Alberto Roverato

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.

Hyper inverse Wishart distribution for non-decomposable graphs and its application to Bayesian inference for Gaussian graphical models

While conjugate Bayesian inference in decomposable Gaussian graphical models is largely solved, the non-decomposable case still poses difficulties concerned with the specification of suitable priors and the evaluation of normalizing constants. In this paper we derive the DY-conjugate prior (Diaconis & Ylvisaker, 1979) for non-decomposable models and show that it can be regarded as a generalization to an arbitrary graph G of the hyper inverse Wishart distribution (Dawid & Lauritzen, 1993). In particular, if G is an incomplete prime graph it constitutes a non-trivial generalization of the inverse Wishart distribution. Inference based on marginal likelihood requires the evaluation of a normalizing constant and we propose an importance sampling algorithm for its computation. Examples of structural learning involving non-decomposable models are given. In order to deal efficiently with the set of all positive definite matrices with non-decomposable zero-pattern we introduce the operation of triangular completion of an incomplete triangular matrix. Such a device turns out to be extremely useful both in the proof of theoretical results and in the implementation of the Monte Carlo procedure.

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.

Reverse engineering molecular regulatory networks from microarray data with qp-graphs.

Reverse engineering bioinformatic procedures applied to high-throughput experimental data have become instrumental in generating new hypotheses about molecular regulatory mechanisms. This has been particularly the case for gene expression microarray data, where a large number of statistical and computational methodologies have been developed in order to assist in building network models of transcriptional regulation. A major challenge faced by every different procedure is that the number of available samples n for estimating the network model is much smaller than the number of genes p forming the system under study. This compromises many of the assumptions on which the statistics of the methods rely, often leading to unstable performance figures. In this work, we apply a recently developed novel methodology based in the so-called q-order limited partial correlation graphs, qp-graphs, which is specifically tailored towards molecular network discovery from microarray expression data with p >> n. Using experimental and functional annotation data from Escherichia coli, here we show how qp-graphs yield more stable performance figures than other state-of-the-art methods when the ratio of genes to experiments exceeds one order of magnitude. More importantly, we also show that the better performance of the qp-graph method on such a gene-to-sample ratio has a decisive impact on the functional coherence of the reverse-engineered transcriptional regulatory modules and becomes crucial in such a challenging situation in order to enable the discovery of a network of reasonable confidence that includes a substantial number of genes relevant to the essayed conditions. An R package, called qpgraph implementing this method is part of the Bioconductor project and can be downloaded from (www.bioconductor.org). A parallel standalone version for the most computationally expensive calculations is available from (http://functionalgenomics.upf.xsedu/qpgraph).

Multidisciplinary Approach to the Treatment of Metabolic and Morphologic Alterations of HIV-Related Lipodystrophy

Abstract Background: Treatment for metabolic and morphologic alterations in HIV-related lipodystrophy include medical therapy, physical exercise, and surgical interventions. Method: We assessed the efficacy and safety of a comprehensive multidisciplinary approach for treating morphological and metabolic alterations of the lipodystrophy syndrome in consecutive patients attending the Metabolic Clinic (MC) of the University of Modena and Reggio Emilia who had at least 2 evaluations over a 48-week period. 245 patients were evaluated: 143 (62.4%) were men, 74 (36.1%) presented with lipoatrophy, 10 (4.9%) with fat accumulation, 93 (45%) with mixed forms, 24 (11.3%) had hypercholesterolemia (LDL >160 mg/dL), 87 (38%) had hypertriglyceridemia (TG >150 mg/dL), 13 (5.7%) had diabetes (glucose >126 mg/dL), and 78 (44%) had insulin resistance (HOMA-IR >4). Results: At follow-up, a significant improvement was observed in both objective and subjective variables. Anthropometric improvement was observed in waist to hip ratio, waist circumference, and right and left cheek dermal thickness measurements. A nonsignificant improvement was observed in fat and lean regional mass by DEXA; CT showed improvement in visceral and subcutaneous adipose tissue. Glucose, HOMA-IR, total cholesterol, and APO B improved. Subjective variables improved in aesthetic satisfaction. Conclusion: We conclude that the medical and surgical interventions proposed in this multidisciplinary therapeutic approach are efficacious and safe in the management of lipodystrophy.

Age-matched cavernous peak systolic velocity: a highly sensitive parameter in the diagnosis of arteriogenic erectile dysfunction

Recently it has been reported that there is a strict correlation between erectile dysfunction (ED) and cardiovascular diseases, but the importance of such relationship still needs to be addressed. Ultrasonographic peak systolic velocity (PSV), is considered a reliable parameter for the diagnosis of arteriogenic ED. However, the cut-off value of PSV<30 cm/s has sufficient sensitivity only in the diagnosis of advanced arteriogenic ED and it is not representative of peripheral vascular alterations. In the present study, we set up an age-adjustment of PSV – calculated with the formula PSV <6.73+age × 0.7 – that permits a more accurate diagnosis of vascular aetiology in ED patients and may predict the presence of carotid wall alterations. We studied 179 consecutive subjects (mean age 52 years, range 23–79 years), with a history of ED of at least 6 months, by means of penile colour doppler ultrasonography (P-CDU) and common carotid arteries colour doppler ultrasonography (CCA-CDU) between June 2003 and September 2004. Statistical analysis was carried out with the statistical software R. PSV and CCAD values showed a statistically significant negative correlation. Age adjustment further improved this relationship permitting to identify an age-dependent PSV cut-off given by the formula PSV <6.73+age × 0.7. The age-adjusted PSV cut-off allows an accurate interpretation of vascular aetiology in ED patients and predicts the presence of carotid wall alterations, from the intima-media pathologic thickness to the plaque formation, with high values of both sensitivity and specificity.

Life expectancy in the immune recovery era: the evolving scenario of the HIV epidemic in northern Italy.

Introduction:National cohort and intercohort studies have been set to describe the differences of life expectancy (LE) of HIV-infected individuals. Objective:The aim of this study was to assess the impact of immune recovery (IR) on LE of patients with HIV undergoing combination antiretroviral therapy. Methods:In this retrospective observational study, outcome measure was LE of patients with HIV compared with LE of northern Italian population. Group categorizations were as follows: patients with no immune recovery (nIR), patients with IR, patients who are immune maintained, and pre-highly active antiretroviral therapy (HAART) and post-HAART. Abridged life tables were constructed from age-specific mortality rates (per 1000 person years) to estimate LE from the age of 20–55 years. Results:A total of 9671 patients, 71% men, were included. After 2005, we assisted to a rapid increase in the overall rate of patients attaining IR in the community coupled with a progressive decrease of AIDS death, but not of non-AIDS deaths. In a 40-year-old patient, LE was 38.10 years [standard error (SE) = 2.60], 30.08 years (SE = 0.98), and 22.9 (SE = 0.69) in the IR, post-HAART group and nIR, respectively, compared with 41.38 years of the general Italian population. An approximately 5-year gap in LE was observed in IR patients. Discussion:We describe IR at a “community” level, related to calendar year and apparent 10 years after HAART introduction. HAART community IR is significantly influencing LE and is associated with the changing clinical picture of HIV disease. An increasing gradient of LE exists between nIR, post-HAART, and IR groups, with the latter, above the age of 40 years only, reaching LE of general population.

Log-mean linear models for binary data

This paper introduces a novel class of models for binary data, which we call log-mean linear models. They are specified by linear constraints on the log-mean linear parameter, defined as a log-linear expansion of the mean parameter of the multivariate Bernoulli distribution. We show that marginal independence relationships between variables can be specified by setting certain log-mean linear interactions to zero and, more specifically, that graphical models of marginal independence are log-mean linear models. Our approach overcomes some drawbacks of the existing parameterizations of graphical models of marginal independence. Copyright 2013, Oxford University Press.

Prevalence of and risk factors for pubic lipoma development in HIV-infected persons.

Background:The natural history of HIV-associated body habitus changes is unclear. In this report, we describe a novel manifestation of HIV-associated lipoaccumulation. Methods:We noted the presence of suprapubic fat pads (pubic lipomas [PLs]) in several patients with preexisting HIV-associated body habitus abnormalities. Subsequently, we evaluated the prevalence of and associated risk factors for development of PLs by undertaking an observational cross-sectional study among patients with known lipodystrophy who attended a metabolic clinic in northern Italy. Inclusion criteria were a physician-confirmed diagnosis of lipodystrophy according to the Multicenter AIDS Cohort Study definition and, for those affected with PL, a readily noticeable PL on physical examination. Results:We evaluated 582 patients with lipodystrophy: 214 female (36.7%) and 368 male (63.3%). The overall PL prevalence was 9.4% (95% confidence interval [CI]: 7.2% to 12.1%; P < 0.0001). PLs were more common among obese than nonobese individuals (34.5%, 95% CI: 17.9% to 5l.3% vs. 8%, 95% CI: 5.9% to 10.6%, respectively; P < 0.0001) and those with preexisting dorsocervical fat pads, commonly called “buffalo humps” (BHs) (18.5%, 95% CI: 12.7% to 25.4% vs. 6.1%, 95% CI: 4.03% to 8.83%, respectively, P < 0.0001; relative risk = 3.02, 95% CI: 1.84% to 4.96%, P < 0.0001). The PL prevalence in the nonobese HIV-infected population (body mass index [BMI] <30, n = 550) was 8.0% (95% CI: 5.9% to 10.6%; P < 0.0001). Logistic regression analyses identified the following factors as associated with a greater likelihood for PL: BMI >30 (β = 0.18, SE = 0.04; P < 0.001), female gender (β = 1.06, SE = 0.31; P < 0.001), and shorter duration of HIV infection (β = −0.005, SE = 0.003; P = 0.04). We used a chain graph model to evaluate risk factors for BH and PL simultaneously. A nonnull interaction between these entities was evident, and this association seemed to be independent of factors positively associated with both (BMI and gender). Conclusions:PL is a newly recognized manifestation of HIV-associated lipoaccumulation that is more likely to occur among those with coexisting dorsocervical fat pads, suggesting the possibility of a common pathogenesis between the 2 entities. Likewise, PLs are more common among women, obese individuals, and those with a shorter duration of HIV infection. We suggest that PL should be considered part of the HIV-associated lipodystrophy syndrome.

Glomerular filtration rates in HIV-infected patients treated with and without tenofovir: a prospective, observational study.

OBJECTIVES The aim of our study was to assess the impact of plasma HIV-1 RNA level [viral load (VL)] variation and tenofovir exposure on kidney functions by analysing changes in calculated glomerular filtration rates (GFRs) over a 48 week period in patients with mild renal impairment. PATIENTS AND METHODS A prospective observational study that included data from all consecutive HIV-infected patients who attended a metabolic clinic was conducted. Included were adult, antiretroviral (ARV)-experienced, tenofovir-naive patients, whose kidney functions were evaluated by calculated GFR using the simplified Modification of Diet in Renal Disease study equation (MDRD). Tenofovir-exposed patients were patients who initiated tenofovir therapy at baseline and tenofovir-unexposed patients were patients whose ARV therapy did not include tenofovir. Participants were stratified into three sub-groups according to the plasma HIV-1 RNA (VL) changes observed: sub-groups 1, 2 and 3 were patients with stable VL < or =50 copies/mL, >0.5 log(10) VL increases and >0.5 VL log(10) decreases, respectively. RESULTS Ninety-nine patients were enrolled and included in the analysis. Within the tenofovir-unexposed group, GFRs remained stable (ANOVA, P = 0.94) over the follow-up period. Within the tenofovir-exposed group, mean GFR changes varied significantly by sub-group (ANOVA, P < 0.01). In particular, GFR changes in sub-group 3 (+8.4 +/- 12.4 mL/min) were different from those seen in sub-group 1 (-1.0 +/- 8.8 mL/min) (P < 0.05) and sub-group 2 (-4.6 +/- 8.8 mL/min) (P < 0.01). CONCLUSIONS Observed improvements in GFR that occurred as a consequence of highly active ARV therapy-induced viral suppression may have more than offset any potential negative effects of tenofovir on renal function.