Profound reduction of HIV-1 reservoir cells over 3 decades of antiretroviral therapy started in early infancy.

HIV-1 reservoir cells persist indefinitely during suppressive antiretroviral therapy (ART) in individuals who acquire infection in adulthood, but little is known about the longitudinal evolution of viral reservoir cells during long-term ART started during early infancy. We studied 2 fraternal twins who acquired HIV-1 perinatally, started ART at week 10 after birth and remained on ART for 28 years. We observed that the frequency of genome-intact proviruses, determined by single-genome near-full-length proviral sequencing, declined by approximately 4,000- to 13,000-fold during this period, indicating enhanced decay rates of intact proviruses even after adjusting for dilution effects from somatic growth.

Footprints of innate immune activity during HIV-1 reservoir cell evolution in early-treated infection.

Antiretroviral treatment (ART) initiation during the early stages of HIV-1 infection is associated with a higher probability of maintaining drug-free viral control during subsequent treatment interruptions, for reasons that remain unclear. Using samples from a randomized-controlled human clinical trial evaluating therapeutic HIV-1 vaccines, we here show that early ART commencement is frequently associated with accelerated and efficient selection of genome-intact HIV-1 proviruses in repressive chromatin locations during the first year after treatment initiation. This selection process was unaffected by vaccine-induced HIV-1-specific T cell responses.

Selection of epigenetically privileged HIV-1 proviruses during treatment with panobinostat and interferon-α2a.

CD4 T cells with latent HIV-1 infection persist despite treatment with antiretroviral agents and represent the main barrier to a cure of HIV-1 infection. Pharmacological disruption of viral latency may expose HIV-1-infected cells to host immune activity, but the clinical efficacy of latency-reversing agents for reducing HIV-1 persistence remains to be proven. Here, we show in a randomized-controlled human clinical trial that the histone deacetylase inhibitor panobinostat, when administered in combination with pegylated interferon-α2a, induces a structural transformation of the HIV-1 reservoir cell pool, characterized by a disproportionate overrepresentation of HIV-1 proviruses integrated in ZNF genes and in chromatin regions with reduced H3K27ac marks, the molecular target sites for panobinostat.

Effects of brain-computer interface with functional electrical stimulation for gait rehabilitation in multiple sclerosis patients: preliminary findings in gait speed and event-related desynchronization onset latency.

Brain-computer Interfaces (BCI) with functional electrical stimulation (FES) as a feedback device might promote neuroplasticity and hence improve motor function. Novel findings suggested that neuroplasticity could be possible in people with multiple sclerosis (pwMS). This preliminary study explores the effects of using a BCI-FES in therapeutic intervention, as an emerging methodology for gait rehabilitation in pwMS.

Does feedback based on FES-evoked nociceptive withdrawal reflex condition event-related desynchronization? An exploratory study with brain-computer interfaces.

Event-related desynchronization (ERD) is used in brain-computer interfaces (BCI) to detect the user's motor intention (MI) and convert it into a command for an actuator to provide sensory feedback or mobility, for example by means of functional electrical stimulation (FES). Recent studies have proposed to evoke the nociceptive withdrawal reflex (NWR) using FES, in order to evoke synergistic movements of the lower limb and to facilitate the gait rehabilitation of stroke patients. The use of NWR to provide sensorimotor feedback in ERD-based BCI is novel; thererfore, the conditioning effect that nociceptive stimuli might have on MI is still unknown.