Lipid profile improvement in virologically suppressed hiv-1-infected patients switched to dolutegravir/ abacavir/lamivudine: Data from the SCOLTA project

open13noIntroduction: Metabolic disorders are common amongst HIV-infected patients. Data from real-life setting on the impact of DTG/ABC/3TC in virologically suppressed HIV-infected patients are scarce. Methods: We investigated the modification of metabolic profile including fasting glucose, lipid profile and markers of insulin resistance (IR) in experienced patients switching from a boosted protease inhibitors (bPI) or a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen to DTG/ABC/3TC in a prospective, observational, multicenter study. Results: We enrolled 131 HIV-infected patients, of whom 91 (69.5%) males, mean age was 50.5±10.6 years. CDC stage was A in 66 (50.4%) patients, of whom 91 (69.5%) had acquired HIV through sexual contacts. The previous regimen was bPI-based in 79 patients (60.3%) and NNRTI-based in 52 (39.7%). Patients switching from NNRTI showed a significant reduction at week 24 in total cholesterol (TC) and low-density lipoprotein cholesterol (LDL). Triglycerides/high-density lipoprotein cholesterol (TG/HDL) ratio, HDL, median TG and TG/HDL ratio did not show significant modification during follow-up times. Among patients switching from a bPI, we observed a significant reduction in TC and LDL at both follow-up times and a slight increase in HDL. Triglycerides/HDL ratio, median TG and TG/HDL ratio showed a decrease over time that became significant at weeks 24 and 48. Blood glucose levels did not significantly vary during the observation period in patients switching from both bPI and NNRTI-based regimens. Conclusion: Our data suggest an improvement in lipid profile and TG/HDL ratio in pretreated HIV-1-infected patients who switched to DTG/ABC/3TC over 48 weeks, especially in those previously receiving a bPI-based regimen.openBagella P.; Squillace N.; Ricci E.; Gulminetti R.; De Socio G.V.; Taramasso L.; Pellicano G.; Menzaghi B.; Celesia B.M.; Dentone C.; Orofino G.; Bonfanti P.; Madeddu G.Bagella, P.; Squillace, N.; Ricci, Elena; Gulminetti, R.; De Socio, G. V.; Taramasso, L.; Pellicano, G.; Menzaghi, B.; Celesia, B. M.; Dentone, C.; Orofino, G.; Bonfanti, P.; Madeddu, G

Statins and aspirin in the prevention of cardiovascular disease among HIV-positive patients between controversies and unmet needs: Review of the literature and suggestions for a friendly use

Background: As in non-infected subjects, statins and aspirin have a pivotal preventive role in reducing the cardiovascular related morbidity and mortality in HIV infected patients. The persistence of immune activation in these subjects, could contribute to accelerate atherosclerosis, therefore, these treatments that reduce inflammation could provide additional cardiovascular protection. However the current guidelines for the use of these drugs in general population are dissimilar, with important differences between American and European ones. Aim of the present position paper is to provide recommendations aimed to overcome the actual differences and limitations among the current ones and to adapt them to the needs of HIV infected patients. Results: We propose to adopt the new ACC/AHA guidelines, simple to use and cost effective, to use the ASCVD score that seems to estimate more accurately the cardiovascular risk among these patients. We suggest to start statin therapy in all patients with a calculated 10-year risk of a cardiovascular event of 10% or greater. Rosuvastatin and atorvastatin should be preferred. LDL-C target may be adopted. Aspirin should be always associated with a statin, in secondary prevention, while in primary prevention it should be reserved only to patients with 65 20% 10-year risk particularly adherent to treatments, and with low risk of bleeding. We suggest to start with a dose of 100 mg/day. Finally, management of antiplatelet agents or novel oral anticoagulants may include selecting antiretrovirals with a lower potential for drug interactions or choosing agents least likely to interact with antiretrovirals. Conclusions: As demonstrated in surveys, HIV physicians are generally highly committed regarding CVD and autonomous in prescribing statins and ASA. Consequently, in the light of the previously discussed discrepancies among the different guidelines and of the incomplete indications regarding HIV-positive persons, the present suggestions could overcome the actual differences and limitations among the current ones

Hypertensive versus HIV-infected patients : Who has the greatest target organ damage? Comparison of carotid plaque prevalence, intima media thickness and renal resistive index in the two groups of patients

Objectives: to compare the prevalence of target-organ damage (TOD), defined as carotid plaque, or intima media thickness, cIMT, >0.9 mm, and that of increased renal resistive index (RRI), among HIV-1-infected patients and uninfected hypertensive patients (HT-non HIV). Methods: HIV-infected patients aged 65 18 years and virologically suppressed were matched with pair-age, sex and BMI HT-non HIV. Patients on antihypertensive treatment were excluded. All patients\u2019 cIMT and RRI were evaluated with ultrasonography. Data were analysed throughout X2test, analysis of variance and logistic regression. Results: Fifty-nine HIV-infected patients were enrolled (71% men) and matched with 59 HT-non HIV. No differences were found in cIMT values (p=0.827) and in the prevalence of TOD between HIV-infected patients and HT-non HIV (36% vs 38%, p= 0.79). Among HIV-infected patients, those hypertensive had significantly higher prevalence of TOD (46% vs 21%, P < 0.05) and higher cIMT (0.747 \ub1 0.104 vs 0.654 \ub1 0.100 mm, p = 0.0185). Patients with TOD were older (p= 0.004) and more frequently current smokers (p= 0.022). At the logistic regression analysis, TOD was significantly related to age (p=0.04, 95%CI 1.0-1.1) and smoke, current (p=0.178, 95%CI1.2-12.8) or previous (p=0.04, 95%CI 1.0-7.2). Mean RRI were identical for both HIV-1 infected and uninfected patients (0.60, SD \ub1 0.05 and 0.60, SD \ub1 0.04, respectively, p=0.996). Conclusions: In our study TOD was associated to hypertension, older age and smoke, but not to HIV serostatus itself, confirming the major importance of traditional risk factors and the need of risk assessment and cardiovascular prevention measures in HIV-infected patients

Weight Gain : A Possible Side Effect of All Antiretrovirals

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

Salvage therapy or simplification of salvage regimens with dolutegravir plus ritonavir-boosted darunavir dual therapy in highly cART-experienced subjects : an Italian cohort

Background: Dolutegravir plus darunavir provide a high genetic barrier to HIV-1 resistance and are suitable for simple salvage regimens. Methods: All HIV-1-infected subjects treated with dolutegravir plus boosted darunavir dual therapy between March 2011 and September 2015 were included in an observational cohort. Data were collected at baseline and at weeks 4, 12, 24 and 48. Results: We enrolled 113 subjects. After week 24, one was lost at follow-up, one dropped out for grade 2 elevation of liver enzymes, one died from illicit drug abuse and one from cancer-related sepsis. The mean age was 51, 26.5% were female and 9.7% were non-Caucasian. Twenty had never experienced failure. A total of 99 had reverse-transcriptase (RT) mutations, 87 had protease inhibitor mutations and 12 had integrase strand transfer inhibitor (INSTI) mutations. Viraemic patients declined from baseline to week 24 from 43.4% to 6.2%, the remainder being due to high baseline viraemia or adherence issues. The proportion of subjects with viraemia 1\u201349 copies/ml remained at 20.4% while those in whom no virus was detected (NVD) increased from 36.3% to 73.5% by week 24. All the 47 subjects who had a 48-week follow-up had <50 copies/ml and 42 (89.4%) had NVD. 18 subjects had reduced sensitivity to darunavir (Stanford median score 15, range 15\u201340), but none rebounded, 6 having a 24-week and 7 a 48-week follow-up. The median variation in serum creatinine was -0.01 (range +0.2 to -0.21) mg/dl. Conclusions: This dual regimen provides a simple salvage regimen and proved safe and effective in this cohort

Use of statins and aspirin to prevent cardiovascular disease among HIV-positive patients : a survey among Italian HIV physicians

We conducted a survey among Italian HIV specialists to study the utilization of statins and aspirin, administering a questionnaire aimed at investigating their use, the use of guidelines and scores, and the management of interactions. The answers were uniform in the different geographic areas. The majority directly prescribe statins and 43% of them prescribe aspirin. The majority follows guidelines and utilize scores to calculate the CV risk. Our survey demonstrates the commitment and autonomy in prescribing statins and aspirin of Italian physicians. There is a rationale to generate guidelines to overcome the differences and limitations among current recommendations

Cholesterol levels in HIV-HCV infected patients treated with lopinavir/r : results from the SCOLTA project.

Background: It is not known whether antiretroviral therapy (ART) including lopinavir/r has a different effect on the lipid metabolism in HIV patients co-infected with HCV. This study investigated changes in lipid levels, comparing patients with HIV infection alone and those with HCV too, in the lopinavir/r cohort of the SCOLTA project. Methods: We analyzed the data for the lopinavir/r nationwide cohort from 25 Italian infectious disease departments, which comprises 743 HIV-infected patients followed prospectively, comparing subjects with HIV-HCV co-infection and those with single-infection. Results: At enrolment, co-infected patients had significantly lower mean cholesterol than HCV negative cases (162 \ub1 43 mg/dL vs. 185 \ub1 52 mg/dL, p = 0.0009). Total and non-HDL cholesterol and triglycerides rose significantly from baseline in HIV single-infection patients, but not in those with co-infection. The patients with dual HIV-HCV infection, treated with an ART regimen including lopinavir/r, have only limited increases in total and non-HDL cholesterol and triglycerides. Conclusions: Changes in serum lipids in co-infected patients differed significantly from those in patients without HCV. It remains to be seen whether this is associated with a lower risk of progression of atherosclerotic disease

Durability of dolutegravir plus boosted darunavir as salvage or simplification of salvage regimens in HIV-1 infected, highly treatment-experienced subjects

Background: Dolutegravir (DTG) plus boosted darunavir (bDRV) is a compact, adherence-friendly salvage regimen with the highest genetic barrier to HIV-1 resistance. Objective: Aim of the present study is to assess the long term (96-week) safety and efficacy of DTG + bDRV in a of multidrug-experienced HIV-1 infected patients, simplifying or building rescue regimens. Methods: All HIV-1-infected subjects from eleven Italian centers switched to DTG + bDRV between March 2014 and September 2015 were included and followed for minimum 96 weeks. Results: The cohort comprises 130 subjects, switched from 42 different, complex or at least twice-daily regimens, mainly for simplification (44.6%), viral failure (30.0%) or toxicity (16.6%). At baseline 118 had documented resistance to 1\u20135 antiretroviral classes and 12 lacked genotypic results either for historical reasons or for problems with primer annealing; 52 (40%) had uncontrolled viral replication, three above 500.000 copies/mL. At week 96 two showed 6550 HIV-1 RNA copies/mL, 23 had 1\u201349 copies/mL and 101 had no virus detected. The proportion of subjects presenting abnormal values at baseline significantly decreased for serum glucose, creatinine, AST, total cholesterol and triglycerides. Conclusions: These long-term data confirm the reliability of the two-drug regimen consisting of bDRV plus DTG in salvage settings in HIV-1 infection