS. Identification and exclusion of RIARDS could potentially improve prognostic and predictive enrichment in clinical trials.

Factors associated with decreased kidney function in HIV-infected adults enrolled in the MTCT-Plus Initiative in sub-Saharan Africa.

BACKGROUND: Pre-existing kidney disease in HIV-infected patients may necessitate dose modification of antiretroviral therapy (ART). Despite increasing ART availability, there are few prevalence studies of chronic kidney disease in HIV-infected individuals across multiple African countries. METHODS: Routine laboratory data obtained before ART initiation were used to evaluate prevalence and predictors of decreased creatinine clearance (CrCl) in participants of the MTCT-Plus Initiative from 7 sub-Saharan countries. Cockcroft-Gault equation was used to estimate CrCl and logistic regression modeling to identify factors associated with CrCl <50 mL/min. RESULTS: Of 2495 individuals evaluated, median age was 30 years (interquartile range: 27-35); 70% were women. Median CD4+ cell count was 295 (interquartile range: 173-450); 78% were World Health Organization stage 1/2. Median CrCl was 95 mL/min. Overall, 3.4% [95% confidence interval (CI): 2.7 to 4.1] of patients had a CrCl <50 mL/min. Age >30 years (odds ratio = 2.06; 95% CI: 1.23 to 3.45) and CD4+ count <50 cells per cubic millimeter (odds ratio = 5.4 for CD4+ <50, 95% CI: 2.5 to 11.9) were associated with CrCl <50 mL/min. CONCLUSIONS: The prevalence of clinically significant kidney disease was low in this relatively healthy population of HIV-infected adults, and few participants would have required ART dose reductions. These findings support recent World Health Organization guidelines to initiate ART without routine laboratory screening. Our findings suggest that available laboratory resources could be targeted to older persons and those with very low CD4+ cell count.

CD4+ cell count testing more effective than HIV disease clinical staging in identifying pregnant and postpartum women eligible for antiretroviral therapy in resource-limited settings.

OBJECTIVE: Identifying antiretroviral therapy (ART) eligible HIV-infected (HIV+) pregnant women and rapidly initiating treatment preserves maternal health and prevents mother-to-child transmission. However, there have been few investigations of the performance of ART eligibility criteria in pregnant and postpartum women in resource-limited settings. METHODS: Pregnant and recently postpartum HIV+ women received CD4+ cell count and World Health Organization (WHO) clinical staging at enrollment into the mother-to-child transmission Plus Initiative. We compared immunologic and clinical criteria based on 2009 WHO ART treatment guidelines (WHO stage 3/4 or CD4+ cell count ≤350 cells/mm³) in identifying ART eligible women. RESULTS: Among 6036 women (62% antepartum, 38% postpartum), 2915 (48%) were ART eligible. Only 23% had WHO stage 3 or 4 disease, whereas 94% met CD4+ cell count criterion. Among 5356 women with WHO stage 1 or 2 disease, 2235 (42%) had CD4+ ≤350 cells per cubic millimeter. Change of CD4+ cell count ART eligibility threshold from ≤200 to ≤350 cells per cubic millimeter increased the proportion of ART eligible women from 21% to 45%. CONCLUSIONS: Use of CD4+ cell count criterion is superior to clinical staging in identifying pregnant and postpartum HIV+ women eligible for ART. Improving access to CD4+ testing is essential to identify and treat eligible women, optimizing maternal and child health outcomes.

Initiation of antiretroviral therapy among pregnant women in resource-limited countries: CD4+ cell count response and program retention.

OBJECTIVE(S): Few data are available from resource-limited countries on long-term outcomes of HIV-infected women who initiate antiretroviral therapy (ART) during pregnancy. DESIGN: Analysis of data from adult patients enrolled in the MTCT-Plus Initiative who initiated ART between 2003 and 2006 in seven countries in Sub-Saharan Africa and Thailand. METHODS: Mean population changes were assessed and multivariable mixed linear regression modeling was used to examine covariate effects on differences in absolute CD4 cell count responses. Kaplan-Meier methods were used to examine program retention combining survival and losses to follow-up. RESULTS: Of 2229 individuals initiating ART, 1688 were women, of which 605 were pregnant (median gestational age 7 months), 1083 were not pregnant, and 541 were men. The average CD4 response by 30 months on ART was 451 cells/microl among women who were pregnant at ART initiation as compared with 435 cells/microl among nonpregnant women (P = 0.53) and 349 cells/microl among men (P < 0.001). In multivariable analysis, lower CD4 cell increase was independently associated with male sex, older age, and lower CD4 cell count at initiation. After 30 months on ART retention was 0.85 with no retention differences between pregnant women, nonpregnant women, and men. CONCLUSION: HIV-infected women in resource-limited countries who start ART during pregnancy have similar or better long-term CD4 cell count responses as compared with other adults. These data support efforts to provide pregnant HIV-infected women with access to ART in resource-limited countries.

Sensitivity analysis and potential uses of a novel gamma interferon release assay for diagnosis of tuberculosis.

Sputum smears for acid-fast bacilli (AFB) are the primary methods for diagnosis of tuberculosis (TB) in many countries. The tuberculin skin test (TST) is the primary method for diagnosis of latent TB infection (LTBI) worldwide. The poor sensitivity of the former and the poor specificity of the latter warrant the development of new tests and strategies to enhance diagnostic capabilities. We evaluated the sensitivity of an "in-tube" gamma interferon release assay (IGRA) using TB-specific antigens in comparison to the TST and the sputum smear for AFB in TB cases in South Africa. The sensitivity of the IGRA for TB was considered a surrogate of sensitivity in LTBI. Among 154 patients with a positive culture for Mycobacterium tuberculosis, the sensitivity of the IGRA for the diagnosis of TB varied by clinical subgroup from 64% to 82%, that of the TST varied from 85% to 94%, and that of two sputum smears for AFB varied from 35% to 53%. The sensitivity of the IGRA in human immunodeficiency virus (HIV)-infected TB cases was 81%. HIV-infected TB patients were significantly more likely to have indeterminate IGRA results and produced quantitatively less gamma interferon in response to TB-specific antigens than HIV-negative TB patients. The overall sensitivity of the TST in all TB cases was higher than that of the IGRA (90% versus 76%, respectively). The combined sensitivities of the TST plus IGRA and TST plus a single sputum smear were 96% and 93%, respectively. The TST combined with IGRA or with a single sputum smear may have a role in excluding the diagnosis of TB in some settings.