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An outbreak of HIV infections among people who inject drugs (PWID) started in 2014 in Luxembourg. We conducted phylogenetic and epidemiological analyses among the PWID infected with HIV in Luxembourg or attending the supervised drug consumption facility (SDCF) to understand the main causes of the outbreak. Between January 2013 and December 2017, analysis of medical files were performed from all PWID infected with HIV at the National Service of Infectious Diseases (NSID) providing clinical care nationwide. PWID were interviewed at NSID and SDCF using a standardized questionnaire focused on drug consumption and risk behaviours. The national drug monitoring system RELIS was consulted to determine the frequency of cocaine/heroin use. Transmission clusters were analysed by phylogenetic analyses using approximate maximum-likelihood. Univariate and multivariate logistic regression analyses were performed on epidemiological data collected at NSID and SDCF to determine risk factors associated with cocaine use. From January 2013 to December 2017, 68 new diagnosis of HIV infection reported injecting drug use as the main risk of transmission at NSID. The proportion of female cases enrolled between 2013-2017 was higher than the proportion among cases enrolled prior to 2013. (33% vs 21%, p < 0.05). Fifty six viral sequences were obtained from the 68 PWID newly diagnosed for HIV. Two main transmission clusters were revealed: one HIV-1 subtype B cluster and one CRF14_BG cluster including 37 and 9 patients diagnosed since 2013, respectively. Interviews from 32/68 (47%) newly diagnosed PWID revealed that 12/32 (37.5%) were homeless and 27/32 (84.4%) injected cocaine. Increased cocaine injection was indeed reported by the RELIS participants from 53 to 63% in drug users with services contacts between 2012 and 2015, and from 5 to 22% in SDCF users between 2012 and 2016. Compared with PWID who injected only heroin (n = 63), PWID injecting cocaine and heroin (n = 107) were younger (mean of 38 vs 44 years, p≤0.001), reported more frequent piercing (≤0.001), shared and injected drugs more often (p≤0.01), and were more frequently HIV positive (p<0.05) at SDCF using univariate logistic regression analysis. Finally, in the multivariate analysis, use of heroin and cocaine was independently associated with younger age, piercing, sharing of drugs, and regular consumption (p<0.05). Injecting cocaine is a new trend of drug use in Luxembourg associated with HIV infection in this recent outbreak among PWID.

Despite the enormous progress made in scaling up antiretroviral therapy (ART) in sub-Saharan Africa, many challenges remain, not least of which are the identification and management of patients who have failed first-line therapy. Less than 3% of patients are receiving second-line treatment at present, whereas 15–25% of patients have detectable viral loads 12 months or more into treatment, of whom a substantial proportion might have virological failure. We discuss the reasons why virological ART failure is likely to be under-diagnosed in the routine health system, and address the current difficulties with standard recommended second-line ART regimens. The development of new diagnostic tools for ART failure, in particular a point-of-care HIV viral-load test, combined with simple and inexpensive second-line therapy, such as boosted protease-inhibitor monotherapy, could revolutionise the management of ART failure in resource-limited settings.

Introduction The World Health Organization (WHO) 2010 guidelines recommended to treat all HIV‐infected children less than two years of age. We described the inclusion process and its correlates of HIV‐infected children initiated on early antiretroviral therapy (EART) at less than two years of age in Abidjan, Côte d'Ivoire, and Ouagadougou, Burkina Faso. Methods All children with HIV‐1 infection confirmed with a DNA PCR test of a blood sample, aged less than two years, living at a distance less than two hours from the centres and whose parents (or mother if she was the only legal guardian or the legal caregiver if parents were not alive) agreed to participate in the MONOD ANRS 12206 project were included in a cohort to receive EART based on lopinavir/r. We used logistic regression to identify correlates of inclusion. Results Among the 217 children screened and referred to the MONOD centres, 161 (74%) were included and initiated on EART. The main reasons of non‐inclusion were fear of father's refusal (48%), mortality (24%), false‐positive HIV infection test (16%) and other ineligibility reasons (12%). Having previously disclosed the child's and mother's HIV status to the father (adjusted odds ratio (aOR): 3.20; 95% confidence interval (95% CI): 1.55 to 6.69) and being older than 12 months (aOR: 2.05; 95% CI: 1.02 to 4.12) were correlates of EART initiation. At EART initiation, the median age was 13.5 months, 70% had reached WHO Stage 3/4 and 57% had a severe immune deficiency. Conclusions Fear of stigmatization by the father and early competing mortality were the major reasons for missed opportunities of EART initiation. There is an urgent need to involve fathers in the care of their HIV‐exposed children and to promote early infant diagnosis to improve their future access to EART and survival.

All infants born to HIV-positive mothers have maternal HIV antibodies, sometimes persistent for 18 months. When Polymerase Chain Reaction (PCR) is not available, August 2006 World Health Organization (WHO) recommendations suggest that clinical criteria may be used for starting antiretroviral treatment (ART) in HIV seropositive children <18 months. Predictors are at least two out of sepsis, severe pneumonia and thrush, or any stage 4 defining clinical finding according to the WHO staging system. From January 2005 to October 2006, we conducted a prospective study on 236 hospitalized children <18 months old with a positive HIV serological test at the national reference hospital in Kigali. The following data were collected: PCR, clinical signs and CD4 cell count. Current proposed clinical criteria were present in 148 of 236 children (62.7%) and in 95 of 124 infected children, resulting in 76.6% sensitivity and 52.7% specificity. For 87 children (59.0%), clinical diagnosis was made based on severe unexplained malnutrition (stage 4 clinical WHO classification), of whom only 44 (50.5%) were PCR positive. Low CD4 count had a sensitivity of 55.6% and a specificity of 78.5%. As PCR is not yet widely available, clinical diagnosis is often necessary, but these criteria have poor specificity and therefore have limited use for HIV diagnosis. Unexplained malnutrition is not clearly enough defined in WHO recommendations. Extra pulmonary tuberculosis (TB), almost impossible to prove in young children, may often be the cause of malnutrition, especially in HIV-affected families more often exposed to TB. Food supplementation and TB treatment should be initiated before starting ART in children who are staged based only on severe malnutrition.

SARS-CoV-2 infection and/or vaccination elicit a broad range of neutralizing antibody responses against the different variants of concern (VOC). We established a new variant-adapted surrogate virus neutralization test (sVNT) and assessed the neutralization activity against the ancestral B.1 (WT) and VOC Delta, Omicron BA.1, BA.2, and BA.5. Analytical performances were compared against the respective VOC to the reference virus neutralization test (VNT) and two CE-IVD labeled kits using three different cohorts collected during the COVID-19 waves. Correlation analyses showed moderate to strong correlation for Omicron sub-variants (Spearman’s r = 0.7081 for BA.1, r = 0.7205 for BA.2, and r = 0.6042 for BA.5), and for WT (r = 0.8458) and Delta-sVNT (r = 0.8158), respectively. Comparison of the WT-sVNT performance with two CE-IVD kits, the “Icosagen SARS-CoV-2 Neutralizing Antibody ELISA kit” and the “Genscript cPass, kit” revealed an overall good correlation ranging from 0.8673 to −0.8773 and a midway profile between both commercial kits with 87.76% sensitivity and 90.48% clinical specificity. The BA.2-sVNT performance was similar to the BA.2 Genscript test. Finally, a correlation analysis revealed a strong association (r = 0.8583) between BA.5-sVNT and VNT sVNT using a double-vaccinated cohort (n = 100) and an Omicron-breakthrough infection cohort (n = 91). In conclusion, the sVNT allows for the efficient prediction of immune protection against the various VOCs.

Abstract The prevalence of active hepatitis B among asymptomatic persons remains unclear in Africa. Of 1206 newly diagnosed persons in Senegal, 12.3% had significant fibrosis and 31.3% had hepatitis B virus (HBV) DNA levels >2000 IU/mL. Overall, 128 (12.9%) were eligible for antiviral therapy. Generalized HBV screening allowed the identification of a large population requiring HBV care.

Introduction The chemokine receptor CCR5 is the main co‐receptor for R5‐tropic HIV‐1 variants. We have previously described a novel 24‐base pair deletion in the coding region of CCR5 among individuals from Rwanda. Here, we investigated the prevalence of hCCR5Δ24 in different cohorts and its impact on CCR5 expression and HIV‐1 infection in vitro. Methods We screened hCCR5Δ24 in a total of 3232 individuals which were either HIV‐1 uninfected, high‐risk HIV‐1 seronegative and seropositive partners from serodiscordant couples, Long‐Term Survivors, or HIV‐1 infected volunteers from Africa (Rwanda, Kenya, Guinea‐Conakry) and Luxembourg, using a real‐time PCR assay. The role of the 24‐base pair deletion on CCR5 expression and HIV infection was assessed in cell lines and PBMC using mRNA quantification, confocal analysis, flow and imaging cytometry. Results and Discussion Among the 1661 patients from Rwanda, 12 individuals were heterozygous for hCCR5Δ24 but none were homozygous. Although heterozygosity for this allele may not confer complete resistance to HIV‐1 infection, the prevalence of the mutation was 2.41% (95%CI: 0.43; 8.37) in 83 Long‐Term Survivors (LTS) and 0.99% (95%CI: 0.45; 2.14) in 613 HIV‐1 exposed seronegative members as compared with 0.35% (95% Cl: 0.06; 1.25) in 579 HIV‐1 seropositive members. The prevalence of hCCR5Δ24 was 0.55% (95%CI: 0.15; 1.69) in 547 infants from Kenya but the mutation was not detected in 224 infants from Guinea‐Conakry nor in 800 Caucasian individuals from Luxembourg. Expression of hCCR5Δ24 in cell lines and PBMC showed that the hCCR5Δ24 protein is stably expressed but is not transported to the plasma membrane due to a conformational change. Instead, the mutant receptor was retained intracellularly, colocalized with an endoplasmic reticulum marker and did not mediate HIV‐1 infection. Co‐transfection of hCCR5Δ24 and wtCCR5 did not indicate a transdominant negative effect of CCR5Δ24 on wtCCR5. Conclusions Our findings indicate that hCCR5Δ24 is not expressed at the cell surface. This could explain the higher prevalence of the heterozygous hCCR5Δ24 in LTS and HIV‐1 exposed seronegative members from serodiscordant couples. Our data suggest an East‐African localization of this deletion, which needs to be confirmed in larger cohorts from African and non‐African countries.

The chemokine receptor CCR5 is the main co?receptor for R5?tropic HIV?1 variants. We have previously described a novel 24?base pair deletion in the coding region of CCR5 among individuals from Rwanda. Here, we investigated the prevalence of hCCR5?24 in different cohorts and its impact on CCR5 expression and HIV?1 infection in vitro. We screened hCCR5?24 in a total of 3232 individuals which were either HIV?1 uninfected, high?risk HIV?1 seronegative and seropositive partners from serodiscordant couples, Long?Term Survivors, or HIV?1 infected volunteers from Africa (Rwanda, Kenya, Guinea?Conakry) and Luxembourg, using a real?time PCR assay. The role of the 24?base pair deletion on CCR5 expression and HIV infection was assessed in cell lines and PBMC using mRNA quantification, confocal analysis, flow and imaging cytometry. Among the 1661 patients from Rwanda, 12 individuals were heterozygous for hCCR5?24 but none were homozygous. Although heterozygosity for this allele may not confer complete resistance to HIV?1 infection, the prevalence of the mutation was 2.41% (95%CI: 0.43; 8.37) in 83 Long?Term Survivors (LTS) and 0.99% (95%CI: 0.45; 2.14) in 613 HIV?1 exposed seronegative members as compared with 0.35% (95% Cl: 0.06; 1.25) in 579 HIV?1 seropositive members. The prevalence of hCCR5?24 was 0.55% (95%CI: 0.15; 1.69) in 547 infants from Kenya but the mutation was not detected in 224 infants from Guinea?Conakry nor in 800 Caucasian individuals from Luxembourg. Expression of hCCR5?24 in cell lines and PBMC showed that the hCCR5?24 protein is stably expressed but is not transported to the plasma membrane due to a conformational change. Instead, the mutant receptor was retained intracellularly, colocalized with an endoplasmic reticulum marker and did not mediate HIV?1 infection. Co?transfection of hCCR5?24 and wtCCR5 did not indicate a transdominant negative effect of CCR5?24 on wtCCR5. Our findings indicate that hCCR5?24 is not expressed at the cell surface. This could explain the higher prevalence of the heterozygous hCCR5?24 in LTS and HIV?1 exposed seronegative members from serodiscordant couples. Our data suggest an East?African localization of this deletion, which needs to be confirmed in larger cohorts from African and non?African countries.

IntroductionThe chemokine receptor CCR5 is the main co‐receptor for R5‐tropic HIV‐1 variants. We have previously described a novel 24‐base pair deletion in the coding region of CCR5 among individuals from Rwanda. Here, we investigated the prevalence of hCCR5Δ24 in different cohorts and its impact on CCR5 expression and HIV‐1 infection in vitro.MethodsWe screened hCCR5Δ24 in a total of 3232 individuals which were either HIV‐1 uninfected, high‐risk HIV‐1 seronegative and seropositive partners from serodiscordant couples, Long‐Term Survivors, or HIV‐1 infected volunteers from Africa (Rwanda, Kenya, Guinea‐Conakry) and Luxembourg, using a real‐time PCR assay. The role of the 24‐base pair deletion on CCR5 expression and HIV infection was assessed in cell lines and PBMC using mRNA quantification, confocal analysis, flow and imaging cytometry.Results and DiscussionAmong the 1661 patients from Rwanda, 12 individuals were heterozygous for hCCR5Δ24 but none were homozygous. Although heterozygosity for this allele may not confer complete resistance to HIV‐1 infection, the prevalence of the mutation was 2.41% (95%CI: 0.43; 8.37) in 83 Long‐Term Survivors (LTS) and 0.99% (95%CI: 0.45; 2.14) in 613 HIV‐1 exposed seronegative members as compared with 0.35% (95% Cl: 0.06; 1.25) in 579 HIV‐1 seropositive members. The prevalence of hCCR5Δ24 was 0.55% (95%CI: 0.15; 1.69) in 547 infants from Kenya but the mutation was not detected in 224 infants from Guinea‐Conakry nor in 800 Caucasian individuals from Luxembourg. Expression of hCCR5Δ24 in cell lines and PBMC showed that the hCCR5Δ24 protein is stably expressed but is not transported to the plasma membrane due to a conformational change. Instead, the mutant receptor was retained intracellularly, colocalized with an endoplasmic reticulum marker and did not mediate HIV‐1 infection. Co‐transfection of hCCR5Δ24 and wtCCR5 did not indicate a transdominant negative effect of CCR5Δ24 on wtCCR5.ConclusionsOur findings indicate that hCCR5Δ24 is not expressed at the cell surface. This could explain the higher prevalence of the heterozygous hCCR5Δ24 in LTS and HIV‐1 exposed seronegative members from serodiscordant couples. Our data suggest an East‐African localization of this deletion, which needs to be confirmed in larger cohorts from African and non‐African countries.

We conducted a prospective study to investigate access to treatment in hepatitis C in 268 prisoners. Hepatitis C positivity had been known for 182 prisoners previously and 19 reported previous attempts to treat (10%). In comparison, during our study, 86/268 prisoners (32%) started therapy (P < 0.0001). They represented 41% of 211 prisoners with a positive viral load. In the genotype 2 or 3 group, 46 prisoners (50%) started therapy versus 40 prisoners (33%) with other genotypes (P = 0.01). This difference was due to prisoners waiting for liver biopsy. On an intention to treat basis, 45 prisoners (52%) achieved sustained virological response 6 months after the end of therapy. We conclude that a stay in prison is an effective opportunity to treat a group of hepatitis C patients which otherwise have very limited access to therapy.