High SARS-CoV-2 seroprevalence among health care workers in Bamako referral hospitals: a prospective multisite cross-sectional study (ANRS COV11)

International audienc

SARS-CoV-2 Neutralizing Responses in Various Populations, at the Time of SARS-CoV-2 Variant Virus Emergence: Evaluation of Two Surrogate Neutralization Assays in Front of Whole Virus Neutralization Test

The SARS-CoV-2 neutralizing antibodies response is the best indicator of effective protection after infection and/or vaccination, but its evaluation requires tedious cell-based experiments using an infectious virus. We analyzed, in 105 patients with various histories of SARS-CoV-2 infection and/or vaccination, the neutralizing response using a virus neutralization test (VNT) against B.1, Alpha, Beta and Omicron variants, and compared the results with two surrogate assays based on antibody-mediated blockage of the ACE2-RBD interaction (Lateral Flow Boditech and ELISA Genscript). The strongest response was observed for recovered COVID-19 patients receiving one vaccine dose. Naïve patients receiving 2 doses of mRNA vaccine also demonstrate high neutralization titers against B.1, Alpha and Beta variants, but only 34.3% displayed a neutralization activity against the Omicron variant. On the other hand, non-infected patients with half vaccination schedules displayed a weak and inconstant activity against all isolates. Non-vaccinated COVID-19 patients kept a neutralizing activity against B.1 and Alpha up to 12 months after recovery but a decreased activity against Beta and Omicron. Both surrogate assays displayed a good correlation with the VNT. However, an adaptation of the cut-off positivity was necessary, especially for the most resistant Beta and Omicron variants. We validated two simple and reliable surrogate neutralization assays, which may favorably replace cell-based methods, allowing functional analysis on a larger scale

Seroprevalence and risk factors for HIV, HCV, HBV and syphilis among blood donors in Mali

International audienceBACKGROUND:HIV, HBV and HCV remain a global public health concern especially in Africa. Prevalence of these infections is changing and identification of risk factors associated with each infection in Mali is needed to improve medical care.METHODS:We conducted a cross-sectional study of all individuals donating blood (n = 8207) in 2018 to the blood bank at university hospital in Bamako, Mali, to assess prevalence and risks factors associated with HIV, HBV, HCV and syphilis infections.RESULTS:HIV-seroprevalence was 2.16% and significantly increased with age, being married and decreasing education level. In multivariate analysis, after adjustements with age, marital status and geographical setting, only education level was associated with HIV-infection (OR, 1.54 [95% CI, 1.15-2.07], p = 0.016). HBsAg prevalence was 14.78% and significantly increased with to be male gender. In multivariate analysis, adjusting for age, marital status and type of blood donation, education level (OR, 1.17 [95%CI, 1.05-1.31], p = 0.02) and male gender (OR, 1.37 [95%CI, 1.14-1.65], p = 0.005) were associated with HBV-infection. HCV-prevalence was 2.32% and significantly increased with living outside Bamako. In multivariate analysis, adjusting for gender, age and education level, living outside Bamako was associated with HCV-infection (OR, 1.83 [95% CI, 1.41-2.35], p < 0.001). Syphilis seroprevalence was very low (0.04%) with only 3 individuals infected. Contrary to a prior study, blood donation type was not, after adjustments, an independent risk factor for each infection.CONCLUSIONS:Overall, HIV and HBV infection was higher in individuals with a lower level of education, HBV infection was higher in men, and HCV infection was higher in people living outside of Bamako. Compared to studies performed in 1999, 2002 and 2007 in the same population, we found that HIV and HCV prevalence have decreased in the last two decades whereas HBV prevalence has remained stable. Our finding will help guide infection prevention and treatment programs in Mali

Characterization of Drug Resistance and the Defective HIV Reservoir in Virally Suppressed Vertically Infected Children in Mali

Abstract Background In the perspective of ART-free HIV remission, vertically infected children treated with suppressive ART from early infancy represent an optimal population model to better understand the genetic complexity of the reservoir. Objectives To evaluate the proportion of defective viral population and the genotypic resistance patterns in cell-associated HIV DNA. Methods In a cohort including 93 ART-treated vertically HIV-infected (VHIV) children in Mali with plasma HIV-1 RNA ≤q50\,copies/mL for at least 6\,months, we studied total HIV DNA, percentage of defective genomes and resistance by reverse transcriptase and protease bulk sequencing from whole blood in dried blood spots. Results Children had a median age of 9.9\,years at the time of inclusion (IQR\,=\,7.6\textendash 13.4) and 3.3\,years (IQR\,=\,2\textendash 7) at ART initiation; median ART duration was 5.5\,years (IQR\,=\,3.7\textendash 7.3). The median level of total HIV DNA was 470\,copies/106\,cells with one patient presenting undetectable HIV DNA (&lt;66\,copies/106\,cells). We observed the presence of at least one stop codon in viruses from 34 patients (37%). The presence of stop codons was not correlated with the level of HIV DNA or duration of ART. We showed a high prevalence of HIV-1 resistance in DNA with 26% of children harbouring virus resistant to at least one NRTI and 40% to at least one NNRTI. Conclusions While these VHIV children were successfully treated for a long time, they showed high prevalence of resistance in HIV DNA and a moderate defective HIV reservoir

INSTI-Based Triple Regimens in Treatment-Naïve HIV-Infected Patients Are Associated With HIV-RNA Viral Load Suppression at Ultralow Levels

International audienceBackground: During antiretroviral therapy (ART), HIV-1-infected patients may present with ultralow (UL) HIV-RNA viral loads (VLs) below quantification levels of current assays. Reasons for UL-VL detection and its relation to virological rebound (VR) are unclear.Methods: HIV-1-infected, ART-naïve patients followed at 2 university hospitals were included. All participants had an HIV-RNA >200 copies/mL at ART initiation and achieved a VL 200 copies/mL or 2 VL > 50 copies/mL) while accounting for frequency of VL measurements.Results: Between 2009 and 2013, 717 patients initiated ART containing 2 nucleos(-t)ide reverse transcriptase inhibitors (NRTIs) plus a non-NRTI (29.4%), a protease inhibitor (58.4%), or an integrase-strand transfer inhibitor (INSTI; 12.1%). During a median (interquartile range) 3.4 (2.3-4.6) years, 676 (94.3%) patients achieved UL-VL not detected. In multivariable analysis, UL-VL not detected overtime was associated with younger age (P 500 vs <350/mm3 (P < .001), and INSTI-containing ART (P = .009). One hundred thirty-one (18.3%) patients had VR during follow-up, which was independently associated with a CD4/CD8 ratio <0.8 during follow-up (P = .01) and time spent with UL-VL not detected (P < .001). When UL-VL not detected occurred for ≥50% of the follow-up duration (n = 290), faster time to reach UL-VL not detected (P < .001), faster CD4+ T-cell count increase (P = .03), and faster CD4/CD8 ratio increase (P = .001) were observed.Conclusions: VL suppression at an ultralow level is associated with INSTI-class ART initiation. Extensive VL suppression below ultralow detection could improve immune reconstitution

Qualitative and quantitative HIV antibodies and viral reservoir size characterization in vertically infected children with virological suppression

International audienceBackground: Absence of detectable viraemia after treatment cessation in some vertically HIV-infected (VHIV) children suggests that early initiation of HAART could lead to functional cure.Objectives: We described the factors associated with HIV antibody levels and the viral reservoir size in HAART-treated VHIV children.Methods: Study included 97 VHIV children with virological suppression, in Bamako, Mali. The anti-gp41 antibody activities and HIV serostatus were assessed. The viral reservoir size was measured by quantifying total cell-associated HIV DNA.Results: Among the children studied, the median total HIV DNA level was 445 copies/106 cells (IQR = 187–914) and the median anti-gp41 antibody activity was 0.29 OD (IQR = 0.18–0.75). Low activity of anti-gp41 antibodies was associated with a younger age of HAART initiation (P = 0.01). Overall, eight HIV-1 seroreversions were identified.Conclusions: Study identified potential candidates with low viral reservoir and low antibody levels or activities for future trials aiming to reduce HIV-1 reservoir to limit HAART duration

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

International audienceBackground: 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. A generalized estimation equation with a Poisson distribution was used to compare changes in the proportion of residual viraemia, detectable semen HIV RNA and HIV DNA within and between the two groups over time. Results: The proportion of participants with residual viraemia at Day 0 (D0) and Week 48 (W48) was 16.7% and 25.0% in the 4/7 days group and 22.4% and 29.7% in the 7/7 days group, respectively (+8.3% versus +7.3%, P = 0.971). The proportion of detectable DNA (>40 copies/106 cells) at D0 and W48 was 53.7% and 57.4% in the 4/7 days group and 56.1% and 51.8% in the 7/7 days group, respectively (+3.7% versus -4.3%, P = 0.358). Semen HIV RNA was detectable (≥100 copies/mL) in 2.2% of participants at D0 and 4.5% at W48 in the 4/7 days group versus 6.1% and 9.1% in the 7/7 days group, respectively (+2.3% versus +3.0%, P = 0.743). Emerging resistance at failure was more frequent in the 4/7 days group detected by Sanger sequencing: 3/6 participants versus 1/4 in the 7/7 days group, and similar with the UDS assay: 5/6 versus 4/4, respectively. Conclusions: These findings support the potency of a 4/7 days maintenance strategy on virological suppression at the reservoirs and emergent resistance level, including minority variants

DORAVIR: A French national survey of people with HIV-1 treated by an antiretroviral regimen including Doravirine

Meeting abstract du "19th European AIDS Conference (#EACS2023)", 18‐21 octobre 2023, VarsovieInternational audienc

DORAVIR: A French national survey of people with HIV-1 treated by an antiretroviral regimen including Doravirine

Meeting abstract du "19th European AIDS Conference (#EACS2023)", 18‐21 octobre 2023, VarsovieInternational audienc

Prevalence of HIV-1 Natural Polymorphisms and Integrase-Resistance-Associated Mutations in African Children

Integrase inhibitors (INIs) are a potent option for HIV treatment. Limited data exist on INI resistance in West Africa, particularly in children living with HIV/AIDS. We determined the prevalence of integrase gene polymorphisms and the frequency of naturally occurring amino acid (aa) substitutions at positions associated with INI resistance. Dried blood spot (DBS) samples were obtained from one hundred and seven (107) HIV-1-infected children aged less than 15 years old in two West African countries, Benin and Mali. All children were naïve to INI treatment, 56 were naïve to anti-retroviral therapy (ART), and 51 had received ART. Genetic sequencing of HIV integrase was successful in 75 samples. The aa changes at integrase positions associated with INI resistance were examined according to the Stanford HIV Genotypic Resistance database. The median ages were 2.6 and 10 years for ART-naïve and -treated children, respectively. The most common subtypes observed were CRF02_AG (74.7%) followed by CRF06_cpx (20%). No major INI-resistance mutations at positions 66, 92, 121, 143, 147, 148, 155, and 263 were detected. The most prevalent INI accessory resistance mutations were: L74I/M (14/75, 18.6%) followed by E157Q (8/75, 10.6%), G163E/N/T/Q (5/75, 6.6%), Q95A/H/P (2/75, 2.6%), and T97A (4/75, 5.3%). Other substitutions observed were M50I/L/P, H51E/P/S/Q, I72V, T112V, V201I, and T206S. Polymorphisms at positions which may influence the genetic barrier and/or drive the selection of specific INI-resistance pathways were detected. However, no transmitted drug resistance (TDR) to INI was detected among samples of INI-naïve patients. These findings support the use of this treatment class for children with HIV-1, particularly in West Africa