Early versus delayed antiretroviral therapy based on genotypic resistance test: Results from a large retrospective cohort study

Rapid start of antiretroviral therapy (ART) pending genotypic resistance test (GRT) has been recently proposed, but the effectiveness of this strategy is still debated. The rate of virological success (VS), defined as HIV-RNA\u2009<\u200950 copies/ml, with and without GRT was compared in drug-na\uefve individuals enrolled in the Italian ARCA cohort who started ART between 2015 and 2018. 521 individuals started ART: 397 without GRT (pre-GRT group) and 124 following GRT (post-GRT group). Overall, 398 (76%) were males and 30 (6%) were diagnosed with AIDS. In the pre-GRT group, baseline CD4+\u2009cell counts were lower (p\u2009<\u20090.001), and viral load was higher (p\u2009<\u20090.001) than in the post-GRT group. The estimated probability of VS in pre-GRT versus post-GRT group was 72.54% (CI95 : 67.78-76.60) versus 66.94% (CI95 : 57.53-74.26) at Week 24 and 92.40% (CI95 : 89.26-94.62) versus 92.92% (CI95 : 86.35-96.33) at Week 48, respectively (p\u2009=\u20090.434). At Week 48, VS was less frequent among individuals with baseline CD4+\u2009cell counts <200 versus >500 (90.33% vs. 97.33%), log viral load <5.00 versus >5.70 log10 cps/ml (97.17% vs 78.16%; p\u2009<\u20090.001), and those treated with protease inhibitors or non-nucleoside reverse transcriptase inhibitors versus those treated with integrase strand transfer inhibitors (p\u2009<\u20090.001). The rate of VS does not seem to be affected by an early ART initiation pending GRT results, but it could be influenced by the composition of the ART regimen, as well as immuno-virological parameters

Evaluating fostemsavir as a therapeutic option for patients with HIV

Introduction: Despite the unquestionable success of antiretroviral therapy achieved in recent years, there are still cases of heavily treated patients who do not achieve or struggle to maintain undetectable HIV-RNA due to drug resistance. New antiretroviral options are needed to address this issue.Area covered: The authors first provide an overview of fostemsavir and its role in the treatment of HTE PLWH. Data from pre-clinical and clinical studies are reviewed and the pharmacokinetic and farmacodynamic properties are highlited. Drug-drug interactions and safety data from available clinical studies are also discussed.Expert opinion: Fostemsavir is a promising antiretroviral belonging to the class of entry inhibitors; its novel mechanism of action represents a very important innovation. Its use will be limited to the heavytreatment-experienced patient population. This use will have to be monitored to avoid abuse and waste of a molecule that for some patients may represent a life-saving drug

Efficacy and tolerability of dolutegravir/lamivudine versus dolutegravir/rilpivirine in switching from a three-drug regimen based on nonnucleoside reverse transcriptase inhibitors: A retrospective cohort study

Real-life comparisons of dolutegravir/rilpivirine (DTG/RPV) and DTG/lamivudine (3TC) regimens in people living with human immunodeficiency virus (PLWHIV) who switched from a standard three-drug regimen based on nonnucleoside reverse transcriptase inhibitors (NNRTIs) are missing. This study aimed to compare DTG/3TC and DTG/RPV in virologically suppressed patients (HIV-RNA < 50 copies/mL) coming from any NNRTI-based regimen in terms of discontinuation due to virologic failure (VF) discontinuation rates due to all causes, and adverse events. As a secondary outcome, we evaluated the difference in creatinine, total cholesterol, CD4, and triglycerides from baseline to weeks 48 after the switch. Of the 415 PLWHs included in the study, 278 (66.9%) switched to DTG/3TC, and 137 (33.1%) switched to DTG/RPV. Overall, 48 PLWHs (11.6%) discontinued the treatment:38 with DTG/3TC and 10 with DTG/RPV with similar discontinuation rates: 5.01 x 100 py (95% confidence interval [CI] 3.64-6.94) and 4.66 x 100 py (95% CI 2.51-8.67), respectively. The most common reason for discontinuation was toxicity (26 patients, 22/278 [7.9%] in the DTG/3TC group and 4/137 [2.9%] in the DTG/RPV group), mainly neurologic toxicity (never above grade 2). We found no differences in discontinuation rates due to treatment adverse events. Two study participants experienced virological failure in the DTG/3TC arm. We observed no significant difference in CD4 cell counts, lipid parameters, or renal function between the two groups at 48 weeks. This study demonstrated that, in clinical practice, a two-drug regimen with DTG/3TC or DTG/RPV is characterized by a low discontinuation rate and VF in virologically suppressed PLWHs switched from an NNRTI-based three antiretroviral drugs regimen

Long-Term Effectiveness of Rilpivirine-Based Single-Tablet Regimens in a Seven-Year, Two-Center Observational Cohort of People Living with HIV

Data on the long-term durability of rilpivirine (RPV) are still scarce. A two-center retrospective study was performed, including all people living with HIV (PLWH) treated with tenofovir disoproxil fumarate/emtricitabine (TDF/FTC)/RPV or tenofovir alafenamide (TAF)/FTC/RPV in the period January 2013-December 2019. Aims of the study were to assess the rate of discontinuation of the RPV single-tablet regimen (STR) and identify factors associated with the risk of discontinuation according to Cox's regression analysis. A total of 684 PLWH were enrolled. Mean duration of RPV-STR treatment was 192.5 (+/- 99.5) weeks for 123 antiretroviral therapy (ART)-naive participants (18%) and 173.3 (+/- 85.6) weeks for 561 ART-experienced study participants (82%). During the study period, the incidence of discontinuation was 7.7 per 100 person-years. The estimated proportions of discontinuation after 48 and 96 weeks were 5.6% and 13.4%, respectively. Causes of discontinuation were loss to follow-up (30%), side effects (15%), ART optimization (14%), virological failure (VF) (12%), death or transfer to another center (9%), low adherence (7%), drug interactions (6%), simplification to dual therapy (3%), and unknown (3%). No differences were observed in cumulative probability of discontinuation between ART-naive and -experienced PLWH. Heterosexual (hazard ratio [HR] 3.0, 95% confidence interval [CI] 1.4-6.8) and mother-to-child (HR 5.3, 95% CI 1.8-15.3) transmission of HIV infection and history of previous VF (HR 1.7, 95% CI 1.2-2.5) were associated with higher risk of discontinuation. High RPV-STR effectiveness and durability were confirmed in our real-life population of PLWH. Given these data, RPV has the potential to be a drug for life in patients selected according to current guidelines

Predictors of Virological Failure Among People Living with HIV Switching from an Effective First-Line Antiretroviral Regimen

15noneAim of this study was to assess the predictors of virological failure (VF) among patients living with HIV (PLWHIV) switching from an effective first-line antiretroviral therapy (ART) regimen, and to evaluate the emergence of resistance-associated mutations. All adult patients enrolled in the Antiviral Response Cohort Analysis cohort who started ART after 2010, with at least 6 months of virological suppression (VS) before ART switch and with an available genotypic resistance test (GRT) at baseline were included. Thirty-two patients out of the 607 PLWHIV included (5.3%) experienced VF after a median of 11 months from ART switch. Younger age (adjusted Hazard Ratio [aHR] 0.96, 95% confidence interval [CI] 0.92-0.99, p = .023), being male who have sex with male (aHR 0.15, 95% CI 0.03-0.69, p = .014), and longer time from VS to ART switch (aHR 0.97, 95% CI 0.95-1.00, p = .021) resulted protective toward VF, while receiving a first-line regimen containing a backbone other than ABC/3TC or TXF/FTC (aHR 3.61, 95% CI 1.00-13.1, p = .050) and a boosted protease inhibitor as anchor drug (aHR 3.34, 95% CI 1.20-9.28, p = .021) were associated with higher risk of VF. GRT at the moment of VF was available only for 13 patients (40.6%). ART switch in patients with stable control of HIV infection is a safe practice, even if particular attention should be paid in certain cases of patients switching from regimens containing low-performance backbones or protease inhibitors.noneMagnasco, Laura; Pincino, Rachele; Pasculli, Giuseppe; Bouba, Yagai; Saladini, Francesco; Bavaro, Davide Fiore; De Vito, Andrea; Lattanzio, Rossana; Corsini, Romina; Zazzi, Maurizio; Incardona, Francesca; Rossetti, Barbara; Bezenchek, Antonia; Borghi, Vanni; Di Biagio, AntonioMagnasco, Laura; Pincino, Rachele; Pasculli, Giuseppe; Bouba, Yagai; Saladini, Francesco; Bavaro, Davide Fiore; De Vito, Andrea; Lattanzio, Rossana; Corsini, Romina; Zazzi, Maurizio; Incardona, Francesca; Rossetti, Barbara; Bezenchek, Antonia; Borghi, Vanni; Di Biagio, Antoni

Early versus delayed antiretroviral therapy based on genotypic resistance test: Results from a large retrospective cohort study

Introduction: Rapid start of antiretroviral therapy (ART) pending genotypic resistance test (GRT) has been recently proposed, but the effectiveness of this strategy is still debated. Patients and methods: The rate of virological success (VS), defined as HIV-RNA <50 copies/ml, with and without GRT was compared in drug-naïve individuals enrolled in the Italian ARCA cohort who started ART between 2015 and 2018. Results: 521 individuals started ART: 397 without GRT (pre-GRT group) and 124 following GRT (post-GRT group). Overall, 398 (76%) were males and 30 (6%) were diagnosed with AIDS. In the pre-GRT group, baseline CD4+ cell counts were lower (p<0.001), and viral load was higher (p<0.001) than in the post-GRT group. The estimated probability of VS in pre-GRT vs. post-GRT group was 72.54% [CI95: 67.78–76.60] vs. 66.94% [CI95: 57.53–74.26] at week 24 and 92.40% [CI95: 89.26-94.62] vs. 92.92% [CI95: 86.35–96.33] at week 48, respectively (p=0.434). At week 48, VS was less frequent among individuals with baseline CD4+ cell counts <200 vs. >500 (90.33% vs. 97.33%), log viral load <5.00 vs. >5.70 log10 cps/mL (97.17% vs 78.16%) (p<0.001). and those treated with protease inhibitors or non-nucleoside reverse transcriptase inhibitors vs. those treated with integrase strand transfer inhibitors (p<0.001). Conclusions: The rate of VS does not seem to be affected by an early ART initiation pending GRT results, but it could be influenced by the composition of the ART regimen, as well as immuno-virological parameters

Predictors of virological failure among people living with HIV switching from an effective first-line antiretroviral regimen.

Objectives: Aim of this study was to assess the predictors of virological failure (VF) among patients living with HIV (PLWHIV) switching from an effective first-line antiretroviral therapy (ART) regimen, and to evaluate the emergence of resistance-associated mutations (RAMs). Methods: All adult patients enrolled in the ARCA cohort who started ART after 2010, with at least 6 months of virological suppression (VS) before ART switch and with an available genotypic resistance test (GRT) at baseline were included. Results: Thirty-two patients out of the 607 PLWHIV included (5.3%) experienced VF after a median of 11 months from ART switch. Younger age (aHR 0.96, 95%CI 0.92- 0.99, p=0.023), being male who have sex with male (aHR 0.15, 95%CI 0.03-0.69, p=0.014) and longer time from VS to ART switch (aHR 0.97, 95%CI 0.95-1.00, p= 0.021) resulted protective towards VF, while receiving a first-line regimen containing a backbone other than ABC/3TC or TXF/FTC (aHR 3.61, 95%CI 1.00-13.1, p=0.050) and a boosted protease inhibitor (bPI) as anchor drug (aHR 3.34, 95%CI 1.20-9.28, p=0.021) were associated with higher risk of VF. GRT at the moment of VF was available only for 13 patients (40.6%). Conclusions: ART switch in patients with stable control of HIV infection is a safe practice, even if particular attention should be paid in certain cases of patients switching from regimens containing low-performance backbones or PIs

T2Bacteria and T2Resistance Assays in Critically Ill Patients with Sepsis or Septic Shock: A Descriptive Experience

The use of rapid molecular tests may anticipate the identification of causative agents and resistance determinants in the blood of critically ill patients with sepsis. From April to December 2021, all intensive care unit patients with sepsis or septic shock who were tested with the T2Bacteria and T2Resistance assays were included in a retrospective, single center study. The primary descriptive endpoints were results of rapid molecular tests and concomitant blood cultures. Overall, 38 combinations of T2Bacteria and T2Resistance tests were performed. One or more causative agent(s) were identified by the T2Bacteria assay in 26% of episodes (10/38), whereas negative and invalid results were obtained in 66% (25/38) and 8% (3/38) of episodes, respectively. The same pathogen detected by the T2Bacteria test grew from blood cultures in 30% of cases (3/10). One or more determinant(s) of resistance were identified by the T2Resistance assay in 11% of episodes (4/38). Changes in therapy based on T2Bacteria and/or T2Resistance results occurred in 21% of episodes (8/38). In conclusion, T2Bacteria/T2Resistance results can influence early treatment decisions in critically ill patients with sepsis or septic shock in real-life practice. Large, controlled studies remain necessary to confirm a favorable impact on patients’ outcomes and antimicrobial stewardship interventions

Bronchoalveolar lavage fluid characteristics and outcomes of invasively mechanically ventilated patients with COVID-19 pneumonia in Genoa, Italy

BACKGROUND: The primary objective of the study is to describe the cellular characteristics of bronchoalveolar lavage fluid (BALF) of COVID-19 patients requiring invasive mechanical ventilation; the secondary outcome is to describe BALF findings between survivors vs non-survivors.MATERIALS AND METHODS: Patients positive for SARS-CoV-2 RT PCR, admitted to ICU between March and April 2020 were enrolled. At ICU admission, BALF were analyzed by flow cytometry. Univariate, multivariate and Spearman correlation analyses were performed.RESULTS: Sixty-four patients were enrolled, median age of 64years (IQR 58-69). The majority cells in the BALF were neutrophils (70%, IQR 37.5-90.5) and macrophages (27%, IQR 7-49) while a minority were lymphocytes, 1%, TCD3+92% (IQR 82-95). The ICU mortality was 32.8%. Non-survivors had a significantly older age (p=0.033) and peripheral lymphocytes (p=0.012) were lower compared to the survivors. At multivariate analysis the percentage of macrophages in the BALF correlated with poor outcome (OR 1.336, CI95% 1.014-1.759, p=0.039).CONCLUSIONS: In critically ill patients, BALF cellularity is mainly composed of neutrophils and macrophages. The macrophages percentage in the BALF at ICU admittance correlated with higher ICU mortality. The lack of lymphocytes in BALF could partly explain a reduced anti-viral response