Natural controlled HIV infection: preserved HIV specific immunity despite undetectable replication competent virus.

Long-term non-progressive HIV infection, characterized by low but detectable viral load and stable CD4 counts in the absence of antiviral therapy, is observed in about 5% of HIV-infected patients. Here we identified four therapy naive individuals who are strongly seropositive for HIV-1 but who lack evidence of detectable HIV p24 antigen, plasma RNA, and proviral DNA in routine diagnostic testing. With an ultrasensitive PCR, we established that frequencies of pol proviral DNA sequences were as low as 0.2-0.5 copies/10(6) PBMC. HIV could not be isolated using up to 30 x 10(6) patient PBMC. One individual was heterozygous for CCR5 Delta 32, but CCR5 expression on CD4(+) T cells was normal to high in all four individuals. In vitro R5 and X4 HIV-1 susceptibility of CD8-depleted PBMC of all study subjects was significantly lower than the susceptibility of CD8-depleted PBMC of healthy blood donors. All individuals expressed protective HLA-B*58s alleles and showed evidence of HIV-specific cellular immunity either by staining with HLA-B*57 tetramers folded with an HIV RT or gag peptide or after stimulation with HIV-1 p24 gag, RT, or nef peptides in ELIspot analysis. HIV-specific CD4(+) T helper cells were demonstrated by proliferation of CD4(+) T cells and intracellular staining for IL-2 and IFN gamma after stimulation with an HIV-gag peptide pool. Sera of all individuals showed antibody-mediated neutralization of both R5 and X4 HIV-1 variants. These data implicate that very low-level antigen exposure is sufficient for sustained HIV-specific immunity and suggest the possibility of a multi-factorial control of HIV infection. (C) 2005 Elsevier Inc. All rights reserve

Follow-up of Contacts of Middle East Respiratory Syndrome Coronavirus-Infected Returning Travelers, the Netherlands, 2014

Notification of 2 imported cases of infection with Middle East respiratory syndrome coronavirus in the Netherlands triggered comprehensive monitoring of contacts. Observed low rates of virus transmission and the psychological effect of contact monitoring indicate that thoughtful assessment of close contacts is prudent and must be guided by clinical and epidemiologic risk factors

Clinical Trials of Immunomodulatory Therapies in Severe Sepsis and Septic Shock

SCOPUS: re.jinfo:eu-repo/semantics/publishe

Incidence of tuberculosis among HIV-infected patients receiving highly active antiretroviral therapy in Europe and North America

Background. We obtained estimates of the incidence of tuberculosis (TB) among patients receiving HAART and identified determinants of the incidence. Methods. We analyzed the incidence of TB during the first 3 years after initiation of HAART among 17,142 treatment-naive, AIDS- free persons starting HAART who were enrolled in 12 cohorts from Europe and North America. We used univariable and multivariable Poisson regression models to identify factors associated with the incidence. Results. During the first 3 years (36,906 person-years), 173 patients developed TB (incidence, 4.69 cases per 1000 person-years). In multivariable analysis, the incidence rate was lower for men who have sex with men, compared with injection drug users (relative rate, 2.46; 95% confidence interval [CI], 1.51-4.01), heterosexuals (relative rate, 2.42; 95% CI, 1.64-3.59), those with other suspected modes of transmission (relative rate, 1.66; 95% CI, 0.91-3.06), and those with a higher CD4(+) count at the time of HAART initiation (relative rate per log(2) cells/mL, 0.87; 95% CI, 0.84-0.91). During 28,846 person-years of follow-up after the first 6 months of HAART, 88 patients developed TB (incidence, 3.1 cases per 1000 person-years of follow-up). In multivariable analyses, a low baseline CD4(+) count (relative rate per log(2) cells/mL, 0.89; 95% CI, 0.83-0.96), 6-month CD4(+) count (relative rate per log(2) cells/mL, 0.90; 95% CI, 0.81-0.99), and a 6-month HIV RNA level 1400 copies/mL (relative rate, 2.21; 95% CI, 1.33-3.67) were significantly associated with the risk of acquiring TB after 6 months of HAART. Conclusion. The level of immunodeficiency at which HAART is initiated and the response to HAART are important determinants of the risk of TB. However, this risk remains appreciable even among those with a good response to HAART, suggesting that other interventions may be needed to control the TB epidemic in the HIV-infected population