Antiretroviral therapy initiated during PHI promotes long-term reduction of HIV reservoir size. In patients with sustained virologic suppression, inflammation may be driven by non-HIV-related factors.

Background Interpretation of the increase in certain inflammatory markers in virally suppressed HIV-infected individuals must rely on an appropriate uninfected control group well characterized for non-HIV-related factors that contribute to chronic inflammation, e.g. smoking, alcohol consumption, or being overweight. We compared the inflammatory profiles of HIV-infected participants under long-term antiretroviral therapy (ART) with those of two HIV-uninfected groups with contrasting health behaviours. Methods We studied 150 HIV-infected participants (42 women, 108 men) under long-term ART (median, 6 years) followed in the ANRS PRIMO cohort since acute/early HIV-1 infection (AHI) diagnosis. Sex and age-matched controls were sampled from i) the ANRS IPERGAY pre-exposure prophylaxis trial among men at high risk for HIV infection and with high frequencies of non-HIV factors of inflammation ii) the ANRS COHVAC cohort of volunteers in vaccine trials with a low-risk profile for HIV infection . We measured the plasma levels of ten inflammatory markers. Findings After adjusting for smoking, alcohol use and body mass index, both HIV-infected men and women had higher levels of sCD14, sCD163, sTNFRII and I-FABP than their high-risk IPERGAY and low-risk COHVAC counterparts. Hierarchical clustering showed a subset of 15 PRIMO participants to have an inflammatory profile similar to that of most HIV-negative participants. These participants already had favourable markers at AHI diagnosis. Interpretation Long-term ART, even when initiated at a low level of immunodeficiency, fails to normalize monocyte/macrophage activation and gut epithelial dysfunction. Persistent inflammation under treatment may be related to an increased inflammatory profile since AHI. Funding ANRS and Paris-Saclay University.

Background We aimed to study whether social patterns of exposure to SARS-CoV-2 infection changed in France throughout the year 2020, in light to the easing of social contact restrictions. Methods A population-based cohort of individuals aged 15 years or over was randomly selected from the national tax register to collect socio-economic data, migration history, and living conditions in May and November 2020. Home self-sampling on dried blood was proposed to a 10% random subsample in May and to all in November. A positive anti-SARS-CoV-2 ELISA IgG result against the virus spike protein (ELISA-S) was the primary outcome. The design, including sampling and post-stratification weights, was taken into account in univariate and multivariate analyses. Results Of the 134,391 participants in May, 107,759 completed the second questionnaire in November, and respectively 12,114 and 63,524 were tested. The national ELISA-S seroprevalence was 4.5% [95%CI: 4.0%-5.1%] in May and 6.2% [5.9%-6.6%] in November. It increased markedly in 18-24-year-old population from 4.8% to 10.0%, and among second-generation immigrants from outside Europe from 5.9% to 14.4%. This group remained strongly associated with seropositivity in November, after controlling for any contextual or individual variables, with an adjusted OR of 2.1 [1.7–2.7], compared to the majority population. In both periods, seroprevalence remained higher in healthcare professions than in other occupations. Conclusion The risk of Covid-19 infection increased among young people and second-generation migrants between the first and second epidemic waves, in a context of less strict social restrictions, which seems to have reinforced territorialized socialization among peers.

We assessed the impact of early antiretroviral treatment (ART) on human immunodeficiency virus (HIV) antibody detection by rapid tests in 44 individuals after several years of successful ART. HIV self-tests and point-of-care tests were negative in 30% and 7%-9% of cases, respectively. These data reinforce the message that patients should never be retested after entering HIV care.

Introduction: Previous studies have reported better immunovirological characteristics in women compared with men after HIV seroconversion. We investigated whether differences persisted under long-term antiretroviral therapy (ART) in individuals treated since acute and early HIV-1 infection (AHI). Methods: Data were obtained for 262 women and 1783 men enrolled between 1996 and 2017 in the French multicentre ANRS PRIMO cohort. We modelled the viral response, long-term immune recovery and HIV DNA decay in the 143 women and 1126 men who initiated ART within the first three months of infection. Results: The participants were mostly white. The mean age was 37 years at AHI diagnosis. Pre-ART viral loads were lower in women than men, 5.2 and 5.6 log 10 copies/mL (p = 0.001). After ART initiation, women more rapidly achieved viral suppression than men (adjusted hazard ratio: 1.33, 95% confidence interval 1.09 to 1.69). They also experienced a faster increase in CD4 + T-cell count and CD4:CD8 ratio during the first months of treatment. Sex-related differences in CD4 + T-cell counts were more pronounced with increasing age. This led to a sustained mean difference of 99 to 168 CD4 + T-cells/µL depending on age between women and men at 150 months of ART. Moreover, CD4:CD8 ratio of women was higher than that of men by 0.31, at 150 months of ART. There was no statistically significant difference between sexes for the levels of HIV DNA over time (mean estimate at the last modelling point: 1.9 log 10 copies/10 6 PBMCs after 70 months of ART for both sexes). Conclusions: The high level of immune recovery and decrease in total HIV DNA levels achieved after ART initiation during AHI reinforce the importance of early diagnosis of HIV infection and immediate ART initiation. The immunological benefit of being female increased throughout prolonged ART duration, which may give women additional protection from adverse clinical events and premature ageing.

Background Previous studies have reported that polymicrobial peritonitis in peritoneal dialysis (PD) is associated with poor outcomes, but recent data from European cohorts are scarce. Methods We included from the French Language Peritoneal Dialysis Registryall patients ≥ 18 years who started PD between January 2014 and November 2020. We compared microbiology and patient characteristics associated with mono- and polymicrobial peritonitis. We assessed patient outcomes after a first polymicrobial peritonitis using survival analysis with competing events. We differentiated microorganisms isolated from dialysis effluent as enteric or non-enteric pathogens. Results 8848 patients contributed 13 023 patient-years of follow-up and 3348 culture-positive peritonitis, including 251 polymicrobial ones. This corresponded to rates of 0.32 and 0.02 episodes/patient-year, respectively. For most patients (72%) who experienced polymicrobial peritonitis, this was their first peritonitis episode. Enteric pathogens were more frequently isolated in poly- than in monomicrobial peritonitis (57 vs 44%, P < 0.001). In both cases of peritonitis with or without enteric pathogens, the poly- versus monomicrobial character of the peritonitis was not associated with mortality in patients who did not switch to hemodialysis (adjusted cause-specific hazard ratio, a.cs-HR, 1.2 [95% CI, 0.3–5.0], P = 0.78 and 1.1 [0.7–1.8], P = 0.73, respectively). However, the risks of death and switch to hemodialysis were higher for monomicrobial peritonitis with enteric pathogens, compared to those without (a.cs-HR, 1.3 [1.1–1.7], P = 0.02 and 1.9 [1.5–2.4], P < 0.0001, respectively). Conclusion Isolation of enteric pathogens, rather than the polymicrobial character of the peritonitis, is associated with poorer outcomes.

Background: We aimed to study whether social patterns of exposure to SARS-CoV-2 infection changed in France throughout the year 2020, in light to the easing of social contact restrictions. Methods: A population-based cohort of individuals aged 15 years or over was randomly selected from the national tax register to collect socio-economic data, migration history, and living conditions in May and November 2020. Home self-sampling on dried blood was proposed to a 10% random subsample in May and to all in November. A positive anti-SARS-CoV-2 ELISA IgG result against the virus spike protein (ELISA-S) was the primary outcome. The design, including sampling and post-stratification weights, was taken into account in univariate and multivariate analyses. Results: Of the 134,391 participants in May, 107,759 completed the second questionnaire in November, and respectively 12,114 and 63,524 were tested. The national ELISA-S seroprevalence was 4.5% [95%CI: 4.0%-5.1%] in May and 6.2% [5.9%-6.6%] in November. It increased markedly in 18-24-year-old population from 4.8% to 10.0%, and among second-generation immigrants from outside Europe from 5.9% to 14.4%. This group remained strongly associated with seropositivity in November, after controlling for any contextual or individual variables, with an adjusted OR of 2.1 [1.7-2.7], compared to the majority population. In both periods, seroprevalence remained higher in healthcare professions than in other occupations. Conclusion: The risk of Covid-19 infection increased among young people and second-generation migrants between the first and second epidemic waves, in a context of less strict social restrictions, which seems to have reinforced territorialized socialization among peers.

COVID-19 pandemic responses have dramatically modified the global ecological and epidemiological landscape of many infectious diseases. However, the pandemic’s impacts on antimicrobial resistance (AMR) are currently poorly understood and lack data. While surges in COVID-19 cases during the first wave of the pandemic may have exacerbated AMR, decreases in antibiotic use may have had the opposite effect. To disentangle how pandemic impacts such as lockdowns and modified antibiotic prescribing may affect AMR, we developed a mathematical model formalizing simultaneous transmission of SARS-CoV-2 and colonization with a bacterial pathogen across six pandemic scenarios. We used simulation to assess the effect of each scenario on the bacterial carriage prevalence, antibiotic resistance rate, and the invasive bacterial disease (IBD) incidence, using parameters based on the commensal community bacterium Streptococcus pneumoniae. Pandemic scenarios without community-wide lockdowns all resulted in a decrease in carriage prevalence of antibiotic-sensitive bacteria and an increase in the prevalence of antibiotic-resistant bacteria, while the addition of a population-wide lockdown resulted in a large reduction in colonization prevalence and IBD incidence for both strains (>70%). This translated to an increase in the antibiotic resistance rate across all scenarios to varying degrees, with lingering effects after the cessation of COVID-19 response measures. In the absence of lockdown, a population-wide surge in antibiotic prescribing coincident with the peak in SARS-CoV-2 infection resulted in the greatest increases in resistance rate (23%) and resistant IBD incidence (6%). Within-host interactions, SARS-CoV-2 variants, and population immunity are found to further drive the magnitude of pandemic impacts on resistant IBD incidence. Sensitivity analyses suggest that the extent of such impacts likely varies across different bacterial species. Although real-life scenarios are significantly more complicated, our findings suggest that COVID-19 pandemic responses may significantly impact antibiotic resistance in the community and support the need for monitoring resistance during pandemic waves.