Antiretroviral concentration measurements as an additional tool to manage virologic failure in resource limited settings: a case control study.

Background: Several studies demonstrate a correlation between sub-therapeutic concentrations of antiretroviral drugs and virologic failure. We examined the sensitivity, specificity and predictive values of sub-therapeutic drug levels in predicting viralogic failure.

Methods: This was a case control study with cases being samples of participants with virologic failure, and controls samples of participants with virologic suppression.

Very low sensitivity of wet mount microscopy compared to PCR against culture in the diagnosis of vaginal trichomoniasis in Uganda: a cross sectional study.

Background: Trichomonas vaginalis (TV) causes the Trichomoniasis Syndrome composed of vaginitis in women, urethritis in men and tube infection in both sexes. This infection is strongly associated with premature rupture of membranes, preterm delivery, low birth weight, promoting HIV sexual transmission and infertility. Prevention of these complications requires accurate early detection and effective treatment of infected individuals.

Hookworm infection is associated with decreased CD4+ T cell counts in HIV-infected adult Ugandans.

Most studies evaluating epidemiologic relationships between helminths and HIV have been conducted in the pre-ART era, and evidence of the impact of helminth infections on HIV disease progression remains conflicting. Less is known about helminth infection and clinical outcomes in HIV-infected adults receiving antiretroviral therapy (ART). We sampled HIV-infected adults for eight gastrointestinal parasites and correlated parasitic infection with demographic predictors, and clinical and immunologic outcomes.

Blood-Derived CD4 T Cells Naturally Resist Pyroptosis during Abortive HIV-1 Infection.

Progression to AIDS is driven by CD4 T cell depletion, mostly involving pyroptosis elicited by abortive HIV infection of CD4 T cells in lymphoid tissues. Inefficient reverse transcription in these cells leads to cytoplasmic accumulation of viral DNAs that are detected by the DNA sensor IFI16, resulting in inflammasome assembly, caspase-1 activation, and pyroptosis. Unexpectedly, we found that peripheral blood-derived CD4 T cells naturally resist pyroptosis.

Cell death by pyroptosis drives CD4 T-cell depletion in HIV-1 infection.

The pathway causing CD4 T-cell death in HIV-infected hosts remains poorly understood although apoptosis has been proposed as a key mechanism. We now show that caspase-3-mediated apoptosis accounts for the death of only a small fraction of CD4 T cells corresponding to those that are both activated and productively infected. The remaining over 95% of quiescent lymphoid CD4 T cells die by caspase-1-mediated pyroptosis triggered by abortive viral infection.

Cost-effectiveness of early initiation of first-line combination antiretroviral therapy in Uganda.

Background: Ugandan national guidelines recommend initiation of combination antiretroviral therapy (cART) at CD4+ T cell (CD4) count below 350 cell/μl, but the implementation of this is limited due to availability of medication. However, cART initiation at higher CD4 count increases survival, albeit at higher lifetime treatment cost. This analysis evaluates the cost-effectiveness of initiating cART at a CD4 count between 250-350 cell/μl (early) versus <250 cell/μl (delayed).

Optimized methods for imaging membrane nanotubes between T cells and trafficking of HIV-1.

A wide variety of cell types, including immune cells, have been observed to frequently interact via transient, long-distance membrane connections. However, considerable heterogeneity in their structure, mode of formation and functional properties has emerged, suggesting the existence of distinct subclasses. Open-ended tunneling nanotubes allow for the trafficking of cytoplasmic material, e.

Aminoquinoline surfen inhibits the action of SEVI (semen-derived enhancer of viral infection).

In semen, proteolytic peptide fragments from prostatic acid phosphatase can form amyloid fibrils termed SEVI (semen-derived enhancer of viral infection). These fibrils greatly enhance human immunodeficiency virus (HIV) infectivity by increasing the attachment of virions to target cells. Therefore, SEVI may have a significant impact on whether HIV is successfully transmitted during sexual contact.

Membrane nanotubes: dynamic long-distance connections between animal cells.

Membrane nanotubes are transient long-distance connections between cells that can facilitate intercellular communication (for example, by trafficking vesicles or transmitting calcium-mediated signals), but they can also contribute to pathologies (for example, by directing the spread of viruses). Recent data have revealed considerable heterogeneity in their structures, processes of formation and functional properties, in part dependent on the cell types involved. Despite recent progress in this young research field, further research is sorely needed.

Membrane nanotubes physically connect T cells over long distances presenting a novel route for HIV-1 transmission.

Transmission of HIV-1 via intercellular connections has been estimated as 100-1000 times more efficient than a cell-free process, perhaps in part explaining persistent viral spread in the presence of neutralizing antibodies. Such effective intercellular transfer of HIV-1 could occur through virological synapses or target-cell filopodia connected to infected cells. Here we report that membrane nanotubes, formed when T cells make contact and subsequently part, provide a new route for HIV-1 transmission.

Reciprocal regulation of human natural killer cells and macrophages associated with distinct immune synapses.

Natural killer (NK) cells directly lyse tumor or viral-infected cells but also an important role for NK cell cytotoxicity in regulating the extent of immune responses is emerging. Here, we show that autologous human macrophages activated NK cell proliferation and cytokine secretion, increased expression of activating receptors, and primed NK cell cytotoxicity against susceptible target cells. Ligation of NK cell 2B4, and not NKp30 (known to be important for DC-mediated NK cell activation), is critical for this macrophage-mediated NK cell activation.

Structurally distinct membrane nanotubes between human macrophages support long-distance vesicular traffic or surfing of bacteria.

We report that two classes of membrane nanotubes between human monocyte-derived macrophages can be distinguished by their cytoskeletal structure and their functional properties. Thin membrane nanotubes contained only F-actin, whereas thicker nanotubes, i.e.

Long-distance calls between cells connected by tunneling nanotubules.

Long membrane tethers between cells, known as membrane nantotubes or tunneling nanotubules, create supracellular structures that allow multiple cell bodies to act in a synchronized manner. Calcium fluxes, vesicles, and cell-surface components can all traffic between cells connected by nanotubes. Thus, complex and specific messages can be transmitted between multiple cells, and the strength of signal will suffer relatively little with the distance traveled, as compared to the use of soluble factors to transmit messages.