Outcomes of Cerebral Venous Thrombosis due to Vaccine-Induced Immune Thrombotic Thrombocytopenia After the Acute Phase.

BACKGROUND: Cerebral venous thrombosis (CVT) due to vaccine-induced immune thrombotic thrombocytopenia (VITT) is a severe condition, with high in-hospital mortality rates. Here, we report clinical outcomes of patients with CVT-VITT after SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) vaccination who survived initial hospitalization. METHODS: We used data from an international registry of patients who developed CVT within 28 days of SARS-CoV-2 vaccination, collected until February 10, 2022. VITT diagnosis was classified based on the Pavord criteria. Outcomes were mortality, functional independence (modified Rankin Scale score 0-2), VITT relapse, new thrombosis, and bleeding events (all after discharge from initial hospitalization). RESULTS: Of 107 CVT-VITT cases, 43 (40%) died during initial hospitalization. Of the remaining 64 patients, follow-up data were available for 60 (94%) patients (37 definite VITT, 9 probable VITT, and 14 possible VITT). Median age was 40 years and 45/60 (75%) patients were women. Median follow-up time was 150 days (interquartile range, 94-194). Two patients died during follow-up (3% [95% CI, 1%-11%). Functional independence was achieved by 53/60 (88% [95% CI, 78%-94%]) patients. No new venous or arterial thrombotic events were reported. One patient developed a major bleeding during follow-up (fatal intracerebral bleed). CONCLUSIONS: In contrast to the high mortality of CVT-VITT in the acute phase, mortality among patients who survived the initial hospitalization was low, new thrombotic events did not occur, and bleeding events were rare. Approximately 9 out of 10 CVT-VITT patients who survived the acute phase were functionally independent at follow-up.

Management of Cerebral Venous Thrombosis Due to Adenoviral COVID-19 Vaccination.

OBJECTIVE: Cerebral venous thrombosis (CVT) caused by vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare adverse effect of adenovirus-based severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) vaccines. In March 2021, after autoimmune pathogenesis of VITT was discovered, treatment recommendations were developed. These comprised immunomodulation, non-heparin anticoagulants, and avoidance of platelet transfusion. The aim of this study was to evaluate adherence to these recommendations and its association with mortality. METHODS: We used data from an international prospective registry of patients with CVT after the adenovirus-based SARS-CoV-2 vaccination. We analyzed possible, probable, or definite VITT-CVT cases included until January 18, 2022. Immunomodulation entailed administration of intravenous immunoglobulins and/or plasmapheresis. RESULTS: Ninety-nine patients with VITT-CVT from 71 hospitals in 17 countries were analyzed. Five of 38 (13%), 11 of 24 (46%), and 28 of 37 (76%) of the patients diagnosed in March, April, and from May onward, respectively, were treated in-line with VITT recommendations (p < 0.001). Overall, treatment according to recommendations had no statistically significant influence on mortality (14/44 [32%] vs 29/55 [52%], adjusted odds ratio [OR] = 0.43, 95% confidence interval [CI] = 0.16-1.19). However, patients who received immunomodulation had lower mortality (19/65 [29%] vs 24/34 [70%], adjusted OR = 0.19, 95% CI = 0.06-0.58). Treatment with non-heparin anticoagulants instead of heparins was not associated with lower mortality (17/51 [33%] vs 13/35 [37%], adjusted OR = 0.70, 95% CI = 0.24-2.04). Mortality was also not significantly influenced by platelet transfusion (17/27 [63%] vs 26/72 [36%], adjusted OR = 2.19, 95% CI = 0.74-6.54). CONCLUSIONS: In patients with VITT-CVT, adherence to VITT treatment recommendations improved over time. Immunomodulation seems crucial for reducing mortality of VITT-CVT. ANN NEUROL 2022;92:562-573.

The 'COmorBidity in Relation to AIDS' (COBRA) cohort: Design, methods and participant characteristics.

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.

Neurofilament light chain protein as a marker of neuronal injury: review of its use in HIV-1 infection and reference values for HIV-negative controls.

INTRODUCTION: Several CSF biomarkers of neuronal injury have been studied in people living with HIV. At this time, the most useful is the light subunit of the neurofilament protein (NFL). This major structural component of myelinated axons is essential to maintain axonal caliber and to facilitate effective nerve conduction. CSF concentrations of NFL provide a sensitive marker of CNS injury in a number of neurological diseases, including HIV-related neuronal injury. Areas Covered: In this review, the authors describe CSF NFL concentrations across the spectrum of HIV-infection, from its early acute phase to severe immunosuppression, with and without neurological conditions, and with and without antiretroviral treatment (n = 516). Furthermore, in order to provide more precise estimates of age-related upper limits of CSF NFL concentrations, the authors present data from a large number (n = 359) of HIV-negative controls. Expert Commentary: Recently a new ultrasensitive diagnostic assay for quantification of NFL in plasma has been developed, providing a convenient way to assess neuronal damage without having to perform a lumbar puncture. This review also considers our current knowledge of plasma NFL in HIV CNS infection.

Cerebral blood flow and cognitive function in HIV-infected men with sustained suppressed viremia on combination antiretroviral therapy.

OBJECTIVE: To assess if HIV-infected patients on long-term successful combination antiretroviral therapy show cerebral blood flow (CBF) alterations in comparison with HIV-uninfected, otherwise similar controls. To explore whether such alterations are associated with HIV-associated cognitive impairment and to explore potential determinants of CBF alterations in HIV. DESIGN: Cross-sectional comparison of CBF in an observational cohort study. METHODS: Clinical, cognitive and MRI data of 100 middle-aged aviremic HIV-infected men on combination antiretroviral therapy and 69 HIV-uninfected controls were collected and compared. From pseudocontinuous arterial spin labeling MRI data, CBF-maps were calculated. The associations of mean gray matter CBF with clinical and cognitive parameters were explored in regression models, followed by a spatial delineation in a voxel-based analysis. RESULTS: CBF was decreased in HIV-infected patients compared with HIV-uninfected controls (P = 0.02), adjusted for age, ecstasy use and waist circumference. Spatially distinct and independent effects of total gray matter volume and HIV-serostatus on CBF were found. Within the HIV-infected group, decreased CBF was associated with increased triglyceride levels (P = 0.005) and prior clinical AIDS (P = 0.03). No association between CBF and cognitive impairment was found. CONCLUSION: Decreased CBF was observed among HIV-infected patients, which was associated with both vascular risk factors as well as with measures of past immune deficiency. These results provide support for increased vascular disease in HIV-infected patients as represented by hemodynamic alteration, but without overt cognitive consequences within the current cohort of patients on long-term successful treatment.

Difference in Aortic Stiffness Between Treated Middle-Aged HIV Type 1-Infected and Uninfected Individuals Largely Explained by Traditional Cardiovascular Risk Factors, With an Additional Contribution of Prior Advanced Immunodeficiency.

BACKGROUND: Patients with HIV, even with suppressed viremia on combination antiretroviral therapy, are at increased risk for cardiovascular disease. The underlying pathophysiology remains to be clarified. Aortic stiffness, known to be associated with cardiovascular disease in the general population, was investigated in a cohort of HIV type 1 (HIV 1)-infected and similar but uninfected individuals. METHODS: Aortic stiffness was assessed by measuring pulse wave velocity (PWV) with an Arteriograph. Five hundred seven HIV-uninfected and 566 HIV 1-infected individuals, predominantly with suppressed viremia on combination antiretroviral therapy, aged ≥45 years, participating in the ongoing AGEhIV Cohort Study were included in the analysis. Multivariable linear regression was used to investigate whether HIV was independently associated with aortic stiffness, adjusting for traditional cardiovascular risk factors. RESULTS: Study groups were comparable in demographics; smoking and hypertension were more prevalent in HIV-infected participants. PWV was higher in the HIV-infected group (7.9 vs. 7.7 m/s, P = 0.004). After adjustment for mean arterial pressure, age, gender, and smoking, HIV status was not significantly associated with aortic stiffness. In HIV-infected participants, having a nadir CD4 T-cell count ≤100 cells per cubic millimeter was independently associated with a higher PWV. CONCLUSIONS: The increased aortic stiffness in HIV-infected participants was largely explained by a higher prevalence of traditional cardiovascular risk factors, particularly smoking. Although HIV itself was not independently associated with higher aortic stiffness, a prior greater degree of immunodeficiency was. This suggests a detrimental effect of immunodeficiency on the aortic wall, possibly mediated by inflammation.

Higher Prevalence of Hypertension in HIV-1-Infected Patients on Combination Antiretroviral Therapy Is Associated With Changes in Body Composition and Prior Stavudine Exposure.

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.

White matter hyperintensities in relation to cognition in HIV-infected men with sustained suppressed viral load on combination antiretroviral therapy.

OBJECTIVES: The objective of this study was to assess whether HIV-infected patients on long-term successful combination antiretroviral therapy (cART) have more extensive white matter hyperintensities (WMH) of presumed vascular origin compared with uninfected controls and whether these intensities are associated with cognitive impairment. Furthermore, we explored potential determinants of increased WMH load long-term suppressed HIV infection. DESIGN: A cross-sectional comparison of WMH in an observational cohort. METHODS: Clinical, cognitive, and MRI data were collected from 103 middle-aged, aviremic HIV-infected men on cART, and 70 HIV-uninfected, otherwise similar controls. In the MRI data, WMH load was quantified by automated approaches and qualitatively reviewed by an experienced neuroradiologist using the Fazekas scale. RESULTS: HIV-infected men had an increased WMH load. Among HIV-infected patients, increased WMH load was independently associated with older age, higher DBP, higher D-dimer levels, and longer time spent with a CD4 cell count below 500 cells/µl. HIV-associated cognitive deficits were associated with increased WMH load. CONCLUSIONS: WMH are more extensive and associated with cognitive deficits in middle-aged, aviremic cART-treated HIV-infected men. The extent of WMH load was associated with both cardiovascular risk factors and past immune deficiency. As cognitive impairment in these same patients is also associated with these risk factors, this may suggest that in the setting of HIV, WMH, and cognitive deficits share a common cause. This supports the importance of optimizing cardiovascular risk management, and early, effective treatment of HIV infection.

T-Cell Activation Independently Associates With Immune Senescence in HIV-Infected Recipients of Long-term Antiretroviral Treatment.

BACKGROUND: Aging-associated noncommunicable comorbidities are more prevalent among human immunodeficiency virus type 1 (HIV)-infected individuals than among HIV-uninfected individuals. Residual HIV-related chronic immune activation and senescence may increase the risk of developing comorbidities. METHODS: Immune phenotyping, thymic output, and telomere length were assessed in 94 HIV-infected individuals who were aged >45 years and receiving antiretroviral therapy (ART; cases) and 95 age-matched uninfected controls. RESULTS: Cases had lower CD4(+) T-cell counts, higher CD8(+) T-cell counts, and increased levels of immune activation (ie, increased soluble CD14 [sCD14] level and increased percentages of CD38(+)HLA-DR(+) cells among both CD4(+) and CD8(+) T cells), regulatory T cells, and percentage of programmed cell death 1 (PD-1)-expressing cells among CD4(+) T cells. Immune senescence levels (ie, percentages of CD27(-)CD28(-) cells or CD57(+) cells) were comparable between cases and controls. Peripheral blood mononuclear cells from cases had shorter telomeres but increased single-joint T-cell receptor excision circle content and CD31(+) naive CD4(+) T cells. Although cytomegalovirus (CMV) antibody titers were higher in cases, CMV-specific T-cell responses were comparable between cases and controls. T-cell senescence in cases was independently associated with T-cell activation but not with CMV-specific immune responses. CONCLUSIONS: Despite long-term receipt of ART, HIV-infected adults had higher levels of immune activation, regulatory T cells, and PD-1-expressing CD4(+) cells and shorter telomeres. The increased soluble CD14 levels and percentage of CD38(+)HLA-DR(+) cells among CD4(+) T cells correlated with shorter telomeres and increased regulatory T-cell levels. This suggests that HIV influences immune function irreversibly, with several pathways that are persistently abnormal during effective ART. Therapies aimed at improving immune health during ART are needed.

Liver fibrosis in HIV-infected individuals on long-term antiretroviral therapy: associated with immune activation, immunodeficiency and prior use of didanosine.

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.

Determinants of reduced cognitive performance in HIV-1-infected middle-aged men on combination antiretroviral therapy.

OBJECTIVE: The spectrum of risk factors for HIV-associated cognitive impairment is likely very broad and includes not only HIV/antiretroviral therapy-specific factors but also other comorbid conditions. The purpose of this current study was to explore possible determinants for decreased cognitive performance. DESIGN AND METHODS: Neuropsychological assessment was performed on 103 HIV-1-infected men with suppressed viraemia on combination antiretroviral therapy for at least 12 months and 74 HIV-uninfected highly similar male controls, all aged at least 45 years. Cognitive impairment and cognitive performance were determined by multivariate normative comparison (MNC). Determinants of decreased cognitive performance and cognitive impairment were investigated by linear and logistic regression analysis, respectively. RESULTS: Cognitive impairment as diagnosed by MNC was found in 17% of HIV-1-infected men. Determinants for decreased cognitive performance by MNC as a continuous variable included cannabis use, history of prior cardiovascular disease, impaired renal function, diabetes mellitus type 2, having an above normal waist-to-hip ratio, presence of depressive symptoms, and lower nadir CD4⁺ cell count. Determinants for cognitive impairment, as dichotomized by MNC, included cannabis use, prior cardiovascular disease, impaired renal function, and diabetes mellitus type 2. CONCLUSION: Decreased cognitive performance probably results from a multifactorial process, including not only HIV-associated factors, such as having experienced more severe immune deficiency, but also cardiovascular/metabolic factors, cannabis use, and depressive symptoms.

Prevalence and determinants of insufficient work ability in older HIV-positive and HIV-negative workers.

PURPOSE: To explore whether the prevalence and determinants of insufficient work ability (WA) of older HIV-positive workers differ from a comparable group of HIV-negative workers. METHODS: Cross-sectional data from 359 HIV-negative and 264 HIV-positive middle-aged individuals (45-65 years) participating in paid labor, collected within the AGEhIV Cohort Study between October 2010-September 2012, were selected. Data were collected by self-administered questionnaires and physical examination. Participants self-rated their current WA, ranging from 0 to 10. WA was dichotomized into insufficient (<6) and sufficient (≥6). Using univariable and multivariable logistic regression, we studied the independent effect of HIV status on insufficient WA and determinants of insufficient WA. RESULTS: Overall, 8% of participants reported insufficient WA (HIV-positive 9 vs. HIV-negative 7%, P = 0.20). Twice as many HIV-positive as HIV-negative individuals were declared partly unfit for work (6 vs. 3%, P = 0.02). HIV status itself was not associated with WA in univariable and multivariable analyses. Multivariable analyses revealed that low educational level, working fewer hours, being partly unfit for work, experiencing a high need for recovery after work, staying home from work ≥2 times in the past 6 months, and reporting depressive symptoms were associated with insufficient WA, independent of HIV status. CONCLUSIONS: HIV-positive individuals aged 45-65 years participating in paid labor seem to function as well at work as HIV-negative individuals. HIV-positive participants were more often formally declared partly unfit for work, but percentages were low in both groups. Knowledge of determinants of insufficient WA may help employers and professionals to optimize WA.

White matter structure alterations in HIV-1-infected men with sustained suppression of viraemia on treatment.

OBJECTIVE: Cognitive impairment is highly prevalent in HIV-1-infected (HIV+) patients, despite adequate suppression of viral replication by combination antiretroviral therapy (cART). Cerebral white matter structure alterations are often associated with cognitive impairment and have commonly been reported in the natural course of HIV infection. However, the existence of these alterations in adequately treated HIV+ patients remains unknown, as well as its possible association with cognitive impairment. DESIGN: We used diffusion tensor imaging (DTI) to investigate whether white matter structure alterations exist in HIV+ patients with sustained suppressed viral replication on cART, and if such alterations are related to HIV-associated cognitive deficits. METHODS: We compared 100 aviraemic HIV+ men on cART with 70 HIV-uninfected, otherwise comparable men. Clinical and neuropsychological assessments were performed. From DTI data, white matter fractional anisotropy and mean diffusion were calculated. Subsequently, tract-based spatial statistics (TBSS) was performed, with and without masking out white matter lesions. RESULTS: HIV+ patients showed diffuse white matter structure alterations as compared with HIV-uninfected controls, observed as widespread decreased fractional anisotropy and an increased mean diffusion. These white matter structure alterations were associated with the number of years spent with a CD4 cell count below 500 cells/µl, but not with HIV-associated cognitive deficits. CONCLUSION: Cerebral white matter structure alterations are found in middle-aged HIV+ men with sustained suppression of viraemia on cART, and may result from periods with immune deficiency when viral toxicity and host-inflammatory responses were at their peak. These white matter structure alterations were not associated with the observed subtle HIV-associated cognitive deficits. VIDEO ABSTRACT: .

HIV infection is independently associated with frailty in middle-aged HIV type 1-infected individuals compared with similar but uninfected controls.

BACKGROUND: Frailty is an age-related syndrome of decreased physiological reserve and resistance to stressors, associated with increased morbidity and mortality in the general elderly population. An increased prevalence of frailty has been reported amongst HIV-infected individuals. METHODS: Fried frailty phenotype was systematically assessed in predominantly virologically suppressed HIV type 1 (HIV-1)-infected and otherwise comparable HIV-uninfected participants aged at least 45 at enrollment into the AGEhIV Cohort Study. Multivariable ordinal logistic regression was used to investigate associations between HIV- and antiretroviral therapy-related covariates, markers of inflammation and body composition and prefrailty/frailty. RESULTS: Data were available for 521 HIV-infected and 513 HIV-uninfected individuals. Prevalence of frailty (10.6 versus 2.7%) and prefrailty (50.7 versus 36.3%) were significantly higher in HIV-infected individuals (Ptrend < 0.001). HIV infection remained statistically significantly associated with prefrailty/frailty after adjustment for age, sex, race/ethnicity, smoking, hepatitis C infection, comorbidities and depression [adjusted odds ratio (ORadj) 2.16, P < 0.001]. A higher waist-to-hip ratio attenuated the coefficient of HIV-infected status (ORadj 1.93, P < 0.001), but not waist- or hip-circumference individually or markers of inflammation. Within the HIV-infected group, parameters related to body composition were most strongly and independently associated with prefrailty/frailty: current BMI less than 20 kg/m2 (OR 2.83, P = 0.01), nadir BMI less than 20 kg/m2 (OR 2.51, P = 0.001) and waist-to-hip ratio (OR 1.79 per 0.1 higher, P < 0.001). CONCLUSION: HIV infection was independently associated with prefrailty/frailty in middle-aged HIV-infected patients compared with HIV-uninfected controls. This partly may be mediated by the higher waist- and lower hip-circumference in the HIV-infected individuals, potentially partially caused by lipodystrophy, and in part be a consequence of historic weight loss associated with advanced HIV-disease.

Multivariate normative comparison, a novel method for more reliably detecting cognitive impairment in HIV infection.

OBJECTIVE: The objective of this study is to assess whether multivariate normative comparison (MNC) improves detection of HIV-1-associated neurocognitive disorder (HAND) as compared with Frascati and Gisslén criteria. METHODS: One-hundred and three HIV-1-infected men with suppressed viremia on combination antiretroviral therapy (cART) for at least 12 months and 74 HIV-uninfected male controls (comparable regarding age, ethnicity, sexual orientation, premorbid intelligence and educational level), aged at least 45 years, underwent neuropsychological assessment covering six cognitive domains (fluency, attention, information processing speed, executive function, memory, and motor function). Frascati and Gisslén criteria were applied to detect HAND. Next, MNC was performed to compare the cognitive scores of each HIV-positive individual against the cognitive scores of the control group. RESULTS: HIV-infected men showed significantly worse performance on the cognitive domains of attention, information processing speed and executive function compared with HIV-uninfected controls. HAND by Frascati criteria was highly prevalent in HIV-infected [48%; 95% confidence interval (95% CI) 38-58] but nearly equally so in HIV-uninfected men (36%; 95% CI 26-48), confirming the low specificity of this method. Applying Gisslén criteria, HAND-prevalence was reduced to 5% (95% CI 1-9) in HIV-infected men and to 1% (95% CI 1-3) among HIV-uninfected controls, indicating better specificity but reduced sensitivity. MNC identified cognitive impairment in 17% (95% CI 10-24) of HIV-infected men and in 5% (95% CI 0-10) of the control group (P = 0.02, one-tailed), showing an optimal balance between sensitivity and specificity. CONCLUSION: Prevalence of cognitive impairment in HIV-1-infected men with suppressed viremia on cART estimated by MNC was much higher than that estimated by Gisslén criteria, while the false positive rate was greatly reduced compared with the Frascati criteria. VIDEO ABSTRACT: :

Low bone mineral density in patients with well-suppressed HIV infection: association with body weight, smoking, and prior advanced HIV disease.

BACKGROUND: Human immunodeficiency virus (HIV) and combination antiretroviral therapy (cART) may both contribute to the higher prevalence of osteoporosis and osteopenia in HIV-infected individuals. METHODS: Using dual-energy X-ray absorptiometry, we compared lumbar spine, total hip, and femoral neck bone mineral density (BMD) in 581 HIV-positive (94.7% receiving cART) and 520 HIV-negative participants of the AGEhIV Cohort Study, aged ≥45 years. We used multivariable linear regression to investigate independent associations between HIV, HIV disease characteristics, ART, and BMD. RESULTS: The study population largely consisted of men who have sex with men (MSM). Osteoporosis was significantly more prevalent in those with HIV infection (13.3% vs 6.7%; P<.001). After adjustment for body weight and smoking, being HIV-positive was no longer independently associated with BMD. Low body weight was more strongly negatively associated with BMD in HIV-positive persons with a history of a Centers for Disease Control and Prevention class B or C event. Interestingly, regardless of HIV status, younger MSM had significantly lower BMD than older MSM, heterosexual men, and women. CONCLUSIONS: The observed lower BMD in treated HIV-positive individuals was largely explained by both lower body weight and more smoking. Having experienced symptomatic HIV disease, often associated with weight loss, was another risk factor. The low BMD observed in younger MSM remains unexplained and needs further study.

Risk of coronary heart disease in patients with HIV infection.

The lives of individuals infected with HIV who have access to combination antiretroviral therapy (cART) are substantially prolonged, which increases the risk of developing non-AIDS comorbidities, including coronary heart disease (CHD). In Europe and the USA, individuals with HIV infection have a ∼1.5-fold increased risk of myocardial infarction relative to uninfected individuals. In Africa, the relative risk of myocardial infarction is unknown, but broadened access to life-extending cART suggests that rates of CHD will rise in this and other resource-constrained regions. Atherogenesis in HIV is affected by complex interactions between traditional and immune risk factors. cART has varied, regimen-specific effects on metabolic risk factors. Overall, cART seems to lessen proatherogenic immune activation, but does not eliminate it even in patients in whom viraemia is suppressed. Current strategies to decrease the risk of CHD in individuals infected with HIV include early initiation of cART regimens with the fewest metabolic adverse effects, and careful management of traditional CHD risk factors throughout treatment. Future strategies to prevent CHD in patients with HIV infection might involve the use of HIV-tailored CHD risk-prediction paradigms and the administration of therapies alongside cART that will further decrease proatherogenic HIV-specific immune activation.

Cross-sectional comparison of the prevalence of age-associated comorbidities and their risk factors between HIV-infected and uninfected individuals: the AGEhIV cohort study.

BACKGROUND: Human immunodeficiency virus (HIV)-infected individuals may be at increased risk of age-associated noncommunicable comorbidities (AANCCs). METHODS: Cross-sectional analyses of AANCC prevalence (including cardiovascular, metabolic, pulmonary, renal, bone, and malignant disease) and risk factors in a prospective cohort study of HIV type 1-infected individuals and HIV-uninfected controls, who were aged ≥45 years and comparable regarding most lifestyle and demographic factors. RESULTS: HIV-infected participants (n = 540) had a significantly higher mean number of AANCCs than controls (n = 524) (1.3 [SD, 1.14] vs 1.0 [SD, 0.95]; P < .001), with significantly more HIV-infected participants having ≥1 AANCC (69.4% vs 61.8%; P = .009). Hypertension, myocardial infarction, peripheral arterial disease, and impaired renal function were significantly more prevalent among HIV-infected participants. Risk of AANCC by ordinal logistic regression was independently associated with age, smoking, positive family history for cardiovascular/metabolic disease, and higher waist-to-hip ratio, but also with HIV infection (odds ratio, 1.58 [95% confidence interval, 1.23-2.03]; P < .001). In those with HIV, longer exposure to CD4 counts <200 cells/µL, and, to a lesser extent, higher levels of high-sensitivity C-reactive protein and soluble CD14, and longer prior use of high-dose ritonavir (≥400 mg/24 hours) were each also associated with a higher risk of AANCCs. CONCLUSIONS: All AANCCs were numerically more prevalent, with peripheral arterial, cardiovascular disease, and impaired renal function significantly so, among HIV-infected participants compared with HIV-uninfected controls. Besides recognized cardiovascular risk factors, HIV infection and longer time spent with severe immunodeficiency increased the risk of a higher composite AANCC burden. There was a less pronounced contribution from residual inflammation, immune activation, and prior high-dose ritonavir use.

HIV-1 infection and cognitive impairment in the cART era: a review.

With the introduction of combination antiretroviral therapy AIDS dementia complex or HIV-associated dementia, as it was termed later, largely disappeared in clinical practice. However, in the past few years, patients, long-term infected and treated, including those with systemically well controlled infection, started to complain about milder memory problems and slowness, difficulties in concentration, planning, and multitasking. Neuropsychological studies have confirmed that cognitive impairment occurs in a substantial (15-50%) proportion of patients. Among HIV-1-infected patients cognitive impairment was and is one of the most feared complications of HIV-1 infection. In addition, neurocognitive impairment may affect adherence to treatment and ultimately result in increased morbidity for systemic disease. So what may be going on in the CNS after so many years of apparently controlled HIV-1 infection is an urgent and important challenge in the field of HIV medicine. In this review we summarize the key currently available data. We describe the clinical neurological and neuropsychological findings, the preferred diagnostic approach with new imaging techniques and cerebrospinal fluid analysis. We try to integrate data on pathogenesis and finally discuss possible therapeutic interventions.