Giovanni Guaraldi

Premature Age-Related Comorbidities Among HIV-Infected Persons Compared With the General Population

BACKGROUND Human immunodeficiency virus (HIV)-infected patients may have a greater risk of noninfectious comorbidities (NICMs) compared with the general population. We assessed the prevalence and risk factors for NICMs in a large cohort of HIV-infected adults and compared these findings with data from matched control subjects. METHODS We performed a case-control study involving antiretroviral therapy (ART)-experienced HIV-infected patients treated at Modena University, Italy, from 2002 through 2009. These patients were compared with age-, sex-, and race-matched adults (control subjects) from the general population included in the CINECA ARNO database. NICMs included cardiovascular disease, hypertension, diabetes mellitus, bone fractures, and renal failure. Polypathology (Pp) was defined as the concurrent presence of ≥2 NICMs. Logistic regression models were constructed to evaluate associated predictors of NICMs and Pp. RESULTS There were 2854 patients and 8562 control subjects. The mean age was 46 years, and 37% were women. Individual NICM and Pp prevalences in each age stratum were higher among patients than among controls (all P <.001). Pp prevalence among patients aged 41-50 years was similar to that among controls aged 51-60 years (P value was not statistically significant); diabetes mellitus, cardiovascular disease, bone fractures, and renal failure were statistically independent after adjustment for sex, age, and hypertension. Logistic regression models showed that independent predictors of Pp in the overall cohort were (all P < .001) age (odds ratio [OR], 1.11), male sex (OR, 1.77), nadir CD4 cell count <200 cells/μL (OR, 4.46), and ART exposure (OR, 1.01). CONCLUSIONS Specific age-related NICMs and Pp were more common among HIV-infected patients than in the general population. The prevalence of Pp in HIV-infected persons anticipated Pp prevalence observed in the general population among persons who were 10 years older, and HIV-specific cofactors (lower nadir CD4 cell count and more prolonged ART exposure) were identified as risk factors. These data support the need for earlier screening for NICMs in HIV-infected patients.

European AIDS Clinical Society (EACS) guidelines on the prevention and management of metabolic diseases in HIV

Metabolic diseases are frequently observed in HIV‐infected persons and, as the risk of contracting these diseases is age‐related, their prevalence will increase in the future as a consequence of the benefits of antiretroviral therapy (ART).

Nonalcoholic Fatty Liver Disease in HIV-Infected Patients Referred to a Metabolic Clinic: Prevalence, Characteristics, and Predictors

BACKGROUND The prevalence and predictors of nonalcoholic fatty liver disease (NAFLD) in human immunodeficiency virus (HIV)-infected highly active antiretroviral therapy-experienced patients and the association of NAFLD with risk of cardiovascular disease and subclinical atherosclerosis are unknown. METHODS We performed a cross-sectional observational study. NAFLD was defined by liver-spleen attenuation values of <1.1 on computed tomography in persons who had neither evidence of chronic viral hepatitis nor a significant history of alcohol consumption. RESULTS We enrolled 225 patients; 163 (72.4%) were men. Mean (+/-SD) HIV infection duration was 145 +/- 60 months, and mean (+/-SD) body mass index (calculated as weight in kilograms divided by the square of height in meters) was 23.75 +/- 3.59. NAFLD was diagnosed in 83 patients (36.9% of the total cohort). The following variables were significantly associated with NAFLD in univariate analyses: sex, waist circumference, body mass index, cumulative exposure to nucleoside reverse-transcriptase inhibitors, visceral adipose tissue, homeostasis model assessment of insulin resistance index, serum alanine and aspartate aminotransferase levels, and ratios of total serum cholesterol to high-density lipoprotein cholesterol. Coronary artery calcium scores and a diagnosis of diabetes were not associated with NAFLD. In multivariable logistic regression analyses, factors associated (P<0.001) with NAFLD were higher serum alanine to aspartate ratio (odds ratio, 4.59; 95% confidence interval, 2.09-10.08), male sex (odds ratio, 2.49; 95% confidence interval, 1.07-5.81), greater waist circumference (odds ratio, 1.07; 95% confidence interval, 1.03-1.11), and longer nucleoside reverse-transcriptase inhibitor exposure (odds ratio, 1.12 per year of exposure; 95% confidence interval, 1.03-1.22). CONCLUSIONS NAFLD is common among HIV-infected persons who have the traditional risk factors for NAFLD (elevations in serum alanine level, male sex, and increased waist circumference) apparent. Exposure to nucleoside reverse-transcriptase inhibitors was an independent risk factor for NAFLD, with an 11% increase in the odds ratio for each year of use.

Clinical epidemiology and survival of progressive multifocal leukoencephalopathy in the era of highly active antiretroviral therapy: Data from the Italian Registry Investigative Neuro AIDS (IRINA)

Human immunodeficiency virus (HIV)-associated progressive multifocal leukoencephalopathy (PML) remains a relevant clinical problem even in the era of highly active antiretroviral therapy (HAART). Aims of the study were to analyze clinical and treatment-related features and the survival probability of PML patients observed within the Italian Registry Investigative Neuro AIDS (IRINA) during a 29-month period of HAART. Intravenous drug use, the presence of focal signs, and the involvement of white matter at neuroradiology increased the risk of having PML. A reduced probability of PML was observed when meningeal signs were reported. Patients starting HAART at PML diagnosis and previously naïve for antiretrovirals showed significantly higher 1-year probability of survival (.58), compared to those continuing HAART (.24), or never receiving HAART (.00). Higher CD4 cell count were associated with a higher survival probability (.45). At multivariate analysis, a younger age, higher CD4, starting HAART at PML diagnosis, the absence of previous acquired immunodeficiency syndrome (AIDS)-defining events, and the absence of a severe neurologic impairment were all associated with a reduced hazard of death. The use of cidofovir showed a trend towards a reduced risk of death.

Nonalcoholic fatty liver disease is associated with an almost twofold increased risk of incident type 2 diabetes and metabolic syndrome. Evidence from a systematic review and meta-analysis.

The magnitude of the risk of incident type 2 diabetes (T2D) and metabolic syndrome (MetS) among patients with nonalcoholic fatty liver disease (NAFLD) is poorly known. We gauged the risk of developing T2D and MetS in patients with NAFLD diagnosed by either serum liver enzymes (aminotransferases or gamma‐glutamyltransferase [GGT]) or ultrasonography.

Prevalence, associated factors, and prognostic determinants of AIDS-related toxoplasmic encephalitis in the era of advanced highly active antiretroviral therapy

BACKGROUND Characteristics, associated factors, and survival probability of toxoplasmic encephalitis (TE) in the era of advanced highly active antiretroviral therapy (HAART) have not been fully clarified. METHODS Data for 205 individuals with acquired immunodeficiency syndrome (AIDS)-related TE were derived from the Italian Registry Investigative NeuroAIDS database, and the cases were studied longitudinally to evaluate prevalence, clinical characteristics, and survival. Moreover, the relationship between the occurrence of TE and exposure to antiretroviral therapy and to TE prophylaxis was evaluated. RESULTS With an overall prevalence of 26%, TE represented the most frequent neurological disorder in the cohort. Female sex, severe immunodeficiency, and absence of primary TE prophylaxis significantly increased the risk of TE, and previous exposure to antiretroviral therapy reduced the probability of disease occurrence. Thirty-six percent of patients who had received antiretroviral therapy developed TE, although in most of these cases, the patient experienced failure of antiretroviral therapy. Of note, 66% of patients who had experienced antiretroviral therapy did not receive prophylaxis for TE at TE diagnosis. The 1-year probability of that infection with human immunodeficiency virus (HIV) would progress or that death would occur after TE was 40% and 23%, respectively. Cognitive symptoms, low CD4(+) cell count, not receiving HAART after TE, and initiating HAART >2 months after TE diagnosis were all significantly associated with an increased probability of progression of HIV infection. Not receiving HAART after diagnosis negatively affected survival. CONCLUSIONS TE remains a highly prevalent disorder of the central nervous system, even in the late HAART era, particularly among severely immunosuppressed patients and in absence of prophylaxis. Considering that persons with TE have a high probability of early death, prophylaxis should be maintained in immunosuppressed patients who experience failure of antiretroviral therapy, and HAART should be initiated as soon as possible after TE diagnosis.

Coronary Aging in HIV-Infected Patients

BACKGROUND Human immunodeficiency virus (HIV)-infected patients often demonstrate accelerated aging processes. We investigated whether the vascular age of a cohort of stable HIV-infected patients receiving antiretroviral therapy (ART) was increased and sought out predictors of increased vascular age. METHODS In this cross-sectional study, 400 HIV-infected patients (mean age, 48 years) attending a cardiometabolic clinic underwent cardiac computed tomography imaging to identify coronary artery calcium (CAC). Vascular age was estimated on the basis of the extent of CAC by means of previously published equations. RESULTS Increased vascular age was observed in 162 patients (40.5%), with an average increase of 15 years (range, 1-43 years) over the chronological age. In univariable analyses, chronological age, male sex, systolic blood pressure, duration of ART, fasting glucose level, fasting serum triglyceride level, total cholesterol level, low-density and high-density lipoprotein cholesterol levels, hypertension, and the presence of the metabolic syndrome were associated with increased vascular age. In multivariable linear regression analyses, current CD4+ cell count was the only predictor of increased vascular age (beta = 0.51; P = .005). CONCLUSIONS Increased vascular age is frequent among HIV-infected patients and appears to be associated with CD4+ cell count. If these findings were to be confirmed in prospective trials, a positive response to ART with an increase in CD4+ cell count may become a marker of increased risk of atherosclerosis development.

Role of PCR in Diagnosis and Prognosis of Visceral Leishmaniasis in Patients Coinfected with Human Immunodeficiency Virus Type 1

ABSTRACT A group of 76 consecutive human immunodeficiency virus (HIV)-positive patients with fever of unknown origin (n = 52) or fever associated with pulmonary diseases was evaluated in order to assess the usefulness of PCR with peripheral blood in the diagnosis and follow-up of visceral leishmaniasis. We identified 10 cases of visceral leishmaniasis among the 52 patients with fever of unknown origin. At the time of diagnosis, all were parasitemic by PCR with peripheral blood. During follow-up, a progressive decline in parasitemia was observed under therapy, and all patients became PCR negative after a median of 5 weeks (range, 6 to 21 weeks). However, in eight of nine patients monitored for a median period of 88 weeks (range, 33 to 110 weeks), visceral leishmaniasis relapsed, with positive results by PCR with peripheral blood reappearing 1 to 2 weeks before the clinical onset of disease. Eight Leishmania infantum and two Leishmania donovani infections were identified by PCR-restriction fragment length polymorphism analysis. PCR with peripheral blood is a reliable method for diagnosis of visceral leishmaniasis in HIV-infected patients. During follow-up, it substantially reduces the need for traditional invasive tests to assess parasitological response, while a positive PCR result is predictive of clinical relapse.

Alendronate Reduces Bone Resorption in HIV-Associated Osteopenia/Osteoporosis

Abstract Purpose: To evaluate the effects of alendronate, vitamin D, and calcium supplementation on bone metabolism and bone mineral density (BMD) in both HIV-infected men and women treated with highly active antiretroviral therapy (HAART). Method: We performed a 52-week prospective, multicenter, randomized, open-label clinical trial. Eligible participants were on stable HAART and had BMD values at the femoral neck or lumbar spine that corresponded to a t score less than -1. Patients were randomized to receive alendronate 70 mg weekly or no alendronate; calcium 1000 mg daily and vitamin D 500 IU daily were provided to all study recipients. Primary endpoint of the study was the change in bone metabolism evaluated by N-telopeptide of type 1 collagen and bone-specific alkaline phosphatase; the secondary endpoint was BMD variation. Results: 18 patients were randomized to the alendronate and 23 to the no-alendronate group (controls). The alendronate-treatment group compared to controls had a significant decrease in serum N-telopeptides, 1914 ± 1433.4 vs. 3967 ± 1650.5 pM/L (p = .005) after 1 year. Lumbar spine BMD increased by 4% in the alendronate group (p = .004) vs. 3.7% (p = .062) in controls, compared to baseline values. Femoral neck BMD decreased by 0.5% in the alendronate group (p = .05) and by 3.5% in the control group (p = .04). No between-groups differences for BMD were found (Δ lumbar-BMD 0.0351 ± 0.0406 in cases and 0.0356 ± 0.073 in controls [p = .977], Δ femoral-BMD –0.085 ± 0.160 in cases and –0.100 ± 0.165 in controls [p = .795]). Conclusion: Alendronate plus vitamin D and calcium was effective in reducing bone resorption. Alendronate improved lumbar BMD and minimized femoral BMD decrease after 52 weeks compared to treatment with vitamin D and calcium alone in patients on HAART with osteopenia/osteoporosis.

Hepatocellular Carcinoma in HIV-Infected Patients: Check Early, Treat Hard

PURPOSE Hepatocellular carcinoma (HCC) is an increasing cause of mortality in HIV-infected patients in the highly active antiretroviral therapy (HAART) era. The aims of this study were to describe HCC tumor characteristics and different therapeutic approaches, to evaluate patient survival time from HCC diagnosis, and to identify clinical prognostic predictors in patients with and without HIV infection. PATIENTS AND METHODS A multicenter observational retrospective comparison of 104 HIV-infected patients and 484 uninfected patients was performed in four Italian centers. HCC was staged according to the Barcelona Clinic Liver Cancer (BCLC) criteria. RESULTS Tumor characteristics of patients with and without HIV were significantly different for age, Eastern Cooperative Oncology Group performance status (PS) score ≤1, and etiology of chronic liver disease. Despite the similar potentially curative option rate and better BCLC stage at diagnosis, the median survival time was significantly shorter in HIV(+) patients. HIV(+) patients were less frequently retreated at relapse. Independent predictors of survival were: BCLC stage, potentially effective HCC therapy, tumor dimension ≤3 cm, HCC diagnosis under a screening program, HCC recurrence, and portal vein thrombosis. Restricting the analysis to HIV(+) patients only, all positive prognostic factors were confirmed together with HAART exposure. CONCLUSION This study confirms a significantly shorter survival time in HIV(+) HCC patients. The less aggressive retreatment at recurrence approach does not balance the benefit of younger age and better BCLC stage and PS score of HIV(+) patients. Thus, considering the prognosis of HIV(+) HCC patients, effective screening techniques, programs, and specific management guidelines are urgently needed.