A Novel Score to Predict Esophageal Varices in Patients with Compensated Advanced Chronic Liver Disease.

BACKGROUND AND AIMS: Several criteria have been described to noninvasively predict the presence of high-risk esophageal varices in patients with compensated advanced chronic liver disease (cACLD). However, a recent study showed that treatment with ß blockers could increase decompensation-free survival in patients with clinically significant portal hypertension, thereby making it important to predict the presence of any esophageal varices. We aimed to develop a simple scoring system to predict any esophageal varices. METHODS: We retrospectively reviewed patients who had vibration-controlled transient elastography (VCTE) at Cook County Hospital, Chicago, USA. Patients with cACLD and liver stiffness measurement (LSM) ≥ 10 kPa with esophagogastroduodenoscopy performed within one year of VCTE were analyzed. We generated a novel score to predict esophageal varices, using the beta coefficient of predictive variables. The score was validated in an external cohort at the University of Iowa Hospital, USA. RESULTS: There were 372 patients in the development cohort and 200 patients in the validation cohort. LSM, platelet count, and albumin were identified as predictors of esophageal varices and were included for generating the Cook County score as "platelet count * - 0.0155872 + VCTE score * 0.0387052 + albumin * - 0.8549209." The area under receiver operating curve for our score was 0.86 for any varices and 0.85 for high risk varices and avoided more endoscopies than the expanded Baveno VI criteria while maintaining a very low miss rate (negative predictive value > 99%). CONCLUSION: We propose a new, highly accurate, and easy-to-use scoring system to predict the presence of not only high-risk but any esophageal varices in patients with cACLD.

TURQUOISE-I Part 1b: Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir with Ribavirin for Hepatitis C Virus Infection in HIV-1 Coinfected Patients on Darunavir.

Background: Ombitasvir/paritaprevir/ritonavir with dasabuvir (OBV/PTV/r + DSV) ± ribavirin (RBV) is approved for hepatitis C virus (HCV) genotype 1 (GT1) treatment in HIV-1 coinfected patients. In healthy controls, coadministration of OBV/PTV/r + DSV + darunavir (DRV) lowered DRV trough concentration (Ctrough) levels. To assess the clinical significance of this change, TURQUOISE-I, Part 1b, evaluated the efficacy and safety of OBV/PTV/r + DSV + RBV in coinfected patients on stable, DRV-containing antiretroviral therapy (ART). Methods: Patients were HCV treatment-naive or interferon-experienced, had CD4+ lymphocyte count ≥200 cells/µL or ≥14%, and plasma HIV-1 RNA suppression on once-daily (QD) DRV-containing ART at screening. Patients were randomized to maintain DRV 800 mg QD or switch to twice-daily (BID) DRV 600 mg; all received OBV/PTV/r + DSV + RBV for 12 weeks. Results: Twenty-two patients were enrolled and achieved SVR12. No adverse events led to discontinuation. Coadministration had minimal impact on DRV maximum observed plasma concentration and area under the curve; DRV Ctrough levels were slightly lower with DRV QD and BID. No patient experienced plasma HIV-1 RNA >200 copies/mL during treatment. Conclusions: HCV GT1/HIV-1 coinfected patients on stable DRV-containing ART achieved 100% SVR12 while maintaining plasma HIV-1 RNA suppression. Despite DRV exposure changes, episodes of intermittent HIV-1 viremia were infrequent.

Sofosbuvir and Velpatasvir for the Treatment of Hepatitis C Virus in Patients Coinfected With Human Immunodeficiency Virus Type 1: An Open-Label, Phase 3 Study.

BACKGROUND: A safe, simple, effective, and pan-genotypic regimen to treat hepatitis C virus (HCV) infection in patients coinfected with human immunodeficiency virus type 1 (HIV-1) remains a medical need. We assessed the efficacy and safety of the NS5B polymerase inhibitor sofosbuvir and the NS5A inhibitor velpatasvir for HCV in patients coinfected with HIV-1. METHODS: This phase 3, open-label, single-arm study at 17 sites in the United States enrolled patients with HCV of any genotype and HIV-1 coinfection, including those with compensated cirrhosis. All patients received sofosbuvir-velpatasvir once daily for 12 weeks. The primary endpoint was sustained virologic response 12 weeks after treatment (SVR12). Efficacy and safety were assessed in all patients receiving at least 1 dose of treatment. RESULTS: Of 106 patients, 91 (86%) were men, 48 (45%) were black, and 19 (18%) had cirrhosis. SVR12 was achieved by 101 of 106 (95% [95% confidence interval {CI}, 89%-99%]) patients: 74 of 78 (95% [95% CI, 87%-99%]) with genotype 1; all 11 (100% [95% CI, 72%-100%]) with genotype 2; 11 of 12 (92% [95% CI, 62%-100%]) with genotype 3; and all 5 (100% [95% CI, 48%-100%]) with genotype 4. All 19 patients with cirrhosis had SVR12. Two patients relapsed, 2 were lost to follow-up, and 1 withdrew consent. Two discontinued treatment due to adverse events and 2 had serious adverse events. The most common adverse events were fatigue (25%), headache (13%), upper respiratory tract infection (8%), and arthralgia (8%). CONCLUSIONS: Sofosbuvir-velpatasvir for 12 weeks was safe and provided high rates of SVR12 in patients coinfected with HCV and HIV-1. CLINICAL TRIALS REGISTRATION: NCT02480712.

Loneliness in Older Black Adults with Human Immunodeficiency Virus Is Associated with Poorer Cognition.

BACKGROUND: The human immunodeficiency virus (HIV) is associated with cognitive impairment, and loneliness is associated with cognitive decline in old age. Older Black adults with HIV may be at particular risk of loneliness due to stigma and lack of social resources. OBJECTIVE: We tested the hypotheses that (1) older Black adults with HIV would show greater loneliness than older White adults with HIV, and (2) greater loneliness among older Black adults with HIV would be associated with poorer cognitive function. METHODS: A total of 370 participants (177 with HIV, 193 without HIV; mean age 58.8 years, standard deviation 6.2 years; mean education 13.4 years, standard deviation 2.9 years; 73.9% male, 68.9% Black) in a community-based cross-sectional study of the Rush Center of Excellence on Disparities in HIV and Aging (CEDHA) completed a 5-item self-report scale used to measure emotional loneliness and a battery of cognitive measures. RESULTS: Contrary to our expectations, older Black adults indicated less overall loneliness than White adults (ß = -0.3893, SE = 0.1466, p = 0.0087) in models controlling for the effects of age, education, sex, global cognition, and income. However, in models with cognitive function as the outcome, an interaction between race and loneliness was observed, such that older Black adults who indicated greater loneliness showed poorer cognitive function relative to White adults (ß = -0.2736, SE = 0.1138, p = 0.0174). CONCLUSION: Older Black adults with HIV reported less loneliness than older White adults; however, the inverse association between loneliness and cognitive function was stronger in Black than White older adults. Additional work is needed to elucidate the mechanisms underlying this interaction.

The immunologic effects of maraviroc intensification in treated HIV-infected individuals with incomplete CD4+ T-cell recovery: a randomized trial.

The CCR5 inhibitor maraviroc has been hypothesized to decrease T-cell activation in HIV-infected individuals, but its independent immunologic effects have not been established in a placebo-controlled trial. We randomized 45 HIV-infected subjects with CD4 counts <350 cells per mm(3) and plasma HIV RNA levels <48 copies per mL on antiretroviral therapy (ART) to add maraviroc vs placebo to their regimen for 24 weeks followed by 12 weeks on ART alone. Compared with placebo-treated subjects, maraviroc-treated subjects unexpectedly experienced a greater median increase in % CD38+HLA-DR+ peripheral blood CD8+ T cells at week 24 (+2.2% vs -0.7%, P = .014), and less of a decline in activated CD4+ T cells (P < .001). The % CD38+HLA-DR+ CD4+ and CD8+ T cells increased nearly twofold in rectal tissue (both P < .001), and plasma CC chemokine receptor type 5 (CCR5) ligand (macrophage-inflammatory protein 1ß) levels increased 2.4-fold during maraviroc intensification (P < .001). During maraviroc intensification, plasma lipopolysaccharide declined, whereas sCD14 levels and neutrophils tended to increase in blood and rectal tissue. Although the mechanisms explaining these findings remain unclear, CCR5 ligand-mediated activation of T cells, macrophages, and neutrophils via alternative chemokine receptors should be explored. These results may have relevance for trials of maraviroc for HIV preexposure prophylaxis and graft-versus-host disease. This trial was registered at www.clinicaltrials.gov as #NCT00735072.

Policosanol for managing human immunodeficiency virus-related dyslipidemia in a medically underserved population: a randomized, controlled clinical trial.

BACKGROUND: Human immunodeficiency virus (HIV) infection is associated with dyslipidemia and increased risk for cardiovascular events; however, the use ofstatins in HIV-infected people is complicated by pharmacokinetic interactions and overlapping toxicities with antiretroviral medications. Policosanol is a dietary supplement derived from sugar cane that is widely used as a statin alternative in Latin America. PRIMARY STUDY OBJECTIVE: To collect feasibility data on sugar cane-derived policosanol to normalize dyslipidemic profiles in a sample of medically underserved HIV-infected people. METHODS/DESIGN: Randomized, controlled, double-blind clinical trial. SETTING: Two infectious disease outpatient clinics located in a Health Resources Service Administration-designated medically underserved neighborhood in Chicago, Illinois. PARTICIPANTS: Fifty-four clinically stable HIV-infected people (91% black) with at least one lipid abnormality that warranted dietary modifications and/or drug therapy. INTERVENTION: Participants received either 20 mg/day of policosanol or placebo for 12 weeks, followed by a 4-week washout and crossover to the other arm. PRIMARY OUTCOME MEASURES: Efficacy measures included the standard lipid panel (low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides) and nuclear magnetic resonance (NMR)-derived lipoprotein particle profiles. Safety measures included CD4+ T lymphocyte counts, plasma HIV ribonucleic acid levels, serum creatinine, and liver function tests. RESULTS: Policosanol supplementation was not associated with normalization of any dyslipidemic parameters as measured by the standard lipid panel or NMR spectroscopy-measured lipoprotein size or concentration. The supplement was well tolerated and was not associated with any changes in parameters of HIV disease progression. CONCLUSIONS: Our findings corroborate recent studies conducted outside Cuba that have failed to find any lipid modulatory effects for policosanol.

Early development of non-hodgkin lymphoma following initiation of newer class antiretroviral therapy among HIV-infected patients - implications for immune reconstitution.

BACKGROUND: In the HAART era, the incidence of HIV-associated non-Hodgkin lymphoma (NHL) is decreasing. We describe cases of NHL among patients with multi-class antiretroviral resistance diagnosed rapidly after initiating newer-class antiretrovirals, and examine the immunologic and virologic factors associated with potential IRIS-mediated NHL. METHODS: During December 2006 to January 2008, eligible HIV-infected patients from two affiliated clinics accessed Expanded Access Program antiretrovirals of raltegravir, etravirine, and/or maraviroc with optimized background. A NHL case was defined as a pathologically-confirmed tissue diagnosis in a patient without prior NHL developing symptoms after starting newer-class antiretrovirals. Mean change in CD4 and log10 VL in NHL cases compared to controls was analyzed at week 12, a time point at which values were collected among all cases. RESULTS: Five cases occurred among 78 patients (mean incidence = 64.1/1000 patient-years). All cases received raltegravir and one received etravirine. Median symptom onset from newer-class antiretroviral initiation was 5 weeks. At baseline, the median CD4 and VL for NHL cases (n = 5) versus controls (n = 73) were 44 vs.117 cells/mm3 (p = 0.09) and 5.2 vs. 4.2 log10 (p = 0.06), respectively. The mean increase in CD4 at week 12 in NHL cases compared to controls was 13 (n = 5) vs. 74 (n = 50)(p = 0.284). Mean VL log10 reduction in NHL cases versus controls at week 12 was 2.79 (n = 5) vs. 1.94 (n = 50)(p = 0.045). CONCLUSIONS: An unexpectedly high rate of NHL was detected among treatment-experienced patients achieving a high level of virologic response with newer-class antiretrovirals. We observed trends toward lower baseline CD4 and higher baseline VL in NHL cases, with a significantly greater decline in VL among cases by 12 weeks. HIV-related NHL can occur in the setting of immune reconstitution. Potential immunologic, virologic, and newer-class antiretroviral-specific factors associated with rapid development of NHL warrants further investigation.

Are we meeting the American Diabetes Association goals for HIV-infected patients with diabetes mellitus?

We determined rates of achieving the American Diabetes Association goals among human immunodeficiency virus (HIV)-infected diabetic patients. American Diabetes Association goals (for hemoglobin A1c, blood pressure, and lipid levels) were defined by 2008 American Diabetes Association guidelines. HIV-infected diabetic patients achieved American Diabetes Association goals at rates similar to those in general medicine clinic patients. A multidisciplinary approach is needed to improve diabetes management in HIV clinics.

Steatosis Rates by Liver Biopsy and Transient Elastography With Controlled Attenuation Parameter in Clinical Experience of Hepatitis C Virus (HCV) and Human Immunodeficiency Virus/HCV Coinfection in a Large US Hepatitis Clinic.

BACKGROUND: Steatosis contributes to liver fibrosis in hepatitis C virus (HCV) and human immunodeficiency virus (HIV)/HCV coinfection. Liver biopsy (LB) is the reference standard for grading steatosis and staging fibrosis, yet recent advances in noninvasive modalities have largely supplanted LB, which may limit recognition of steatosis. We evaluated steatosis rates by LB and transient elastography (TE) with controlled attenuation parameter (CAP) among HCV-infected and HIV/HCV-coinfected patients in a US clinic. METHODS: Patients with chronic HCV infection during pretreatment evaluation by LB (n = 421; December 2001 through May 2014) and TE with CAP (n = 1157; May 2016 through May 2017) were included. Fibrosis and steatosis rates by LB and TE with CAP were stratified by HCV versus HIV/HCV coinfection status. RESULTS: Steatosis was not reported in 26.1% of LBs. Moderate to severe steatosis (grade ≥S2) was detected more often with CAP than with LB (in 24.0% vs 11.4% of patients, respectively). Median CAP values were higher in patients with HCV monoinfection than in those with coinfection (230 vs 215.5 dB/m, respectively; P < .001). With TE, the rate of advanced fibrosis (values F3-F4) was higher in HCV monoinfection than in coinfection (25.9% vs 14.8%, respectively; P <.001). With both LB and TE, advanced fibrosis (F3-F4) was significantly associated with moderate to severe steatosis (S2-S3) in HCV monoinfection compared with HIV/HCV coinfection (33.3% vs 4.4%, respectively for LB [P = 0.003] and 36.0% vs 29.0% for TE [P = 0.008]). CONCLUSIONS: In patients with chronic HCV undergoing liver fibrosis staging, steatosis was detected more often with CAP than LB, with median CAP values higher in HCV monoinfection than HIV/HCV coinfection. Steatosis severity may be increasing in the modern HCV treatment era.

Retracted: Electronic Clinical Decision Support Intervention to Increase Hepatitis C Screening and Linkage to Care Among Baby Boomers in Urban Safety Net Health Systems.

The article entitled, "Electronic Clinical Decision Support Intervention to Increase Hepatitis C Screening and Linkage to Care Among Baby Boomers in Urban Safety Net Health Systems," by Armstrong et al., published online ahead of print (2019 Oct 8) in Population Health Management [doi: 10.1089/pop.2019.0105], requires a retraction due to duplicate publication in the Journal of Community Medicine & Health Education (JCMHE) in February of 2019, and then in Population Health Management in October of 2019. As it is against the standard protocols of peer review to publish original research in two different journals, Population Health Management is officially retracting the article from its literature. Population Health Management is dedicated to adhering to the policies and best practices of scientific publishing and the community it serves.

White matter anisotropy and depression symptoms in patients with HIV.

HIV is associated with increased risk for depression. Normal appearing white matter (NAWM) fractional anisotropy in 15 HIV-seropositive (HIV+) adults with depressive symptoms was compared to 15 HIV+ adults without depressive symptoms. HIV+ adults with depressive symptoms showed increased NAWM fractional anisotropy within the left thalamus, the temporal, and frontal regions, as well as the right cingulate. Discrete components of depression were associated with distinct regional NAWM fractional anisotropy increases. These results demonstrate altered neural complexity in HIV+ adults with depressive symptoms and support the notion that depression is multifactorial with different morphological alterations contributing to discrete aspects of depression.

Effects of Fish Oil on HIV-Related Inflammation and Markers of Immunosenescence: A Randomized Clinical Trial.

OBJECTIVE: To explore the safety and efficacy of fish oil to modulate parameters of inflammation and immunosenescence in HIV-infected older adults. DESIGN: This study uses a randomized, controlled, double-blind clinical trial. SETTING: The study was conducted in an outpatient HIV/AIDS clinic in a large urban Midwestern city in the United States. SUBJECTS: A total of 37 clinically stable HIV-infected adults between the ages of 40 and 70 years of age participated. INTERVENTIONS: Fish oil 1.6 g/day was administered for 12 weeks or placebo. OUTCOME MEASURES: Inflammatory cytokine production, surface markers of immunosenescence, and adverse events were measured. RESULTS: After 12 weeks of supplementation, there were no significant differences between the treatment and control groups on any measures of inflammation or immunosenescence in both CD4+ and CD8+ T lymphocytes. More participants in the treatment group reported adverse gastrointestinal events compared with the control group. CONCLUSIONS: A 12-week supplementation regimen of 1.6 g/day of fish oil did not favorably modulate parameters of inflammation or immune senescence in HIV-infected adults. Future studies should test agents that directly target mechanisms that underlie HIV-related inflammation to determine whether reducing inflammation can reverse immunosenescence.

Vitamin D deficiency and periodontal clinical attachment loss in HIV-seropositive women: A secondary analysis conducted in the Women's Interagency HIV Study (WIHS).

OBJECTIVE: The aim of this study was to test a hypothesized positive association between low vitamin D (VitD) serum levels and the severity of periodontal disease in women with HIV infection. STUDY DESIGN: This was a cross-sectional secondary analysis of data from an oral substudy conducted within the Chicago site of the Women's Interagency HIV Study. Serum VitD levels and clinical attachment loss (CAL) measurements were available for 74 women with HIV infection. VitD levels were treated as both continuous and categorical variables in bivariate and multivariate analyses. Mean clinical attachment loss (mCAL) was determined for each subject by obtaining the averages of measurements taken at 4 sites in each measured tooth. RESULTS: Average age of study participants (n = 74) was 39.6 years (standard deviation 7.2), and the majority were African Americans (70.3%) with VitD deficiency (58.1%). VitD deficiency was positively associated with higher mCAL (P = .012). After adjustment for race, age, smoking, and HIV viral load, an association was found between VitD deficiency and mCAL (Beta 0.438; P = .036). CONCLUSIONS: We identified a previously unreported association between VitD deficiency and mCAL in women with HIV infection. Larger and more inclusive, multisite, longitudinal studies are warranted to investigate whether these findings can be generalized to all individuals with HIV infection in the current treatment era and to determine causality.

Neopterin is associated with hippocampal subfield volumes and cognition in HIV.

OBJECTIVE: HIV infection sets off an immediate immune response and inflammatory cascade that can lead to neuronal injury and cognitive impairment, but the relationship between immune markers, regional brain volumes, and cognition remains understudied in HIV-infected adults. METHODS: Cross-sectional associations were examined between serum immune markers of activation (neopterin) and inflammation (interleukin [IL]-1ß, IL-6, tumor necrosis factor alpha, and C-reactive protein) with regional brain volumes (cortical, subcortical, total gray matter, hippocampus, and subfields) and cognition in 66 HIV-infected, virally suppressed, adults who underwent 3.0-T MRI as part of the Research Core of the Rush Center of Excellence on Disparities in HIV and Aging. Immune markers were assayed from frozen plasma, values were entered into linear regression models as predictors of regional brain volumes, and interactive effects of immune response and regional brain volumes on cognition were examined. RESULTS: No inflammatory marker was associated with any regional brain volume. Higher neopterin level was associated with lower total hippocampal, presubiculum, and cornu ammonis (CA) subfield volumes. Higher neopterin level and lower total hippocampal volume were independently associated with lower episodic memory, and neopterin level fully mediated the effect of hippocampal atrophy on episodic memory. Higher neopterin levels were associated with lower presubiculum, CA1, and CA4/dentate volumes and lower semantic memory, working memory, and global cognition. CONCLUSION: Immune activation in response to HIV infection, measured by neopterin, has a deleterious and targeted effect on regional brain structure, which can be visualized with clinically available MRI measures of hippocampus and its subfields, and this effect is associated with lower cognitive function.

Cardiovascular risk and risk management in HIV-infected patients.

Patients with HIV infection are at risk of cardiovascular disease from the same factors posing risk in the general population--eg, smoking, dyslipidemia, hypertension, obesity, and diabetes. HIV infection itself and antiretroviral therapy pose additional risk, but available data indicate that the relative rate of myocardial infarction is low and declining in the HIV-infected population. Cardiovascular risk should be addressed before initiation of antiretroviral therapy and frequently during follow-up, and decisions to alter therapy on the basis of adverse changes in metabolic risk factors should be made on an individual basis. Virologic control is the primary goal for HIV-infected persons with cardiovascular risk, and is the primary consideration in determining when to start antiretroviral therapy and when to change regimens. This article summarizes a presentation on cardiovascular risk and risk management in HIV-infected persons made by Oluwatoyin Adeyemi, MD, at an International AIDS Society-USA Continuing Medical Education course in Chicago in May 2007.

Perceived significance of isolated HBcAb in patients with HIV: a survey of practitioners.

The prevalence of the isolated hepatitis B core Ab phenotype (hepatitis B surface antigen negative [HBsAg-] hepatitis B surface antibody negative [HBsAb-], and hepatitis B core antibody positive [HBcAb+] is particularly high among human HIV-positive patients. Controversy exists regarding both the significance of this phenotype and the risk of progressive liver disease as well as the need for hepatitis B vaccination in this population. A survey of 40 HIV primary care providers (PCPs) at an urban outpatient HIV clinic was conducted in 2005 regarding these two issues and a summary of the findings are presented in this report. Seventy-eight percent thought that these patients' infection had resolved and were immune, half thought they were at risk for progressive liver disease, and 6 (15%) routinely administered hepatitis B vaccine to patients with this phenotype. The wide variety in attitudes and practices among providers in a single clinic suggests the need for further research and development of management guidelines in this group of patients.

Utility of repeat genotypic resistance testing and clinical response in patients with three class resistance and virologic treatment failure.

We sought to determine the utility of repeat genotypic resistance testing (GRT) and the clinical response in HIV-1-infected patients with known resistance to three of the major classes of antiretroviral drugs. The HIV-1 genetic sequences for 20 patients who had high-level 3 class resistance demonstrated on a prior GRT (3C-GRT 1) measured during the period from November 1, 2000 through July 1, 2004 were retrospectively evaluated. At the time of 3C-GRT 1, the median CD4 count and HIV-1 RNA viral load were 168 cells/mm(3) and 4.5 log copies per milliliter, respectively. The median time to the second GRT (3C-GRT 2) was 17 months. At that time, the median CD4 count and VL were 140 cells/mm(3) and 4.9 log copies per milliliter (p = 0.8 and p = 0.12, respectively). On 3C-GRT 2, all patients retained essentially identical mutations, with the exception of the loss of the M184V mutation in 6 patients. After 3C-GRT 2, all patients continued on protease inhibitor-containing highly active antiretroviral therapy (HAART) regimens. At 24 weeks after 3C-GRT 2, there was no significant change in CD4 count or HIV-1 RNA viral load (p = 0.68 and p = 0.30, respectively). Repeat GRT in patients with documented high-level 3 class resistance does not provide new or clinically useful information. Under continued antiretroviral selective pressure, the viral genetic sequences in this patient population remained stable. In addition, continuing HAART regimens containing protease inhibitors appeared to forestall further immunological and virologic deterioration in patients with multiple resistance mutations. Providers should focus on obtaining access to combinations of novel agents for patients with 3 class resistance rather than repeated GRT.