Lipid Metabolism and Cardiovascular Risk in HIV-1 Infection and HAART: Present and Future Problems

Many infections favor or are directly implicated with lipid metabolism perturbations and/or increased risk of coronary heart disease (CHD). HIV itself has been shown to increase lipogenesis in the liver and to alter the lipid profile, while the presence of unsafe habits, addiction, comorbidities, and AIDS-related diseases increases substantially the risk of cardiovascular disease (CVD) in the HIV-infected population. Antiretroviral therapy reduces such stimuli but many drugs have intrinsic toxicity profiles impacting on metabolism or potential direct cardiotoxicity. In a moment when the main guidelines of HIV therapy are predating the point when to start treating, we mean to highlight the contribution of HIV-1 to lipid alteration and inflammation, the impact of antiretroviral therapy, the decisions on what drugs to use to reduce the probability of having a cardiovascular event, the increasing use of statins and fibrates in HIV-1 infected subjects, and finally the switch strategies, that balance effectiveness and toxicity to move the decision to change HIV drugs. Early treatment might reduce the negative effect of HIV on overall cardiovascular risk but may also evidence the impact of drugs, and the final balance (reduction or increase in CHD and lipid abnormalities) is not known up to date

Long-term data on the efficacy and tolerability of lamivudine plus dolutegravir as a switch strategy in a multi-centre cohort of HIV-1-infected, virologically suppressed patients

BACKGROUND: Results from clinical trials and observational studies suggest that lamivudine plus dolutegravir (3TC+DTG) could be an effective and tolerated option for simplification in human immunodeficiency virus (HIV)-1-positive patients. MATERIALS AND METHODS: This observational study enrolled HIV-1-infected, virologically suppressed patients switching to 3TC+DTG. Kaplan-Meyer survival analysis was performed to evaluate time to virological failure (VF; defined by a single HIV-RNA determination ≥1000 copies/mL or by two consecutive HIV-RNA determinations ≥50 copies/mL) and time to treatment discontinuation (TD; defined as interruption of either 3TC or DTG), Cox regression was performed to assess predictors, and linear mixed model was performed for repeated measures to measure changes in immunological and metabolic parameters. RESULTS: Five hundred and fifty-six patients were eligible for analysis. Their median CD4+ count at baseline was 668 cells/mm3 and median time of virological suppression was 88 months. Estimated probabilities of maintaining virological suppression at 96 and 144 weeks of follow-up were 97.5% [standard deviation (SD) 0.8] and 96.5% (SD 1.0), respectively. Years since HIV diagnosis was the only predictor of VF. In patients with time of virological suppression <88 months, the rate of VF was higher in the presence of the M184V mutation. Estimated probabilities of remaining on 3TC+DTG at 96 and 144 weeks of follow-up were 79.2% (SD 1.9) and 75.2% (SD 2.2), respectively. A significant increase in CD4 cell count (+44 cells/mm3, P=0.015), CD4/CD8 ratio (+0.10, P=0.002) and high-density lipoprotein cholesterol (+5.4 mg/dL, P=0.036) was found at 144 weeks of follow-up; meanwhile, total cholesterol (-9.1 mg/dL, P=0.007) and triglycerides (-2.7, P=0.009) decreased significantly. CONCLUSIONS: These findings confirm the efficacy and tolerability of 3TC+DTG in virologically suppressed patients. Copyright © 2019 Elsevier Ltd. All rights reserved

Cohort profile: The Observational cohort for the study of DOlutegravir in Antiretroviral Combination REgimens (ODOACRE)

The Observational cohort for the study of DOlutegravir in Antiretroviral Combination REgimens (ODOACRE) cohort was established in Italy in 2016 to evaluate the overall efficacy and tolerability of dolutegravir (DTG)-based antiretroviral (ARV) regimens in clinical practice

Dolutegravir Plus Lamivudine as First-Line Regimen in a Multicenter Cohort of HIV-1-Infected Patients: Preliminary Data from Clinical Practice

Editor: The results from the ACTG 5353 trial1 and GEMINI trials2 have demonstrated the efficacy of a dual therapy with dolutegravir plus lamivudine as first-line regimen in treatment-naive HIV-positive patients. This regimen, already closely evaluated as a switch option in treatment-experienced patients, for whom it has shown a good tolerability profile and a high virological efficacy in the long term,3,4 is increasingly becoming a promising option for the treatment of a large portion of HIV-infected patients. We would like to present the preliminary data from a multicenter study on antiretroviral therapy (ART)-naive patients starting lamivudine plus dolutegravir in clinical practice. At baseline and at each follow-up visit viroimmunological markers of HIV infection, including plasma HIV-RNA level, were collected (quantitative assay, detection limit of 37 copies/mL). We evaluated the proportion of patients reaching virological suppression (defined as HIV-RNA <50 copies/mL) during follow-up time. The study was approved by each local ethics committee (promoting center protocol number: 5284/15) and all patients signed an informed consent. We enrolled 10 patients: 6 (60%) men, with a median age of 50 years (interquartile range [IQR] 30\u201355). At baseline, median HIV-RNA was 4.84 log10 copies/mL (IQR 4.64\u20134.96), whereas median CD4+ cell count was 342 cell/mm3 (IQR 301\u2013419). Two patients presented a peak HIV-RNA >100,000 copies/mL. One patient, with a peak HIV-RNA of 55,833 copies/mL, after 3 weeks from ART initiation, achieved a HIV-RNA of 104 copies/mL, but no following virological determinations are at the moment available. The other nine patients reached 8 weeks of follow-up; among them, eight reached the virological suppression, whereas one patient, who started with a peak HIV-RNA of 102.657 copies/mL, had a HIV-RNA determination of 55 copies/mL. The seven patients who reached 24 weeks of follow-up had a HIV-RNA quantification <50 copies/mL; of them, five reached 48 weeks of follow-up and all of them had an undetectable viral load (Table 1)

96-week results of a dual therapy with darunavir/ritonavir plus rilpivirine once a day vs triple therapy in patients with suppressed viraemia: virological success and non-HIV related morbidity evaluation

Antiretroviral therapies have been tested with the goal of maintaining virological suppression with a particular attention in limiting drug-related toxicity. With this aim we designed the DUAL study: a randomized, open-label, multicenter, 96 weeks-long pilot exploratory study in virologically suppressed HIV-1+ patients with the aim of evaluating the immunovirological success and the impact on non-HIV related morbidity of switching to a dual therapy with darunavir-ritonavir (DRV/r) and rilpivirine (RPV). We recruited patients who received a PI/r-containing HAART for ≥6 months, HIV-RNA 60 mL/min/1,73m2, without DRV or RPV RAMs. We randomized patients in arm A: RPV + DRV/r QD or arm B: ongoing triple therapy. The primary endpoint has been defined as the percentage of patients with HIV-RNA < 50 cp/mL at week 48 (ITT). VACS index, Framingham CVD risk (FRS) and urinary RBP (uRBP) were calculated. We used Chi-square or Fisher statistics for categorical variables and Mann-Whitney U for continuous ones. Forty-one patients were enrolled (22 in arm A, 14 in arm B, plus 5 screening failures): 30 patients reached 96 weeks: 100% had HIV-RNA < 50 cp/mL in arm A versus 91.7% in arm B. Similar changes were observed in median CD4/mL between baseline and week 96 (+59 versus − 31, p: n.s.). Thirty-one in arm A and 23 in arm B adverse events took place, whereas only 1 was serious (arm A: turbinate hypertrophy, unrelated to HAART). Among the 6 discontinuations (3 in A, 3 in B), only 1 was related to adverse event (arm A: G3 depression, insomnia, weakness). VACS index, median FRS and median uRBP values did not vary from baseline to week 96. At 96-weeks all patients switched to a QD 2-drug regimen based on DRV/r + RPV maintained HIV-RNA suppression, but a single patient who showed a virological failure at week 4. CD4 counts increased overtime without significant differences between the two arms. The novel dual regimen was well tolerated with the same amount of discontinuation as the control arm. VACS index, FRS and uRBP did not differ between arms at week 96

Long term data on the efficacy and tolerability of lamivudine plus dolutegravir as a switch strategy in a multicenter cohort of HIV1-infected, virologically suppressed patients

Abstract Background. Results from clinical trials and observational studies suggest that lamivudine plus dolutegravir could be an effective and tolerated option for simplification in HIV-1 positive patients. Materials and Methods. This was an observational study enrolling HIV-1-infected, virologically suppressed patients switching to lamivudine plus dolutegravir. We performed Kaplan-Meyer survival analysis to evaluate time to virological failure (VF, defined by a single HIV-RNA ≥1,000 copies/mL or by two consecutive HIV-RNA ≥ 50 copies/mL) and treatment discontinuation (TD, defined as the interruption of either 3TC or DTG), Cox-regression to assess predictors and linear mixed model for repeated measures to measure changes in immunological and metabolic parameters. Results. Five-hundred fifty-six patients were eligible for the analysis: median CD4+ count at baseline was 668 cell/mm3, while median time of virological suppression was 88 months. Estimated probabilities of maintaining virological suppression at weeks 96 and 144 were 97.5% (SD ±0.8) and 96.5% (SD ±1.0). Years from HIV diagnosis were the only predictor of VF. In patients with time of virological suppression &lt;88 months, the rate of VF was higher in the presence of the M184V mutation. Estimated probabilities of remaining on 3TC+DTG at 96 and 144 weeks were 79.2% (SD ±1.9) and 75.2% (SD ±2.2). A significant increase in CD4 cell count (+44 cell/mm3, p=0.015), CD4/CD8 ratio (+0.10, p=0.002) and HDL cholesterol (+5.4 mg/dl, p=0.036) was found after 144 weeks; meanwhile total cholesterol (-9.1 mg/dl, p=0.007) and triglycerides (-2.7, p=0.009) significantly decreased. Conclusions. Our findings confirm the efficacy and tolerability of 3TC+DTG in virologically suppressed patients

Hepatitis C virus: determinants of patients' management costs

While Hepatitis C Virus (HCV) is a significant economic burden for healthcare providers, limited evidence is available on determinants of resources absorption, both in treatment-experienced and treatment-naïve HCV patients. The present study aimed to investigate the principal determinants of HCV management costs.4-8 November 201

Decay rate of antiS1/S2 IgG serum levels after 6 months of BNT162b2 vaccination in a cohort of COVID-19-naive and COVID-19-experienced subjects

Vaccination toward SARS-CoV-2 reduced mortality and ‘boosters’ are being implemented. We offer scientific contribution about IgG production in the COVID-19 experienced population. From January 2021 to March 2021, 183 residents and staff from the Elderly Nursing Home “San Giuseppe Moscati” who had received two doses of the BNT162b2 vaccine were enrolled. The antibody response was assessed by the DiaSorin LIAISON-CLIA S1/S2® IgG solution. Cutoff levels for response (>39 BAU/mL) and neutralizing activity (>208 BAU/mL) were derived from DiaSorin official data. Serology was assessed before and after the first vaccination, and 2 weeks and 6 months after the second vaccination. Anti-S IgG in COVID-19 experienced, baseline IgG producers spiked after the first vaccination to median 5044 BAU/mL and decayed at 6 months to 2467.4 BAU/mL. Anti-S IgG in COVID-19 experienced, baseline IgG non-producers spiked after the second vaccination to median 1701.7 BAU/mL and decayed at 6 months to 904.8 BAU/mL. Anti-S IgG in COVID-19 naïve subjects spiked after the second vaccination to median 546 BAU/mL and decayed at 6 months to 319.8 BAU/mL. The differences between sequential timepoint levels in each group were statistically significant (p < .0001). Serology analysis revealed different kinetics between COVID-19 experienced subjects depending on baseline response, possibly predicting different IgG persistence in blood