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

Durability of lopinavir/ritonavir monotherapy in individuals with viral load ≤50 copies/ml in an observational setting

BACKGROUND: The main objective is to evaluate the efficacy and durability of lopinavir-ritonavir monotherapy (LPV/r-MT) in virologically controlled HIV-positive individuals switching from combination antiretroviral therapy (cART). METHODS: Criteria to be included in this observational study were to have initiated for the first time LPV/r-MT after ≥2 consecutive HIV RNA≤50 copies/ml achieved on a ≥3-drug-including regimen. The main end points were time to virological rebound (VR; defined in two ways: time of first of two consecutive viral load [VL]>50 and >200 copies/ml), time to discontinuation/intensification and time to experience either a single VL>200 copies/ml or discontinuation/intensification (treatment failure [TF]). Individuals' follow-up accrued from the date of starting LPV/r-MT to event or last available VL. Kaplan-Meier curves and Cox regression analyses were used. RESULTS: A total of 228 individuals were included: median age 46 years (IQR 40-50), 36% females, 36% intravenous drug users and 25% HCV-coinfected. Median CD4(+) T-cell count at nadir was 215 cell/mm(3) (IQR 116-336) and at baseline was 615 cell/mm(3) (IQR 436-768). By 36 months after switching to LPV/r-MT, the proportion of individuals with VR (confirmed VL>200 copies/ml) was 11% and with TF was 35%. In the multivariable Cox model the factors associated with a lower risk of TF was the duration of viral suppression <50 copies/ml prior to baseline (ARH=0.92; 95% CI 0.85, 0.99; P=0.024, per 6 months longer) and having LPV/r as part of last cART (ARH=0.45; 95% CI 0.21, 0.95; P=0.037). CONCLUSIONS: In daily clinical practice, we confirm a relatively safe approach of treatment simplification to LPV-MT in a selected population with long-lasting virological control

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

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

Effectiveness of switching to darunavir/cobicistat in virologically-suppressed HIV-positive patients receiving ritonavir-boosted protease inhibitor-based regimen : the &quot;STORE&quot; Study

Objective: This study investigates the effectiveness and tolerability of switching to darunavir/cobicistat (DRV/c)-based antiretroviral regimen (ART) from a ritonavir-boosted protease inhibitor (PI/r)-based regimen in virologically suppressed human immunodeficiency virus (HIV)-positive patients. DRV trough values were also investigated. Setting: Prospective, multicenter, single-country, non-interventional, cohort study. Methods: This study included patients on a PI/r-based ART for at least twelve months having plasma HIV-1 RNA &lt;50 copies/mL for at least six months. Primary endpoint: HIV-1 RNA &lt;50 copies/mL at 48 \ub1 6 weeks from baseline. A secondary analysis was performed using the time to loss of virological response (TLOVR) algorithm. Biochemical parameters including DRV trough samples were collected as per clinical practice and measured using high-performance liquid chromatography. Results: Of 336 patients enrolled, 282 completed the study: 70.8% had plasma HIV-1 RNA &lt;50 copies/mL at 48 weeks; using the TLOVR algorithm, 82.7% maintained virological suppression. Virological failure (VF) was observed in 6 patients (1.8%). Adverse event (AE)-related discontinuations were 4.5%. After 48 weeks, we found a significant improvement in both triglycerides (median, 130.0 mg/dL to 113.5 mg/dL, p=0.0254) and HDL cholesterol (48 to 49 mg/dL, p&lt;0.0001) but no change in other biomarkers. DRV trough concentrations in 56 subjects showed a median value of 2862.5 (1469.5-4439.0) ng/mL, higher in females than in males (4221 ng/mL vs. 2634 ng/mL, p=0.046). Conclusions: In stable HIV-1 positive virologically suppressed patients, the switch to DRV/c-based ART was beneficial in terms of low rates of VF and AEs due to its high tolerability and improvement in triglycerides