Real-world data on long-acting intramuscular maintenance therapy with cabotegravir and rilpivirine mirror Phase 3 results.

Introduction: Cabotegravir, an integrase strand transfer inhibitor, and rilpivirine, an NNRTI, constitute the first long-acting (LA), injectable, two-drug ART regimen approved for the maintenance of virological suppression in persons living with HIV-1 (PLHIV). The aim of this study was to assess clinical effectiveness and tolerability of LA cabotegravir/rilpivirine in a real-world setting.

Patients And Methods: We conducted a retrospective, single centre study, including all PLHIV receiving LA cabotegravir/rilpivirine as standard-of-care in our tertiary centre even if initiated in clinical trials.

Plasma concentrations of antiretroviral drugs in a successful 4-days-a-week maintenance treatment strategy in HIV-1 patients (ANRS 170-Quatuor trial).

Objectives: Charaterization of the plasma concentrations of antiretrovirals in a 4-days-a-week maintenance treatment strategy in the ANRS-170-QUATUOR study.

Methods: Patients were randomized in two groups receiving triple therapy taken 4-days-ON and 3-days-OFF (4/7) or continuous therapy (7/7). Plasma antiretroviral concentrations were monitored during the 'ON-treatment period' (Day 3 or 4 of the 4-day treatment block) and the 'OFF-treatment period' (Day 3 of the 3-day drug cessation) for the 4/7 group, or before the daily drug intake for the 7/7 group, until week-48 (W48).

Four days/week antiretroviral maintenance strategy (ANRS 170 QUATUOR): substudies of reservoirs and ultrasensitive drug resistance.

Background: In a 4 days/week (4/7 days) maintenance strategy (ANRS-170 QUATUOR trial), the virological impact of an intermittent strategy was assessed by ultrasensitive virological analyses of reservoirs and resistance.

Methods: HIV-1 total DNA, ultra-sensitive plasma viral load (USpVL) and semen VL were measured in the first 121 participants. Sanger and ultra-deep sequencing (UDS) were performed on the HIV-1 genome (Illumina technology) according to the ANRS consensus.

Same-day initiation of bictegravir/emtricitabine/tenofovir alafenamide: Week 48 results of the FAST study-IMEA 055.

Background: Initiating same-day ART for newly HIV-diagnosed individuals reduces secondary HIV transmissions and the risk of them being lost to follow-up between diagnosis and initiation of ART.

Methods: The FAST study was a national, prospective, single-arm study assessing the efficacy, safety and feasibility of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) in a same-day initiation model. ART had to be started on the first medical appointment, before any laboratory results were available.

Risk Factors Associated with Severe/Critical COVID-19 in People Living with HIV-1.

Introduction: Our objective was to determine the risk factors of a "severe/critical" form of COVID-19 in a cohort of people living with HIV-1 (PLWH1) followed in the Bichat University Hospital center in PARIS, FRANCE.

Methods: This study was an observational retrospective monocentric cohort of PLWH1 diagnosed with COVID-19 between February 1 st and November 31 st, 2020. Risk factors associated with "severe/critical" forms were determined using stepwise forward selection.

Inhaled ciclesonide for outpatient treatment of COVID-19 in adults at risk of adverse outcomes: a randomised controlled trial (COVERAGE).

Objectives: To assess the efficacy of inhaled ciclesonide in reducing the risk of adverse outcomes in COVID-19 outpatients at risk of developing severe illness.

Methods: COVERAGE is an open-label, randomized controlled trial. Outpatients with documented COVID-19, risk factors for aggravation, symptoms for ≤7 days, and absence of criteria for hospitalization are randomly allocated to either a control arm or one of several experimental arms, including inhaled ciclesonide.

A 4-days-on and 3-days-off maintenance treatment strategy for adults with HIV-1 (ANRS 170 QUATUOR): a randomised, open-label, multicentre, parallel, non-inferiority trial.

Background: Intermittent (on 4 days per week) antiretroviral therapy (ART) for patients with HIV-1 might be more convenient, better tolerated, and cheaper than continuous treatment. We aimed to establish the efficacy and safety of a 4-days-on and 3-days-off (intermittent) maintenance regimen versus a standard 7 day (continuous) maintenance regimen.

Methods: In a randomised, open-label, multicentre, parallel, non-inferiority trial, we randomly assigned (1:1) adults with HIV-1 infection with a plasma viral load (pVL) of less than 50 copies per mL for more than 12 months and no drug-resistance mutations to either the intermittent regimen or their existing continuous maintenance regimen, with stratification according to third therapeutic agent (protease inhibitor, non-nucleoside reverse transcriptase inhibitor, or integrase-strand transfer inhibitor).

Prevalence of genotypic baseline risk factors for cabotegravir + rilpivirine failure among ARV-naive patients.

Background: Multivariable baseline factor analysis across cabotegravir + rilpivirine clinical trials showed that HIV-1 subtypes A6/A1 and the presence of rilpivirine resistance-associated mutations (RAMs) were associated with an increased risk of virological failure of this dual therapy. The aim of this study was to describe the prevalence of genotypic baseline risk factors for cabotegravir + rilpivirine failure among ARV-naive patients.

Patients And Methods: From 2010 to 2020, 4212 sequences from ARV-naive patients were collected from three large Parisian academic hospital genotypic databases.

Pharmacological data of a successful 4-days-a-week regimen in HIV antiretroviral therapy (ANRS 162-4D trial).

Introduction: Few data are available on plasma concentrations of antiretroviral therapy (ARV) during intermittent treatment.

Objective: To compare plasma concentrations in OFF vs ON treatment periods at several time points during treatment.

Methods: During a successful 48-week multicenter study (ANRS 162-4D trial) of 4 days with treatment (ON) followed by 3 days without treatment (OFF) in adults treated by two nucleoside analogues and a third agent belonging to a boosted protease-inhibitor (PI, darunavir [DRV], atazanavir [ATV], lopinavir [LPV]) or a non-nucleoside-reverse-transcriptase inhibitor (NNRTI, efavirenz [EFV], etravirine [ETR], rilpivirine [RPV]) conducted in 100 patients (96% success), we determined the plasma concentrations of ARV.

SARS-COV2 infection in 30 HIV-infected patients followed-up in a French University Hospital.

Introduction: An acute respiratory disease caused by a novel coronavirus (SARSCOV2) is spreading from China since January 2020. Surprisingly, few cases of Covid-19 have been reported in people living with HIV (PLWHIV).

Methods: Here we present a series of 30 PLWHIV diagnosed for SARS-COV2 infection.

Pharmacovirological analyses of blood and male genital compartment in patients receiving dolutegravir + lamivudine dual therapy as a switch strategy (ANRS 167 LAMIDOL trial).

Objectives: To describe plasma residual HIV viraemia, cellular HIV reservoir size, blood plasma drug concentrations and their male genital tract penetration during the maintenance dual therapy dolutegravir + lamivudine.

Patients And Methods: ANRS167 LAMIDOL enrolled 104 virologically suppressed patients to switch to dolutegravir + lamivudine. In this pharmacovirological substudy, ultrasensitive plasma viral load (USpVL) and plasma drug concentrations were measured at Day 0 (D0), Week 24 (W24) and W48 of dolutegravir + lamivudine, and HIV-DNA was measured at W-8 and W48.

Cryptococcus genetic diversity and mixed infections in Ivorian HIV patients: A follow up study.

Genetic diversity analyses were performed by sero-genotyping and multi-locus sequence typing on 252 cryptococcal isolates from 13 HIV-positive Ivorian patients followed-up for cryptococcal meningitis. Antifungal susceptibility analyses were performed according to the CLSI M27A3 method. The majority (67.

Implementation of an intensive adherence intervention in patients with second-line antiretroviral therapy failure in four west African countries with little access to genotypic resistance testing: a prospective cohort study.

Background: The decision about whether to switch to third-line antiretroviral therapy (ART) in patients with treatment failure on second-line therapy is difficult in settings with little access to genotypic resistance testing. In this study, we used a standardised algorithm including a wide range of adherence-enhancing interventions followed by a new viral load measurement to decide whether to switch to third-line therapy in this situation. The decision, made on the basis of effectiveness of the adherence reinforcement to drive viral resuppression, did not use genotypic resistance testing.

HIV Infection in North African Patients.

North Africa is one of the rare regions where the HIV epidemic is growing. In France, 5% of the migrants discovering their HIV infection are from North Africa. The objective of this study was to compare the sociodemographic characteristics and outcomes of North African and French HIV-infected patients.

New mechanisms of resistance in virological failure to protease inhibitors: selection of non-described protease, Gag and Gp41 mutations.

Objectives: To further characterize HIV-1 viruses of patients experiencing unexplained virological failure (VF) on PI-containing regimens, ultradeep sequencing was performed on protease, gag and gp41 genes in patients failing a first-line treatment.

Methods: All naive patients initiating an antiretroviral treatment based on boosted darunavir, atazanavir or lopinavir and experiencing VF without any transmitted drug resistance mutation detected by Sanger sequencing on protease and reverse transcriptase genes were selected. Ultradeep sequencing (IlluminaTM Nextera®) was performed on protease, gag and gp41 genes in plasma before initiation of treatment and at VF to identify emergent mutations.

"Real life" use of raltegravir during pregnancy in France: The Coferal-IMEA048 cohort study.

Introduction: Limited "real life" data on raltegravir (RAL) use during pregnancy are available. Thus, we aimed at describing effectiveness and safety of RAL-based combined antiretroviral therapy (cART) in this setting.

Methods: HIV-1-infected women receiving RAL during pregnancy between 2008 and 2014 in ten French centers were retrospectively analysed for: (1) proportion of women receiving RAL anytime during pregnancy who achieved a plasma HIV-RNA (pVL) < 50 copies/mL at delivery, and (2) description of demographics, immuno-virological parameters and safety in women and new-borns.

Concomitant Use of Cotrimoxazole and Atazanavir in HIV-infected Patients: A Therapeutic Drug Monitoring and Pharmacovigilance Based Dual Approach.

Background: Cotrimoxazole is the main antibiotic used in primary prophylaxis for opportunistic infections in advanced HIV infection. This drug can inhibit one of the metabolic pathways of atazanavir (ATV), such as the cytochromes P450 (CYP) 2C8/2C9 and could interfere with its safety and efficacy.

Objective: We studied the drug-drug interaction (DDI) between cotrimoxazole and ATV by using therapeutic drug monitoring (TDM) and pharmacovigilance (PV) approaches.

Incidence of and risk factors for medical care interruption in people living with HIV in recent years.

Objectives: With HIV treatment as a prevention strategy, retention in care remains a key for sustained viral suppression. We sought to identify HIV-infected patients at risk for medical care interruption (MCI) in a high-income country.

Methods: The HIV-infected patients enrolled had to attend the clinic at least twice between January 2010 and October 2014 and were followed up until May 2016.

HIV-1 protease, Gag and gp41 baseline substitutions associated with virological response to a PI-based regimen.

Objectives: To assess, at ART initiation, the impact of baseline substitutions in protease, Gag and gp41 regions on the virological response to a first-line PI-based regimen.

Patients And Methods: One hundred and fifty-four HIV-infected ART-naive patients initiating a PI-based regimen including darunavir (n = 129) or atazanavir (n = 25) were assessed, including 36 experiencing virological failure (VF). Whole pol, gag and gp41 genes were sequenced at ART baseline by ultra-deep sequencing (UDS) using Illumina® technology.

Dolutegravir and lamivudine maintenance therapy in HIV-1 virologically suppressed patients: results of the ANRS 167 trial (LAMIDOL).

Objectives: To evaluate the dolutegravir+lamivudine combination in virologically suppressed patients living with HIV.

Methods: The ANRS 167 LAMIDOL trial was an open-label, single arm, multicentre trial assessing once-daily dolutegravir (50 mg)+lamivudine (300 mg) in virologically suppressed HIV-1 patients on first-line triple-drug regimens. The main criteria for inclusion in the trial were plasma viral load (pVL) ≤50 copies/mL for ≥2 years, CD4 nadir >200 cells/mm3 and WT HIV prior to treatment initiation.

Week 96 efficacy of lopinavir/ritonavir monotherapy in virologically suppressed patients with HIV: a randomized non-inferiority trial (ANRS 140 DREAM).

Background: Sparing of antiretroviral drug classes could reduce the toxicity and cost of maintenance treatment for HIV infection.

Objectives: To evaluate the non-inferiority of efficacy and the safety of lopinavir/ritonavir (r) monotherapy versus a single-tablet regimen of efavirenz, emtricitabine and tenofovir (EFV/FTC/TDF) over 2 years.

Methods: Adults on stable ART with plasma HIV-1 RNA viral load <50 copies/mL for the past 12 months and no documented treatment failure were randomized to receive either lopinavir/r or EFV/FTC/TDF for 2 years.

High virological suppression regardless of the genotypic susceptibility score after switching to a dolutegravir-based regimen: week 48 results in an observational cohort.

Objectives: To assess, in a clinical cohort, the efficacy of switching current ART in virologically suppressed patients to a dolutegravir-based regimen, regardless of the genotypic susceptibility score (GSS).

Patients And Methods: This was an observational single-centre study assessing ART-treated patients with plasma viral load (pVL) <50 copies/mL who were switched to a dolutegravir-based regimen with 1 year of follow-up. PCR negative was defined as an undetected PCR signal.