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

Reduced probability of improving viro-immunological state in subjects with vertical transmission of HIV reaching adult age: A multicenter retrospective cohort study

Introduction: Young adults with vertical transmission (VT) of human immunodeficiency virus (HIV) represent a fragile population. This study evaluates factors associated with viro-immunological outcome of these patients. Methods: We performed a multicenter study including HIV-infected subjects with VT ≥ 18 years old from six Italian clinics. Subjects were observed from birth to death, lost to follow-up, or last visit until December 31, 2019. Condition of "optimal viro-immunological status" (OS) was defined as the simultaneous presence of HIV ribonucleic acid (RNA) < 50 copies/mL, CD4+ > 500 cells/mm3 , and CD4+/CD8+ ratio ≥ 1. Results: A total of 126 subjects were enrolled. At 18 years of age, 52/126 (44.4%) had HIV-RNA > 50 copies/mL, 47/126 (38.2%) had CD4+ < 500/mm3 , and 78/126 (67.2%) had CD4+/CD8+ < 1; 28 subjects (23.7%) presented in the condition of OS. Having a CD4+/CD8+ ratio ≥ 1 at 18 years of age was related with an increased probability of shift from suboptimal viro-immunological status (SOS) to OS (HR: 7.7, 95% confidence interval [CI]: 4.23-14.04), and a reduced risk of shift from the OS to the SOS (HR: 0.49, 95% CI: 0.26-0.92). Acquired immunodeficiency syndrome (AIDS) diagnosis significantly reduced the probability of shift from a viro-immunological SOS to OS (HR: 0.09, 95% CI: 0.03-0.30). Subjects who had not achieved an OS at 18 years of age had an increased risk of discontinuation of combination antiretroviral therapy (cART, p = .019). Conclusions: Only a small proportion of subjects with VT of HIV reached the adult age with "OS". Transition to the adult care with a compromised viro-immunological condition represents a negative driver for future optimal infection control, with a higher risk of discontinuation of cART and a reduced probability to improve the immunological status later in the years

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

Lopinavir/Ritonavir and Darunavir/Cobicistat in Hospitalized COVID-19 Patients: Findings From the Multicenter Italian CORIST Study

Background: Protease inhibitors have been considered as possible therapeutic agents for COVID-19 patients. Objectives: To describe the association between lopinavir/ritonavir (LPV/r) or darunavir/cobicistat (DRV/c) use and in-hospital mortality in COVID-19 patients. Study Design: Multicenter observational study of COVID-19 patients admitted in 33 Italian hospitals. Medications, preexisting conditions, clinical measures, and outcomes were extracted from medical records. Patients were retrospectively divided in three groups, according to use of LPV/r, DRV/c or none of them. Primary outcome in a time-to event analysis was death. We used Cox proportional-hazards models with inverse probability of treatment weighting by multinomial propensity scores. Results: Out of 3,451 patients, 33.3% LPV/r and 13.9% received DRV/c. Patients receiving LPV/r or DRV/c were more likely younger, men, had higher C-reactive protein levels while less likely had hypertension, cardiovascular, pulmonary or kidney disease. After adjustment for propensity scores, LPV/r use was not associated with mortality (HR = 0.94, 95% CI 0.78 to 1.13), whereas treatment with DRV/c was associated with a higher death risk (HR = 1.89, 1.53 to 2.34, E-value = 2.43). This increased risk was more marked in women, in elderly, in patients with higher severity of COVID-19 and in patients receiving other COVID-19 drugs. Conclusions: In a large cohort of Italian patients hospitalized for COVID-19 in a real-life setting, the use of LPV/r treatment did not change death rate, while DRV/c was associated with increased mortality. Within the limits of an observational study, these data do not support the use of LPV/r or DRV/c in COVID-19 patients

Virological efficacy of dual therapy with lamivudine and dolutegravir in HIV-1-infected virologically suppressed patients: long-term data from clinical practice

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HIV DNA Decay in a Treatment-Naive Patient Starting Dolutegravir Plus Lamivudine with Resistance Mutations to Integrase Inhibitors: A Case Report

Editor: Recent data from clinical trials highlight the efficacy of a two-drug strategy with lamivudine (3TC) plus dolutegravir (DTG) as first-line regimen in treatment-naive HIV-infected people living with HIV (PLWH).1 PLWH with transmitted resistance mutations, however, were not included in the two GEMINI trials and thus no data are available on the efficacy of such regimens in PLWH with primary resistances. In a recently published report,2 we described our initial experience in a small cohort of treatment-naive PLWH starting 3TC plus DTG in clinical practice. We would like to further analyze the case of a 23-year-old subject with Y188C and D232N resistance mutations starting 3TC+DTG. The D232N mutation, in particular, is a nonpolymorphic mutation selected in patients previously exposed to raltegravir3 and has been related to potential resistance to first-generation integrase inhibitors (INIs) raltegravir and elvitegravir. The subject was diagnosed with HIV infection in March 2019, with a peak HIV RNA value of 114,866 copies/mL and a nadir CD4+ cell count of 328 cell/mm3. Genotypic test was also performed, showing the mentioned resistance mutations. He subsequently started the two-drug regimen with a rapid decline in HIV RNA, reaching 48 copies/mL after 3 weeks from treatment initiation. His HIV RNA load became undetectable after 8 weeks and as of today, after 24 weeks, it is still undetectable. We also observed a steady improvement in immunological parameters; after 24 weeks his CD4+ cell count was 1,091 cell/mm3. Given the presence of the transmitted resistances, we further investigated the subject's virological status by evaluating total HIV-1 DNA levels, a marker of low-grade inflammation and viral reservoir dynamics.4 In our patient, baseline HIV-1 DNA quantification was 3.00 log10 copies/106 leukocytes. Initial decay was sharp, as HIV DNA levels decreased to 2.69 log10 copies/106 leukocytes after 4 weeks of treatment and to 2.37 log10 copies/106 leukocytes after 8 week

Reduced soluble CD14 levels after switching from a dual regimen with lamivudine plus boosted protease inhibitors to lamivudine plus dolutegravir in virologically suppressed HIV-infected patients

Background: HIV-induced systemic immune activation and inflammation have been associated with morbidity and mortality in virologically suppressed patients. Objective: To evaluate the impact of treatment switch from a dual regimen with lamivudine (3TC) plus ritonavir-boosted protease inhibitors (PI/r) to 3TC plus dolutegravir (DTG) on the monocyte activation marker soluble CD14 (sCD14) and other inflammatory biomarkers, interleukin-6 (IL-6), C-reactive protein (CRP), intestinal fatty acid–binding protein (I-FABP) and D-dimer. Methods: We performed a retrospective case-crossover study on integrase inhibitors-naïve virologically suppressed patients while on 3TC + PI/r dual maintenance therapy for ≥48 weeks who switched to 3TC + DTG and maintained this regimen for ≥48 weeks. Biomarkers plasma levels were tested by ELISA assays on stored samples at three time points: at switch (BL), 48 weeks before (−48 W) and 48 weeks after switch (+48 W). Results: A total of 67 patients were included. Median sCD14 levels were stable from −48 W to BL (from 6.07 to 6.04 log10 pg/mL, p = 0.235) but showed a statistically significant decrease after switch: from 6.04 (IQR 5.92-6.12) at BL to 5.95 (IQR 5.84–6.07) log10 pg/mL at + W48 (p < 0.001). Concurrently, an improvement in lipid profile was observed, even thought it was not correlated to the change in sCD14. The levels of IL-6, CRP, I-FABP and D-dimer remained stable before and after the switch to 3TC + DTG. Conclusions: In virologically suppressed HIV-infected patients on a 3TC + PI/r dual therapy, switching to 3TC + DTG was associated with a significant decline in sCD14. These data suggest reduced monocyte activation following substitution of boosted PI with DTG, which could have important clinical implications

Clinical presentation of human monkeypox virus infection during the 2022 outbreak: descriptive case series from a large italian Research Hospital

Abstract Background In May 2022, a new case of Monkeypox Virus (MPX) was reported in a non-endemic area, the United Kingdom, and since then, the number of confirmed cases in Europe has been increasing until WHO, on May 10 2023, declared that MPOX is no longer a public health emergency of international concern. We aimed to describe the clinical and microbiological characteristics of sixteen patients with a confirmed diagnosis of MPX followed by a single Italian clinical centre, the Fondazione Policlinico Universitario Agostino Gemelli, between May 20 and August 30. Materials and methods A prospective observational study has been conducted, collecting microbiological samples during the time of the infection, as well as epidemiological and clinical data of the patients. All patients provided written informed consent. Results During clinical practice, 16 individuals presenting with consistent symptoms tested positive for MPX on a polymerase chain reaction. All patients were men having sex with men (MSM). The most frequent clinical presentation was a vesicular erythematous cutaneous rash, mainly distributed on the genital and perianal area, but also regarding limbs, face, neck, chest and back in some of the patients. Systemic symptoms, such as fever or lymphadenopathy, involved eight patients. The symptom most frequently reported by patients was pruritus in the area of the vesicles. Thirteen patients also reported pain. Nine patients were HIV-1 coinfected, but no significant differences have been observed compared to other cohort patients. The median time between the onset of symptoms and the healing was 19.5 days (IQR 14.0–20.3). Conclusions Our cohort of patients presented a mild manifestation of the disease with no complications and no need for antiviral therapy nor hospitalization. This population seems different from the ones reported in the literature during the previous outbreaks in endemic areas in epidemiological data and clinical manifestations but also from a cohort of patients described in the literature from the 2022 outbreak, suggesting the importance for healthcare workers to keep in mind the possibility of an MPX infection in the differential diagnosis of patients presenting with consistent symptoms, even in non-endemic areas, to ensure efficient isolation of the patient for infection control purposes and effective management of the infection preventing the development of MPOX-related complications