BACKGROUND AND AIMS:The path to hepatitis C virus (HCV) elimination is complicated by individuals who become lost to follow-up (LTFU) during care, particularly before receiving effective HCV treatment. We aimed to determine factors contributing to LTFU and whether LTFU is associated with mortality.METHODS:In this secondary analysis, we constructed a database including individuals with HCV who were either LTFU (data from the nationwide HCV retrieval project, CELINE) or treated with directly acting antivirals (DAA) (data from Statistics Netherlands) between 2012 and 2019. This database was linked to mortality data from Statistics Netherlands. Determinants associated with being LTFU versus DAA-treated were assessed using logistic regression, and mortality rates were compared between groups using exponential survival models. These analyses were additionally stratified on calendar periods: 2012-2014, 2015-2017 and 2018-2019.RESULTS:About 254 individuals, LTFU and 5547 DAA-treated were included. Being institutionalized (OR = 5.02, 95% confidence interval (CI) = 3.29-7.65), household income below the social minimum (OR = 1.96, 95% CI = 1.25-3.06), receiving benefits (OR = 1.74, 95% CI = 1.20-2.52) and psychiatric comorbidity (OR = 1.51, 95% CI = 1.09-2.10) were associated with LTFU. Mortality rates were significantly higher in individuals LTFU compared to those DAA-treated (2.99 vs. 1.15/100 person-years (PY), p < .0001), while in those DAA-treated, mortality rates slowly increased between 2012-2014 (.22/100PY) and 2018-2019 (2.25/100PY).CONCLUSION:In the Netherlands, individuals who are incarcerated/institutionalized, with low household income, or with psychiatric comorbidities are prone to being LTFU, which is associated with higher mortality. HCV care needs to be adapted for these vulnerable individuals.

Background We previously reported T-cell senescence to be similar in people with human immunodeficiency virus (PWH) with suppressed viremia (predominantly men who have sex with men [MSM]) and human immunodeficiency virus (HIV)-negative otherwise comparable controls but greater than in healthy blood donors. This led us to compare CD4+ and CD8+ T-cell counts and CD4+/CD8+ ratios between HIV-negative MSM and men who only have sex with women (MSW) and relate observed differences in behavioral factors and infectious exposures, including cytomegalovirus (CMV) infection. Methods In 368 HIV-negative MSM and 72 HIV-negative MSW, T lymphocyte phenotyping was performed 3 times biennially. Baseline CMV serology and sexually transmitted infection (STI) incidence and/or STI seroprevalence, sexual, and substance-use behavior data were collected during study visits. Results Men who have sex with men, compared with MSW, had higher CD8+ counts (551 vs 437 cells/mm3, P < .001), similar CD4+ counts (864 vs 880 cells/mm3, P = .5), and lower CD4+/CD8+ ratios (1.84 vs 2.47, P < .001). Differences were most pronounced for MSM with >10 recent sex partners and partly explained by higher CMV seroprevalence in MSM. Conclusions These findings suggest that factors other than HIV may, in both PWH and certain HIV-negative MSM, contribute to a low CD4+/CD8+ ratio. Whether this, like in PWH, contributes to comorbidity risk in HIV-negative MSM requires further study.

Background. Frailty is associated with mortality and morbidity in the general geriatric population, but less is known about its impact among the aging but generally younger population with human immunodeficiency virus (HIV). Methods. The impact of frailty on all-cause mortality during 6 years of follow-up and incident comorbidity during 4 years of follow-up was assessed among 598 HIV-positive and 550 comparable HIV-negative participants aged >= 45 years of the AGE(h)IV Cohort Study. Frailty encompasses 5 domains; weight loss, low physical activity, exhaustion, decreased grip strength, and slow gait speed. Presence of >= 3 denotes frailty, 1-2 prefrailty, and 0 robust. Multivariable Cox and logistic regression models were used to assess the independent relationships of frailty with both outcomes, adjusting for HIV infection and traditional risk factors. Results. At baseline, 7.5% (n = 86) of participants were frail. During follow-up, 38 participants died. Mortality rate was significantly higher among frail participants: 25.7/1000 person-years of follow-up (PYFU) (95% confidence interval [CI], 14.2-46.4) compared with prefrail (7.2/1000 PYFU [95% CI, 4.7-11.2]) and robust (2.3/1000 PYFU [95% CI, 1.1-4.9]). In fully adjusted analyses, frailty remained strongly associated with death (hazard ratio, 4.6 [95% CI, 1.7-12.5]) and incident comorbidity (odds ratio, 1.9 [95% CI, 1.1-3.1]). No interactions were observed between frailty and HIV status in all analyses. Conclusions. Frailty is a strong predictor of both mortality and incident comorbidity independent from other risk factors.

Although cognitive impairments are still prevalent in the current antiretroviral therapy era, limited investigations have compared the prevalence of cognitive disorder in people living with HIV (PLWH) and its determinants in different regions and ethnicities. We compared cognitive performance across six domains using comparable batteries in 134 PLWH aged ≥45 years from the COBRA study (Netherlands, UK), and 194 PLWH aged ≥18 years from the NeuroAIDS Project (South Korea). Cognitive scores were standardized and averaged to obtain domain and global T-scores. Associations with global T-scores were evaluated using multivariable regression and the ability of individual tests to detect cognitive impairment (global T-score ≤45) was assessed using the area-under-the-receiver-operating-characteristic curve (AUROC). The median (interquartile range) age of participants was 56 (51, 62) years in COBRA (88% white ethnicity, 93% male) and 45 (37, 52) years in NeuroAIDS (100% Korean ethnicity, 94% male). The rate of cognitive impairment was 18.8% and 18.0%, respectively ( p = 0.86). In COBRA, Black-African ethnicity was the factor most strongly associated with cognitive function (11.1 [7.7, 14.5] lower scores vs. white ethnicity, p < 0.01), whereas in NeuroAIDS, age (0.6 [0.1, 1.3] per 10-year, p<0.01) and education (0.7 [0.5, 0.9] per year, p<0.01) were significantly associated with cognitive function with anemia showing only a weak association (−1.2 [−2.6, 0.3], p=0.12). Cognitive domains most associated with cognitive impairment were attention (AUROC = 0.86) and executive function (AUROC = 0.87) in COBRA and processing speed (AUROC = 0.80), motor function (AUROC = 0.78) and language (AUROC = 0.78) in NeuroAIDS. Two cohorts of PLWH from different geographical regions report similar rates of cognitive impairment but different risk factors and cognitive profiles of impairment.

BACKGROUND:Pulmonary function impairments are more common among people living with HIV (PLWH), as are contributing risk behaviors. To understand the effects of human immunodeficiency virus (HIV) infection independent of risk behaviors, pulmonary function was evaluated in lifestyle-comparable HIV-infected and -uninfected AGEhIV cohort participants. METHODS:Prevalence of obstructive lung disease in 544 HIV-infected and 529 HIV-uninfected participants was determined using spirometry. Logistic regression was used to assess HIV as a determinant of obstructive lung disease. Additional explanatory models were constructed to explain observed differences. RESULTS:The unadjusted obstructive lung disease prevalence was similar in HIV-infected (23.0%) and -uninfected (23.4%) participants. Multivariable logistic regression analysis showed an effect modification whereby obstructive lung disease prevalence among persons with limited smoking experience was notably lower among HIV-infected compared with HIV-uninfected participants. This resulted from a lower forced vital capacity (FVC) in HIV-infected participants but similar 1-second forced expiratory volume (FEV1), especially in those with limited smoking experience. CONCLUSIONS:The lower FVC in HIV-infected participants could indicate HIV-related restrictive or fibrotic pulmonary changes. Factors that decrease the FVC could obscure emphysematous changes in the lungs of PLWH when using the FEV1/FVC ratio as single diagnostic measure. CLINICAL TRIALS REGISTRATION:NCT01466582.

Introduction:HIV-1-infected MSM more often experience sexual dysfunctions than the general population. We assessed associations between HIV-1 status and decreased sexual functioning among MSM. Methods:We used cross-sectional data from 399 HIV-1-infected MSM mostly on combination antiretroviral therapy (cART) and 366 HIV-1-uninfected MSM aged at least 45 years participating in the AGE(h)IV Cohort Study. The study questionnaire included questions on erectile function, sexual satisfaction, and sexual desire. Multivariable logistic regression models were constructed to assess the association between HIV-1 status and these three sexual domains. We also explored HIV-1-related and ART-related parameters in multivariable models among HIV-1-infected participants. Results:Decreased erectile function (13.0 vs. 3.4%, P<0.001), decreased satisfaction (17.8 vs. 11.8%, P=0.02), and decreased desire (7.0 vs. 3.6% P=0.03) were each more prevalent in HIV-1-infected than in HIV-1-uninfected participants. In multivariable models adjusted for age, ethnicity, waist-to-hip ratio, age-associated comorbidities, depression, frailty, use of antihypertensive and antidepressant medication, we found HIV-1 status significantly associated with decreased erectile function [adjusted odds ratio (aOR) 2.53, 95% CI 1.23-5.20], but not with decreased satisfaction (aOR 1.34, 95% CI 0.83-2.16), or decreased desire (aOR 1.77, 95% CI 0.80-3.91). Among HIV-1-infected participants, current exposure (aOR 5.39, 95% CI 2.09-13.92) and cumulative duration of exposure (aOR per year 1.20, 95% CI 1.07-1.35) to lopinavir/ritonavir were significantly associated with decreased erectile function in multivariable analysis. DConclusion:Among MSM aged at least 45 years, HIV-1 status was independently associated with decreased erectile function. Exposure to lopinavir/ritonavir appeared to be an independent risk factor for decreased erectile function among MSM with HIV-1. Copyright (C) 2018 Wolters Kluwer Health, Inc. All rights reserved.

The HIV-infected population in the Netherlands is aging, both as a result of effective combination antiretroviral therapy, and the relative increase in the number of newly diagnosed HIV infections among older people. As the mean age of HIV-positive patients increases, so does the prevalence of non-HIV-associated comorbidities, possibly at higher rates than observed in the general population. As people with HIV continue to age, they will be more likely to experience multimorbidity, polypharmacy, and to receive care from diverse healthcare professionals. It is therefore important that all healthcare professionals have up-to-date knowledge of HIV and the emerging health-care challenges concerning aging people with HIV.

Background Persons living with HIV on combination antiretroviral therapy (cART) may be at increased risk of the development of age-associated non-communicable comorbidities (AANCC) at relatively young age. It has therefore been hypothesised that such individuals, despite effective cART, may be prone to accelerated aging. Objective The COmorBidity in Relation to AIDS (COBRA) cohort study was designed to investigate the potential causal link between HIV and AANCC, amongst others, in a cohort of middle-aged individuals with HIV with sustained viral suppression on cART and otherwise comparable HIV-negative controls. Methods Longitudinal cohort study of HIV-positive subjects ≥45 years of age, with sustained HIV suppression on cART recruited from two large European HIV treatment centres and similarly-aged HIV-negative controls recruited from sexual health centres and targeted community groups. Both HIV-positive and HIV-negative subjects were assessed at study entry and again at follow-up after 2 years. Results Of the 134 HIV-positive individuals with a median (IQR) age of 56 (51, 62) years recruited, 93% were male, 88% of white ethnicity and 86% were men who have sex with men (MSM). Similarly, the 79 HIV-negative subjects had a median (IQR) age of 57 (52, 64) and 92% were male, 97% of white ethnicity and 80% were MSM. Conclusions The results from the COBRA study will be a significant resource to understand the link between HIV and AANCC and the pathogenic mechanisms underlying this link. COBRA will inform future development of novel prognostic tools for earlier diagnosis of AANCC and of novel interventions which, as an adjunct to cART, may prevent AANCC.

Background Despite successful antiretroviral therapy, people living with human immunodeficiency virus (PLWH) experience higher rates of age-related morbidity, including abnormal brain structure, brain function, and cognitive impairment. This has raised concerns that PLWH may experience accelerated aging-related brain pathology. Methods We performed a multicenter longitudinal study of 134 virologically suppressed PLWH (median age, 56.0 years) and 79 demographically similar human immunodeficiency virus (HIV)-negative controls (median age, 57.2 years). To measure cognitive performance and brain pathology, we conducted detailed neuropsychological assessments and multimodality neuroimaging (T1-weighted, T2-weighted, diffusion magnetic resonance imaging [MRI], resting-state functional MRI, spectroscopy, arterial spin labeling) at baseline and at 2 years. Group differences in rates of change were assessed using linear mixed effects models. Results One hundred twenty-three PLWH and 78 HIV-negative controls completed longitudinal assessments (median interval, 1.97 years). There were no differences between PLWH and HIV-negative controls in age, sex, years of education, smoking or alcohol use. At baseline, PLWH had poorer global cognitive performance (P < .01), lower gray matter volume (P = .04), higher white matter hyperintensity load (P = .02), abnormal white matter microstructure (P < .005), and greater brain-predicted age difference (P = .01). Longitudinally, there were no significant differences in rates of change in any neuroimaging measure between PLWH and HIV-negative controls (P > .1). Cognitive performance was longitudinally stable in both groups. Conclusions We found no evidence that middle-aged PLWH, when receiving successful treatment, are at increased risk of accelerated aging-related brain changes or cognitive decline over 2 years.

Background. Cardiovascular disease (CVD) is expected to contribute a large noncommunicable disease burden among human immunodeficiency virus (HIV)-infected people. We quantify the impact of prevention interventions on annual CVD burden and costs among HIV-infected people in the Netherlands. Methods. We constructed an individual-based model of CVD in HIV-infected people using national ATHENA (AIDS Therapy Evaluation in The Netherlands) cohort data on 8791 patients on combination antiretroviral therapy (cART). The model follows patients as they age, develop CVD (by incorporating a CVD risk equation), and start cardiovascular medication. Four prevention interventions were evaluated: (1) increasing the rate of earlier HIV diagnosis and treatment; (2) avoiding use of cART with increased CVD risk; (3) smoking cessation; and (4) intensified monitoring and drug treatment of hypertension and dyslipidemia, quantifying annual number of averted CVDs and costs. Results. The model predicts that annual CVD incidence and costs will increase by 55% and 36% between 2015 and 2030. Traditional prevention interventions (ie, smoking cessation and intensified monitoring and treatment of hypertension and dyslipidemia) will avert the largest number of annual CVD cases (13.1% and 20.0%) compared with HIV-related interventions-that is, earlier HIV diagnosis and treatment and avoiding cART with increased CVD risk (0.8% and 3.7%, respectively)-as well as reduce cumulative CVD-related costs. Targeting high-risk patients could avert the majority of events and costs. Conclusions. Traditional CVD prevention interventions can maximize cardiovascular health and defray future costs, particularly if targeting high-risk patients. Quantifying additional public health benefits, beyond CVD, is likely to provide further evidence for policy development.

BackgroundBrain structural abnormalities have been reported in persons living with human immunodeficiency virus (HIV; PLWH) who are receiving suppressive combination antiretroviral therapy (cART), but their pathophysiology remains unclear.MethodsWe investigated factors associated with brain tissue volumes and white matter microstructure (fractional anisotropy) in 134 PLWH receiving suppressive cART and 79 comparable HIV-negative controls, aged ≥45 years, from the Comorbidity in Relation to AIDS cohort, using multimodal neuroimaging and cerebrospinal fluid biomarkers.ResultsCompared with controls, PLWH had lower gray matter volumes (-13.7 mL; 95% confidence interval, -25.1 to -2.2) and fractional anisotropy (-0.0073; 95% confidence interval, -.012 to -.0024), with the largest differences observed in those with prior clinical AIDS. Hypertension and the soluble CD14 concentration in cerebrospinal fluid were associated with lower fractional anisotropy. These associations were independent of HIV serostatus (Pinteraction = .32 and Pinteraction = .59, respectively) and did not explain the greater abnormalities in brain structure in relation to HIV infection.ConclusionsThe presence of lower gray matter volumes and more white matter microstructural abnormalities in well-treated PLWH partly reflect a combination of historical effects of AIDS, as well as the more general influence of systemic factors, such as hypertension and ongoing neuroinflammation. Additional mechanisms explaining the accentuation of brain structure abnormalities in treated HIV infection remain to be identified.

Background. Human immunodeficiency virus (HIV)-infected individuals are at increased risk of chronic kidney disease (CKD). Human immunodeficiency virus infection, traditional CKD risk factors, and combination antiretroviral therapy (cART) may all contribute.Methods. We compared prevalence of renal impairment (estimated glomerular filtration rate [eGFR] <60 mL/min/1.73m(2)), albuminuria (albumin/creatinine ratio >= 3 mg/mmol), and proximal renal tubular dysfunction (retinol-binding protein/creatinine ratio >2.93 mu g/mmol and/or fractional phosphate excretion >20% with plasma phosphate <0.8 mmol/L) in 596 HIV-infected and 544 HIV-uninfected AGE(h)IV Cohort Study participants. We also assessed whether being HIV-infected on cART, with follow-up censored when cART regimen was modified, was associated with greater eGFR decline or worsening albuminuria (increase >= 10%/year with change in albuminuria category).Results. Human immunodeficiency virus infection was independently associated with renal impairment (adjusted odds ratio [aOR] = 2.1; 95% confidence interval [CI] = 1.0-4.4), albuminuria (aOR = 5.8; 95% CI = 3.7-9.0), and proximal renal tubular dysfunction (aOR = 7.0; 95% CI = 4.9-10.2]). Among 479 HIV-infected and 377 HIV-uninfected individuals (median follow-up = 3.9/4.1 years, respectively) included in longitudinal analyses, being HIV-infected and remaining on unmodified cART was independently associated with greater eGFR decline (-0.56; 95% CI = -0.87 to -0.24 mL/min/1.73m(2)/year) and worsening albuminuria (aOR = 2.3; 95% CI = 1.3-4.0).Conclusions. In these middle-aged individuals, HIV infection was independently associated with renal impairment, albuminuria, and proximal renal tubular dysfunction. Human immunodeficiency virus-infected individuals on cART (predominantly containing tenofovir disoproxil fumarate) were also more likely to experience eGFR decline and worsening albuminuria compared with HIV-uninfected individuals.

Purpose of review This review describes what is known concerning the burden of hypertension among people living with HIV (PLHIV), and also addresses relevant topics with respect to its risk factors and clinical management. Recent findings Hypertension is highly prevalent in HIV-positive populations, and may be more common than in HIV-negative populations. Risk factors contributing to the development of hypertension in PLHIV include demographic factors, genetic predisposition, lifestyle, comorbidities such as obesity, antiretroviral therapy-related changes in body composition, and potentially also immunodeficiency, immune activation and inflammation, as well as effects from antiretroviral therapy itself. Clinical management of hypertension in PLHIV requires awareness for drug–drug interactions between antiretroviral drugs and antihypertensive drugs. Awareness, treatment, and control of hypertension in PLHIV is currently suboptimal and should be improved. Summary The burden of hypertension among PLHIV is high and its pathophysiology most likely multifactorial. Elucidating the exact pathophysiology of hypertension in PLHIV is vital as this may provide new targets to impact and improve clinical management. In the meantime, efforts should be made to improve hypertension management as per existing clinical guidelines in order to safeguard cardiovascular health and quality of life in PLHIV.

Background We aimed to identify the prevalence of cardiovascular risk factors, and investigate preventive cardiovascular medication use and achievement of targets as per Dutch cardiovascular risk management guidelines among human immunodeficiency virus (HIV)-positive and HIV-negative individuals. Design The design was a cross-sectional analysis within an ongoing cohort study. Methods Data on medication use and cardiovascular disease prevalence were available for 528 HIV-positive and 521 HIV-negative participants. We identified cardiovascular risk factors and applied cardiovascular risk management guidelines, mainly focusing on individuals eligible for (a) primary prevention because of high a priori cardiovascular risk, or for (b) secondary prevention. Results One hundred and three (20%) HIV-positive and 77 (15%) HIV-negative participants were classified as having high cardiovascular risk; 53 (10%) HIV-positive and 27 (5%) HIV-negative participants were eligible for secondary prevention. Of HIV-positive individuals 57% at high cardiovascular risk and 42% of HIV-positive individuals eligible for secondary prevention had systolic blood pressures above guideline-recommended thresholds. Cholesterol levels were above guideline-recommended thresholds in 81% of HIV-positive individuals at high cardiovascular risk and 57% of HIV-positive individuals eligible for secondary prevention. No statistically significant differences were observed between HIV-positive and HIV-negative participants regarding achievement of targets, except for glycaemic control (glycated haemoglobin ≤ 53 mmol/mol) among individuals using diabetes medication (90% vs 50%, p = 0.017) and antiplatelet/anticoagulant use for secondary prevention (85% vs 63%, p = 0.045), which were both superior among HIV-positive participants. Conclusions Cardiovascular risk management is suboptimal in both HIV-positive and HIV-negative individuals and should be improved.

Objective: To establish whether HIV disease is associated with abnormal levels of age-related brain atrophy, by estimating apparent brain age using neuroimaging and exploring whether these estimates related to HIV status, age, cognitive performance, and HIV-related clinical parameters. Methods: A large sample of virologically suppressed HIV-positive adults (n = 162, age 45–82 years) and highly comparable HIV-negative controls (n = 105) were recruited as part of the Comorbidity in Relation to AIDS (COBRA) collaboration. Using T1-weighted MRI scans, a machine-learning model of healthy brain aging was defined in an independent cohort (n = 2,001, aged 18–90 years). Neuroimaging data from HIV-positive and HIV-negative individuals were then used to estimate brain-predicted age; then brain-predicted age difference (brain-PAD = brain-predicted brain age − chronological age) scores were calculated. Neuropsychological and clinical assessments were also carried out. Results: HIV-positive individuals had greater brain-PAD score (mean ± SD 2.15 ± 7.79 years) compared to HIV-negative individuals (−0.87 ± 8.40 years; b = 3.48, p < 0.01). Increased brain-PAD score was associated with decreased performance in multiple cognitive domains (information processing speed, executive function, memory) and general cognitive performance across all participants. Brain-PAD score was not associated with age, duration of HIV infection, or other HIV-related measures. Conclusion: Increased apparent brain aging, predicted using neuroimaging, was observed in HIV-positive adults, despite effective viral suppression. Furthermore, the magnitude of increased apparent brain aging related to cognitive deficits. However, predicted brain age difference did not correlate with chronological age or duration of HIV infection, suggesting that HIV disease may accentuate rather than accelerate brain aging.

BackgroundLong-term comorbidities such as cognitive impairment remain prevalent in otherwise effectively treated people living with human immunodeficiency virus (HIV). We investigate the relationship between cognitive impairment and brain structure in successfully treated patients using multimodal neuroimaging from the Comorbidity in Relation to AIDS (COBRA) cohort.MethodsCognitive function, brain tissue volumes, and white matter microstructure were assessed in 134 HIV-infected patients and 79 controls. All patients had suppressed plasma HIV RNA at cohort entry. In addition to comprehensive voxelwise analyses of volumetric and diffusion tensor imaging, we used an unsupervised machine learning approach to combine cognitive, diffusion, and volumetric data, taking advantage of the complementary information they provide.ResultsCompared to the highly comparable control group, cognitive function was impaired in 4 of the 6 cognitive domains tested (median global T-scores: 50.8 vs 54.2; P < .001). Patients had lower gray but not white matter volumes, observed principally in regions where structure generally did not correlate with cognitive function. Widespread abnormalities in white matter microstructure were also seen, including reduced fractional anisotropy with increased mean and radial diffusivity. In contrast to the gray matter, these diffusion abnormalities correlated with cognitive function. Multivariate neuroimaging analysis identified a neuroimaging phenotype associated with poorer cognitive function, HIV infection, and systemic immune activation.ConclusionsCognitive impairment, lower gray matter volume, and white matter microstructural abnormalities were evident in HIV-infected individuals despite fully suppressive antiretroviral therapy. White matter abnormalities appear to be a particularly important determinant of cognitive dysfunction seen in well-treated HIV-infected individuals.

A rapidly growing body of evidence has shown that chromatin undergoes radical alterations as an organism ages, but how these changes relate to aging itself is an open question. It is likely that these processes contribute to genomic instability and loss of transcriptional fidelity, which in turn drives deleterious age-related phenotypes. Interventions associated with increased healthspan and longevity such as reduced insulin/IGF signalling (IIS), inhibition of mTOR and energy depletion resulting in SIRT1/AMPK activation, all have beneficial effects which ameliorate multiple facets of age-associated decline. The impact of these interventions on the epigenome is less certain. In this review we highlight the potential of these interventions to act directly upon the epigenome and promote a youthful chromatin landscape, maintaining genetic and transcriptional memory throughout the lifecourse. We propose that this is a fundamental mechanism through which these interventions are able to curtail the incidence of age-related disease. By revisiting these well characterised interventions, we may be able to identify targetable effectors of chromatin function and use this knowledge to enhance healthspan and longevity in human populations through the measured application of dietary and small molecule interventions.

BACKGROUND:It is unclear whether HIV infection is associated with liver fibrosis in the absence of chronic hepatitis B or C virus (HBV/HCV) coinfection. We compared prevalence of liver fibrosis, noninvasively assessed by the Fibrosis-4 (FIB-4) index, between HIV-infected patients and uninfected controls, and explored determinants of a higher FIB-4 score, indicative of more liver fibrosis. METHODS:FIB-4 was assessed in HIV-uninfected and HIV-1-infected, predominantly virologically suppressed participants of the AGEhIV Cohort Study without HBV and/or HCV coinfection, and aged at least 45. Using multivariable regression, we investigated associations between FIB-4 and HIV-status, HIV-disease characteristics, antiretroviral drugs and markers of microbial translocation and immune activation. RESULTS:Prevalence of advanced liver fibrosis (FIB-4 ≥ 3.25) was low: 1.4% in HIV-infected and 1.0% in HIV-uninfected participants. After adjustment for age, sex, ethnicity, detectable anti-hepatitis B core/anti-HCV antibodies and excessive alcohol intake, HIV remained significantly associated with higher FIB-4 (+4.2%, P = 0.05). Prior exposure to didanosine, longer duration of a CD4 cell count below 500 cells/μl and a lower CD4 cell count at enrollment were each associated with a higher FIB-4. Markers of immune activation (soluble CD163, activated CD8 T-lymphocytes and regulatory T-lymphocytes) were associated with a higher FIB-4 in HIV-infected but not HIV-uninfected study participants. CONCLUSION:HIV infection was independently associated with higher FIB-4 scores, indicating more advanced liver fibrosis, though the difference in FIB-4 scores between HIV-infected and HIV-uninfected was small. Higher levels of immune activation were associated with liver fibrosis in HIV-infected, even in the absence of HBV or HCV infection, but not in HIV-uninfected individuals.

BACKGROUND Individuals infected with human immunodeficiency virus (HIV) have a higher risk of cardiovascular disease, potentially partly mediated by a higher prevalence of hypertension. We therefore examined the prevalence and determinants of hypertension in HIV-1-infected patients compared with appropriate HIV-negative controls. METHODS Data from 527 HIV-1-infected and 517 HIV-uninfected participants at the time of enrollment into the ongoing AGEhIV Cohort Study were analyzed. Hypertension was defined as systolic blood pressure ≥140 mmHg, diastolic blood pressure ≥90 mmHg, and/or self-reported use of antihypertensive drugs. RESULTS Hypertension prevalence was higher among HIV-1-infected individuals compared with controls (48.2% vs 36.4%; odds ratio [OR], 1.63; 95% confidence interval [CI], 1.27-2.09). In logistic regression models adjusted for age, sex, ethnicity, family history of hypertension, smoking, alcohol use, physical activity, and body mass index, the association between HIV and hypertension remained statistically significant (ORHIV, 1.65; 95% CI, 1.25-2.19), but was attenuated after additional adjustment for waist-to-hip ratio (ORHIV, 1.29; 95% CI, .95-1.76). Among HIV-1-infected individuals, particularly among those with mono/dual nucleoside reverse transcriptase inhibitor therapy prior to combination antiretroviral therapy, stavudine exposure was independently associated with hypertension (ORstavudine, 1.54; 95% CI, 1.04-2.30). This association was attenuated after additional adjustment for either waist-to-hip ratio (ORstavudine, 1.30; 95% CI, .85-1.96) or hip circumference (ORstavudine, 1.40; 95% CI, .93-2.11). CONCLUSIONS Our findings suggest that changes in body composition, involving both abdominal obesity and stavudine-induced peripheral lipoatrophy, might contribute to the higher prevalence of hypertension in HIV-1-infected patients. CLINICAL TRIALS REGISTRATION NCT01466582.