Correlation Between Use of Antiretroviral Adherence Devices by HIV-Infected Youth and Plasma HIV RNA and Self-Reported Adherence. Our objective was to investigate antiretroviral adherence device use by HIV-infected youth and assess associations of device use with viral suppression and self-reported adherence. This cross-sectional, multisite, clinic-based study included data from 1,317 HIV-infected individuals 12-24 years of age that were prescribed antiretroviral therapy.
Structures of PI4KIIIβ complexes show simultaneous recruitment of Rab11 and its effectors. Phosphatidylinositol 4-kinases (PI4Ks) and small guanosine triphosphatases (GTPases) are essential for processes that require expansion and remodeling of phosphatidylinositol 4-phosphate (PI4P)-containing membranes, including cytokinesis, intracellular development of malarial pathogens, and replication of a wide range of RNA viruses. However, the structural basis for coordination of PI4K, GTPases, and their effectors is unknown. Here, we describe structures of PI4Kβ (PI4KIIIβ) bound to the small GTPase Rab11a without and with the Rab11 effector protein FIP3. The Rab11-PI4KIIIβ interface is distinct compared with known structures of Rab complexes and does not involve switch regions used by GTPase effectors. Our data provide a mechanism for how PI4KIIIβ coordinates Rab11 and its effectors on PI4P-enriched membranes and also provide strategies for the design of specific inhibitors that could potentially target plasmodial PI4KIIIβ to combat malaria.
Accuracy of visual inspection with acetic acid to detect cervical cancer precursors among HIV-infected women in Kenya. Visual inspection with acetic acid (VIA) is becoming a more widely recommended and implemented screening tool for cervical cancer prevention programs in low-resource settings. Many of these settings have a high prevalence of HIV-infected women. We carried out a cross-sectional validation study to define the sensitivity, specificity and predictive values of VIA among HIV-infected women. Women enrolled in HIV care at the Family AIDS Care and Education Services clinic in Kisumu, Kenya, were recruited for participation. All participants underwent VIA followed by colposcopy performed by a second blinded clinician.
Impact of GeneXpert MTB/RIF® on Patients and Tuberculosis Programs in a Low-Burden Setting: A Hypothetical Trial. Guidelines recommend routine nucleic-acid amplification testing (NAAT) in patients with presumed tuberculosis (TB), but these tests have not been widely adopted. GeneXpert MTB/RIF (Xpert), a novel, semi-automated TB NAAT with enhanced operational characteristics, has renewed interest in this technology, but data from low-burden countries are limited. We sought to estimate Xpert's potential clinical and public health impact on empiric treatment, contact investigation, and housing in patients undergoing TB evaluation. We performed a prospective, cross-sectional study with two-month follow-up comparing Xpert with standard strategies for evaluating outpatients for active pulmonary TB at the San Francisco Department of Public Health TB Clinic between May 2010 and June 2011. We determined the diagnostic accuracy of standard empiric TB treatment, contact investigation, and housing algorithms in reference to Mycobacterium tuberculosis culture and compared them with a single Xpert test. We estimated the potential incremental value of Xpert in diagnosing individuals correctly, and reductions in unnecessary treatment, contact investigation, and housing.
Galectin-9 Is Rapidly Released During Acute HIV-1 Infection and Remains Sustained at High Levels Despite Viral Suppression Even in Elite Controllers. Galectin-9 (Gal-9) is a β-galactosidase-binding lectin that promotes apoptosis, tissue inflammation, and T cell immune exhaustion, and alters HIV infection in part through engagement with the T cell immunoglobulin mucin domain-3 (Tim-3) receptor and protein disulfide isomerases (PDI). Gal-9 was initially thought to be an eosinophil attractant, but is now known to mediate multiple complex signaling events that affect T cells in both an immunosuppressive and inflammatory manner. To understand the kinetics of circulating Gal-9 levels during HIV infection we measured Gal-9 in plasma during HIV acquisition, in subjects with chronic HIV infection with differing virus control, and in uninfected individuals.
Chemically modified peptides based on the membrane proximal external region of HIV-1 envelope induce high titer, epitope specific non-neutralizing antibodies in rabbits. Broadly neutralizing monoclonal antibodies (bNAbs), 2F5 and 4E10, bind to the membrane proximal external region (MPER) of gp41 and also cross react with phospholipids. In this study, we investigated if chemical modifications on MPER adjacent to 2F5 and 4E10 epitopes would break tolerance using mimetics of inflammation-associated post-translational modifications to induce 2F5- and 4E10-like bNAbs. We synthesized a series of chemically modified peptides spanning the MPER. Serine, threonine and tyrosine residues in the peptides were modified with sulfate, phosphate or nitrate moieties and presented in liposomes for rabbit immunizations.
Identification of the hikikomori syndrome of social withdrawal: Psychosocial features and treatment preferences in four countries. Hikikomori, a form of social withdrawal first reported in Japan, may exist globally but cross-national studies of cases of hikikomori are lacking. Our aim was to identify individuals with hikikomori in multiple countries and describe features of the condition. Participants were recruited from sites in India, Japan, Korea and the United States. Hikikomori was defined as a 6-month or longer period of spending almost all time at home and avoiding social situations and social relationships, associated with significant distress/impairment. Additional measures included the University of California, Los Angeles (UCLA) Loneliness Scale, Lubben Social Network Scale (LSNS-6), Sheehan Disability Scale (SDS) and modified Cornell Treatment Preferences Index.
Enhancing global health and education in Malawi, Zambia, and the United States through an interprofessional global health exchange program. This article describes participant outcomes of an interprofessional collaboration between health professionals and faculty in Malawi, Zambia, and the United States (US). One strategy critical for improving global health and addressing Millennium Development goals is promotion of interprofessional education and collaboration. Program participants included 25 health professionals from Malawi and Zambia, and 19 faculty/health professionals from Alabama and California. African Fellows participated in a 2 week workshop on Interprofessional Education in Alabama followed by 2 weeks working on individual goals with faculty collaborators/mentors. The US Fellows also spent 2 weeks visiting their counterparts in Malawi and Zambia to develop plans for sustainable partnerships.
HIV Prevention Services and Testing Utilization Behaviors among Men Who Have Sex with Men at Elevated Risk for HIV in Chongqing, China. Our objective was to investigate barriers and correlates of the use of HIV prevention services and HIV testing behaviors among men who have sex with men in Chongqing. Methods include three consecutive cross-sectional surveys provided demographic, sexual behavior, HIV/syphilis infection, HIV prevention service, and testing behavior data.
Tenofovir diphosphate concentrations and prophylactic effect in a macaque model of rectal simian HIV transmission. This study evaluated the relationship between intracellular tenofovir diphosphate concentrations in peripheral blood mononuclear cells and prophylactic efficacy in a macaque model for HIV pre-exposure prophylaxis (PrEP). Macaques were challenged with simian HIV (SHIV) via rectal inoculation once weekly for up to 14 weeks. A control group (n = 34) received no drug, a second group (n = 6) received oral tenofovir disoproxil fumarate/emtricitabine 3 days before each virus challenge and a third group (n = 6) received the same dosing plus another dose 2 h after virus challenge. PBMCs were collected just before each weekly virus challenge. The relationship between tenofovir diphosphate in PBMCs and prophylactic efficacy was assessed with a Cox proportional hazards model.
GlobalResearch at UCSF presents the broad scope of health research that is being conducted by UCSF researchers worldwide