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Background Study aim was to evaluate the safety and durability of darunavir/cobicistat (DRV/c) in a real life setting. Methods Multicentre prospective cohort study performed in the context of SCOLTA (Surveillance Cohort Long-Term Toxicity Antiretrovirals). Patients were evaluated at baseline, week 24 and 48. Changes were evaluated using the paired t test or signed rank test. The multivariable analysis was performed using a general linear model, after ranking of not normally distributed variables. Results A total of 249 patients were included, 72 (29%) were in DRV/c-based dual therapies (DT). Hypercholesterolemia, HC, (total cholesterol (TC) ≥ 200 mg/dL or low density-C (LDL-C) ≥ 130 or statin use) was present in 121 (48.6%) and hypertriglyceridemia, (triglycerides (TG) ≥ 200 mg/dl or fibrate use) in 41 (16.5%) patients. Blood lipid profile did not change significantly in either the global population or patients with HC. After a median observation of 17 months (IQR 13–20), 59 (25.3%) patients discontinued DRV/c, of which 13 were in DT. The durability DT resulted higher than that of triple therapy (log-rank test p = 0.01). Main reasons for stopping DRV/c were simplification (15 patients), adverse events (13 patients), planned discontinuation for treatment initiation with DAA (4 patients), treatment failure (2 patients); death (2 patients), other causes (10 patients). Twenty-six were lost to follow-up. Conclusions DRV/c was safe and well tolerated. Dual therapies showed a better profile of tolerability and a longer durability compared to triple therapies.

Background: Dyslipidemia represents a significant non-infectious comorbidity among people living with HIV. The aim of this study is to evaluate the impact on lipid profile of switches from an efavirenz (EFV) or protease inhibitor/ritonavir (PI/r)-based regimen to a rilpivirine (RPV) or a once-daily integrase inhibitor-based regimen. Methods: We analyzed data from SCOLTA prospective database. All patients with HIV-RNA < 50 copies/ml in therapy with two NRTI + EFV or PI/r were included if they switched from EFV to dolutegravir (group EFV-DTG), elvitegravir (EFV-EVG), or RPV (EFV-RPV) and from PI/r to DTG (PI/r-DTG), PI/r to EVG (PI/r-EVG), or PI/r to RPV (PI/r-RPV). Total cholesterol (TC), TC/HDL ratio, LDL-cholesterol (LDL) and triglycerides (TG) were compared at baseline, six months and one year. Comparisons among groups were performed by a general linear model. Results: Four hundred and ninety patients were enrolled, 24.9% female, mean age 47.3 years (±10.1). According to ART switch, 11.4% were classified in group EFV-DTG, 3.9% in EFV-EVG, 23.9% in EFV-RPV, 17.6% in PI/r-DTG, 17.8% in PI/r-EVG, and 25.5% in PI/r-RPV. After adjusted analysis, TC significantly decreased in all groups but EFV-EVG, TC/HDL in all but EFV-DTG and EFV-EVG, while the reduction of TG was significant only in switches to RPV (EFV-RPV and PI/r-RPV). The one year decrease of TC, TC/HDL, LDL and TG was higher in patients with higher baseline levels of the same variable (p < .0001 for all). Conclusions: In SCOLTA, all switches from PI/r regimens gave advantages on lipid profile, while stopping EFV had consistently favorable lipid effects only if replaced by RPV.

Weight gain and body mass index (BMI) increase are central issues in patients living with HIV who need to minimize the risk of metabolic disease. Information collected through the SCOLTA cohort revealed significant 1-year BMI increase in patients treated with dolutegravir (P = .004), raltegravir (P = .0004), elvitegravir (P = .004), darunavir (P = .0006), and rilpivirine (P = .029). BMI gain correlated with low baseline BMI (P = .002) and older age (P = .0007) in Centers for Disease Control and Prevention stages A/B, with lower BMI (P = .005) and CD4+ T-cell count (P = .007) at enrollment in stage C.

Muscle alterations ranging from asymptomatic creatine phosphokinase (CPK) increases to rhabdomyolysis and central nervous system (CNS) symptoms have been reported in patients receiving raltegravir. Muscle symptoms and CPK increases were investigated in a cohort of HIV-infected patients receiving raltegravir-based antiretroviral therapy, and possible associated predictors were evaluated. The SCOLTA Project is a prospective, observational, multicentre study created to assess the incidence of adverse events in patients receiving new antiretroviral drugs in clinical practice. In total, 496 HIV-infected patients were enrolled [333 (67.1%) male]. CDC stage was C in 196 patients (39.5%). Mean age at enrolment was 45.9 ± 9.3 years. Median follow-up was 21 months. Twenty-six patients (5.2%) reported muscle symptoms (16 muscle pain and 17 weakness; 7 had both). Of 342 patients with normal baseline CPK values, 72 (21.1%) had a CPK increase. Seven patients (1.4%) discontinued raltegravir because of muscular events (three for muscle pain/weakness and four CPK increases). No cases of rhabdomyolysis were observed. Patients with muscle symptoms were more frequently receiving in their regimen than those not receiving atazanavir (P = 0.04) and were more likely to also report CNS symptoms (P < 0.0001). Significant predictors of muscle symptoms were CNS symptoms and use of atazanavir. Female sex was associated with a reduced risk of CPK increase. In conclusion, muscle symptoms and CPK elevations occurred frequently and caused most discontinuations due to adverse events. Their monitoring in patients receiving raltegravir should be considered, especially when co-administered with atazanavir or when CNS symptoms are also present.

Background Among people living with HIV (PLWH), the prevalence of non-HIV related co-morbidities is increasing. Aim of the present study is to describe co-morbidity and multi-morbidity, their clustering mode and the potential disease-disease interactions in a cohort of Italian HIV patients. Methods Cross-sectional analysis conducted by the Coordinamento Italiano per lo Studio di Allergia e Infezioni da HIV (CISAI) on adult subjects attending HIV-outpatient facilities. Non-HIV co-morbidities included: cardiovascular disease, diabetes mellitus, hypertension, oncologic diseases, osteoporosis, probable case of chronic obstructive pulmonary disease (COPD), hepatitis C virus (HCV) infection, psychiatric illness, kidney disease. Multi-morbidity was defined as the presence of two or more co-morbidities. Results One thousand and eighty-seven patients were enrolled in the study (mean age 47.9 ± 10.8). One hundred-ninety patients (17.5%) had no co-morbidity, whereas 285 (26.2%) had one condition and 612 (56.3%) were multi-morbid. The most recurrent associations were: 1) dyslipidemia + hypertension (237, 21.8%); 2) dyslipidemia + COPD (188, 17.3%); 3) COPD + HCV-Ab+ (141, 12.9%). Multi-morbidity was associated with older age, higher body mass index, current and former smoking, CDC stage C and longer ART duration. Conclusions More than 50% of PLHW were multi-morbid and about 30% had three or more concurrent comorbidities. The identification of common patterns of comorbidities address the combined risks of multiple drug and disease-disease interactions.

Persons Living with HIV (PLWH) are at higher risk of cardiovascular disease (CVD) than the general population. Carotid ultrasound is a non-invasive diagnostic tool, aimed at the assessment of vascular anatomy and function. Our present aim is to generate a National Register of color-Doppler ultrasonography (Archi-Prevaleat) to better evaluate the characteristics of vascular lesions in PLWH on a large number of data.

Tenofovir disoproxil fumerate (TDF) is an effective nucleoside reverse transcriptase inhibitor for HIV infection but it is potentially nephrotoxic. A selective mithochondrial toxicity has been hypothesized. To assess early markers of renal toxicity, we evaluated a cohort of antiretroviral (ARV)-experienced HIV patients who had been switched from a thymidinic backbone to either a TDF/emtricitabine regimen (TDF; 73 patients) or an abacavir/lamivudine (ABV) regimen (28 patients). Markers of mitochondrial toxicity (cytochrome c, Cyc) or cytosolic (α-glutathione S transferase, α-GST) together with common indicators of renal damage were assessed at baseline (T0) and after 1 (T1), 3 (T2), 6 (T3), and 12 (T4) months of patient exposure to therapy. Clinical features of both groups were comparable at T0. There was no significant variation in estimated glomerular filtration rate (eGRF), median urine protein excretion, or microalbuminuria and serum phosphate levels in both groups during the study period. There was a significant increase in urinary excretion of phosphate in patients on TDF compared to those on ABV at T3 and T4. Fractional excretion of uric acid was also altered in the two treatment groups; there was no change in the ABV (constantly less than 0.10), but a progressive increase in TDF patients. Serum potassium levels were significantly lower in ABV than in TDF treated patients. Urine concentrations of α-GST showed a nonsignificant variation in both groups, while Cyc excretion was significantly higher at T1 and T3 in TDF-treated compared to ABV-treated patients. In conclusion, TDF may be associated with subclinical mitochondrial damage, inducing at a later stage increased urinary excretion of phosphate and uric acid, as markers of incipient tubular injury.

Objectives: The aim of this study was to evaluate the cardiovascular risk among patients treated for more than 5 years with regimens based on nevirapine or efavirenz. Patients and methods: A total of 276 patients were retrospectively evaluated, 156 of whom were treated with nevirapine and 120 with efavirenz, by examining traditional risk factors and detecting the presence of subclinical carotid lesions with colour-Doppler ultrasonography. Results: When comparing the data at baseline and follow-up in the nevirapine group, total cholesterol, low-density lipoprotein cholesterol (LDLc) and triglycerides showed a significant decrease, while high-density lipoprotein cholesterol increased. Ultrasound data, obtained in a subgroup of 67 patients, did not show significant changes for those treated with nevirapine. In the efavirenz group, total cholesterol, LDLc, triglycerides, glycaemia, body mass index and the number of patients with a pathological ultrasound significantly increased. When comparing the two groups at baseline and follow-up, nevirapine patients had significantly higher values of total cholesterol, LDLc and triglycerides at baseline, while total cholesterol and LDLc differed non-significantly at follow-up; triglycerides became significantly lower in the nevirapine arm with respect to the efavirenz group. Glycaemia was comparable between the two groups at baseline, while it was significantly lower in the nevirapine group at follow-up. The number of pathological ultrasound findings was significantly higher in the efavirenz group at follow-up. Conclusions: Patients treated with nevirapine demonstrated a better lipid and glucose profile and a lower tendency to develop subclinical atherosclerotic lesions.

The quality of life of the HIV-infected population in developed countries has substantially improved over the years. Accordingly, the clinical limitations in the surgical treatment of the HIV-infected patients are becoming fewer, and the number of HIV-infected patients undergoing surgical interventions of all types is increasing. However, available data on the incidence and risk factors for post-surgical complications, such as surgical site infections (SSI), in HIV-infected patients are still limited and often controversial. The aim of this study was to determine the incidence and the associated risk factors for SSI in HIV-infected patients.A 1-year observational prospective multicenter surveillance study was conducted in 11 Italian Infectious Diseases Clinical Centers from which 305 consecutive HIV-infected patients undergoing different surgical procedures were enrolled. Postdischarge surveillance was conducted within 30 days after surgery. A number of variables were included in a multivariate analysis aimed at assessing potential risk factors for SSI, including body mass index, diabetes, Hepatitis C (HCV) and hepatitis B virus infection, lipodistrophy, HIV viral load, CD4 cell count and white blood cell count, preoperative hospital stay, National Nosocomial Infection Surveillance (NNIS) risk score, and any antimicrobial prophylaxis.SSI occurred in 29 of 305 (9.5%) patients, of which 17 (58.6%) SSI occurred during hospital stay, and 12 (41.4%) occurred during the postdischarge period. The SSI of the 29 patients were classified as superficial (21, 72.4%), deep (four, 13.8%), organ/space (one, 3.4%), and sepsis (three, 10.3%). Nearly 50% of the superficial and 50% of the deep SSI occurred during the postdischarge period. Organ/space infection and sepsis accounted for 13.7% of all SSI and were observed during the in-hospital stay. The multivariate analysis revealed that HCV co-infection was significantly associated to SSI occurrence. Total hospital stay was longer among patients with SSI than among those without SSI (p = 0.041).Although 92.5% of our HIV-infected patients presented a NNIS scoreor = 1, the SSI rate was twofold higher than that reported in Italian and European studies for the general population, with more severe clinical presentations. This is the first report of an association between HCV-HIV co-infection and SSI occurrence. Additionally, the viro-immunological status of our patients was not related to SSI occurrence, which suggests the need for further research for other potential risk factors that may be implicated in the occurrence of SSI.

Chronic iatrogenic scleroderma is a possible obstacle to the absorption of subcutaneously administered drugs. This study correlated the clinical and histopathological pattern of injection-site reactions (ISRs) to the pharmacokinetics of enfuvirtide in patients with HIV. Fourteen patients treated with an enfuvirtide-based antiretroviral regimen for a median of 45 weeks were enrolled and their ISRs were evaluated. Twelve patients with evidence of ISRs underwent cutaneous biopsies using a 4-mm punch. The maximum plasma enfuvirtide concentration (Cmax) and the area under the enfuvirtide concentration-time curve (AUC) were assessed using blood sampling. Four different macroscopic patterns of ISR were identified: A — no evidence of cutaneous lesions; B — transient infiltrative lesions that auto-resolved within 24 hours; C — transient nodular lesions that auto-resolved within 7–15 days; and D–stable lesions after more than 30 days. Histological examination showed three morphological patterns: (1) acute urticaria/vasculitis-like pattern, (2) subacute pattern and (3) chronic scleroderma-like pattern. No differences among patients with the various patterns of ISRs were observed, except for a higher Cmax and AUC in patients with pattern 1. These results confirm that although iatrogenic scleroderma is not related to impaired enfuvirtide absorption, higher Cmax and AUC values are observed in patients with urticaria/vasculitis-like patterns.