Mojgan Hessamfar

Objectives: To characterize real‐world treatment switching in France to bictegravir (BIC or B) or dolutegravir (DTG)‐based regimens with a focus on treatment persistence, effectiveness (HIV‐1 RNA ≤50 copies/ml) and particular attention to the prevalence and incidence of comorbidities. Methods: People living with HIV from the prospective ANRS‐CO3‐AquiVIH‐NA cohort, who switched from effective antiretroviral treatment (ART) to a BIC‐ or DTG‐based regimen between 2018 and 2021, were eligible for analysis. Results: A total of 2275 people living with HIV were included (52% receiving B/F/TAF, 8% DTG/3TC/ABC, 18% DTG/RPV, 22% DTG/3TC) with a median age of 53–56 years and a comorbidity prevalence of 71%–75% across treatment groups (chronic kidney disease (CKD) 15%–25%, diabetes mellitus 15%–19%, hypertension 57%–64%). Viral suppression rates at month 18 (LOCF, last observation carried forward) using a missing‐equals‐excluded (M = E) approach were 97% on B/F/TAF, 95% on DTG/3TC/ABC, 97% on DTG/RPV and 96% on DTG/3TC. Discontinuation rates were 16.5% for B/F/TAF, 37.5% for DTG/3TC/ABC, 16.7% for DTG/RPV and 17.3% for DTG/3TC, driven by adverse events in 5.6%, 12.5%, 5.6% and 6.1%, respectively. Comorbidity incidence rates/1000 person years in those free of the respective disease were 39 for hypertension, 22 for diabetes mellitus, 13 for cardiovascular events and 5 for CKD. Conclusions: In this real‐world cohort, treatment persistence 18 months after therapy switch was similar for B/F/TAF, DTG/RPV and DTG/3TC, but significantly lower for DTG/3TC/ABC. All regimens maintained high levels of viral suppression. Furthermore, the cohort illustrates the disease burden experienced by middle‐aged and elderly people living with HIV and highlights the importance of adapting ART to the specific needs of this population.

Background: Dexamethasone and tocilizumab are used to treat severely ill COVID-19 patients admitted to intensive care units (ICUs). We explored whether combination therapy increased the risk of superinfection compared to dexamethasone alone. Methods: This observational, retrospective study included critically ill COVID-19 adult patients admitted to our ICU because of respiratory failure. Patients received dexamethasone with (Group 1) or without (Group 2) tocilizumab. Data were collected from electronic medical files. Results: A total of 246 patients were included, of whom 150 received dexamethasone and tocilizumab, while 96 received dexamethasone alone. Acute respiratory distress syndrome was evident on admission in 226 patients, 56 of whom required mechanical ventilation (MV). Superinfections, mainly respiratory, were diagnosed in 59 patients, including 34/150 (23%) in Group 1 and 25/96 (26%) in Group 2 (p = 0.32). After multivariate analysis, the factors associated with a higher risk of superinfection included hematological malignancy (hazard ratio (HR): 2.47 (1.11–5.47), p = 0.03), MV (HR: 3.74 (1.92–7.26), p = 0.0001), and a higher SAPS-II score on admission (HR: 1.03 (1.01–1.06), p = 0.006). Conclusion: In critically ill COVID-19 patients, the addition of tocilizumab to dexamethasone was not associated with an increased risk of superinfection.

We proposed a new HIV-1 therapeutic vaccine based on conserved cytotoxic T lymphocyte (CTL) epitopes of archived HIV-1 DNA according to their affinity to the dominant HLA-A and -B alleles of the population investigated. Our proposal (Hla Fitted VAC, HFVAC) was composed of 15 peptides originating from the RT, gag and nef parts of proviral DNA. Our aim was to investigate baseline immune reactivity to the vaccine in HIV-1 chronically infected patients at success of antiretroviral therapy (ART) who would be eligible for a therapeutic vaccine. Forty-one patients were tested. Most of them had been infected with HIV-1 subtype B and all had been receiving successful ART for 2 to 20 years. The predominant HLA-A and -B alleles were those of a Caucasian population. ELISPOT was carried out using the HFVAC peptides. In 22 patients, the PD-1 marker was investigated on CD4+ and CD8+ T cells by flow cytometry in order to evaluate global T cell exhaustion. ELISPOT positivity was 65% overall and 69% in patients exhibiting at least one HLA allele fitting with HFVAC. The percentages of CD4+ and CD8+ T cells expressing PD-1 were high (median values 23.70 and 32.60, respectively), but did not seem to be associated with an impairment of the immune response investigated in vitro. In conclusion, reactivity to HFVAC was high in this ART-treated population with dominant HLA alleles, despite potential cellular exhaustion associated with the PD-1 marker.

One of the approaches by which the scientific community is seeking to cure HIV is the use of therapeutic vaccination. Previous studies have highlighted the importance of the virus-specific CD8+ T cell cytotoxic responses for the immune control of HIV and have oriented research on vaccine constructs based on CTL epitopes from circulating HIV-1 strains. The clinical trials with therapeutic vaccines to date have had limited success likely due to (i) a discrepancy between archived CTL epitopes in the viral reservoir and those in circulating viruses before antiretroviral therapy (ART) initiation and (ii) the lack of strong affinity between the selected CTL epitopes and the HLA grooves for presentation to CD8+ cells. To overcome these limitations, we launched the Provir/Latitude 45 study to identify conserved CTL epitopes in archived HIV-1 DNA according to the HLA class I alleles of aviremic patients, most of whom are under ART. The near full-length genomes or Gag, Pol and Nef regions of proviral DNA were sequenced by Sanger and/or Next Generation Sequencing (NGS). The HLA-A and B alleles were defined by NGS or molecular analysis. The TuTuGenetics software, which moves a sliding window of 8 to 10 amino acids through the amino acid alignment, was combined with the Immune Epitope Data Base (IEDB) to automatically calculate the theoretical binding affinity of identified epitopes to the HLA alleles for each individual. We identified 15 conserved epitopes in Pol (11), Gag (3), and Nef (1) according to their potential presentation by the dominant HLA-A and B alleles and now propose to use the corresponding conserved peptides in a multi-epitopic vaccine (HLA-fitted VAC, HFVAC).

To describe trends and determinants of severe morbidity in HIV-infected women and men. A French prospective cohort of HIV-infected patients of both sexes and all transmission categories. We used hospital admission data from January 2000 to December 2008. A severe morbid event (SME) was defined as a clinical event requiring hospitalization for ≥48 h, several events could be reported during hospitalization. Yearly incidence rates of SME were estimated and compared using Generalized Estimating Equations. Among 4,987 patients (27% women), followed for a median of 8.7 years, 1,473 (30%) were hospitalized (3,049 hospitalizations for 5,963 SME). The yearly incidence rate of hospitalization decreased in men, from 155 in 2000 to 80/1,000 person-years (PY) in 2008 and in women, from 125 to 71/1,000 PY, (p50 years, HIV RNA >10,000 copies, CD4 3, AIDS stage, hepatitis C co-infection and cardiovascular risk factors (diabetes, high blood pressure, and tobacco use) were associated with SME. HIV-infected individuals in care in France require less and less frequently hospitalization. Women are now presenting with severe hepatic and cardio-vascular events. Disparities in SME between men and women are primarily explained by different exposure patterns to risk factors. Women should be targeted to benefit cardiovascular prevention policies as well as men.