Stable Combination Antiretroviral Therapy Research Articles

Cardiovascular risk factors and carotid intima-media thickness with neurocognitive dysfunction in people living with HIV on stable combination anti-retroviral therapy

The goal of this clinical research was to determine the relationship between carotid intima-media thickness (cIMT), cardiovascular risk factors, and neuro-cognitive function in people living with HIV (PLHIV) and were on stable combination anti-retroviral therapy (cART). This is a cross-sectional study performed at a single center, including 149 patients who visited the anti-retroviral therapy center of our tertiary care hospital. Among the PLHIV of our research, 62.4% had at least one associated cardiovascular risk factor, and 61.1% of them had abnormally high cIMT (≥ 0.9 mm on any one side, p = 0.035). These factors and being the male gender (p = 0.028) were associated with a greater Framingham 10-year risk percentage. Hypercholesterolemia was observed in 30.9% of the PLHIV and a higher body mass index (≥ 25 kg/m2) was found in 26.8% of them. The cognitive impairment was milder in 71.8% of cases and moderate in 9.4% of PLHIV. The Chi-square test revealed that a higher proportion of participants who had lower HDL-C levels (p = 0.045), smokers (p = 0.029), systolic blood pressure ≥ 140 mmHg (p = 0.012), and lower educational status (p = 0.017) had a poorer cognitive performance. In our sample population, a higher prevalence of elevated cIMT, cardiovascular risk factors, and mild and moderate cognitive deficiency was observed in PLHIV, who were on stable cART. However, routine assessment of the neuropsychological functions and management of modifiable risk factors are not performed in our patients. Further exploration of the relationship between cardiovascular risks, cIMT, and cognitive impairment in PLHIV is essential to formulate the guidelines and delay the onset of neurocognitive disorders in these patients.

Comparison of Resting State Functional Connectivity in Persons With and Without HIV: A Cross-sectional Study.

This study examined the effects of human immunodeficiency virus (HIV) on resting state functional connectivity (RSFC) in a large cohort of people with HIV (PWH) and healthy controls without HIV (PWoH). Within PWH analyses focused on the effects of viral suppression and cognitive impairment on RSFC. A total of 316 PWH on stable combination antiretroviral therapy and 209 demographically matched PWoH were scanned at a single institution. Effects of the virus were examined by grouping PWH by detectable (viral load > 20 copies/mL; VLD) and undetectable (VLU) viral loads and as being cognitively impaired (CI) (Global Deficit Score ≥ 0.5) or cognitively normal (CN). Regression analysis, object oriented data analysis, and spring embedded graph models were applied to RSFC measures from 298 established brain regions of interest comprising 13 brain networks to examine group differences. No significant RSFC differences were observed between PWH and PWoH. Within PWH, there were no significant differences in RSFC between VLD and VLU subgroups and CI and CN subgroups. There were no significant effects of HIV on RSFC in our relatively large cohort of PWH and PWoH. Future studies could increase the sample size and combine with other imaging modalities.

Sleep disturbances and their correlation with cardiovascular risk, obesity, and mood disorders in people with HIV.

The relationship between sleep disorders (SDs), cardiovascular risk (CVR), and mood disorders (MDs) has been studied in detail in the general population, but far less in people with HIV (PWH). Cross-sectional analysis in single centre cohort of PWH. Sleep quality was assessed using by Epworth Sleepiness Scale (ESS), Insomnia Severity Index (ISI), Berlin Questionnaire (BQ), Pittsburgh Sleep Quality Index (PSQI); anxiety and depression were evaluated by the Generalized Anxiety Disorder-7 and Patient Health Questionnaire-9. Demographic, clinical and HIV-related data were collected, and Framingham and Data collection on Adverse effects of anti-HIV Drugs (DAD)-10 scores were computed in modelling associations with each SDs scale. Data were collected for 721 PWH on stable combination antiretroviral therapy (cART) (median age of 53 years, 71.8% males, 96% with undetectable HIV RNA, 50.3% on cART potentially affecting sleep, and 20.4% on hypno-inducing drugs), 76.9% had SDs 60.3, 31.3, 31.1, and 7.9% at PSQI, BQ, ISI, and ESS, respectively. Anxiety and depression were detected in 28.3 and 16.1% participants, respectively. BQ score was independently associated with high BMI ( P < 0.001), Framingham risk >10% ( P < 0.001), and both DAD-10R and -10F score >10% ( P < 0.001 and P = 0.031). PSQI and ISI scores were independently associated with depression and anxiety ( P < 0.001). No association between SDs and specific antiretroviral regimens, nor HIV-related parameters was detected. In our cohort of PWH on stable ART, despite the alarmingly higher prevalence, SDs were associated with the same determinants (cardiovascular risk factors and MDs) observed in the general population.

Reversal of Viral Latency and Induction of Gag-Specific T-Cell Responses in HIV-1-Infected Adults Through Cyclic Treatment Interruption of Rosuvastatin: A Proof-of-Concept Study.

HIV-1 infection remains incurable through combination antiretroviral therapy. Previous studies have shown statins have immunomodulatory effects, and interruption of statins may cause an immune rebound. In this proof-of-concept study, we longitudinally assessed the impact of immune rebound by cyclic treatment-interruption (CTI) of rosuvastatin on the reversal of HIV latency. The HIV-1-infected persons with stable viral control were considered to be enrolled for CTI of rosuvastatin with a fixed 12-week interval for 72 weeks (3 treatment-interruption cycles). HIV-1 Gag-specific T-cell responses, cell-associated RNA, and proviral DNA were determined. From Feb 2017 to Dec 2019, 10 subjects were enrolled. During the 72-week follow-up, their CD4+ T-cell counts did not significantly change, and plasma HIV RNA remained undetectable. Transient but remarkable increases in levels of cell-associated RNA, Gag-specific interferon-γ production from CD4+ T cells and Gag-specific CD8+ cytotoxic capacity were detected shortly after stopping rosuvastatin in every cycle of CTI of rosuvastatin. Furthermore, there was a 2.63-fold reduction (range, 1.41-4.82) in proviral DNA levels (P = 0.005) during the 72-week follow-up. A significant linear association was demonstrated between their nadir CD4+ T-cell counts and the fold decrease in proviral DNA levels (R = 0.81, P = 0.004). It may be possible to reverse viral latency in CD4+ T cells, activate Gag-specific T cells, and reduce viral reservoir size through CTI of rosuvastatin in HIV-1-infected subjects with stable combination antiretroviral therapy, especially in those with nadir CD4+ T-cell counts > 350 cells/μL.

Pathomechanisms of HIV-Associated Cerebral Small Vessel Disease: A Comprehensive Clinical and Neuroimaging Protocol and Analysis Pipeline.

Rationale: We provide an in-depth description of a comprehensive clinical, immunological, and neuroimaging study that includes a full image processing pipeline. This approach, although implemented in HIV infected individuals, can be used in the general population to assess cerebrovascular health.Aims: In this longitudinal study, we seek to determine the effects of neuroinflammation due to HIV-1 infection on the pathomechanisms of cerebral small vessel disease (CSVD). The study focuses on the interaction of activated platelets, pro-inflammatory monocytes and endothelial cells and their impact on the neurovascular unit. The effects on the neurovascular unit are evaluated by a novel combination of imaging biomarkers.Sample Size: We will enroll 110 HIV-infected individuals on stable combination anti-retroviral therapy for at least three months and an equal number of age-matched controls. We anticipate a drop-out rate of 20%.Methods and Design: Subjects are followed for three years and evaluated by flow cytometric analysis of whole blood (to measure platelet activation, platelet monocyte complexes, and markers of monocyte activation), neuropsychological testing, and brain MRI at the baseline, 18- and 36-month time points. MRI imaging follows the recommended clinical small vessel imaging standards and adds several advanced sequences to obtain quantitative assessments of brain tissues including white matter microstructure, tissue susceptibility, and blood perfusion.Discussion: The study provides further understanding of the underlying mechanisms of CSVD in chronic inflammatory disorders such as HIV infection. The longitudinal study design and comprehensive approach allows the investigation of quantitative changes in imaging metrics and their impact on cognitive performance.

Correlates of telomere length shortening in peripheral leukocytes of HIV-infected individuals and association with leukoaraiosis.

Telomere length (TL) is a marker of cellular and biological aging. Human immunodeficiency virus (HIV) infection has been reported to be associated with short TLs, which suggests that accelerated biological aging occurs in some cellular compartments of HIV+ individuals. In this study, we measured the TLs of peripheral leukocytes of HIV+ and healthy individuals and examined the biological and environmental correlates of TL. We also investigated the influence of TL on leukoaraiosis, an indicator of cerebral small vessel disease, in HIV+ individuals. Three hundred and twenty-five HIV+ individuals who received stable combination antiretroviral therapy (cART) for >1 year and achieved viral loads of <40 RNA copies/mL were enrolled along with 147 healthy individuals. Relative TLs of leukocytes were estimated by quantitative real-time polymerase chain reaction. Leukoaraiosis was assessed in 184 HIV+ individuals by fluid-attenuated inversion recovery magnetic resonance imaging. We analyzed several covariates, including markers of HIV infection, cART, and social/environmental factors; variables associated with TL length in univariate analyses were incorporated into multivariate models. The TLs of peripheral leukocytes of HIV+ individuals were significantly shorter than those of healthy individuals, and the rate of LT length decline with increasing age was greater. Linear regression analysis showed that in HIV+ individuals, increasing age, cART without integrase-stand transfer inhibitors (INSTI), failure to achieve viral loads of <40 copies/mL within 1 year of initiating cART, and substance use were significantly associated with shorter TLs, even after adjustment for the effects of age. Logistic regression analysis indicated an increasing risk of leukoaraiosis was associated with older age, shorter TLs, hypertension, and carotid artery plaque. Multivariate regression analysis indicated that older age and shorter TLs were significant risk factors for leukoaraiosis. In summary, our data showed that TL shortening in HIV+ individuals was independently associated with leukoaraiosis, and was associated with age, control of viral loads, use of INSTI, and substance use. Our results suggest that effective viral control and less toxic cART can help reduce TL shortening and improve outcomes among HIV+ individuals.

IHIVARNA phase IIa, a randomized, placebo-controlled, double-blinded trial to evaluate the safety and immunogenicity of iHIVARNA-01 in chronically HIV-infected patients under stable combined antiretroviral therapy

BackgroundHIV therapeutic vaccination aims to improve the immune responses against HIV in order to control viral replication without the need for combined antiretroviral therapy (cART). iHIVARNA-01 is a novel vaccine combining mRNA delivery and T-cell immunogen (HTI) based on conserved targets of effective antiviral T-cell responses. In addition, it holds adequate stimuli required for activating antigen presenting cells (APC)s and co-activating specific T-cells (TriMix), including human CD40L, constitutively active TLR4 (caTLR4) and CD70. We propose that in-vivo targeting of dendritic cells (DCs) by direct administration of a HIV mRNA encoding these immune modulating proteins might be an attractive alternative to target DCs in vitro.Methods/designThis is a phase-IIa, randomized, double-blinded, placebo-controlled, multicenter study in chronically HIV-1 infected patients under stable cART. One of the three study arms is randomly allocated to subjects. Three vaccinations with either HIVACAT T-cell immunogen (HTI)-TriMix (iHIVARNA-01), TriMix or water for injection (WFI) (weeks 0, 2 and 4) are administered by intranodal injection in the inguinal region. Two weeks after the last immunization (week 6) cART is stopped for 12 weeks. The two primary endpoints are: (1) safety and tolerability of intranodal iHIVARNA-01 vaccination compared with TriMix or WFI and (2) induced immunogenicity, i.e., increase in the frequency of HIV-specific T-cell responses between baseline, week 6 and 12 weeks after treatment interruption in iHIVARNA-01-treated patients as compared to the control groups, immunized with TriMix-mRNA or WFI measured by an IFNγ ELISPOT assay. Secondary endpoints include the evaluation of time to viral rebound, plasma viral load (pVL) at w18, the proportion of patients with control of viral load, induction of T-cell responses to new HIV epitopes, polyfunctionality of HIV-specific T-cells, CD8+ T-cell in-vitro HIV suppressive capacity, the effect on viral reservoir (measured by proviral DNA and cell-associated RNA), assessment of viral immune escape by mutation and mRNA expression profiles of host immune genes.DiscussionThis trial aims to direct target DC in situ with mRNA encoding HTI and TriMix for co-stimulation. Intranodal injection circumvents laborious DC isolation and handling in the laboratory. The trial extends on the safety results of a phase-I dose-escalating trial. This candidate vaccine could complement or even replace cART for chronic HIV infection and could be applicable to improve the care and cost of HIV infection.Trial registrationEudraCT 2016-002724-83 (22 September 2016); ClinicalTrials.gov, ID: NCT02888756. Registered on 23 August 2016.

Travel-related health events and their risk factors in HIV-infected sub-Saharan migrants living in France and visiting their native country: The ANRS VIHVO cohort study.

Literature on health events in HIV-infected travellers is scarce, particularly in sub-Saharan African (SSA) migrants. We investigated health events in HIV-infected SSA migrants living in France during and after travel to their native country. All had a pre-travel plasma viral load (pVL) below 200 copies/mL and were on stable combined antiretroviral therapy (cART). Logistic regression models were used to assess the risk factors for at least one adverse health event or febrile event. Among 264 HIV migrants, pre-travel median CD4 count was 439/mm3 and 27 migrants (6%) experienced a low-level viremia between 50 and 200 copies/mL. One hundred (38%) experienced at least one event (13 experienced two events). The most common events were gastrointestinal, including diarrhoea (n = 29, 26%), respiratory events (n = 20, 18%), and malaria (n = 17, 15%; 1 death). In multivariable analysis, a pre-travel low-level viremia and a lack of pre-travel medical advice significantly increased the risk for any event (OR 4.31, 95% CI, 1.41-13.1; and OR 3.62, 95% CI, 1.38-9.47; respectively). A lack of pre-travel advice significantly increased the risk for febrile event. Early and tailored counselling on pre-travel medical advice regarding diarrhoea and vector-borne diseases prophylactic measures in HIV-infected SSA migrants should be emphasised before travel to Africa.

HIV and age underlie specific patterns of brain abnormalities and cognitive changes in high functioning patients.

Findings on the influence of age and HIV on brain and cognition remain equivocal, particularly in aviremic subjects without other age or HIV-related comorbidities. We aimed to (a) examine the effect of HIV status and age on structural brain measurements and cognition, and (b) apply the machine learning technique to identify brain morphometric and cognitive features that are most discriminative between aviremic subjects with HIV on stable combination antiretroviral therapy (cART) and healthy controls. Fifty-three HIV-seropositive patients and 62 healthy controls underwent neuropsychological testing (executive functions, attention, memory, learning, psychomotor speed, fluency) and volumetric MRI scans. Voxel-based morphometry, ANCOVAs, machine learning, and multivariate regression were conducted to determine the between group differences in terms of relationship of HIV status, age, and their interaction on neurocognitive and structural brain measures. Volume and gray matter (GM) thickness of the caudate, parahippocampus, insula, and inferior frontal gyrus were smaller in seropositive subjects in comparison with healthy controls (HC). They also performed worse in complex attention and cognitive fluency tasks. Support vector machine (SVM) analysis revealed that the best between-groups classification accuracy was obtained based on cognitive scores encompassing complex attention and psychomotor speed, as well as volumetric measures of white matter and total gray matter; third, fourth, and lateral ventricles; amygdala; caudate; and putamen. Both voxel-based morphometry (VBM) and regression analysis yielded that HIV and aging independently increase brain vulnerability and cognitive worsening. Patients with HIV on effective cART demonstrate smaller volumetric measures and worse cognitive functioning relative to seronegative individuals. There is no interaction between HIV infection and aging. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Real World Patient-reported Outcomes in HIV-infected Adults Switching to EVIPLERA®, Because of a Previous Intolerance to cART. PRO-STR Study.

Background:To investigate the impact of switching from stable Combined Antiretroviral Therapy (cART) to single-tablet regimen (RPV/FTC/TDF=EVIPLERA®/COMPLERA®) on patient-reported outcomes in HIV-infected adults who cannot tolerate previous cART, in a real-world setting.Methods:PRO-STR is a 48-week observational, prospective, multicenter study. Presence and magnitude of symptoms (main endpoint), health-related quality-of-life (HRQoL), adherence, satisfaction with treatment and patient preferences were assessed.Results:Three hundred patients with 48-week follow-up, who switched to EVIPLERA® (mean age: 46.6 years; male: 74.0%; 74.7% switched from a non-nucleoside reverse-transcriptase-inhibitor, 25.3% from a protease inhibitor + ritonavir) were included. There was no statistical difference in median CD4+ cell count (baseline: 678.5 cells/mm3; 48-week: 683.0 cells/mm3) neither in virological suppression (≤50 copies/mL) (baseline: 98.3%; 48-week: 95.3%). The most frequent reasons for switching were neuropsychiatric (62.3%), gastrointestinal (19.3%) and biochemical/metabolic (19.3%) events. Only 7.7% of patients permanently discontinued therapy. At 48-week, all outcomes showed an improvement compared to baseline. Overall, there was a significant decrease (p-value≤0.05) in number and magnitude of symptoms, while HRQoL, satisfaction and adherence improved significantly. Most patients prefered EVIPLERA® than previous cART. According to the type of intolerance, HRQoL was improved, but only significantly in patients with neuropsychiatric and gastrointestinal symptoms. Adherence improved significantly in patients with metabolic disturbances and satisfaction with EVIPLERA® was higher in the three groups.Conclusion:Switching to EVIPLERA® from non-nucleoside reverse-transcriptase-inhibitor or protease inhibitor-based regimens due to toxicity, improved the presence/magnitude of symptoms, HRQoL, and preference with treatment. EVIPLERA® maintained a virological response, CD4+ cell count and maintained or improved adherence.

Cytomegalovirus-Specific CD4+ T-cell Responses and CMV-IgG Levels Are Associated With Neurocognitive Impairment in People Living With HIV

Mechanisms leading to neurocognitive impairment (NCI) in people living with HIV (PLWHIV) on stable combination antiretroviral therapy (cART) remain unknown. We investigated the association between immunity against cytomegalovirus (CMV), HIV-specific variables, and NCI in PLWHIV on stable cART and with low comorbidity. Fifty-two PLWHIV on stable cART and 31 HIV-uninfected controls matched on age, sex, education, and comorbidity were tested with a neurocognitive test battery, and CMV-immunoglobulin G (CMV-IgG) levels were measured. In PLWHIV, CMV-specific (CMV-pp65 and CMV-gB) CD4 and CD8 T-cell responses were measured using intracellular cytokine staining and flow cytometry. NCI was defined as a global deficit scale score (GDS score) ≥0.5. GDS scores and domain-specific scores defined severity of NCI. Logistic and linear multivariable regression analyses were used. NCI was detected in 30.8% of PLWHIV, and HIV was associated with an adjusted odds ratio (aOR) of 5.18 [95% confidence interval (CI): 1.15 to 23.41, P = 0.033] for NCI. In PLWHIV, higher CMV-specific CD4 T-cell responses increased the probability of NCI with an aOR of 1.68 (95% CI: 1.10 to 2.57) for CMV-pp65 or an aOR of 3.73 (95% CI: 1.61 to 16.98) for CMV-gB, respectively. Similar associations were not found with CMV-IgG or CMV-specific CD8 T cells, but when assessing severity of NCI, higher CMV-IgG (per 100 U/mL) was associated with worse GDS scores (β = 0.08) (0.01-0.16), P = 0.044), specifically in the domain of speed of information processing (β = 0.20 (0.04-0.36, P = 0.019). PLWHIV had increased risk of NCI. Excess risk may be associated with CMV-specific CD4 T-cell responses and CMV-IgG. Larger longitudinal studies investigating the impact of immunity against CMV on risk of NCI are warranted.

Vagal dysfunction and small intestinal bacterial overgrowth: novel pathways to chronic inflammation in HIV.

Chronic inflammation in HIV-infected individuals drives disease progression and the development of comorbidities, despite viral suppression with combined antiretroviral therapy. Here, we sought evidence that vagal dysfunction, which occurs commonly as part of HIV-associated autonomic neuropathy, could exacerbate inflammation through gastrointestinal dysmotility, small intestinal bacterial overgrowth (SIBO), and alterations in patterns of soluble immune mediators. This is a cross-sectional observational study. Forty participants on stable combined antiretroviral therapy with gastrointestinal symptoms, and no causes for vagal or gastrointestinal dysfunction other than HIV, underwent autonomic testing, hydrogen/methane breath testing for SIBO, and gastric emptying scintigraphy. A panel of 41 cytokines, high-mobility group box 1, and markers of bacterial translocation (lipopolysaccharide) and monocyte/macrophage activation (sCD14 and sCD163) were tested in plasma. We found that participants with vagal dysfunction had delayed gastric emptying and higher prevalence of SIBO. SIBO was associated with IL-6, but not sCD14; lipopolysaccharide could not be detected in any participant. We also found alteration of cytokine networks in participants with vagal dysfunction, with stronger and more numerous positive correlations between cytokines. In the vagal dysfunction group, high mobility group box 1 was the only soluble mediator displaying strong negative correlations with other cytokines, especially those cytokines that had numerous other strong positive correlations. The current study provides evidence that the vagal component of HIV-associated autonomic neuropathy is associated with changes in immune and gastrointestinal function in individuals with well treated HIV. Further study will be needed to understand whether therapies targeted at enhancing vagal function could be of benefit in HIV.

Effort and neuropsychological performance in HIV-infected individuals on stable combination antiretroviral therapy.

The expression of cognitive symptoms associated with HIV varies over time and across individuals. This pattern may reflect transient contextual factors, including the degree of effort exerted by individuals undergoing cognitive testing. The present study examined whether effort corresponds to the expression of persistent HIV-related cognitive impairment among individuals receiving combination antiretroviral therapy (cART). HIV+ individuals (n=111) averaged 48.2 (14.9)years of age and 13.0 (2.7)years of education and HIV- individuals (n=92) averaged 34.9 (17.2)years of age and 13.5 (1.9)years of education. Participants completed a neuropsychological battery and a clinically validated measure of effort (Test of Memory Malingering, trial 1). Results revealed that the vast majority of HIV+ (85%) and HIV- (89%) individuals performed above published guidelines for adequate effort. Furthermore, the expression of cognitive impairment in HIV was not related to effort performance. The results were unchanged when examining HIV+ individuals with and without viral suppression. Finally, disability and disability-seeking status, and a proxy measure of apathy did not correspond to effort levels in HIV+ individuals. These findings suggest that variability in the expression of cognitive impairment in the cART era is unlikely to represent overt effort failures or other confounds unrelated to the disease. Persistent cognitive impairment in HIV likely represents historical and/or ongoing disease mechanisms despite otherwise successful treatment.

Incidence of Postsuppression Virologic Rebound in Perinatally HIV-Infected Asian Adolescents on Stable Combination Antiretroviral Therapy

PurposeTo assess the incidence and predictors of postsuppression virologic rebound (VR) among adolescents on stable combination antiretroviral therapy in Asia. MethodsPerinatally HIV-infected Asian adolescents (10–19 years) with documented virologic suppression (two consecutive viral loads [VLs] <400 copies/mL ≥6 months apart) were included. Baseline was the date of the first VL <400 copies/mL at age ≥10 years or the 10th birthday for those with prior suppression. Cox proportional hazards models were used to identify predictors of postsuppression VR (VL >1,000 copies/mL). ResultsOf 1,379 eligible adolescents, 47% were males. At baseline, 22% were receiving protease inhibitor–containing regimens; median CD4 cell count (interquartile range [IQR]) was 685 (448–937) cells/mm3; 2% had preadolescent virologic failure (VF) before subsequent suppression. During adolescence, 180 individuals (13%) experienced postsuppression VR at a rate of 3.4 (95% confidence interval: 2.9–3.9) per 100 person-years, which was consistent over time. Median time to VR during adolescence (IQR) was 3.3 (2.1–4.8) years. Wasting (weight-for-age z-score <−2.5), being raised by grandparents, receiving second-line protease inhibitor–based regimens, starting combination antiretroviral therapy after 2005, and having preadolescent VF were independent predictors of adolescent VR. At VR, median age, CD4 cell count, and VL (IQR) were 14.8 (13.2–16.4) years, 507 (325–723) cells/mm3, and 4.1 (3.5–4.7) log10 copies/mL, respectively. ConclusionsA modest and consistent incidence of postsuppression VR was documented during adolescence in our cohort. Having poor weight, receiving second-line regimens, and prior VF were associated with an increased VR rate. Adolescents at higher risk of VR may benefit from more intensive VL monitoring to enhance adherence management.

Lipid Profiles After Therapy with Direct-Acting Antivirals in HCV Mono-infected and HCV/HIV Co-infected Patients

Introduction: Chronic hepatitis C (HCV) infection is associated with significant decreases in low-density cholesterol (LDL-c) and triglycerides (TG). Potential mechanisms include interactions between lipid metabolism and HCV life-cycle, HCV-associated inflammation, or hepatic fibrosis. Limited data suggest that interferon-based HCV therapy results in increased lipid levels. It is unclear if HCV therapy with direct-acting antivirals (DAA Rx) alters lipid profiles, and, if so, whether these changes differ among HCV mono-infected (HCV) and HCV/HIV co-infected (HCV/HIV) patients and whether they correlate with hepatic fibrosis scores (FIB-4). Methods: We compared LDL-c, TG, and FIB-4 scores at baseline (BL) until 1-year after end of DAA Rx in HCV and HCV/HIV patients with sustained virologic response after DAA Rx at a Veterans Affairs Medical Center from 01/2014 until 10/2015. We analyzed changes and correlations using Wilcoxon signed rank test and Spearman's rho, respectively. Results: 118 consecutive patients were included in the analyses, 23 (19%) of whom were HIV/HCV (all on stable combination antiretroviral therapy with HIV viral loads < 100 copies/mL). Median age was 61 years, inter-quartile range (IQR): 58-65, 95% were male. Median BL HCV viral load (VL) was 6.4 log copies/mL, (IQR 6.0-6.8), 81% had HCV-genotype 1, 91% received sofosbuvir-based therapy, 86% for 12 weeks, and 31 patients took anti-hyperlipidemic therapy. Median BL FIB-4 score was significantly lower in HIV/HCV than in HCV: 2.1 (IQR 1.7-3.5) vs. 4.5, (IQR 2.9-6.4), p < 0.001 while the median BL LDL was not different: 80 mg/dL (IQR 60-107) vs. 66 mg/dL (IQR 54-81), p=0.13. BL LDL-c and BL HCV VL were inversely correlated in HCV (r=-0.28, p=0.009) but not in HIV/HCV (p=0.45). After DAA Rx, median FIB-4 scores declined more in HCV: -1.8 (IQR -0.6 to -3.3) than in HIV/HCV: -0.3 (IQR 0 to -0.6), p=0.01. Median LDL-c increased similarly: +25 mg/dL (IQR 6-36, p < 0.001) in HCV and +25mg/dL (IQR -5 to +41, p=0.003) in HIV/HCV. LDL-c and FIB-4 changes were inversely correlated (r=-0.35; p=0.046) in HCV patients only. Overall median TG declined: -20 mg/dL (IQR +10 to -45, p=0.01) with no differences between groups (p=0.95). Conclusion: Successful DAA Rx was accompanied by significant LDL-c increases regardless of HIV coinfection status. In HCV patients - in whom fibrosis scores were much higher at baseline - this was inversely correlated with FIB-4 improvements.

Significant Decrease in Plasma Levels of D-Dimer, Interleukin-8, and Interleukin-12 After a 12-Month Treatment with Rosuvastatin in HIV-Infected Patients Under Antiretroviral Therapy.

Statins have shown anti-inflammatory and immune-modulatory properties in both general and HIV-infected population, but their effect on plasma D-dimer levels is controversial and it has not been investigated to date in HIV-positive patients. The aim of our study was to assess the effect of rosuvastatin on D-dimer and other serum inflammation markers among these subjects. Prospective, cohort study of HIV-1-infected adult patients receiving a stable combination antiretroviral therapy (cART), who started a lipid-lowering therapy with rosuvastatin (10 mg daily) and were followed up for at least 12 months. The primary endpoint was the change at month 12 in the median plasma concentration of D-dimer. The secondary endpoints included the variation in median plasma levels of these inflammatory biomarkers: interleukin-8 (IL-8), interleukin-10 (IL-10), and interleukin-12 (IL-12). Sixty-two patients were enrolled in the study, and the endpoints were available for 54 subjects. After 12 months, a significant decrease in median plasma concentration of D-dimer was observed (-21.4%; interquartile range [IQR], -35.5; -4.2; p = .029). With regard to the inflammatory biomarkers, a significant decrease in median levels of IL-8 (-24.6%; IQR, -30.8; -1.8; p = .012) and IL-12 (-18.7%; IQR, -25.8; +2.5; p = .033) was also observed. Rosuvastatin led to a significant reduction in serum lipid values and showed a good tolerability profile. Our findings show that a 12-month treatment with rosuvastatin associated with an effective cART can significantly decrease the plasma levels of D-dimer, IL-8, and IL-12, and suggest a potential role for this statin to reduce activated coagulation and systemic inflammation among HIV-infected persons.

Off-label use of rilpivirine in combination with emtricitabine and tenofovir in HIV-1-infected pediatric patients: A multicenter study.

To assess the safety and efficacy of rilpivirine in combination with emtricitabine and tenofovir (RPV/FTC/TDF) as a once-daily single-tablet regimen (STR) in HIV-1-infected children and adolescents we performed a multicenter case series study of HIV-1-infected patients. Inclusion criteria were initiation of therapy with RPV/FTC/TDF before the age of 18. Patients were divided into undetectable viral load (uVL) group, HIV-1 RNA < 20 copies/mL on stable combined antiretroviral therapy (cART), and detectable viral load (dVL) group, HIV-1 RNA ≥ 20 copies/mL at RPV/FTC/TDF initiation. Patients were monitored from the date of RPV/FTC/TDF initiation until June 30, 2015, RPV/FTC/TDF discontinuation or failure to follow-up. Seventeen patients (8 in uVL and 9 in dVL group) with age between 11.6 and 17.6 were included. Reasons for switching were toxicity (n = 4) and simplification (n = 4) in uVL; viral failure (n = 8) and cART initiation (n = 1) in the dVL group. After a median follow-up of 90 (uVL) and 40 weeks (dVL), 7/8 (86%) patients maintained and 8/9 (89%) achieved and maintained HIV-1 suppression. Median CD4 count increased from 542 to 780/μL (uVL, P = 0.069) and 480 to 830/μL (dVL, P = 0.051). Five patients (2 in uVL and 3 in dVL) improved their immunological status from moderate to no immunosuppression. Serum lipid profiles improved in both groups; cholesterol dropped significantly in the dVL group (P = 0.008). Grade 1 laboratory adverse events (AEs) were observed in 3 patients. No clinical AEs occurred. Adherence was complete in 9 patients (5 in uVL and 4 in dVL); 1 adolescent interrupted treatment. Once-daily STR with RPV/FTC/TDF may be a safe and effective choice in selected HIV-1-infected adolescents and children.

Incidence and risk factors for Tenofovir induced nephrotoxicity among patients with HIV on stable combination antiretroviral therapy(c ART) in South India

Incidence and risk factors for Tenofovir induced nephrotoxicity among patients with HIV on stable combination antiretroviral therapy(c ART) in South India

Symptoms of Autonomic Dysfunction in Human Immunodeficiency Virus.

This retrospective study evaluated the frequencies of symptoms associated with autonomic dysfunction in human immunodeficiency virus (HIV)-infected patients on stable combined antiretroviral therapy. Patients infected with HIV reported higher frequencies of dysautonomia symptoms compared with HIV-negative patients, particularly in the autonomic domains related to urinary, sleep, gastroparesis, secretomotor, pupillomotor, and male sexual dysfunction.

Plasma and Cerebrospinal Fluid Biomarkers Predict Cerebral Injury in HIV-Infected Individuals on Stable Combination Antiretroviral Therapy.

HIV-associated brain injury persists despite combination antiretroviral therapy, but contributing factors remain poorly understood. We postulated that inflammation-associated biomarkers will be associated with cerebral injury on proton magnetic resonance spectroscopy in chronically HIV-infected subjects. Five biomarkers were measured in 197 HIV-infected subjects: soluble CD14, MCP-1, IP-10, MIP-1β, and fractalkine. Levels of N-acetyl aspartate (NAA), Choline (Cho), Myoinositol (MI), Glutamate + Glutamine (Glx), and Creatine (Cr) were acquired in the midfrontal cortex (MFC), frontal white matter, and basal ganglia (BG). Predictive models were built through linear regression, and the best models were chosen using the Akaike Information Criterion. Increases in plasma or CSF MCP-1 were associated with lower NAA/Cr in the MFC and BG, whereas metabolite changes in the frontal white matter for NAA/Cr, GlxCr, and Cho/Cr were explained almost exclusively by a single factor, sCD14. Plasma and CSF levels of this factor were also significantly associated with Glx/Cr in MFC and BG. Higher CSF FKN was associated with higher NAA/Cr in BG. Best predictors for higher Cho/Cr in BG and MFC were CSF sCD14 and CSF MIP-1β. Plasma and CSF IP-10 were only associated with Cho/Cr in MFC. Of the 3 models that simultaneously accounted for both plasma and CSF, there were more associations between CSF biomarkers and magnetic resonance spectroscopy metabolites. Markers of inflammation and immune activation, in particular MCP-1 and sCD14, predominantly reflecting CNS sources, contribute to the persistence of brain injury in a metabolite and region-dependent manner in chronically HIV-infected patients on stable combination antiretroviral therapy.