Incidence of COVID-19 mRNA vaccine symptomatic breakthrough infections during Omicron circulation in adults with or without infection prior to vaccination.

OBJECTIVES: COVID-19 vaccine breakthrough infections were frequently reported during circulation of the Omicron variant. The ANRS|MIE CoviCompareP study investigated these infections in adults vaccinated and boosted with BNT162b2 [Pfizer-BioNTech] and with/without SARS-CoV-2 infection before vaccination. METHODS: In the first half of 2021, healthy adults (aged 18-45, 65-74 and 75 or older) received either one dose of BNT162b2 (n = 120) if they had a documented history of SARS-CoV-2 infection at least five months previously, or two doses (n = 147) if they had no history confirmed by negative serological tests. A first booster dose was administered at least 6 months after the primary vaccination, and a second booster dose, if any, was reported in the database. Neutralizing antibodies (NAbs) against the European (D614G) strain and the Omicron BA.1 variant were assessed up to 28 days after the first booster dose. A case-control analysis was performed for the 252 participants who were followed up in 2022, during the Omicron waves. RESULTS: From January to October 2022, 78/252 (31%) had a documented symptomatic breakthrough infection after full vaccination: 21/117 (18%) in those who had been infected before vaccination vs. 57/135 (42%) in those who had not. In a multivariate logistic regression model, factors associated with a lower risk of breakthrough infection were older age, a higher number of booster doses, and higher levels of Omicron BA.1 NAb titers in adults with infection before vaccination, but not in those without prior infection. CONCLUSION: Our results highlight the need to consider immune markers of protection in association with infection and vaccination history.

Low level of baseline resistance in recently HCV-infected men who have sex with men with high-risk behaviours.

OBJECTIVES: Presence of baseline hepatitis C virus (HCV) resistance-associated substitutions (RASs) can impair treatment outcome of direct-acting antivirals. We investigated the prevalence of pre-treatment HCV resistance among recently HCV-infected men who have sex with men (MSM) with high risk behaviours, either human immunodeficiency virus (HIV) co-infected or at high risk of HIV acquisition and under pre-exposure prophylaxis (PrEP). METHODS: NS5A and NS3 fragments were deep sequenced on pre-treatment samples of 72 subjects using Illumina MiSeq paired-end sequencing technology. Ultra-deep sequencing data were analysed by SmartGene® platform. RASs mentioned in the literature were analysed and interpreted depending on genotype (GT) at 10% cut-off. RESULTS: HCV genotyping showed 36 (50.0%) GT1a, 31 (43.1%) GT4d and 5 (6.9%) GT3a infections. Fifty-five patients (76.4%) were co-infected with HIV and 15 (20.8%) received PrEP. In GT1a viruses, NS3 RASs were found in 4/30 viruses (13.3%; S122 G/N, R155 K and I170 V) and Q80 K polymorphism was present in 14/30 viruses (46.7%). No NS3 RASs were detected in GT4d and GT3a viruses. NS5A RASs were detected in 3/36 GT1a viruses (8.3%; Q30E/R, L31 M and H58 L). NS5A subtype-specific polymorphisms L30R and T58 P were found at high frequencies in 31/31 (100%) and 16/31 (51.6%) GT4d viruses, respectively. One RAS M31 L was also observed along with the polymorphisms L30R and T58 P. No NS5A RASs were detected in GT3a viruses. CONCLUSION: A low level of RASs to NS3 and NS5A inhibitors in pre-treatment samples was detected in the study population. Our findings reassure the clinical management of HCV infection in this high-risk population.

Coverage of Sex Acts by Event-Driven Pre-exposure Prophylaxis: A Sub-Study of the ANRS IPERGAY Trial.

We assessed the coverage of sex acts by event-driven pre-exposure prophylaxis (ED-PrEP) over a 2-month period in 54 participants in the open label phase of the ANRS Ipergay trial. Participants received an electronic monitoring system device to record bottle openings. Self-questionnaires collected daily information on PrEP intake and sexual behavior. Intake was also estimated through returned pill counts. Full coverage of sex acts was defined as at least one pill taken both within 24 h before and within 48 h following sex. There was a strong correlation (r = - 0.92) between the number of bottle openings and returned pill counts. During the study, 42 participants (78%) practiced ED-PrEP and 12 (22%) daily PrEP with bottle openings at least 5 days/week whatever their sexual activity. Out of the 154 reported receptive anal sex acts, 81% were condomless: among them, PrEP coverage was hight: 97% among those practicing daily PrEP and 82% among those using ED-PrEP.

Uncommon Detection of Mixed HCV Genotype Infections in Recently Infected Men Who Have Sex with Men.

INTRODUCTION: Mixed hepatitis C virus (HCV) genotype (GT) infections are clinically important as different genotypes have varied sensitivities to direct-acting antivirals (DAAs). A high prevalence of mixed GT infections was observed in individuals who inject drugs and had multiple HCV exposures. The prevalence of mixed HCV GT infections in men who have sex with men (MSM) and high-risk behaviors was investigated by ultra-deep sequencing (UDS). METHODS: NS5B fragment was sequenced from viruses of patients with recent HCV infection: there were 50 HIV-positive and 18 HIV-negative patients, including 13 from the ANRS Pre-Exposure Prophylaxis (PrEP) IPERGAY study. UDS data were analysed using Geneious (version 10.3.2). Phylogenetic trees were constructed using FastTree (version 2.1). RESULTS: HCV sequencing showed GT1a (47.1%), GT4d (41.2%), GT3a (8.8%) and GT2k (2.9%). We detected three (4.4%) mixed GT infections: one between predominant GT4d and minority GT1a, one between predominant GT4d and minority GT1b, and one between predominant GT1a and minority GT4d virus. The rates of minority GT viral populations detected in viruses of the three patients with mixed GT infections were 0.32%, 10.7%, and 1.3%, respectively. The first two patients were HIV co-infected and the third was HIV-negative under PrEP. The anti-HCV treatment was successful in all three patients. CONCLUSION: This work showed uncommon mixed HCV GT infections in MSM at high risk of multiple HCV exposures. The impact of these infections on treatment response has not been established but further studies on more patients are necessary. To prevent treatment failure in this population, regular monitoring of treatment response is needed, particularly when pan-genotypic treatment is not used.

Shared HCV Transmission Networks Among HIV-1-Positive and HIV-1-Negative Men Having Sex With Men by Ultradeep Sequencing.

OBJECTIVE: Several studies reported hepatitis C virus (HCV) transmission networks among men having sex with men (MSM) in Europe and the spread of HCV strains from HIV-HCV coinfected toward HCV monoinfected MSM. We aimed to investigate HCV transmission dynamics among HIV-positive and HIV-negative MSM by ultradeep sequencing (UDS). DESIGN AND METHODS: NS5B fragment (388 bp) was sequenced from virus of 50 HIV-positive and 18 HIV-negative patients diagnosed with recent HCV infection. UDS data were analyzed by Geneious (version 10.3.2). Phylogenetic trees were constructed by FastTree (version 2.1) and submitted to ClusterPicker (version 1.2.3) for transmission chain detection at different thresholds of maximum genetic distance (MGD) (3% for Sanger, 3% and 4.5% for UDS). RESULTS: Ten, 17, and 18 HCV transmission chains were identified by Sanger at 3%, UDS at 3% and at 4.5% of MGD, respectively. Of 68 subjects enrolled, 38 (55.9%), 38 (55.9%), and 43 (65.3%) individuals were involved in transmission networks found by Sanger at 3%, UDS at 3%, and at 4.5% of MGD, respectively. Mixed transmission chains including HIV-positive and HIV-negative subjects were detected for 8/10 chains by Sanger at 3%, for 9/17 by UDS at 3%, and for 10/18 by UDS at 4.5% of MGD. Overall, the number of HIV-negative individuals clustering with HIV-positive ones was 9/18 by Sanger, 9/18 by UDS at 3%, and 10/18 by UDS at 4.5% of MGD. CONCLUSIONS: HIV-positive and HIV-negative MSM shared HCV transmission networks, which emphasizes the need for HCV surveillance and prevention measures in these communities regardless of the HIV status.

Current management of late onset neonatal bacterial sepsis in five European countries.

UNLABELLED: Late onset neonatal sepsis (LOS) has a high mortality and the optimal management is poorly defined. We aimed to evaluate new expert panel-derived criteria to define LOS and characterize the current management and antibiotic susceptibility of LOS-causing organisms in Europe. A prospective observational study enrolled infants aged 4 to 90 days in five European countries. Clinical and laboratory findings as well as empiric treatment were recorded and patients were followed until the end of antibiotic therapy. Failure was defined as a change of primary antibiotic, no resolution of clinical signs, appearance of new signs/pathogens or death. Antibiotic therapy was considered appropriate if the organism was susceptible to at least one empiric antibiotic. 113 infants (median age 14 days, 62 % ≤1500 g) were recruited; 61 % were culture proven cases (28 CoNS, 24 Enterobacteriaceae, 11 other Gram-positives and 6 Gram-negative non-fermentative organisms). The predictive value of the expert-panel criteria to identify patients with a culture proven LOS was 61 % (95 % CI 52 % to 70 %). Around one third of Enterobacteriaceae were resistant to ampicillin + or cefotaxime + gentamicin but only 10 % to meropenem. Empiric treatment contained a total of 43 different antibiotic regimens. All-cause mortality was 8 % with an additional 45 % classified as failure of empiric therapy, mainly due to change of primary antibiotics (42/60). CONCLUSIONS: The expert panel-derived diagnostic criteria performed well identifying a high rate of culture proven sepsis. Current management of LOS in Europe is extremely variable suggesting an urgent need of evidence-based guidelines.

Long-term effects of intermittent interleukin-2 therapy in chronic HIV-infected patients (ANRS 048-079 Trials).

OBJECTIVE: Interleukin (IL)-2 therapy leads to significant CD4 cell increases in HIV-infected patients. Since phase III trials are ongoing, studies supporting the long-term feasibility of this strategy are needed. METHODS: We studied the long-term outcomes of 131 patients treated with IL-2 in two studies initiated either before (ANRS 048) or following (ANRS 079) the advent of HAART. RESULTS: At the last assessment (median follow-up 3.4 years), these patients experienced a gain of 428 cells/microl and a decrease in plasma HIV RNA to 1.70 log10 copies/ml. In both studies, high CD4 cell counts were maintained with a median of ten 5-day cycles of subcutaneous IL-2. Median time since the last cycle was 2 years. At last assessment, 59% of 048 patients maintained a non-HAART regimen. Detailed analysis at week 170 showed that median CD4 cell counts were 856 (048) and 964 (079) cells/microl. This corresponded to a gain from baseline of 515 (048) and 627 (079) cells/microl. The median viral load decreases from baseline and corresponded to 1.70 (048) and 1.88 (079) log10 copies/ml. Comparisons across the studies showed that CD4 gains and viral load changes were similar whether HAART or non-HAART was used. The frequency of cycling, but not CD4 cell counts, viral loads or antiviral regimen at baseline, was predictive of long-term CD4 gain (P = 0.03). CONCLUSION: Altogether, these observations support IL-2 as a long-term therapeutic strategy in HIV infection.