Drive time to care and retention in HIV care: Rural-urban differences among Medicaid enrollees in the United States South.

Purpose: Less than 50% of people with HIV (PWH) in the United States are retained in care, a key step along the HIV care continuum. We examined the impact of geographic access to care on retention in care for urban and rural PWH.

Methods: We used Medicaid claims and clinician data (Medicaid Analytic eXtract and MAX Provider Characteristics, 2009-2012) for 13 Southern states plus the District of Columbia.

Brief Report: Physician Reimbursement and Retention in HIV Care: Racial Disparities in the US South.

Background: Retention in HIV care remains a national challenge. Addressing structural barriers to care may improve retention. We examined the association between physician reimbursement and retention in HIV care, including racial differences.

Cytomegalovirus viremia and risk of disease progression and death in HIV-positive patients starting antiretroviral therapy.

Objective: The aim of this study was to assess the prevalence of cytomegalovirus (CMV) viremia in HIV-positive patients starting antiretroviral therapy (ART) and to evaluate its impact on clinical outcomes.

Design: A retrospective analysis of four clinical trials (INSIGHT FIRST, SMART, START, and ANRS REFLATE TB).

Methods: Stored plasma samples from participants were used to measure CMV viremia at baseline prior to initiating ART and at visits through 1 year of follow-up after ART initiation.

Human Immunodeficiency Virus-Experienced Clinician Workforce Capacity: Urban-Rural Disparities in the Southern United States.

Background: Human immunodeficiency virus (HIV)-experienced clinicians are critical for positive outcomes along the HIV care continuum. However, access to HIV-experienced clinicians may be limited, particularly in nonmetropolitan areas, where HIV is increasing. We examined HIV clinician workforce capacity, focusing on HIV experience and urban-rural differences, in the Southern United States.

Associations between baseline biomarkers and lung function in HIV-positive individuals.

Objective: The aim of this study was to analyse the association of baseline biomarker data with cross-sectional lung function and subsequent decline in lung function in HIV-positive persons.

Design: Lung function was modelled in all START pulmonary substudy participants who had baseline biomarker data and good-quality spirometry. In longitudinal analyses, we restricted to those participants with at least one good-quality follow-up spirometry test.

A Guinea pig cytomegalovirus resistant to the DNA maturation inhibitor BDCRB.

Herpesvirus DNA packaging is an essential step in virion morphogenesis and an important target for antiviral development. The halogenated benzimidazole 2-bromo-5,6-dichloro-1-β-d-ribofuranosyl-1H-benzimidazole (BDCRB) was the first compound found to selectively disrupt DNA packaging. It has activity against human cytomegalovirus as well as guinea pig cytomegalovirus.

Sequence homology between HLA-bound cytomegalovirus and human peptides: A potential trigger for alloreactivity.

Human cytomegalovirus (hCMV) reactivation may often coincide with the development of graft-versus-host-disease (GVHD) in stem cell transplantation (SCT). Seventy seven SCT donor-recipient pairs (DRP) (HLA matched unrelated donor (MUD), n = 50; matched related donor (MRD), n = 27) underwent whole exome sequencing to identify single nucleotide polymorphisms (SNPs) generating alloreactive peptide libraries for each DRP (9-mer peptide-HLA complexes); Human CMV CROSS (Cross-Reactive Open Source Sequence) database was compiled from NCBI; HLA class I binding affinity for each DRPs HLA was calculated by NetMHCpan 2.8 and hCMV- derived 9-mers algorithmically compared to the alloreactive peptide-HLA complex libraries.

Effects of atorvastatin on biomarkers of immune activation, inflammation, and lipids in virologically suppressed, human immunodeficiency virus-1-infected individuals with low-density lipoprotein cholesterol <130 mg/dL (AIDS Clinical Trials Group Study A5275).

Background: Persistent immune activation and inflammation in virologically suppressed human immunodeficiency virus (HIV) infection are linked to excess cardiovascular risk.

Objective: To evaluate atorvastatin as a strategy to reduce cardiovascular risk.

Methods: A5275 was a multicenter, prospective, randomized, double-blind, placebo-controlled, cross-over pilot study of atorvastatin (10 mg/day for 4 weeks then 20 mg/day for 16 weeks) with a planned enrollment of 97 HIV-infected participants ≥18 years old, receiving boosted protease inhibitor-based antiretroviral therapy for ≥6 months, with plasma HIV-1 RNAs below limits of quantification ≥180 days, and fasting low-density lipoprotein (LDL) cholesterol ≥70 and <130 mg/dL.

Pulmonary effects of immediate versus deferred antiretroviral therapy in HIV-positive individuals: a nested substudy within the multicentre, international, randomised, controlled Strategic Timing of Antiretroviral Treatment (START) trial.

Background: Observational data have been conflicted regarding the potential role of HIV antiretroviral therapy (ART) as a causative factor for, or protective factor against, COPD. We therefore aimed to investigate the effect of immediate versus deferred ART on decline in lung function in HIV-positive individuals.

Methods: We did a nested substudy within the randomised, controlled Strategic Timing of Antiretroviral Treatment (START) trial at 80 sites in multiple settings in 20 high-income and low-to-middle-income countries.

A Phase 1 Study of 4 Live, Recombinant Human Cytomegalovirus Towne/Toledo Chimera Vaccines in Cytomegalovirus-Seronegative Men.

Background:  Human cytomegalovirus (HCMV) infection causes disease in newborns and transplant recipients. A HCMV vaccine (Towne) protects transplant recipients.

Methods:  The genomes of Towne and the nonattenuated Toledo strain were recombined, yielding 4 Towne/Toledo chimera vaccines.

HIV replication, inflammation, and the effect of starting antiretroviral therapy on plasma asymmetric dimethylarginine, a novel marker of endothelial dysfunction.

Background: HIV infection is associated with premature development of cardiovascular disease. Understanding the effects of HIV replication on endothelial dysfunction and platelet activation may identify treatment targets to reduce cardiovascular disease risk.

Methods: A subgroup of HIV-infected participants in the Strategies for Management of Antiretroviral Therapy study off antiretroviral therapy (ART) at entry enabled a randomized comparison of immediate versus deferred ART initiation of changes in asymmetric dimethylarginine (ADMA), soluble CD40 ligand (sCD40L), and P-selectin levels.

Plasma levels of soluble CD14 independently predict mortality in HIV infection.

Background: Chronic human immunodeficiency virus (HIV) infection is associated with intestinal permeability and microbial translocation that contributes to systemic immune activation, which is an independent predictor of HIV disease progression. The association of microbial translocation with clinical outcome remains unknown.

Methods: This nested case-control study included 74 subjects who died, 120 of whom developed cardiovascular disease and 81 of whom developed AIDS during the Strategies for Management of Anti-Retroviral Therapy (SMART) study with matched control subjects.

Biomarkers of immune dysfunction in HIV.

Purpose Of Review: HIV infection is characterized by chronic immune system activation and inflammatory cytokine production. This review will highlight recent developments using plasma and cellular biomarkers of immune system activation and dysfunction to predict mortality and opportunistic disease in HIV-infected individuals.

Recent Findings: HIV infection results in features characteristic of early aging of the immune system or 'immune senescence', driven by chronic antigen exposure and immune system activation.

Changes in inflammatory and coagulation biomarkers: a randomized comparison of immediate versus deferred antiretroviral therapy in patients with HIV infection.

Objectives: Among a subgroup of participants in the Strategies for Management of Antiretroviral Therapy (SMART) Trial that were naïve to antiretroviral therapy (ART) or off ART (6 months or longer) at study entry, risk of AIDS and serious non-AIDS events were increased for participants who deferred ART compared with those randomized to (re)initiate ART immediately. Our objective was to determine whether ART initiation in this group reduced markers of inflammation and coagulation that have been associated with increased mortality risk in SMART. Changes in these biomarkers have been described after stopping ART, but not after starting ART in SMART.

Determination of the underlying cause of death in three multicenter international HIV clinical trials.

Purpose: Describe processes and challenges for an Endpoint Review Committee (ERC) in determining and adjudicating underlying causes of death in HIV clinical trials.

Method: Three randomized HIV trials (two evaluating interleukin-2 and one treatment interruption) enrolled 11,593 persons from 36 countries during 1999-2008. Three ERC members independently reviewed each death report and supporting source documentation to assign underlying cause of death; differences of opinion were adjudicated.

Review of tenofovir-emtricitabine.

Highly active antiretroviral therapy has significantly reduced HIV-related morbidity and mortality. Increasingly, fixed-dose antiretroviral combinations with equal or greater potency than traditional antiretrovirals, along with fewer side effects, reduced toxicity, and simplified dosing convenience are being utilized. Tenofovir-emtricitabine (TDF-FTC) represents one of the more recent fixed-dose combinations.

Definition of the minimal cis-acting sequences necessary for genome maturation of the herpesvirus murine cytomegalovirus.

Herpesvirus DNA replication proceeds via concatemeric replicative intermediates that are comprised of head-to-tail-linked genomes. Genome maturation is carried out by the terminase, a protein complex that mediates both insertion of concatemer DNA into capsids and its subsequent cleavage to release genomes within these capsids. This cleavage is sequence specific, but the governing cis-acting DNA sequences are only partially characterized.

When to start antiretroviral therapy.

The current literature is controversial in providing evidence to determine the optimal time to initiate therapy among patients with HIV. However, there is evidence that initiating early treatment might provide benefits by treating primary HIV infection, preserving normal immune function, suppressing HIV viral replication, deferring clinical progression, and reducing HIV transmission. The biggest challenges in initiating treatment early are issues related with long-term management, including toxicities, adherence, and drug resistance.

Impact of 2-bromo-5,6-dichloro-1-beta-D-ribofuranosyl benzimidazole riboside and inhibitors of DNA, RNA, and protein synthesis on human cytomegalovirus genome maturation.

Herpesvirus genome maturation is a complex process in which concatemeric DNA molecules are translocated into capsids and cleaved at specific sequences to produce encapsidated-unit genomes. Bacteriophage studies further suggest that important ancillary processes, such as RNA transcription and DNA synthesis, concerned with repeat duplication, recombination, branch resolution, or damage repair may also be involved with the genome maturation process. To gain insight into the biochemical activities needed for herpesvirus genome maturation, 2-bromo-5,6-dichloro-1-beta-d-ribofuranosyl benzimidazole riboside (BDCRB) was used to allow the accumulation of human cytomegalovirus concatemeric DNA while the formation of new genomes was being blocked.

Dramatic effects of 2-bromo-5,6-dichloro-1-beta-D-ribofuranosyl benzimidazole riboside on the genome structure, packaging, and egress of guinea pig cytomegalovirus.

The halogenated benzimidazoles BDCRB (2-bromo-5,6-dichloro-1-beta-D-riborfuranosyl benzimidazole riboside) and TCRB (2,5,6-trichloro-1-beta-D-riborfuranosyl benzimidazole riboside) were the first compounds shown to inhibit cleavage and packaging of herpesvirus genomes. Both inhibit the formation of unit length human cytomegalovirus (HCMV) genomes by a poorly understood mechanism (M. R.

Terminally repeated sequences on a herpesvirus genome are deleted following circularization but are reconstituted by duplication during cleavage and packaging of concatemeric DNA.

The mechanisms underlying cleavage of herpesvirus genomes from replicative concatemers are unknown. Evidence from herpes simplex virus type 1 suggests that cleavage occurs by a nonduplicative process; however, additional evidence suggests that terminal repeats may also be duplicated during the cleavage process. This issue has been difficult to resolve due to the variable numbers of reiterated terminal repeats that the herpes simplex virus type 1 genome can contain.