SARS-CoV-2 testing, positivity, and factors associated with COVID-19 among people with HIV across Europe in the multinational EuroSIDA cohort.

BACKGROUND: Although people with HIV might be at risk of severe outcomes from infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; coronavirus 2019 [COVID-19]), regional and temporal differences in SARS-CoV-2 testing in people with HIV across Europe have not been previously described. METHODS: We described the proportions of testing, positive test results, and hospitalizations due to COVID-19 between 1 January 2020 and 31 December 2021 in the EuroSIDA cohort and the factors associated with being tested for SARS-CoV-2 and with ever testing positive. RESULTS: Of 9012 participants, 2270 (25.2%, 95% confidence interval [CI] 24.3-26.1) had a SARS-CoV-2 polymerase chain reaction test during the study period (range: 38.3% in Northern to 14.6% in Central-Eastern Europe). People from Northern Europe, women, those aged <40 years, those with CD4 cell count <350 cells/mm3, and those with previous cardiovascular disease or malignancy were significantly more likely to have been tested, as were people with HIV in 2021 compared with those in 2020. Overall, 390 people with HIV (4.3%, 95% CI 3.9-4.8) tested positive (range: 2.6% in Northern to 7.1% in Southern Europe), and the odds of testing positive were higher in all regions than in Northern Europe and in 2021 than in 2020. In total, 64 people with HIV (0.7%, 95% CI 0.6-0.9) were hospitalized, of whom 12 died. Compared with 2020, the odds of positive testing decreased in all regions in 2021, and the associations with cardiovascular disease, malignancy, and use of tenofovir disoproxil fumarate disappeared in 2021. Among study participants, 58.9% received a COVID-19 vaccine (range: 72.0% in Southern to 14.8% in Eastern Europe). CONCLUSIONS: We observed large heterogeneity in SARS-CoV-2 testing and positivity and a low proportion of hospital admissions and deaths across the regions of Europe.

Sarcopenic obesity and reduced BMD in young men living with HIV: body composition and sex steroids interplay.

PURPOSE: Sex steroids play a key role on male bone homeostasis and body composition (BC), their role in men living with HIV (MLWH) is less recognized. This study aimed at investigating the prevalence of low BMD, sarcopenia, and sarcopenic obesity (SO) and their relationship with sex steroids in MLWH aged < 50. METHODS: Prospective, cross-sectional, observational study on MLWH younger than 50 (median age 47.0 years). BC and BMD were evaluated with DXA. Two different definitions of sarcopenia were applied: appendicular lean mass/height2 (ALMI) < 7.26 kg/m2 or appendicular lean mass/body weight (ALM/W) < 28.27%. Low BMD was defined for Z-score < -2.0. Sarcopenia coupled with obesity identified SO. Serum total testosterone (T) and estradiol (E2) were measured by LC-MS/MS; free testosterone (cFT) was calculated by Vermeulen equation. RESULTS: Sarcopenia was detected in 107 (34.9%) and 44 (14.3%) out of 307 MLWH according to ALMI and ALM/W, respectively. The prevalence of SO was similar by using both ALMI (11.4%) and ALM/W (12.4%). Sarcopenic and SO MLWH had lower total T and cFT in both the definition for sarcopenia. BMD was reduced in 43/307 (14.0%). Serum E2 < 18 pg/mL was an independent contributing factor for sarcopenia, SO, and low BMD. CONCLUSIONS: T and E2 are important determinants of BC even in MLWH. This is among the first studies investigating the distribution of obesity phenotypes and the prevalence of SO among MLWH showing that SO is present in 11-12% of enrolled MLWH regardless of the definition used. However, deep differences emerged using two different diagnostic definitions.

Application of guidelines for the management of nonalcoholic fatty liver disease in three prospective cohorts of HIV-monoinfected patients.

OBJECTIVES: Current guidelines recommend use of a diagnostic algorithm to assess disease severity in cases of suspected nonalcoholic fatty liver disease (NAFLD). We applied this algorithm to HIV-monoinfected patients. METHODS: We analysed three prospective screening programmes for NAFLD carried out in the following cohorts: the Liver Disease in HIV (LIVEHIV) cohort in Montreal, the Modena HIV Metabolic Clinic (MHMC) cohort and the Liver Pathologies in HIV in Palermo (LHivPa) cohort. In the LIVEHIV and LHivPa cohorts, NAFLD was diagnosed if the controlled attenuation parameter (CAP) was ≥ 248 dB/m; in the MHMC cohort, it was diagnosed if the liver/spleen Hounsfield unit (HU) ratio on abdominal computerized tomography scan was < 1.1. Medium/high-risk fibrosis category was defined as fibrosis-4 (FIB-4) ≥ 1.30. Patients requiring specialist referral to hepatology were defined as either having NAFLD and being in the medium/high-risk fibrosis category or having elevated alanine aminotransferase (ALT). RESULTS: A total of 1534 HIV-infected adults without significant alcohol intake or viral hepatitis coinfection were included in the study. Of these, 313 (20.4%) patients had the metabolic comorbidities (obesity and/or diabetes) required for entry in the diagnostic algorithm. Among these patients, 123 (39.3%) required specialist referral to hepatology, according to guidelines. A total of 1062 patients with extended metabolic comorbidities (any among obesity, diabetes, hypertension and dyslipidaemia) represented most of the cases of NAFLD (79%), elevated ALT (75.9%) and medium/high-risk fibrosis category (75.4%). When the algorithm was extended to these patients, it was found that 341 (32.1%) would require specialist referral to hepatology. CONCLUSIONS: According to current guidelines, one in five HIV-monoinfected patients should undergo detailed assessment for NAFLD and disease severity. Moreover, one in ten should be referred to hepatology. Expansion of the algorithm to patients with any metabolic comorbidities may be considered.

2019 update of the European AIDS Clinical Society Guidelines for treatment of people living with HIV version 10.0.

BACKGROUND: The European AIDS Clinical Society (EACS) Guidelines cover key aspects of HIV management with major updates every two years. GUIDELINE HIGHLIGHTS: The 2019 Guidelines were extended with a new section focusing on drug-drug interactions and other prescribing issues in people living with HIV (PLWH). The recommendations for treatment-naïve PLWH were updated with four preferred regimens favouring unboosted integrase inhibitors. A two-drug regimen with dolutegravir and lamivudine, and a three-drug regimen including doravirine were also added to the recommended initial regimens. Lower thresholds for hypertension were expanded to all PLWH and for cardiovascular disease prevention, the 10-year predicted risk threshold for consideration of antiretroviral therapy (ART) modification was lowered from 20% to 10%. Frailty and obesity were added as new topics. It was specified to use urine albumin to creatinine ratio to screen for glomerular disease and urine protein to creatinine ratio for tubular diseases, and thresholds were streamlined with the Kidney Disease: Improving Global Outcomes (KDIGO) recommendations. Hepatitis C virus (HCV) treatment recommendations were split into preferred and alternative treatment options. The algorithm for management of recently acquired HCV infection was updated and includes recommendations for early chronic infection management. Treatment of resistant tuberculosis (TB) was streamlined with the World Health Organization (WHO) recommendations, and new tables on immune reconstitution inflammatory syndrome, on when to start ART in the presence of opportunistic infections and on TB drug dosing were included. CONCLUSIONS: The EACS Guidelines underwent major revisions of all sections in 2019. They are available in four different formats including a new interactive web-based version and are translated into Chinese, French, German, Japanese, Portuguese, Russian and Spanish.

The EuroSIDA study: 25 years of scientific achievements.

The EuroSIDA study was initiated in 1994 and follows adult people living with HIV (PLHIV) in 100 collaborating clinics across 35 countries covering all European regions, Israel and Argentina. The study aims to study the long-term virological, immunological and clinical outcomes of PLHIV and to monitor temporal changes and regional differences in outcomes across Europe. Annually collected data include basic demographic characteristics, information on AIDS- and non-AIDS-related clinical events, and details about antiretroviral therapy (ART), hepatitis C treatment and other medications, in addition to a range of laboratory values. The summer 2016 data set held data from a total of 23 071 individuals contributing 174 481 person-years of follow-up, while EuroSIDA's unique plasma repository held over 160 000 samples. Over the past 25 years, close to 300 articles have been published in peer-reviewed journals (h-index 52), covering a range of scientific focus areas, including monitoring of clinical and virological outcomes, ART uptake, efficacy and adverse events, the influence of hepatitis virus coinfection, variation in the quality of HIV care and management across settings and regions, and biomarker research. Recognizing that there remain unresolved issues in the clinical care and management of PLHIV in Europe, EuroSIDA was one of the cohorts to found The International Cohort Consortium of Infectious Disease (RESPOND) cohort consortium on infectious diseases in 2017. In celebration of the EuroSIDA study's 25th anniversary, this article aims to summarize key scientific findings and outline current and future scientific focus areas.

Significant chronic airway abnormalities in never-smoking HIV-infected patients.

OBJECTIVES: The aim of the study was to describe chronic lung disease in HIV-infected never-smokers by looking at clinical, structural and functional abnormalities. METHODS: This comparative cross-sectional study included 159 HIV-infected never-smoking patients [mean (± standard deviation) age 54.6 ± 9.1 years; 13.2% female; 98.1% with undetectable viral load] and 75 nonmatched never-smoking controls [mean (± standard deviation) age 52.6 ± 6.9 years; 46.7% female]. We examined calcium scoring computer tomography (CT) scans or chest CT scans, all with a lung-dedicated algorithm reconstruction, to assess emphysema and airway disease (respiratory bronchiolitis and/or bronchial wall thickening), tested pulmonary function using spirometry, lung volumes and the diffusion lung capacity of carbon monoxide (DLCO), and assessed respiratory symptoms using the Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT). RESULTS: Twenty-five (17.2%) of the HIV-infected patients versus two (2.7%) of the controls had a CAT score > 10. Only 5% of the HIV-infected patients showed FEV1% < 80%, and 25% had DLCO < 75% of the predicted value. Based on the CT scans, they had increased prevalences, compared with the controls, of airway disease (37% versus 7.9%, respectively) and emphysema (18% versus 4%, respectively), with more severe and more frequent centrilobular disease. After correction for age, sex and clinical factors, HIV infection was significantly associated with CAT > 10 [odds ratio (OR) 7.7], emphysema (OR 4), airway disease (OR 4.5) and DLCO < 75% of predicted (OR 4). CONCLUSIONS: Although comparisons were limited by the different enrolment methods used for HIV-infected patients and controls, the results suggest that never-smoking HIV-infected patients may present with chronic lung damage characterized by CT evidence of airway disease. A minority of them showed respiratory symptoms, without significant functional abnormalities.

Evolution of major non-HIV-related comorbidities in HIV-infected patients in the Italian Cohort of Individuals, Naïve for Antiretrovirals (ICONA) Foundation Study cohort in the period 2004-2014.

OBJECTIVES: The management of HIV disease is complicated by the incidence of a new spectrum of comorbid noncommunicable diseases (NCDs). It is important to document changes in the prevalence of NCDs over time. The aim of the study was to describe the impact of ageing on HIV markers and on the prevalence of NCDs in people living with HIV (PLWHIV) in the Italian Cohort of Individuals, Naïve for Antiretrovirals (ICONA) seen for care in 2004-2014. METHODS: Analyses were conducted separately for a closed cohort (same people seen at both times) and an open cohort (all people under follow-up). We used the χ2 test for categorical factors and the Wilcoxon test for quantitative factors to compare profiles over time. RESULTS: The closed cohort included 1517 participants and the open cohort 3668 under follow-up in 2004 and 6679 in 2014. The median age of the open cohort was 41 [interquartile range (IQR) 37-46] years in 2004 and 44 (IQR 36-52) years in 2014. Analysis of the closed cohort showed an increase in the prevalence of some NCDs [the prevalence of dyslipidaemia increased from 75% in 2004 to 91% in 2014, that of hypertension from 67 to 84%, and that of cardiovascular disease (CVD) from 18 to 32%] and a decrease in renal function (5% with eGFR < 60 mL/min per 1.73 m2 in 2004 versus 30% in 2014); the percentage of people in the high-risk group for the Framingham CHD score more than tripled (from 13 to 45%). Results in the open cohort were similar. CONCLUSIONS: The burden of NCDs in our PLWHIV population markedly worsened over a 10-year time-span, which is likely to be a result of the effects of both ageing and HIV infection as well as their interaction. Special attention must be given to the management and prevention of NCDs.

Reliability of calcium-phosphorus (Ca/P) ratio as a new, accurate and inexpensive tool in the diagnosis of some Ca-P disorders.

PURPOSE: The serum calcium/phosphorus (Ca/P) ratio is an accurate tool to differentiate patients with primary hyperparathyroidism (PHPT) from healthy subjects. However, other disorders of the Ca-P metabolism might impair the Ca/P ratio, such as hypophosphatemia (HypoP) not PHPT related. The aim of this study is to examine the diagnostic value of Ca/P ratio in the diagnosis of PHPT and HypoP not PHPT related. METHODS: Single-center, retrospective, case-control study, including 150 patients with PHPT and 306 patients with HypoP, compared with 150 controls. HypoP patients were enrolled among HIV-infected patients by selecting those with Fanconi-like syndrome due to antiretroviral treatment. Parameters which were measured were serum Ca, P, parathyroid hormone (PTH), 25-OH vitamin D, albumin and creatinine). RESULTS: The Ca/P ratio was significantly higher in PHPT and HypoP patients, compared to controls (p < 0.0001). At receiver operator characteristic (ROC) curve analysis, the cut-off of 3.56 (2.75 SI) for Ca/P ratio was able to identify patients with PHPT and HypoP (sensitivity 95%; specificity 93%). Among patients with Ca/P ratio above 3.56, the thresholds of 10.3 mg/dL (2.6 mmol/L) for serum Ca (sensitivity 93%; specificity 98%) and 80.5 pg/mL for PTH (sensitivity 91%; specificity 91%) were defined for the specific diagnosis of PHPT. CONCLUSIONS: The Ca/P ratio above 3.56 (2.75 SI) is a highly accurate tool to identify PHPT and HypoP not PHPT-related patients. Thanks to its simplicity, this index can be proposed as a screening and first-line examination in the diagnostic work-up when a disorder of Ca-P metabolism is suspected or should be ruled out.

The increasing burden and complexity of multi-morbidity and polypharmacy in geriatric HIV patients: a cross sectional study of people aged 65 - 74 years and more than 75 years.

BACKGROUND: Geriatric Patients Living with HIV/AIDS (GEPPO) is a new prospective observational multicentre cohort consisting of all the HIV-positive geriatric patients being treated at 10 clinics in Italy, and HIV-negative controls attending a single geriatric clinic. The aim of this analysis of the GEPPO cohort was to compare prevalence and risk factors of individual non-communicable diseases (NCD), multi-morbidity (MM) and polypharmacy (PP) amongst HIV positive and HIV negative controls at enrolment into the GEPPO cohort. METHODS: This cross-sectional study was conducted between June 2015 and May 2016. The duration of HIV infection was subdivided into three intervals: < 10, 10-20 and > 20 years. The NCD diagnoses were based on guidelines defined criteria, including cardiovascular disease, hypertension, type 2 diabetes, chronic kidney disease, dyslipidaemia, chronic obstructive pulmonary disease. MM was classified as the presence of two or more co-morbidities. The medications prescribed for the treatment of comorbidities were collected in both HIV positive and HIV negative group from patient files and were categorized using the Anatomical Therapeutic Chemical (ATC) classification. PP was defined as the presence of five or more drug components other than anti-retroviral agents. RESULTS: The study involved a total of 1573 patient: 1258 HIV positive and 315 HIV negative). The prevalence of individual comorbidities was similar in the two groups with the exception of dyslipidaemia, which was more frequent in the HIV-positive patients (p <  0.01). When the HIV-positive group was stratified based on the duration of HIV infection, most of the co-morbidities were significantly more frequent than in control patients, except for hypertension and cardiovascular disease, while COPD was more prevalent in the control group. MM and PP were both more prevalent in the HIV-positive group, respectively 64% and 37%. CONCLUSIONS: MM and PP burden in geriatric HIV positive patients are related to longer duration of HIV-infection rather than older age per se.

Ageing and inflammation in patients with HIV infection.

Nowadays, HIV+ patients have an expected lifespan that is only slightly shorter than healthy individuals. For this reason, along with the fact that infection can be acquired at a relatively advanced age, the effects of ageing on HIV+ people have begun to be evident. Successful anti-viral treatment is, on one hand, responsible for the development of side effects related to drug toxicity; on the other hand, it is not able to inhibit the onset of several complications caused by persistent immune activation and chronic inflammation. Therefore, patients with a relatively advanced age, i.e. aged more than 50 years, can experience pathologies that affect much older citizens. HIV+ individuals with non-AIDS-related complications can thus come to the attention of clinicians because of the presence of neurocognitive disorders, cardiovascular diseases, metabolic syndrome, bone abnormalities and non-HIV-associated cancers. Chronic inflammation and immune activation, observed typically in elderly people and defined as 'inflammaging', can be present in HIV+ patients who experience a type of premature ageing, which affects the quality of life significantly. This relatively new condition is extremely complex, and important factors have been identified as well as the traditional behavioural risk factors, e.g. the toxicity of anti-retroviral treatments and the above-mentioned chronic inflammation leading to a functional decline and a vulnerability to injury or pathologies. Here, we discuss the role of inflammation and immune activation on the most important non-AIDS-related complications of chronic HIV infection, and the contribution of aging per se to this scenario.

Correlates of frailty phenotype and frailty index and their associations with clinical outcomes.

OBJECTIVES: Frailty is a predictor of adverse health outcomes and can be measured across the life course, including among people living with HIV. The purpose of this study was to examine two commonly used measures of frailty - the frailty index (FI) and frailty phenotype - to assess common characteristics and to describe associations with multimorbidity, falls, and disability in people aging with HIV. METHODS: This was a cross-sectional observational study including 482 consecutive HIV-infected patients (mean age 53.9 ± SD 6.9 years; 75% male) attending the multidisciplinary metabolic clinic at the University of Modena, Italy. Frailty was measured with the frailty phenotype and a 37-item FI. RESULTS: The mean FI score was 0.28±0.1 and frailty phenotype categories were: 3.1% frail, 51.9% pre-frail, and 45% robust. The duration of antiretroviral therapy was significantly different across levels of frailty as measured by both frailty tools (P < 0.01), but the nadir CD4 count was only significant for the FI (P = 0.01); current CD4 count was not significantly different across frailty levels using either tool. Both frailty measures were associated with multimorbidity; the FI was associated with Instrumental Activities of Daily Living impairment and falls history, whereas the frailty phenotype was not. CONCLUSIONS: The frailty phenotype and the FI demonstrated similar characteristics in patients at a tertiary-level HIV clinic. The FI had a stronger association with age, nadir CD4 count, comorbidities, falls, and disability. Integrating frailty assessments in clinical practice will be crucial for the development of interventions in age-related conditions, including disability and falls, in older persons living with HIV.

Pregnant with HIV before age 25: data from a large national study in Italy, 2001-2016.

Young pregnant women with HIV may be at significant risk of unplanned pregnancy, lower treatment coverage, and other adverse pregnancy outcomes. In a large cohort of pregnant women with HIV in Italy, among 2979 pregnancies followed in 2001-2016, 9·0% were in women <25 years, with a significant increase over time (2001-2005: 7·0%; 2006-2010: 9·1%; 2011-2016: 12·2%, P < 0·001). Younger women had a lower rate of planned pregnancy (23·2% vs. 37·7%, odds ratio (OR) 0·50, 95% confidence interval (CI) 0·36-0·69), were more frequently diagnosed with HIV in pregnancy (46·5% vs. 20·9%, OR 3·29, 95% CI 2·54-4·25), and, if already diagnosed with HIV before pregnancy, were less frequently on antiretroviral treatment at conception (<25 years: 56·3%; ⩾25 years: 69·0%, OR 0·58, 95% CI 0·41-0·81). During pregnancy, treatment coverage was almost universal in both age groups (98·5% vs. 99·3%), with no differences in rate of HIV viral suppression at third trimester and adverse pregnancy outcomes. The data show that young women represent a growing proportion of pregnant women with HIV, and are significantly more likely to have unplanned pregnancy, undiagnosed HIV infection, and lower treatment coverage at conception. During pregnancy, antiretroviral treatment, HIV suppression, and pregnancy outcomes are similar compared with older women. Earlier intervention strategies may provide additional benefits in the quality of care for women with HIV.

An Update on Heart Transplantation in Human Immunodeficiency Virus-Infected Patients.

Cardiovascular diseases have become a significant cause of morbidity in patients with human immunodeficiency virus (HIV) infection. Heart transplantation (HT) is a well-established treatment of end-stage heart failure (ESHF) and is performed in selected HIV-infected patients in developed countries. Few data are available on the prognosis of HIV-infected patients undergoing HT in the era of combined antiretroviral therapy (cART) because current evidence is limited to small retrospective cohorts, case series, and case reports. Many HT centers consider HIV infection to be a contraindication for HT; however, in the era of cART, HT recipients with HIV infection seem to achieve satisfactory outcomes without developing HIV-related events. Consequently, selected HIV-infected patients with ESHF who are taking effective cART should be considered candidates for HT. The present review provides epidemiological data on ESHF in HIV-infected patients from all published experience on HT in HIV-infected patients since the beginning of the epidemic. The practical management of these patients is discussed, with emphasis on the challenging issues that must be addressed in the pretransplant (including HIV criteria) and posttransplant periods. Finally, proposals are made for future management and research priorities.

Independent association of subclinical coronary artery disease and emphysema in HIV-infected patients.

OBJECTIVES: Chronic obstructive pulmonary disease (COPD) and coronary artery disease are inflammatory states with a significant clinical impact. The relationship between them has not been investigated in patients with HIV infection. We assessed the presence of subclinical emphysema and coronary artery disease using chest computed tomography (CT) imaging in a cohort of HIV-infected patients receiving antiretroviral therapy. METHODS: Gated chest CT scans were performed in 1446 consecutive patients to assess the presence and severity of coronary artery calcium (CAC) (classified as a score of 0, 1-100 or > 100) and emphysema (classified using a visual semiquantitative scale: 0, absent; 1-4, mild to moderate; > 4, severe). Univariable and multivariable logistic regression analyses were performed to identify factors independently associated with CAC and emphysema. RESULTS: The emphysema score was significantly higher in patients with CAC scores of 1-100 and > 100 compared with those with a CAC score of 0. After adjustments for age, sex, smoking status, pack-years of smoking, visceral adiposity and duration of HIV infection, the presence of any emphysema was significantly associated with a CAC score > 0 [odds ratio (OR) 1.43; 95% confidence interval (CI) 1.08-1.88; P = 0.012]. The association persisted after adjustment for the Framingham risk score (OR 1.52; 95% CI 1.16-1.99; P = 0.002). There was a dose-dependent effect in the association between emphysema score and CAC score. CONCLUSIONS: In this cross-sectional study of HIV-infected patients, there was an independent association between emphysema and CAC, after adjustment for traditional cardiovascular risk factors, suggesting a common pathogenesis of these chronic inflammatory conditions in a chronic inflammatory disease such as HIV infection.

Serum total estradiol, but not testosterone is associated with reduced bone mineral density (BMD) in HIV-infected men: a cross-sectional, observational study.

SUMMARY: By investigating the relationship between serum testosterone, estradiol, and bone mineral density (BMD) in a large cohort of HIV-infected men, estradiol was associated with BMD, relative estrogen deficiency being involved in bone loss in men with hypogonadism, in addition to all HIV-related factors. Increased aromatization in adipose tissue does not counteract HIV-related bone loss. INTRODUCTION: The purpose of this study is to evaluate the relationship between serum testosterone, estradiol, and BMD in a large cohort of HIV-infected men. METHODS: We investigated biochemical, hormonal parameters, and BMD in 1204 HIV-infected men (age 45.64 ± 7.33 years) participating in a cross-sectional, observational study. Among other parameters, the main outcome measures were serum total testosterone and estradiol, gonadotropins, 25-hydroxyvitamin D [25(OH)D], parathormone (PTH), calcium, phosphorous, femoral, and lumbar BMD. RESULTS: In men with HIV, the prevalence of osteoporosis and osteopenia is 15.1 and 63.2% with 25(OH)D insufficiency being very common (60.1%). After age adjustment, BMD is positively associated with estradiol, but not testosterone, at linear (p < 0.001) and stepwise (p < 0.05) multiple regression. Lumbar BMD significantly increases across the estradiol quartiles but not among testosterone quartiles. Femoral and lumbar BMD are significantly higher in men with estradiol ≥ 27 pg/mL than in those with estradiol <27 pg/mL. Apart from estradiol, only age, calcium, and BMI predict BMD at stepwise linear multiple regression, but the strength of this association is weak. CONCLUSIONS: Estradiol, but not testosterone, is associated with BMD in HIV-infected men and exerts a protective role on bone especially when it is above 27 pg/mL. Relative estrogen deficiency is a potential mechanism involved in bone loss in hypogonadal HIV-infected men, in addition to all HIV-related factors. Increased aromatization in adipose tissue does not counteract HIV-related bone loss. Finally, reduced BMD in young-to-middle-aged HIV-infected men might be considered a peculiar hallmark of HIV infection due to its relevant prevalence, representing one of the several pieces composing the complicated puzzle of premature aging related to HIV infection.

HCV-HIV coinfected pregnant women: data from a multicentre study in Italy.

PURPOSE: To provide information about main pregnancy outcomes in HIV-HCV coinfected women and about the possible interactions between HIV and HCV in this particular population. METHODS: Data from a multicenter observational study of pregnant women with HIV, conducted in Italian University and Hospital Clinics between 2001 and 2015, were used. Eligibility criteria for analysis were HCV coinfection and at least one detectable plasma HCV-RNA viral load measured during pregnancy. Qualitative variables were compared using the Chi-square or the Fisher test and quantitative variables using the Mann-Whitney U test. The Spearman's coefficient was used to evaluate correlations between quantitative variables. RESULTS: Among 105 women with positive HCV-RNA, median HCV viral load was substantially identical at the three trimesters (5.68, 5.45, and 5.86 log IU/ml, respectively), and 85.7 % of the women had at least one HCV-RNA value >5 log IU/ml. Rate of preterm delivery was 28.6 % with HCV-RNA <5 log IU/ml and 43.2 % with HCV-RNA >5log (p = 0.309). Compared to women with term delivery, women with preterm delivery had higher median HCV-RNA levels (third trimester: 6.00 vs. 5.62 log IU/ml, p = 0.037). Third trimester HIV-RNA levels were below 50 copies/ml in 47.7 % of the cases. No cases of vertical HIV transmission occurred. Rate of HCV transmission was 9.0 % and occurred only with HCV-RNA levels >5 log IU/ml. CONCLUSIONS: Coinfection with HIV and HCV has relevant consequences in pregnancy: HIV coinfection is associated with high HCV-RNA levels that might favour HCV transmission, and HCV infection might further increase the risk of preterm delivery in women with HIV. HCV/HIV coinfected women should be considered a population at high risk of adverse outcomes.

Incidence and factors associated with the risk of sexually transmitted diseases in HIV-infected people seen for care in Italy: data from the Icona Foundation cohort.

OBJECTIVES: The aims of this study were to identify temporal trends in the incidence of sexually transmitted diseases (STDs) in a cohort of HIV-infected people and to evaluate factors associated with the risk of a new STD diagnosis. METHODS: All HIV-infected patients in the Icona Foundation Study cohort enrolled after 1998 were included in this study. STD incidence rates (IRs) were calculated and stratified by calendar period. Predictors of STDs were identified using a Poisson regression model with sandwich estimates for standard errors. RESULTS: Data for 9168 participants were analysed [median age 37.3 (range 18-81) years; 74% male; 30% men who have sex with men (MSM)]. Over 46 736 person-years of follow-up (PYFU), 996 episodes of STDs were observed [crude IR 21.3/1000 PYFU; 95% confidence interval (CI) 20.0-22.6/1000 PYFU]. In multivariable Poisson regression analysis, MSM [rate ratio (RR) 3.03; 95% CI 2.52-3.64 versus heterosexuals], calendar period (RR 1.67; 95% CI 1.42-1.97 for 2008-2012 versus 1998-2002), HIV RNA > 50 HIV-1 RNA copies/mL (RR 1.44; 95% CI 1.19-1.74 versus HIV RNA ≤ 50 copies/mL) and a current CD4 count < 100 cells/µL (RR 4.66; 95% CI 3.69-5.89; P < 0.001 versus CD4 count > 500 cells/µL) were associated with an increased risk of STDs. In contrast, older age (RR 0.82 per 10 years older; 95% CI 0.77-0.89) and being currently on ART (RR 0.38; 95% CI 0.33-0.45) compared with being ART-naïve or on a treatment interruption were associated with a lower risk of developing STDs. CONCLUSIONS: An increase in the incidence of STDs was observed in more recent years. Interventions to prevent STDs and potential spread of HIV should target the younger population, MSM and people currently not receiving ART.

Surrogate markers of visceral adipose tissue in treated HIV-infected patients: accuracy of waist circumference determination.

OBJECTIVES: The accuracy of the use of anthropometrics to quantify visceral adipose tissue (VAT) in treated HIV-infected patients is unknown. We evaluated the predictive accuracy of waist circumference (WC) with and without dual-energy X-ray absorptiometry (DXA)-derived trunk : limb fat ratio [fat mass ratio (FMR)] as surrogates for VAT determined using computerized axial tomography (CT-determined VAT). METHODS: We performed a retrospective cohort analysis of treated HIV-infected male patients followed at the Modena HIV Clinic. We developed prediction equations for VAT using linear regression analysis and Spearman correlations. Receiver operating characteristic (ROC) analysis evaluated the accuracy of WC alone or with FMR at discrete VAT thresholds. RESULTS: The 1500 Caucasian male patients had a median age of 45 years, body mass index (BMI) of 24, WC of 87 cm, VAT area of 127 cm(2) and body fat percentage of 14%. The correlation between WC-predicted VAT and CT-VAT was 0.613, and this increased significantly if FMR was added. The WC-associated R(2) of 0.35 increased to 0.51 if the prediction equation included WC plus FMR. The area under the ROC curve (AUC) using WC was 0.795-0.820 at all VAT thresholds. The positive predictive value (PPV) and negative predictive value (NPV) changed reciprocally at CT-VAT thresholds from 75 to 200 cm(2) and ranged from 0.72 to 0.74, respectively, at a representative VAT of 125 cm(2). Adding the FMR to the predictive equations increased the AUC in the range of 0.854-0.889 with the PPV and NPV increasing minimally, ranging from 0.780 to 0.821. Limits of precision were wide, especially at the highest CT-VAT levels, and varied from 24 to 68 cm(2). CONCLUSIONS: WC is a limited surrogate for CT-VAT in this population and DXA-derived parameters do not improve performance indices to a clinically relevant level. These findings should inform the applicability of WC to predict VAT in treated HIV-infected male patients.

The natural history of HIV-associated lipodystrophy in the changing scenario of HIV infection.

OBJECTIVES: In long-term HIV-infected patients, peripheral lipoatrophy (LA) and central lipohypertrophy (LH) appear to be related to the same insults (virus and antiretroviral drugs), but are likely to be associated with different fat depot physiologies. The objective of this study was to describe the natural history of lipodystrophy assessed using dual energy X-ray absorptiometry (DEXA) and computed tomography (CT) in a large HIV out-patients metabolic clinic. METHODS: An observational retrospective study was carried out including HIV-infected patients recruited at the Metabolic Clinic of Modena, Modena, Italy, who were assessed for lipodystrophy and had at least two anthropometric evaluations using DEXA for leg fat per cent mass and abdominal CT for visceral adipose tissue (VAT). Factors associated with leg fat per cent and VAT changes were analysed using multivariable generalized estimating equation (GEE) regression models. RESULTS: A total of 6789 DEXAs and 7566 CT scans were evaluated in the observation period. A total of 1840 patients were included; the mean age was 45.2 ± 7.2 (standard deviation) years, 621 (34%) were women, and the median HIV infection duration was 176 (interquartile range 121-232) years. According to the GEE multivariable regression analysis, leg fat per cent evaluated with DEXA appeared to increase over calendar years (ß = 0.92; P < 0.001); moreover, a progressive increase in VAT was observed in the cohort (ß = 5.69; P < 0.001). No association with antiretroviral drugs was found. CONCLUSIONS: In our study, neither LA nor LH appeared to be associated with antiretroviral drug exposure. We observed a progressive increase in LH in HIV-infected patients over calendar years. This anthropometric change, together with loss of appendicular lean mass, could describe a physiological aging process in HIV-infected patients.

Rate, predictors, and consequences of late antenatal booking in a national cohort study of pregnant women with HIV in Italy.

OBJECTIVE: To evaluate the prevalence and consequences of late antenatal booking (13 or more weeks gestation) in a national observational study of pregnant women with HIV. METHODS: The clinical and demographic characteristics associated with late booking were evaluated in univariate analyses using the Mann-Whitney U test for quantitative data and the chi-square test for categorical data. The associations that were found were re-evaluated in multivariable logistic regression models. Main outcomes were preterm delivery, low birthweight, nonelective cesarean section, birth defects, undetectable (<50 copies/mL) HIV plasma viral load at third trimester, delivery complications, and gender-adjusted and gestational age-adjusted Z scores for birthweight. RESULTS: Rate of late booking among 1,643 pregnancies was 32.9%. This condition was associated with younger age, African provenance, diagnosis of HIV during pregnancy, and less antiretroviral exposure. Undetectable HIV RNA at third trimester and preterm delivery were significantly more prevalent with earlier booking (67.1% vs 46.3%, P < .001, and 23.2% vs 17.6, P = .010, respectively), whereas complications of delivery were more common with late booking (8.2% vs 5.0%, P = .013). Multivariable analyses confirmed an independent role of late booking in predicting detectable HIV RNA at third trimester (adjusted odds ratio [AOR], 1.7; 95% CI, 1.3-2.3; P < .001) and delivery complications (AOR, 1.8; 95% CI, 1.2-2.8; P = .005). CONCLUSIONS: Late antenatal booking was associated with detectable HIV RNA in late pregnancy and with complications of delivery. Measures should be taken to ensure an earlier entry into antenatal care, particularly for African women, and to facilitate access to counselling and antenatal services. These measures can significantly improve pregnancy management and reduce morbidity and complications in pregnant women with HIV.