Efficacy and Durability of Dolutegravir- or Darunavir-Based Regimens in ART-Naïve AIDS- or Late-Presenting HIV-Infected Patients.

Background: Since limited data are available, we aimed to compare the efficacy and durability of dolutegravir and darunavir in advanced naïve patients.

Methods: Retrospective multicenter study including AIDS- or late-presenting (def. CD4 ≤ 200/µL) HIV-infected patients starting dolutegravir or ritonavir/cobicistat-boosted darunavir+2NRTIs.

Efficacy and durability of two- vs. three-drug integrase inhibitor-based regimens in virologically suppressed HIV-infected patients: Data from real-life ODOACRE cohort.

Objectives: The aim of the present study was to compare the efficacy and durability of treatment switch to two-drug (2DR) vs. three-drug (3DR) integrase inhibitor (InSTI)-based regimens in a real-life setting.

Methods: Within the ODOACRE cohort, we selected adult patients with HIV RNA < 50 copies/mL switching to an InSTI-based 2DR or 3DR.

Integrase Inhibitors Use and Cytomegalovirus Infection Predict Immune Recovery in People Living With HIV Starting First-Line Therapy.

Background: We explored predictors of CD4/CD8 ratio improvement and optimal immunological recovery (OIR) after initiation of antiretroviral therapy (ART) in naive people living with HIV (PLWH).

Methods: Retrospective multicenter study including naive PLWH starting ART with 2 nucleos(t)ide reverse transcriptase inhibitors + 1 integrase strand transfer inhibitor (InSTI) or non-NRTI or protease inhibitor (PI). PLWH were followed from the time of ART initiation (baseline) to the discontinuation of first-line regimen, virological failure, death, or loss to follow-up.

Overall Tolerability of Integrase Inhibitors in Clinical Practice: Results from a Multicenter Italian Cohort.

International guidelines recommend the use of integrase strand transfer inhibitor (INI)-based regimens as first-line antiretroviral (ARV) in both naive and experienced HIV-infected patients. We analyzed a multicenter cohort of HIV-infected patients, both naive and experienced, starting an ARV, including an INI. Chi-square test and nonparametric tests were used to assess differences in categorical and continuous variables, respectively.

Evaluation of virological response and resistance profile in HIV-1 infected patients starting a first-line integrase inhibitor-based regimen in clinical settings.

Background: Virological response and resistance profile were evaluated in drug-naïve patients starting their first-line integrase inhibitors (INIs)-based regimen in a clinical setting.

Study Design: Virological success (VS) and virological rebound (VR) after therapy start were assessed by survival analyses. Drug-resistance was evaluated at baseline and at virological failure.

HIV MDR is still a relevant issue despite its dramatic drop over the years.

Objectives: To evaluate the prevalence and therapeutic relevance of drug resistance among isolates from ART-experienced HIV-1-infected patients over the past two decades in Italy.

Methods: Dynamics of resistance to one, two and three or more antiretroviral classes were evaluated from 1999-2018. Virological success (VS) after the latest therapy switch was evaluated according to cumulative class resistance and cumulative genotypic susceptibility score (Stanford HIV_DB algorithm).

Naïve/Effector CD4 T cell ratio as a useful predictive marker of immune reconstitution in late presenter HIV patients: A multicenter study.

A significant proportion of HIV-infected patients experiencing a late diagnosis highlights the need to define immunological protocols able to help the clinicians in identifying patients at higher risk for immunological failure. The aim of the study was to evaluate the feasibility of easy cytometric tests in defining the effect of antiretroviral treatment (cART) on immunological homeostasis and in identifying predictive markers of early immune recovery. Chronic HIV infected patients (n = 202) were enrolled in a prospective multicentric study, and their immunological profile was studied before (w0) and after 24 weeks (w24) of antiretroviral treatment (cART) using a standardized flow cytometric panel.

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

Purpose: 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.

Participants: The ODOACRE cohort enrols all adult HIV-1-infected patients, both treatment-naïve and treatment-experienced, starting a DTG-based ARV regimen, in 11 clinical centres in Italy from 2014.

Findings To Date: In recent years, various works by the ODOACRE cohort have been produced, demonstrating the high efficacy and tolerability of DTG-based ARV regimens in clinical practice, both in ART-naïve (in the setting of acute HIV-1 infection and late presenters patient) and experienced patients.

Impact of Antiretroviral Therapy on the Risk of Recurrence in HIV-1 Infected Patients with Kaposi Sarcoma: A Multicenter Cohort Experience.

Kaposi sarcoma (KS) remains a relevant malignancy in human immunodeficiency virus (HIV)-infected patients with a non-standardized management; despite past suggestions that ritonavir-boosted protease inhibitor (bPI)-based regimens could be preferable, no combination antiretroviral therapy (cART) regimen was demonstrated to outperform the others and the impact of new drugs, drug classes or paradigms was never investigated nor proven better than previous therapeutic regimes. In order to do this, we retrospectively collected data regarding HIV-infected patients with a diagnosis of KS last seen in six Italian centers after 1 January 2013. A total of 104 KS cases in 99 patients was analyzed for 945.

Impact of NRTI resistance mutations on virological effectiveness of antiretroviral regimens containing elvitegravir: a multi-cohort study.

Background: Antiretroviral drug resistance mutations remain a major cause of treatment failure.

Objectives: To evaluate the impact of NRTI resistance mutations on virological effectiveness of elvitegravir-containing regimens.

Materials And Methods: We selected treatment-experienced HIV-1-infected patients starting elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) or elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (E/C/F/TDF), with at least one protease/reverse transcriptase genotype available before switching and at least one HIV-1 RNA viral load (VL) measurement during follow-up.

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.

Efficacy and safety of dolutegravir-based regimens in advanced HIV-infected naïve patients: results from a multicenter cohort study.

The aims were to describe efficacy and tolerability of regimens containing dolutegravir (DTG) in advanced ART-naïve people living with HIV (PLHIV) from the clinical practice. The frequency of Immune Reconstitution Inflammatory Syndrome (IRIS), the estimated time of discontinuation of the first ART regimen and the time to reach virological suppression in a multicenter cohort of AIDS-presenters or late-presenters with CD4 <350/μL were assessed. We included 272 PLHIV: 120 (44%) AIDS-presenters and 152 (56%) late-presenters.

Viro-immunological efficacy and tolerability of dolutegravir-based regimens compared to regimens based on other integrase strand inhibitors, protease inhibitors or non-nucleoside reverse transcriptase inhibitors in patients with acute HIV-1 infection: A multicenter retrospective cohort study.

Objectives: The aim of this study was to compare the tolerability and viro-immunological efficacy of dolutegravir-based regimens (DTG group) with regimens based on EVG, RAL, PI or NNRTI (NODTG group) in patients with acute HIV-1 infections (AHI).

Methods: All patients diagnosed with AHI and on antiretroviral therapy (ART) between January 2015 and December 2017 from five centers in Italy were included and followed-up to 30 April 2018. AHI was defined by the presence of the positive p24 antigen with negative or indeterminate western blot.

Recreational drugs and STI diagnoses among patients attending an STI/HIV reference clinic in Rome, Italy.

Background: An observational study was conducted to assess recreational drug use in association with recent STIs among clients of an STI/HIV reference centre in Rome, Italy.

Methods: Attendees self-compiled a questionnaire concerning sexual behaviours and drug use, including the nine drugs used for sex (amphetamines, poppers, cocaine, ketamine, erectile dysfunction agent (EDA), steroids and the three chemsex drugs, ie, chems: γ-hydroxybutyric acid/γ-butyrolactone, crystal and Mcat).

Results: Overall, 703 patients participated, with men who have sex with men (MSM) accounting for 50.

Characterisation of HIV-1 molecular transmission clusters among newly diagnosed individuals infected with non-B subtypes in Italy.

Objective: We evaluated the characteristics of HIV-1 molecular transmission clusters (MTCs) in 1890 newly diagnosed individuals infected with non-B subtypes between 2005 and 2017 in Italy.

Methods: Phylogenetic analyses were performed on sequences to characterise subtypes/circulating recombinant forms and identify MTCs. MTCs were divided into small (SMTCs, 2-3 sequences), medium (MMTCs, 4-9 sequences) and large (LMTCs, ≥10 sequences).

Oral testing for high-risk human papillomavirus DNA and E6/E7 messenger RNA in healthy individuals at risk for oral infection.

Background: Testing for oral high-risk human papillomavirus (HPV) DNA may be useful for identifying individuals at increased risk for HPV-driven oropharyngeal cancer (OPC). However, positivity for HPV DNA provides no information on the transforming potential of the infection. In contrast, the detection of high-risk HPV E6/E7 messenger RNA (mRNA) may help to identify clinically significant infections because of the indispensable role of E6/E7 viral oncoproteins in the carcinogenic process.

Human papillomavirus detection in matched oral rinses, oropharyngeal and oral brushings of cancer-free high-risk individuals.

Objectives: The detection of oral Human Papillomavirus (HPV) may be of clinical utility because of the major role HPV plays in the etiology of oropharyngeal cancer. However, oral HPV testing is not standardized and the best sampling method has yet to be identified. We aimed to compare HPV findings in matched oral rinse-and-gargles (rinses), oropharyngeal brushings and oral brushings.

SLC22A2 variants and dolutegravir levels correlate with psychiatric symptoms in persons with HIV.

Background: Neuropsychiatric symptoms (NPs) have been reported with dolutegravir use. We hypothesized that increasing dolutegravir trough concentrations (Ctrough) and/or polymorphism in the SLC22A2 gene, encoding the organic cation transporter-2 (OCT2), which is involved in monoamine clearance in the CNS and is inhibited by dolutegravir, might be associated with NPs.

Methods: A cross-sectional cohort of HIV-positive patients treated with a dolutegravir-containing regimen underwent determination of allelic discrimination for SLC22A2 808 C → A polymorphism and dolutegravir Ctrough.

Genetic divergence of HIV-1 B subtype in Italy over the years 2003-2016 and impact on CTL escape prevalence.

HIV-1 is characterized by high genetic variability, with implications for spread, and immune-escape selection. Here, the genetic modification of HIV-1 B subtype over time was evaluated on 3,328 pol and 1,152 V3 sequences belonging to B subtype and collected from individuals diagnosed in Italy between 2003 and 2016. Sequences were analyzed for genetic-distance from consensus-B (Tajima-Nei), non-synonymous and synonymous rates (dN and dS), CTL escapes, and intra-host evolution over four time-spans (2003-2006, 2007-2009, 2010-2012, 2013-2016).

Vaccine-preventable anal infections by human papillomavirus among HIV-infected men who have sex with men.

Aim: HIV-infected men who have sex with men (MSM) show the highest prevalence of anal HPV infection. Anal prevalence of the HPVs targeted by the quadrivalent HPV vaccine (4vHPV) and nonavalent HPV vaccine (9vHPV) was estimated in this population.

Materials & Methods: Anal specimens were collected from HIV-infected MSM attending a sexually transmitted infection/HIV center.

A comparison between two dolutegravir-based two-drug regimens as switch strategies in a multicentre cohort of HIV-1-infected patients.

Background: Two-drug regimens are increasingly used in clinical practice as switch strategies. We compared the efficacy and safety of two dolutegravir (DTG)-based dual therapies: DTG plus lamivudine (3TC group) versus DTG plus rilpivirine (RPV group).

Methods: In a multicentre cohort of virologically suppressed (HIV RNA <50 copies/ml) HIV+ patients switching to DTG+3TC or DTG+RPV we analysed the incidence of virological failures (VF) and treatment discontinuations (TD), as well as their predictors.

Impact of transmitted HIV-1 drug resistance on the efficacy of first-line antiretroviral therapy with two nucleos(t)ide reverse transcriptase inhibitors plus an integrase inhibitor or a protease inhibitor.

Objectives: To examine the impact of transmitted drug resistance (TDR) on response to first-line regimens with integrase strand transfer inhibitors (INSTIs) or boosted protease inhibitors (bPIs).

Methods: From an Italian observational database (ARCA) we selected HIV-1-infected drug-naive patients starting two NRTIs and either an INSTI or a bPI, with an available pre-ART resistance genotype. The endpoint was virological failure (VF; plasma HIV-1 RNA >200 copies/mL after week 24).

Evolution of transmitted HIV-1 drug resistance and viral subtypes circulation in Italy from 2006 to 2016.

Objectives: The aim was to evaluate the evolution of transmitted HIV-1 drug resistance (TDR) prevalence in antiretroviral therapy (ART)-naïve patients from 2006 to 2016.

Methods: HIV-1 sequences were retrieved from the Antiviral Response Cohort Analysis (ARCA) database and TDR was defined as detection of at least one mutation from the World Health Organization (WHO) surveillance list.

Results: We included protease/reverse transcriptase sequences from 3573 patients; 455 had also integrase sequences.