Reduction of inflammation and T cell activation after 6 months of cART initiation during acute, but not in early chronic HIV-1 infection.

OBJECTIVES: To investigate the impact of early combined antiretroviral therapy (cART) on inflammation biomarkers and immune activation during acute and early chronic HIV-1 infection. METHODS: We included 12 acute (AHI), 11 early chronic (EcHI), and 18 late chronic HIV-1-infected (LcHI) individuals who were treated with cART and 18 HIV-1-uninfected (HIV-neg) individuals. Plasmatic levels of inflammation biomarkers, CD8+CD38+HLA-DR+ T cell frequencies, CD4 T cell counts, CD4/CD8 ratio, total HIV-1 DNA and plasmatic viral load were evaluated. Mann-Whitney test, Pearson and Spearman correlation, and linear regression models were used for statistical analyses. RESULTS: IP-10, IL-18, and sCD163 were significantly elevated at pre-ART in the AHI and EcHI groups, showing a significant reduction after 6 months of cART in the AHI group, achieving similar levels to the HIV-neg group. For the EcHI group, the IP-10 and sCD163 levels were also significantly reduced on M6-ART; however, IP-10 levels remained higher than in the HIV-neg group, and no significant reduction of IL-18 levels was observed. The CD8+ T cell activation levels were elevated in the AHI and EcHI groups at pre-ART and showed a significant reduction on M6-ART, but they were similar to levels seen for HIV-neg only after 12 months of cART. At pre-ART, IP-10 levels but not IL-18 levels were positively correlated with HIV-1 viral load in the AHI group. CONCLUSIONS: Early initiation of cART in HIV infection can reduce systemic inflammation, but the earlier normalization of the inflammation markers was only observed when cART was initiated in the acute phase of infection. A slower dynamic of reduction was observed for CD8+ T cell activation.

Chikungunya fever: How accurate is the clinical-epidemiological diagnosis compared to the gold standard of molecular and serological laboratory diagnosis?

OBJECTIVE: To evaluate the accuracy of the current World Health Organization' (WHO) Chikungunya fever (CHIKF) clinical-epidemiological case definition against the gold standard of laboratory diagnosis. METHODS: This was a prospective study of patients seeking medical care at an Emergency Department in the metropolitan area of Rio de Janeiro, Brazil, from January to June 2018. Clinical features were recorded. Screening for CHIKF was performed using the RT-qPCR and ELISA-IgM antibody assay. Clinical features of CHIKF RT-qPCR/IgM positive cases were compared with those with other febrile illnesses. RESULTS: 27,900 ED visits were recorded, of which 172 (0.61 %) patients were screened for arboviral illness. The prevalence of laboratory-confirmed CHIKF (Lab-CHIKF) was 110/172 [64 %]. Chikungunya virus RNA was detected in 92/172 (53.5 %) patients, while in 18/80 (10.5 %), only IgM was positive. Compared to CHIKV-negative subjects, patients with CHIKF presented much earlier after the onset of symptoms (2 [1-4] vs. 3.5 [2.5-5], p = 0.007), and more frequently reported arthritis (61.8 % vs. 33.9 %, p < 0.0001), arthralgia (96.4 % vs. 79 %, p < 0.0001), and conjunctivitis (35.5 % vs. 16.1 %, p = 0.007). After adjustments for other clinical predictors, arthritis/arthralgia [aOR: 6 (95 % CI 1.8-19.7)] and the presence of conjunctivitis [aOR: 2.85 (95 % CI 1.30-6.24] were positively associated with lab-CHIKF. The sensitivity, specificity, positive predictive value, and negative predictive value of the WHO CHIKF clinical case definition was 96.3 %, 20.9 %, 68.3 % and 76.4 %, respectively, and accuracy was 0.69 [AUC: 0.69 (95 % CI 0.61-0.75)]. CONCLUSION: The WHO case definition needs to be improved for better accuracy, especially in areas in epidemics in areas with co-circulation of arboviruses.