Predictors of incomplete viral response and virologic failure in patients with acute and early HIV infection. Results of Italian Network of ACuTe HIV InfectiON (INACTION) cohort.

OBJECTIVES: The aim of this study was to evaluate the factors that can influence an incomplete viral response (IVR) after acute and early HIV infection (AEHI). METHODS: This was a retrospective, observational study including patients with AEHI (Fiebig stages I-V) diagnosed between January 2008 and December 2014 at 20 Italian centres. IVR was defined by: (1) viral blip (51-1000 HIV-1 RNA copies/mL after achievement of < 50 HIV-1 RNA copies/mL); (2) virologic failure [> 1000 copies/mL after achievement of < 200 copies/mL, or ≥ 200 copies/mL after 24 weeks on an antiretroviral therapy (ART)]; (3) suboptimal viral response (> 50 copies/mL after 48 weeks on ART or two consecutive HIV-1 RNA levels with ascending trend during ART). Cox regression analysis was used to calculate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) for IVR. RESULTS: In all, 263 patients were studied, 227 (86%) males, with a median [interquartile range (IQR)] age of 38 (30-46) years. During a median follow-up of 13.0 (5.7-31.1) months, 38 (14.4%) had IVR. The presence of central nervous system (CNS) symptoms was linked to a higher risk of IVR (HR = 4.70, 95% CI: 1.56-14.17), while a higher CD4/CD8 cell count ratio (HR = 0.13, 95% CI: 0.03-0.51 for each point increase) and first-line ART with three-drug regimens recommended by current guidelines (HR = 0.40, 95% CI: 0.18-0.91 compared with other regimens including four or five drugs, older drugs or non-standard backbones) were protective against IVR. CONCLUSIONS: Patients with lower CD4/CD8 ratio and CNS symptoms could be at a higher risk of IVR after AEHI. The use of recommended ART may be relevant for improving short-term viral efficacy in this group of patients.

Non-AIDS defining cancers: a comprehensive update on diagnosis and management.

The increasing incidence of chronic pathologies and especially non-AIDS defining cancers, such as lung cancer, hepatocellular carcinoma, breast cancer, colorectal cancer, prostate cancer, and Hodgkin's lymphoma after the introduction of combined antiretroviral therapy requires the infectious diseases specialist to know how and when to suspect and diagnose cancer in people living with HIV. The aim of this review is to provide updated studies and information about non-AIDS defining cancers and their management in PLWH sheading a light on possible futures scenarios.

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.

Auditing HIV Testing Rates across Europe: Results from the HIDES 2 Study.

European guidelines recommend the routine offer of an HIV test in patients with a number of AIDS-defining and non-AIDS conditions believed to share an association with HIV; so called indicator conditions (IC). Adherence with this guidance across Europe is not known. We audited HIV testing behaviour in patients accessing care for a number of ICs. Participating centres reviewed the case notes of either 100 patients or of all consecutive patients in one year, presenting for each of the following ICs: tuberculosis, non-Hodgkins lymphoma, anal and cervical cancer, hepatitis B and C and oesophageal candidiasis. Observed HIV-positive rates were applied by region and IC to estimate the number of HIV diagnoses potentially missed. Outcomes examined were: HIV test rate (% of total patients with IC), HIV test accepted (% of tests performed/% of tests offered) and new HIV diagnosis rate (%). There were 49 audits from 23 centres, representing 7037 patients. The median test rate across audits was 72% (IQR 32-97), lowest in Northern Europe (median 44%, IQR 22-68%) and highest in Eastern Europe (median 99%, IQR 86-100). Uptake of testing was close to 100% in all regions. The median HIV+ rate was 0.9% (IQR 0.0-4.9), with 29 audits (60.4%) having an HIV+ rate >0.1%. After adjustment, there were no differences between regions of Europe in the proportion with >0.1% testing positive (global p = 0.14). A total of 113 patients tested HIV+. Applying the observed rates of testing HIV+ within individual ICs and regions to all persons presenting with an IC suggested that 105 diagnoses were potentially missed. Testing rates in well-established HIV ICs remained low across Europe, despite high prevalence rates, reflecting missed opportunities for earlier HIV diagnosis and care. Significant numbers may have had an opportunity for HIV diagnosis if all persons included in IC audits had been tested.

Ageing with HIV: a multidisciplinary review.

INTRODUCTION: After the introduction of highly active antiretroviral treatment, the course of HIV infection turned into a chronic disease and most of HIV-positive patients will soon be over 50 years old. MATERIAL AND METHODS: This paper reviews the multiple aspects that physicians have to face while taking care of HIV-positive ageing patients including the definitions of frailty and the prevalence and risk factors of concomitant diseases. From a therapeutic point of view pharmacokinetic changes and antiretroviral-specific toxicities associated with ageing are discussed; finally therapeutic approaches to frailty are reviewed both in HIV-positive and negative patients. CONCLUSION AND DISCUSSION: We conclude by suggesting that the combined use of drugs with the least toxicity potential and the promotion of healthy behaviours (including appropriate nutrition and exercise) might be the best practice for ageing HIV-positive subjects.

Raltegravir-based therapy in a cohort of HIV/HCV co-infected individuals.

The relationship between hepatic tolerance and hepatitis C virus (HCV) co-infection has not been extensively studied in clinical practice. We assessed the efficacy and safety of raltegravir-based therapy in an Italian cohort of HIV/HCV co-infected patients. One hundred and forty patients with HIV/HCV co-infection initiating raltegravir from SCOLTA project (Surveillance Cohort Long-Term Toxicity Antiretrovirals) were examined. Of them, 43 were women, with mean age of 45.4±6.4years; 65 (46%) had undetectable HIV-RNA<50copies/mL and 75 (54%) HIV-RNA≥50copies/mL. According to CDC classification, 49 (35%) were in stage C. Based on Fib4 score at the time of starting raltegravir, patients were classified in class I in 41 cases, class II in 68 and in class III in 31 cases. Globally, the Fib4 score slightly decreased during 24months follow-up, from 2.2 to a value of 1.8. Hepatic adverse events of any grade were observed in 67 patients, of which only 2 cases (3%) had severe liver toxicity (grade 3-4). Only one patient had to discontinue the therapy because of adverse events. According to univariate analysis, being in CDC stage C represented a risk for the development of liver toxicity, with a hazard ratio (HR) of 2.27 (95% CI 1.06-4.84, P=0.033). None of the other variables considered (age, sex, years since detection of HIV and HCV-RNA detectable, years of previous HIV therapy, concomitant therapy with PI or NRTI, CD4+ cell count, Fib4, and transaminases level at baseline) resulted statistically correlated to the outcome. In conclusion, raltegravir-based regimens can be safely used in HCV infected patients; in this study, the hepatic toxicity has been found to be more frequent in patients with an advanced HIV disease (CDC stage C), independently of HIV-RNA suppression at raltegravir initiation.

Kidney disease in HIV-infected patients.

The introduction of highly active antiretroviral therapy (HAART) has reduced mortality and improved life expectancy of HIV-positive patients. However, increased survival is associated with increased prevalence of comorbidities, such as cardiovascular disease, hepatic and renal disease. Kidney disease, including HIV-associated nephropathy, acute renal failure and chronic kidney disease, represents one of the main causes of morbidity and mortality, especially if associated to other risk factors, i.e. hypertension, diabetes, older age, black race and hepatitis C coinfection. Careful evaluation of renal function may help identifying kidney disease in its early stages. In addition, proper management of hypertension and diabetes is recommended. Even if HAART has changed the natural course of HIV-associated nephropathy, reducing the risk of End-stage Renal Disease (ERDS), some antiretroviral regimens have been related with the development of acute or chronic kidney disease. Further studies are needed to optimize the management of renal disease among HIV-infected patients.

High prevalence of undiagnosed anxiety symptoms among HIV-positive individuals on cART: a cross-sectional study.

INTRODUCTION: Anxiety disorders are frequent in HIV-infected individuals, can pre-exist or occur during HIV infection. We evaluated with a self-reported questionnaire whether anxiety is related to HIV clinical status and therapeutic success in a cohort of HIV-positive subjects in Sicily. PATIENTS AND METHODS: We enrolled 251 patients on combination antiretroviral therapy (cART) for at least six months; Self Rating Anxiety State SAS 054 was used to diagnose anxiety and a Z score ≥ 45 points was considered diagnostic. RESULTS: 47% of patients were diagnosed with anxiety. Patients showing symptoms related to anxiety had experienced a high number of therapeutic switches (fourth line or more). CONCLUSIONS: These data confirm a high prevalence of anxiety symptoms among subjects with HIV infection in Eastern Sicily. Physicians should be aware of the extent of the problem and should be able to adequately manage anxiety in the setting of HIV infection.

LPS and HIV gp120 modulate monocyte/macrophage CYP27B1 and CYP24A1 expression leading to vitamin D consumption and hypovitaminosis D in HIV-infected individuals.

AIM: Vitamin D deficiency is very common among HIV-infected subjects. We cross-sectionally evaluated the prevalence and risk factors for hypovitaminosis D in 91 HIV-infected Italian patients. PATIENTS AND METHODS: We studied in a cohort of 91 HIV-infected Italian patients the metabolism of Vitamin D by evaluating the in vitro expression of CYP27B1, CYP24A1 and vitamin D receptor (VDR) by monocytes and macrophages stimulated with the viral envelope protein gp120 or lipopolysaccharide (LPS). RESULTS: The prevalence of vitamin D deficiency (25OHD < 10 ng/ml) and vitamin D insufficiency (25OHD 10-30 ng/ml) was 31% and 57%, respectively. In univariate analysis, female sex (p = 0.01), increasing age (p = 0.05), higher highly sensitive-C reactive protein (p = 0.025), higher parathyroid hormone (PTH) (p = 0.043) and lower BMI (p = 0.04) were associated with vitamin D deficiency. In multivariate analysis, the association was still significant only for PTH (p = 0.03) and female sex (p = 0.03). Monocyte stimulation with LPS (100 ng/ml) or gp120 (1 µg/ml) significantly upregulated CYP27B1 mRNA expression. Moreover, gp120 significantly increased VDR mRNA levels. On the contrary, neither LPS nor gp120 modified CYP24A1 levels. Macrophage stimulation with LPS (100 ng/ml) significantly upregulated CYP27B1 and CYP24A1 mRNA expression. When monocytes were cultured in the presence of 25OHD (40 ng/ml) and stimulated with LPS we detected significantly lower levels of 25OHD in the supernatant. CONCLUSIONS: Vitamin D deficiency was very common in our cohort of HIV-infected patients. Chronic inflammation, including residual viral replication, may contribute to hypovitaminosis D, by modulating vitamin D metabolism and catabolism. Systematic screening may help identifying subjects requiring supplementation.

Late presentation of HIV infection: predictors of delayed diagnosis and survival in Eastern Sicily.

OBJECTIVES: Across Europe, more than one third of patients are diagnosed with HIV infection late. Late presentation for care has been associated with higher risk of clinical progression and mortality. In the present study, we evaluated the prevalence, epidemiological characteristics and survival probability of patients with late and very late presentation, newly diagnosed with HIV infection in Catania, Italy, from 1985 to 2010. PATIENTS AND METHODS: According to the European Consensus definition, Late Presenters (LP) were defined as subjects presenting for care with a CD4+ T-cell count below 350 cells/µl or with an AIDS-defining event, regardless of CD4+ T-cell count; patients with advanced HIV disease (Very Late Presenters) (VLP) were those presenting with a CD4+ T-cell count below 200 cells/µl or with an AIDS-defining event, regardless of CD4+ T-cell count. RESULTS: 620 patients were included in the study. 345 (55.6%) subjects were LP, 35% of them were asymptomatic; 246 (39.7%) were VLP. In univariate analysis, late presentation was related to age (p < 0.001), to heterosexual exposure to HIV infection (70% of heterosexual subjects were LP) (p < 0.005) and to being diagnosed during the calendar period from 1991 to 2000 (p < 0.001). Very late presentation was related to age (p < 0.001), male sex (p < 0.01), heterosexual risk (p < 0.001) and to being diagnosed during the calendar period from 1991 to 2000 (p < 0.001). In multivariate analysis, age (p < 0.0001), being older than 50 years old (p = 0.02), years of diagnosis 1991-1995 (p < 0.005) and 1996-2000 (p < 0.05) in the subgroup of late presenters and age (p < 0.0001), being older than 50 years old (p < 0.005), male sex (p < 0.0001), years of diagnosis 1991-1995 (p < 0.05) and 1996-2000 (p < 0.005) in the subgroup of very late presenters maintained statistical significance. The survival probability within LP and VLP group was statistically lower than no LP/VLP (log rank test p < 0.0005 and p < 0.0001, respectively). For both LP (p < 0.002) and VLP (p < 0.0001), survival probability was significantly lower in the pre-HAART era, in comparison with the period of mono/dual therapy and the HAART era. CONCLUSIONS: More than fifty percent of patients in our setting were diagnosed late with HIV infection and, consequently, treated late. Late and very late presentation were associated with lower survival probability. The implementation of strategies focused on targeted prevention efforts and HIV testing programs appears fundamental to diagnose and treat HIV infection as early as possible.

Cryptococcal meningitis in an HIV-1-infected person: relapses or IRIS? Case report and review of the literature.

After starting highly active antiretroviral therapy (HAART), HIV-infected patients may experience what is termed immune reconstitution inflammatory syndrome (IRIS). IRIS is characterized by a paradoxical inflammatory response to either previously or recently treated infections or unmasked subclinical infections, when the patient regains the ability to mount a suitable immune response against specific antigens or pathogens. Cryptococcal IRIS (C-IRIS) is thought to be mediated by recovery of Cryptococcus-specific immune responses, resulting in exaggerated host inflammatory responses. In HIV-positive subjects, two distinct modes of presentation of C-IRIS are recognized, "paradoxical" and "unmasking" C-IRIS. "Paradoxical" C-IRIS presents as worsening or recurrence of treated cryptococcal disease following HAART initiation, despite microbiological treatment success. In the "unmasking" form, patients with no prior diagnosis may develop acute symptoms of cryptococcosis, such as meningitis or necrotizing lymphadenopathy, after starting HAART. Here, we present the case of an HIV-positive man, who developed cryptococcal meningitis two months after having started HAART and experienced several meningeal relapses and a "paradoxical" C-IRIS during the following year.

Trimethoprim-sulfamethoxazole-associated severe hypoglycaemia: a sulfonylurea-like effect.

AIM: To report hypoglycaemia, a life-threatening adverse event, associated with trimethoprim-sulfamethoxazole. A sulfonylurea-like effect, leading to insulin raise, was investigated. METHODS: Two cases of trimethoprim-sulfamethoxazole-associated hypoglycaemia in 2 patients with a diagnosis of new HIV-1-infection presenting with Pneumocystis jiroveci pneumonia are reported. The patients had no predisposing factors, such as renal or liver impairment, interfering with trimethoprim-sulfamethoxazole elimination, thus leading to hypoglycaemia. Insulin plasma levels were measured in both patients. RESULTS: Severe hypoglycaemia was associated with increased serum levels of insulin up to 84 microU/ml (normal values < 10 microU/ml). Continuous dextrose infusion was necessary, further suggesting the sulfonylurea-like effect of sulfamethoxazole. Interestingly, plasma levels of insulin progressively raised after trimethoprim-sulfamethoxazole administration. CONCLUSIONS: Only 18 cases of trimethoprim-sulfamethoxazole associated hypoglycaemia are reported in the literature. Hypoglycaemia is a life-threatening condition, likely underreported, to consider when trimethoprim-sulfamethoxazole administration is required, even in the absence of predisposing factors or other hypoglycaemic agents. Physician should bear in mind the potential trimethoprim-sulfamethoxazole-associated adverse event especially when prolonged treatments and elevated dosage are used.

Influence of hepatitis G virus coinfection on the clinical course of chronic hepatitis C.

Hepatitis G virus (HGV) is a parenterally transmitted virus, frequently associated with hepatitis C virus infection. Hepatitis G virus RNA was detected by reverse transcription-polymerase chain reaction in the serum of 40 patients with chronic hepatitis C. Nine (22.5%) patients had evidence of hepatitis G virus viraemia. No significant epidemiological or virological differences could be demonstrated between subjects infected with both hepatitis G virus and hepatitis C virus and subjects infected with hepatitis C virus alone. Aminotransferase values were comparable between the two groups, whereas higher levels of cholestatic enzymes (P< 0.001) were reported in the hepatitis G virus/hepatitis C virus-positive patients. A liver biopsy was performed on all 40 patients no later than 6 months before recruitment. The mean histological activity index did not differ between hepatitis G virus-positive and hepatitis G virus-negative patients, whereas specific histological features such as macrovesicular steatosis, portal granulomas, and bile duct damage were more commonly observed among the coinfected patients. The results indicate that coinfection with hepatitis G virus probably does not have a significant effect on hepatitis C virus-induced hepatic damage.

Serum cytokines as predictors of clinical outcome in AIDS-related intestinal cryptosporidiosis.

BACKGROUND: Clinical variability in the natural course of cryptosporidiosis in patients affected by acquired immunodeficiency syndrome has been correlated to the degree of T-cell immunosuppression; however, cryptosporidiosis can occur as a self-limiting disease even in patients with very low T-lymphocyte count. AIMS: We tested the serum values of a panel of cytokines in AIDS patients with cryptosporidial enteritis in order to evaluate their role in predicting the clinical outcome of the disease. PATIENTS AND METHODS: Thirty one HIV-positive patients with cryptosporidiosis and a CD4+ count of less than 100/mm3 were studied. Interleukin-2, Interleukin-4, Interleukin-10, Interferon-gamma, Interleukin-12, Tumor Necrosis Factor alpha values were measured in serum at diagnosis. RESULTS: Interleukin-4 and Interleukin-10 concentration was significantly lower in patients with mild disease whereas serum Interleukin-2 and -12 was higher in this same group. The serum level of Interferon-gamma did not differ in relation to the severity of the disease. Patients with self-limiting diarrhoea showed significantly lower levels of Tumor Necrosis Factor-alpha than subjects who did not show any clinical improvement. CONCLUSIONS: In our study, it has been shown that cytokine levels in serum may represent early predictive markers both for the severity of symptoms and the clinical outcome of cryptosporidial enteritis in AIDS patients with a low CD4+ count.

[Multiple osteo-articular involvement due to methicillin-resistant Staphylococcus aureus septicaemia: clinical and therapeutic evaluation] / Localizzazione osteoarticolare multipla in corso di sepsi da Staphylococcus aureus meticillino-resistente: considerazioni clinico-terapeutiche.

Here we report a rare case of septic spondilodiskitis by methicillin-resistant Staphylococcus aureus, complicated by the atypical involvement of two articular sites such as manubrio-clavicular joints and right wrist. The source of the septic process was identified in hand's eczematous lesions and paronychia. A first therapeutical attempt performed by combining teicoplanin with netilmicin or rifampicin was useless. A new course with vancomycin instead of teicoplanin favoured the prompt remission of symptoms. Following 10 weeks of continuous treatment, we observed the complete disappearance of all radiological signs of vertebral damage. Though rarely, polyarthritis may complicate a Staphylococcus aureus bacteraemia. An adequate chemio-antibiotic course may lead to definitive recovery and avoid surgery.