c Preexposure prophylaxis (PrEP) using antiretroviral drugs is effective in reducing the risk of human immunodeficiency virus type 1 (HIV-1) infection, but adherence to the PrEP regimen is needed. To improve adherence, a long-acting injectable formulation of the nonnucleoside reverse transcriptase (RT) inhibitor rilpivirine (RPV LA) has been developed. However, there are concerns that PrEP may select for drug-resistant mutations during preexisting or breakthrough infections, which could promote the spread of drug resistance and limit options for antiretroviral therapy. To address this concern, we administered RPV LA to macaques infected with simian immunodeficiency virus containing HIV-1 RT (RT-SHIV). Peak plasma RPV levels were equivalent to those reported in human trials and waned over time after dosing. RPV LA resulted in a 2-log decrease in plasma viremia, and the therapeutic effect was maintained for 15 weeks, until plasma drug concentrations dropped below 25 ng/ml. RT mutations E138G and E138Q were detected in single clones from plasma virus in separate animals only at one time point, and no resistance mutations were detected in viral RNA isolated from tissues. Wild-type and E138Q RT-SHIV displayed similar RPV susceptibilities in vitro, whereas E138G conferred 2-fold resistance to RPV. Overall, selection of RPV-resistant variants was rare in an RT-SHIV macaque model despite prolonged exposure to slowly decreasing RPV concentrations following injection of RPV LA.

To further understand. Experiments were done to characterize the eis promoter in M. smegmatis and M. tuberculosis H37Ra. The putative ؊10 and ؊35 regions matched the Escherichia coli 70 consensus 67 and 83%, respectively, making it a group A/SigA-like mycobacterial promoter. Expression of site-directed variants of the core promoter region, determined by flow cytometry using gfp as a reporter, showed that the putative ؊10 region is essential for eis expression. In addition, site-directed alteration of the eis promoter to the consensus E. coli 70 promoter elements increased gfp transcription to levels similar to that driven by the heat shock promoter, phsp60, of Mycobacterium bovis BCG. Upstream promoter deletion analysis showed that a 200-and 412-bp region of the promoter was necessary for maximum expression of gfp in M. smegmatis and M. tuberculosis H37Ra, respectively. Random mutagenesis of the 412-bp eis promoter, using a catechol 2,3-dioxygenase screen and activity assay, defined nucleotides upstream of the core promoter region that are essential to eis expression in both M. smegmatis and M. tuberculosis H37Ra, including a region homologous to a DinR cis element.Tuberculosis (TB) continues to be the world's most destructive human bacterial infectious disease. Current estimates show that more than two million people die from TB each year, and TB remains a major cause of premature death (18). Mortality due to TB is a major global health crisis due to AIDS and the increasing prevalence of multidrug-resistant strains of Mycobacterium tuberculosis, although effective treatments are available. Despite the elucidation of the genome sequence of several M. tuberculosis strains (5, 14) and available genetic tools to identify genes involved in TB pathogenesis (13,16,23,26), the molecular basis of its ability to survive within host cells and evade host immune responses is unknown. Understanding the molecular mechanisms of pathogenesis is essential for the development of better methods of diagnosis, treatment, and prevention. One way to heighten our understanding of M. tuberculosis pathogenesis is to examine the regulation of potential virulence genes, in particular the promoters and other elements that govern their expression.Approximately 130 mycobacterial promoters have been characterized to date, but only 76 have been categorized into the four groups (A to D) of mycobacterial promoters (15). Identified promoters comprise less than 3% of the potential promoters in the genome of M. tuberculosis. The majority of the categorized promoters are from Mycobacterium smegmatis and Mycobacterium paratuberculosis, with less than 25% derived from M. tuberculosis itself. This indicates that we know little about promoter function in mycobacteria and even less about promoters from M. tuberculosis. Therefore, there is a need for detailed studies on M. tuberculosis promoter characterization and function, especially for genes that may play a role in the survival of M. tuberculosis within macrophages.The eis gene of M. tuberculosis H37Rv...

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BackgroundHIV has transitioned from an acute illness to a chronic disease due to potent antiretroviral therapy (ART). People living with HIV (PLWH) must be highly compliant which is difficult due to multiple barriers. The HIV care continuum was developed as a series of steps that PLWH take in their treatment cascade. At our HIV clinic, 90% of the patients are virally suppressed (viral load <200 copies/mL). Although this is higher than the national average, PLWH who are not virally suppressed and not retained in care carry the highest risk of transmission. We have several resources to engage patients, but text messaging has not been utilized for at-risk patients at the clinic or at the academic center.MethodsThe aim is to demonstrate that a pilot study of a text messaging-based intervention will increase the proportion of PLWH along the care continuum. The pre-intervention data consists of the clinic population with a viral load ≥200 copies/mL between July 1, 2017 and June 30, 2018. After chart review, eligible patients were consented to receive weekly text messages with content regarding appointment and medication reminders, and motivational messages. In the consented group, effectiveness of the intervention will be measured by tracking their appointments, viral loads, and ART prescriptions.ResultsAfter chart review, 80 patients were eligible, and 18 patients were consented for the intervention. In the eligible group, the average length of care is 8 years (range 0 to 26) and average number of years since initial ART prescription is 6.8 (range 0 to 20). The average viral load is 27,372 copies/mL. Amongst the consented group (n = 18), compared with the pre-intervention, there was a 6% increase in those who made an appointment, 33% increase in those who kept an appointment, 50% increase in those who had a viral load <200, and 62% increase in those who had ART dispensed post-intervention.ConclusionThe intervention group is small due to difficulties in consenting this vulnerable population. This is an observational study that demonstrated the impact of text messaging a high-risk population with minimal harm that not only improved the local HIV care continuum, but also addressed the barriers to care. The next steps are to determine how this method can link other at-risk patients to care at a large HIV clinic at a tertiary center. Disclosures All authors: No reported disclosures.