Translocated microbiome composition determines immunological outcome in treated HIV infection.

The impact of the microbiome on HIV disease is widely acknowledged although the mechanisms downstream of fluctuations in microbial composition remain speculative. We detected rapid, dynamic changes in translocated microbial constituents during two years after cART initiation. An unbiased systems biology approach revealed two distinct pathways driven by changes in the abundance ratio of Serratia to other bacterial genera.

Impact of Integrase Inhibition Compared With Nonnucleoside Inhibition on HIV Reservoirs in Lymphoid Tissues.

Background: HIV is produced in lymphoid tissues (LT) and stored on the follicular dendritic cell network in LT. When antiretroviral therapy is started, plasma viremia decays in 2 phases; the first within days of starting therapy and the second over weeks. Raltegravir (RAL), an integrase inhibitor, has been associated with only a single rapid phase of decay, and we speculated this may be due to higher intracellular concentration (IC) of RAL in LT.

Lymphoid tissue fibrosis is associated with impaired vaccine responses.

Vaccine responses vary by geographic location. We have previously described how HIV-associated inflammation leads to fibrosis of secondary lymph nodes (LNs) and T cell depletion. We hypothesized that other infections may cause LN inflammation and fibrosis, in a process similar to that seen in HIV infection, which may lead to T cell depletion and affect vaccine responses.

An innovative medical school curriculum to address human papillomavirus vaccine hesitancy.

Background: Vaccination rates against Human Papillomavirus (HPV) in the US remain alarmingly low. Physicians can significantly influence a parent's decision to vaccinate their children. However, medical education often lacks training on specific strategies for communicating with vaccine hesitant parents.

Defining total-body AIDS-virus burden with implications for curative strategies.

In the quest for a functional cure or the eradication of HIV infection, it is necessary to know the sizes of the reservoirs from which infection rebounds after treatment interruption. Thus, we quantified SIV and HIV tissue burdens in tissues of infected nonhuman primates and lymphoid tissue (LT) biopsies from infected humans. Before antiretroviral therapy (ART), LTs contained >98% of the SIV RNA and DNA cells.

A simplified mycobacterial growth inhibition assay (MGIA) using direct infection of mouse splenocytes and the MGIT system.

We describe a simplified Mycobacterial Growth Inhibition Assay (MGIA) for pre-clinical assessment of vaccine-mediated protection in mice. The assay is accomplished by directly infecting splenocytes from vaccinated mice with Mycobacterium tuberculosis and quantifying mycobacteria using Mycobacterial Growth Indicator Tubes (MGIT). Vaccine-mediated immunogenicity detected by this assay correlated with protection.

Large number of rebounding/founder HIV variants emerge from multifocal infection in lymphatic tissues after treatment interruption.

Antiretroviral therapy (ART) suppresses HIV replication in most individuals but cannot eradicate latently infected cells established before ART was initiated. Thus, infection rebounds when treatment is interrupted by reactivation of virus production from this reservoir. Currently, one or a few latently infected resting memory CD4 T cells are thought be the principal source of recrudescent infection, but this estimate is based on peripheral blood rather than lymphoid tissues (LTs), the principal sites of virus production and persistence before initiating ART.

Persistent HIV-1 replication is associated with lower antiretroviral drug concentrations in lymphatic tissues.

Antiretroviral therapy can reduce HIV-1 to undetectable levels in peripheral blood, but the effectiveness of treatment in suppressing replication in lymphoid tissue reservoirs has not been determined. Here we show in lymph node samples obtained before and during 6 mo of treatment that the tissue concentrations of five of the most frequently used antiretroviral drugs are much lower than in peripheral blood. These lower concentrations correlated with continued virus replication measured by the slower decay or increases in the follicular dendritic cell network pool of virions and with detection of viral RNA in productively infected cells.

Intraoperative high-resolution ultrasound: a new technique in the management of peripheral nerve disorders.

Object: Surgical treatment of nerve lesions in continuity remains difficult, even in the most experienced hands. The regenerative potential of those injuries can be evaluated by intraoperative electrophysiological studies and/or intraneural dissection. The present study examines the value of intraoperative high-frequency ultrasound as an imaging tool for decision making in the management of traumatic nerve lesions in continuity.