Introduction Since 2015, the World Health Organization (WHO) has recommended that all people living with HIV (PLHIV) initiate antiretroviral treatment (ART), irrespective of CD4+ count or clinical stage. National adoption of universal treatment has accelerated since WHO's 2015 “Treat All” recommendation; however, little is known about the translation of this guidance into practice. This study aimed to assess the status of Treat All implementation across regions, countries, and levels of the health care delivery system. Methods Between June and December 2017, 201/221 (91%) adult HIV treatment sites that participate in the global IeDEA research consortium completed a survey on capacity and practices related to HIV care. Located in 41 countries across seven geographic regions, sites provided information on the status and timing of site‐level introduction of Treat All, as well as site‐level practices related to ART initiation. Results Almost all sites (93%) reported that they had begun implementing Treat All, and there were no statistically significant differences in site‐level Treat All introduction by health facility type, urban/rural location, sector (public/private) or country income level. The median time between national policy adoption and site‐level introduction was one month. In countries where Treat All was not yet adopted in national guidelines, 69% of sites reported initiating all patients on ART, regardless of clinical criteria, and these sites had been implementing Treat All for a median period of seven months at the time of the survey. The majority of sites (77%) reported typically initiating patients on ART within 14 days of confirming diagnosis, with 60% to 62% of sites implementing Treat All in East, Southern and West Africa reporting same‐day ART initiation for most patients. Conclusions By mid‐ to late‐2017, the Treat All strategy was the standard of care at almost all IeDEA sites, including rural, primary‐level health facilities in low‐resource settings. While further assessments of site‐level capacity to provide high‐quality HIV care under Treat All and to support sustained viral suppression after ART initiation are needed, the widespread introduction of Treat All at the service delivery level is a critical step towards global targets for ending the HIV epidemic as a public health threat.

BackgroundEnveloped viruses utilize cellular membranes to bud from infected cells. The process of virion assembly and budding is often facilitated by the presence of certain conserved motifs within viral proteins in conjunction with cellular factors. We hence examined the West Nile Virus (WNV) Envelope protein for the presence of any such motifs and their functional characterization.ResultsWe identified conserved 461PXAP464 and 349YCYL352 motifs in the WNV envelope glycoprotein bearing resemblance to retroviral late domains. Disruptive mutations of PXAP to LAAL and of the highly conserved Cys350 in the YCYL motif, led to a severe reduction in WNV particle production. Similar motifs in case of retroviruses are known to interact with components of host sorting machinery like PXAP with Tsg101 and YXXL with Alix. However, in the case of WNV, siRNA mediated depletion of Alix or Tsg101 did not have an effect on WNV release. Molecular modeling suggested that while the 461PXAP464 motif is surface accessible and could potentially interact with cellular proteins required for WNV assembly, the 349YCYL352 motif was found to be internal with Cys350 important for protein folding via disulphide bonding.ConclusionsThe conserved 461PXAP464 and 349YCYL352 motifs in the WNV envelope are indispensable for WNV particle production. Although these motifs bear sequence similarity to retroviral late domains and are essential for WNV assembly, they are functionally distinct suggesting that they are not the typical late domain like motifs of retroviruses and may play a role other than Alix/Tsg101 utilization/dependence.

"Carbapenems" are a specific subset of antibiotics considered to possess a higher spectrum of antimicrobial activity (Papp-Wallace, Endimiani, Taracila, & Bonomo, 2011) against Grampositive and Gram-negative bacteria. Even so, there are pathogens which are resistant to carbapenems due to the presence of carbapenemase genes (CP genes) which have the ability to hydrolyze carbapenems.

Liver disease is a growing burden among people living with HIV (PLHIV) in resourcelimited settings. As an indicator of liver disease, risk factors of high alanine aminotransferase (ALT) and cirrhosis were assessed among PLHIV in the TREAT Asia HIV Observational Database (TAHOD). Patients on combination antiretroviral therapy (cART) with a pre-cART ALT measurement and at least one follow-up ALT measurement were included. Factors associated with high ALT (ALT levels > 5 times its upper limit of normal) were analyzed using repeated measure logistic regression over a 10-year follow-up period. Liver cirrhosis was defined as having an AST to Platelet Ratio Index score > 1.5, fibrosis-4 score > 3.25, or a clinical diagnosis of cirrhosis. Cox regression analysis stratified by site was used to analyze factors associated with cirrhosis among those in follow-up after 2015. Of 5182 patients, 101 patients (1.9%) had high ALT levels with hepatitis C virus (HCV) antibody positive (odds ratio [OR]: 4.98, 95% confidence interval [CI]: 2.82-8.77, p < 0.001) and ever high alcohol consumption (OR: 2.33, 95% CI: 1.00-5.46, p = 0.050) as likely factors. Among 6318 PLHIV in the liver cirrhosis analysis, 151 (2%) developed cirrhosis (incidence rate = 0.82 per 100 person-years). Those HCV-antibody positive (hazard ratio [HR]: 5.54, 95% CI: 3.75-8.18, p < 0.001) and had high alcohol consumption (HR: 2.06, 95% CI: 1.23-3.45, p = 0.006) were associated with liver cirrhosis. HCV-antibody positive and high alcohol consumption are factors associated with high ALT. With raised ALT levels as a known factor associated with liver cirrhosis, greater efforts are required in managing ALT levels and reducing the risk of developing liver cirrhosis among those positive for HCV-antibody and those who consume alcohol.