Background The increasing availability of anti-retroviral therapy (ART) has improved survival and quality of life for many infected with HIV, but can also engender drug resistance. This review summarizes the available information on drug-resistance in adults in resource-limited settings (RLSs). Methods The online databases PubMed and Google Scholar, pertinent conference abstracts, and references from relevant articles were searched for publications available before November 2011. Data collected after ART roll-out were reviewed. Results Seven studies fulfilled the criteria for the analysis of acquired drug resistance while 22 fulfilled the criteria for the analysis of transmitted drug resistance (TDR). Acquired resistance was detected in 7·2% of patients on ART for 6–11 months, compared to 11·1% at 12—23 months, 15·0% at 24–35 months, and 20·7% at ≥36 months. Multi-class drug resistance also increased steadily with time on ART. The overall rate of TDR in all resource-limited countries studied was 6·6% (469/7063). Patients in countries in which ART had been available for ≥5 years were 1.7 times more likely to have transmitted drug-resistance than those living in a country where ART had been available for <5 years (p<0·001). The reported prevalence of transmitted HIVDR was 5·7% (233/4069) in Africa, 7·6% (160/2094) in Asia, and 8·4% (76/900) in Brazil. Conclusions The emergence of drug resistance following access to antiretroviral therapy in RLSs resembles what was seen in resource-rich countries and highlights the need for virologic monitoring for drug failure, drug resistance testing, and alternative drug regimens that have proven beneficial in these resource-rich settings.

Background: The tumor microenvironment (TME) is critical to every aspect of cancer biology.Organotypic tumor slice cultures (TSCs) preserve the original TME and have demonstrated utility in predicting drug sensitivity, but the association between clinicopathologic parameters and in vitro TSC behavior has not been well-defined.Methods: One hundred and eight fresh tumor specimens from liver resections at a tertiary academic center were procured and precisely cut with a Vibratome to create 250 μm × 6 mm slices. These fixed-dimension TSCs were grown on polytetrafluoroethylene inserts, and their metabolic activities were determined by a colorimetric assay. Correlation between baseline activities and clinicopathologic parameters was assessed. Tissue CEA mRNA expression was determined by RNAseq.Results: By standardizing the dimensions of a slice, we found that adjacent tumor slices have equivalent metabolic activities, while those derived from different tumors exhibit >30-fold range in baseline MTS absorbances, which correlated significantly with the percentage of tumor necrosis based on histologic assessment. Extending this to individual cancers, we were able to detect intra-tumoral heterogeneity over a span of a few millimeters, which reflects differences in tumor cell density and Ki-67 positivity. For colorectal cancers, tissue CEA expression based on RNAseq of tumor slices was found to correlate with clinical response to chemotherapies. Conclusions:We report a standardized method to assess and compare human cancer growth ex vivo across a wide spectrum of tumor samples. TSC reflects the state of tumor behavior and heterogeneity, thus providing a simple approach to study of human cancers with an intact TME.

This is a review of the first 50 patients attending a colocated continuity clinic with harm reduction services to women experiencing homelessness in north Seattle. Among those tested, patients had high rates of curable sexually transmitted infections (44%), injection opioid use (36%), transactional sex (69%), unintended pregnancy (10%), and human immunodeficiency virus infections (10%).

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In the United States, the frequent amalgamation of homelessness, drug use, and exchange of sex for money, shelter, food, or drugs increases the risk of serious health conditions, including trauma and HIV. 1 Women who are unhoused have an all-cause mortality 5 to 8 times higher than housed women. 2 Seattle, Washington, is facing a housing crisis, with a 31% increase in homelessness from 2008 to 2018 3 and a growing epidemic of opioid and methamphetamine use. In 2018, these overlapping epidemics created the context for an HIV outbreak in Seattle among unhoused heterosexual people. 4 Several US cities have created mobile health clinics in an effort to engage unhoused people in medical care. 5 In July 2018, the Safe, Healthy, Empowered (SHE) Clinic was founded to provide care for unhoused women colocated at Aurora Commons, a drop-in community center with a longstanding relationship with unhoused people in Seattle. Patients at the SHE Clinic reflect the unhoused population's high rates of injection drug use, exchange sex, unplanned pregnancy, and sexually transmitted infections. 6 In this cohort study, we evaluated the association between use of the SHE Clinic and the frequency of nonemergent emergency department (ED) visits among women living unhoused who exchange sex and inject drugs. MethodsSurvey data collected from an observational cohort of 76 women 18 years or older at Aurora Commons included self-identified demographic characteristics, fertility desires, and HIV risk factors.Participants provided oral and written consent for surveys and abstraction of electronic medical record data. REDCap (Research Electronic Data Capture software (Vanderbilt University) was used for survey collection and consenting participants. This study received ethical approval from the University of Washington Institutional Review Board. The study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline.The SHE Clinic operates 4 hours a week and provides walk-in care. Participants with at least 1 visit to the SHE Clinic before February 2, 2019, were compared with participants with no visits. A manual review of participants' electronic medical records from February 1, 2018, through August 1, 2019, was conducted to find the dates and chief concerns for ED visits in the Seattle area (10 facilities, 91% of the area EDs). Two clinician investigators (J.S. and M.L.G.) classified each ED visit as emergent or nonemergent. Emergency department visits for sexual assault, trauma, drug overdose, mental health crisis, or illness resulting in hospitalization were classified as emergent visits. Descriptive data analyses were performed with Stata version 15.0 software (StataCorp). Emergency department visit rates were calculated per woman per month, and paired Wilcoxon signed rank tests were used to compare the frequency of ED visits in the 6 months before and after a woman's first SHE Clinic visit or a midperiod reference date for nonadopters. + Invited CommentaryAuthor affiliations and article inf...