Performance of the Euroimmun Aspergillus Antigen ELISA for the Diagnosis of Invasive Pulmonary Aspergillosis in Bronchoalveolar Lavage Fluid.

Invasive pulmonary aspergillosis (IPA) is a life-threatening disease that affects mainly immunocompromised hosts. Galactomannan testing from serum and bronchoalveolar lavage fluid (BALF) represents a cornerstone in diagnosing the disease. Here, we evaluated the diagnostic performance of the novel -specific galactomannoprotein (GP) enzyme-linked immunosorbent assay (ELISA; Euroimmun Medizinische Labordiagnostika) compared with the established Platelia GM ELISA (GM; Bio-Rad Laboratories) for the detection of antigen in BALF.

Soluble suppression of tumorigenicity 2 levels are not predictive of non-AIDS events during antiretroviral therapy-mediated viral suppression.

: Before initiation of antiretroviral therapy (ART), levels of soluble suppression of tumorigenicity 2 (sST2) were not elevated in people living with HIV who later developed non-AIDS events (including myocardial infarction and stroke), compared with controls. However, higher sST2 levels measured pre-ART were a significant predictor of death while on ART. Future studies should explore the potential of sST2 to serve as a short-term predictor of non-AIDS events during viral suppression.

Evaluation of the Aptima HIV-1 Quant Dx Assay for HIV-1 RNA Quantitation in Different Biological Specimen Types.

The search for a cure for HIV infection has highlighted the need for increasingly sensitive and precise assays to measure viral burden in various tissues and body fluids. We describe the application of a standardized assay for HIV-1 RNA in multiple specimen types. The fully automated Aptima HIV-1 Quant Dx assay (Aptima assay) is FDA cleared for blood plasma HIV-1 RNA quantitation.

Longitudinal Viral Dynamics in Semen During Early HIV Infection.

Background: Multiple viruses coinfect the male genital tract, influencing each other’s replication and perhaps affecting human immunodeficiency virus (HIV) pathogenesis and disease progression.

Methods: This study included 453 longitudinal seminal samples from 195 HIV-infected men from the San Diego Primary Infection Resource Consortium and 67 seminal samples from HIV-negative healthy controls. Seminal HIV RNA and DNA from 7 human herpesviruses (HHVs) were measured by real-time polymerase chain reaction.

Early Antiretroviral Therapy Is Associated with Lower HIV DNA Molecular Diversity and Lower Inflammation in Cerebrospinal Fluid but Does Not Prevent the Establishment of Compartmentalized HIV DNA Populations.

Even when antiretroviral therapy (ART) is started early after infection, HIV DNA might persist in the central nervous system (CNS), possibly contributing to inflammation, brain damage and neurocognitive impairment. Paired blood and cerebrospinal fluid (CSF) were collected from 16 HIV-infected individuals on suppressive ART: 9 participants started ART <4 months of the estimated date of infection (EDI) ("early ART"), and 7 participants started ART >14 months after EDI ("late ART"). For each participant, neurocognitive functioning was measured by Global Deficit Score (GDS).

HIV Trafficking Between Blood and Semen During Early Untreated HIV Infection.

Background: Understanding the dynamics of HIV across anatomic compartments is important to design effective eradication strategies. In this study, we evaluated viral trafficking between blood and semen during primary HIV infection in 6 antiretroviral-naive men who have sex with men.

Methods: Deep sequencing data of HIV env were generated from longitudinal blood plasma, peripheral blood mononuclear cells, and seminal plasma samples.

Replication of Human Herpesviruses Is Associated with Higher HIV DNA Levels during Antiretroviral Therapy Started at Early Phases of HIV Infection.

Unlabelled: Asymptomatic replication of human herpesviruses (HHV) is frequent in HIV-infected men and is associated with increased T-cell activation and HIV disease progression. We hypothesized that the presence of replication of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) (the most frequently detected HHV) might influence HIV DNA decay during antiretroviral therapy (ART). We investigated 607 peripheral blood mononuclear cell (PBMC) samples from 107 CMV-seropositive, HIV-infected men who have sex with men, who started ART within a median of 3 months from their estimated date of infection (EDI) and were monitored for a median of 19 months thereafter.

Circulating HIV DNA Correlates With Neurocognitive Impairment in Older HIV-infected Adults on Suppressive ART.

Older HIV-infected adults have a higher risk of neurocognitive impairment, but the underlying mechanisms are poorly understood. Here, we investigated the associations between levels of HIV DNA in peripheral blood, soluble markers of inflammation and cellular trafficking in blood and cerebrospinal fluid (CSF) and neurocognitive functioning among 18 younger (22-40 years) and 26 older (50-71 years) HIV-infected subjects, who were administered a comprehensive neurocognitive battery. Older HIV-infected individuals presented higher levels of inflammation in CSF and blood compared to younger individuals, but no difference was observed in HIV DNA levels.

Cytomegalovirus replication in semen is associated with higher levels of proviral HIV DNA and CD4+ T cell activation during antiretroviral treatment.

Asymptomatic cytomegalovirus (CMV) replication occurs frequently in the genital tract in untreated HIV-infected men and is associated with increased immune activation and HIV disease progression. To determine the connections between CMV-associated immune activation and the size of the viral reservoir, we evaluated the interactions between (i) asymptomatic seminal CMV replication, (ii) levels of T cell activation and proliferation in blood, and (iii) the size and transcriptional activity of the HIV DNA reservoir in blood from 53 HIV-infected men on long-term antiretroviral therapy (ART) with suppressed HIV RNA in blood plasma. We found that asymptomatic CMV shedding in semen was associated with significantly higher levels of proliferating and activated CD4(+) T cells in blood (P < 0.

Virologic correlates of anti-CMV IgG levels in HIV-1-infected men.

In human immunodeficiency virus (HIV)-infected individuals, higher levels of anti-cytomegalovirus (CMV) immunoglobulin G (IgG) antibody have been associated with increased immune activation, increased HIV transmission, cardiovascular complications, and neurocognitive impairment. However, the mechanism of these observations is unknown. This analysis of 228 HIV-infected men found that higher CMV IgG levels were positively associated with older age and antiretroviral treatment.

Shedding of HIV and human herpesviruses in the semen of effectively treated HIV-1-infected men who have sex with men.

Background: Current antiretroviral therapy (ART) suppresses human immunodeficiency virus (HIV) in blood to undetectable levels in most infected individuals; however, some men shed HIV in semen despite suppressed levels in blood.

Methods: This study included 114 chronically HIV type 1-infected men who have sex with men, who were receiving ART with blood plasma HIV <500 copies/mL. Asymptomatic participants were screened for bacterial sexually transmitted infections (STIs) and nonspecific genital inflammation.

Cytomegalovirus DNA in semen and blood is associated with higher levels of proviral HIV DNA.

Over three-fourths of human immunodeficiency virus (HIV)-infected men who have sex with men (MSM) have at least one herpesvirus detected in their semen, and cytomegalovirus (CMV) is the most prevalent. The presence of CMV is associated with higher T-cell immune activation and with HIV disease progression in treated and untreated individuals. In this study of 113 antiretroviral (ART)-naive HIV-infected MSM, we found that CMV replication in blood and semen was associated with higher levels of HIV DNA in peripheral blood mononuclear cells.

Role of seminal shedding of herpesviruses in HIV Type 1 Transmission.

To investigate the role of genital shedding of herpesviruses in human immunodeficiency virus type 1 (HIV) transmission, we compared 20 HIV-infected men who did and 26 who did not transmit HIV to their sex partners. As described previously, HIV transmission was associated with the potential source partner having higher levels of HIV RNA in blood and semen, having lower CD4(+) T cell counts, having bacterial coinfections in the genital tract, and not using antiretroviral therapy. This study extended these findings by observing significant associations between HIV transmission and the following characteristics, especially among therapy-naive potential source partners: seminal cytomegalovirus (CMV) shedding, seminal Epstein-Barr virus shedding, and levels of anti CMV immunoglobulin in blood plasma.

Sexual transmission of predicted CXCR4-tropic HIV-1 likely originating from the source partner's seminal cells.

We present a case of sexual transmission of HIV-1 predicted to have CXCR4-tropism during male-to-male sexual exposure. Phylogenetic analyses exclude cell-free virus in the seminal plasma of the source partner and possibly point to the seminal cells as the origin of the transmission event.

Impact of seminal cytomegalovirus replication on HIV-1 dynamics between blood and semen.

The genital tract of individuals infected with human immunodeficiency virus type 1 (HIV-1) is an anatomic compartment that supports local HIV-1 and cytomegalovirus (CMV) replication. This study investigated the association of seminal CMV replication with changes in HIV-1 clonal expansion, evolution and phylogenetic compartmentalization between blood and semen. Fourteen paired blood and semen samples were analyzed from four untreated subjects.

Herpes viruses and HIV-1 drug resistance mutations influence the virologic and immunologic milieu of the male genital tract.

Objectives: To further understand the role that chronic viral infections of the male genital tract play on HIV-1 dynamics and replication.

Design: Retrospective, observational study including 236 paired semen and blood samples collected from 115 recently HIV-1 infected antiretroviral naive men who have sex with men.

Methods: In this study, we evaluated the association of seminal HIV-1 shedding to coinfections with seven herpes viruses, blood plasma HIV-1 RNA levels, CD4 T-cell counts, presence of transmitted drug resistance mutations (DRMs) in HIV-1 pol, participants' age and stage of HIV-infection using multivariate generalized estimating equation methods.

Associations between virologic and immunologic dynamics in blood and in the male genital tract.

To determine the influence of asymptomatic genital viral infections on the cellular components of semen and blood, we evaluated the associations between the numbers and activation statuses of CD4+ and CD8+ T lymphocytes in both compartments and the seminal levels of cytomegalovirus (CMV), herpes simplex virus (HSV), and human immunodeficiency virus 1 (HIV). Paired blood and semen samples were collected from 36 HIV-infected antiretroviral-naïve individuals and from 40 HIV-uninfected participants. We performed multiparameter flow cytometry analysis (CD45, CD45RA, CD3, CD4, CD8, and CD38) of seminal and blood cellular components and measured HIV RNA and CMV and HSV DNA levels in seminal and blood plasma by real-time PCR.