Validation of a SARS-CoV-2 Surrogate Neutralization Test Detecting Neutralizing Antibodies against the Major Variants of Concern.

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.

Case series of four re-infections with a SARS-CoV-2 B.1.351 variant, Luxembourg, February 2021.

We describe four SARS-CoV-2 re-infections with a B.1.351 variant in 2021, in healthcare workers (HCWs) previously infected in 2020, before detection of this variant in Europe. Cases live in France, near the border with Luxembourg, where variants B.1.351 and B.1.1.7 circulated. All work in the same hospital unit where a cluster of COVID 19 with B1.351 variant occurred, affecting patients and HCWs. Before the cluster onset, HCWs used surgical masks, as per recommendations. After cluster onset, HCWs used FFP2 masks.

Novel CYP2B6 enzyme variants in a Rwandese population: functional characterization and assessment of in silico prediction tools.

Cytochrome P450 CYP2B6 is a highly polymorphic enzyme that metabolizes numerous drugs, pesticides, and environmental toxins. Sequence analysis of a Rwandese population identified eight functionally uncharacterized nonsynonymous variants c.329G>T (p.G110V), c.341T>C (p.I114T), c.444G>T (p.E148D), c.548T>G (p.V183G), c.637T>C (p.F213L), c.758G>A (p.R253H), c.835G>C (p.A279P), and c.1459C>A (p.R487S), and five novel alleles termed CYP2B6*33 to CYP2B6*37 were assigned. Recombinant expression in COS-1 cells and functional characterization using the antidepressant bupropion and the antiretroviral efavirenz (EFV) as substrates demonstrated complete or almost complete loss-of-function for variants p.G110V, p.I114T, p.V183G, and p.F213L, whereas p.E148D, p.R253H, p.A279P, and p.R487S variants were functional. The data were used to assess the predictive power of eight online available functional prediction programs for amino-acid changes. Although none of the programs correctly predicted the functionality of all variants, substrate docking simulation analyses indicated similar conformational changes by all four deleterious mutations within the enzyme's active site, thus explaining lack of enzymatic function for both substrates. Because low-activity alleles of CYP2B6 are associated with impaired EFV metabolism and adverse drug response, these results are of potential utility for personalized treatment strategies in HIV/AIDS therapy.

Incarceration history is associated with HIV infection among community-recruited people who inject drugs in Europe: A propensity-score matched analysis of cross-sectional studies.

AIMS: We measured the association between a history of incarceration and HIV positivity among people who inject drugs (PWID) across Europe. DESIGN, SETTING AND PARTICIPANTS: This was a cross-sectional, multi-site, multi-year propensity-score matched analysis conducted in Europe. Participants comprised community-recruited PWID who reported a recent injection (within the last 12 months). MEASUREMENTS: Data on incarceration history, demographics, substance use, sexual behavior and harm reduction service use originated from cross-sectional studies among PWID in Europe. Our primary outcome was HIV status. Generalized linear mixed models and propensity-score matching were used to compare HIV status between ever- and never-incarcerated PWID. FINDINGS: Among 43 807 PWID from 82 studies surveyed (in 22 sites and 13 countries), 58.7% reported having ever been in prison and 7.16% (n = 3099) tested HIV-positive. Incarceration was associated with 30% higher odds of HIV infection [adjusted odds ratio (aOR) = 1.32, 95% confidence interval (CI) = 1.09-1.59]; the association between a history of incarceration and HIV infection was strongest among PWID, with the lowest estimated propensity-score for having a history of incarceration (aOR = 1.78, 95% CI = 1.47-2.16). Additionally, mainly injecting cocaine and/or opioids (aOR = 2.16, 95% CI = 1.33-3.53), increased duration of injecting drugs (per 8 years aOR = 1.31, 95% CI = 1.16-1.48), ever sharing needles/syringes (aOR = 1.91, 95% CI = 1.59-2.28) and increased income inequality among the general population (measured by the Gini index, aOR = 1.34, 95% CI = 1.18-1.51) were associated with a higher odds of HIV infection. Older age (per 8 years aOR = 0.84, 95% CI = 0.76-0.94), male sex (aOR = 0.77, 95% CI = 0.65-0.91) and reporting pharmacies as the main source of clean syringes (aOR = 0.72, 95% CI = 0.59-0.88) were associated with lower odds of HIV positivity. CONCLUSIONS: A history of incarceration appears to be independently associated with HIV infection among people who inject drugs (PWID) in Europe, with a stronger effect among PWID with lower probability of incarceration.

Liver Disease and Treatment Needs of Asymptomatic Persons Living With Hepatitis B in Senegal.

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.

Predicting significant fibrosis in hepatitis C patients in Luxembourg using serological markers.

OBJECTIVE: The aim of our study was to assess the diagnostic performance of various serological markers and scores for predicting significant fibrosis retrospectively in a population of patients referring to our hospital for liver biopsy and chronic hepatitis C. MATERIALS AND METHODS: Stored serum obtained from 186 patients were tested for a number of biological markers putatively associated with liver fibrosis. Fibrotest and Forns scores were compared with liver fibrosis pathology scored according to the METAVIR system by multiple logistic regression. RESULTS: The prevalence of significant fibrosis was 44%. Aspartate amino transferase (AST) and gamma-glutamyltransferase (GGT) were most correlated with METAVIR staging, followed by platelet counts and alpha2-macroglobulin. The negative predictive value was 77% and 83% and the positive predictive value was 100% and 84% for the Forns score and the Fibrotest, respectively. In multivariate analysis AST, GGT and alpha2-macroglobulin had independent predictive power. CONCLUSIONS: The accuracy of serological markers in predicting significant fibrosis is limited, because approximately two thirds of patients lie into an indeterminate "grey zone". Serological markers might be useful for patients reluctant to undergo liver biopsy but current predictive scoring systems are too inaccurate to replace biopsies in a routine manner.

HIV outbreaks among people who inject drugs in Europe, North America, and Israel.

During 2011-16, HIV outbreaks occurred among people who inject drugs (PWID) in Canada (southeastern Saskatchewan), Greece (Athens), Ireland (Dublin), Israel (Tel Aviv), Luxembourg, Romania (Bucharest), Scotland (Glasgow), and USA (Scott County, Indiana). Factors common to many of these outbreaks included community economic problems, homelessness, and changes in drug injection patterns. The outbreaks differed in size (from under 100 to over 1000 newly reported HIV cases among PWID) and in the extent to which combined prevention had been implemented before, during, and after the outbreaks. Countries need to ensure high coverage of HIV prevention services and coverage higher than the current UNAIDS recommendation might be needed in areas in which short acting drugs are injected. In addition, monitoring of PWID with special attention for changing drug use patterns, risk behaviours, and susceptible subgroups (eg, PWID experiencing homelessness) needs to be in place to prevent or rapidly detect and contain new HIV outbreaks.

Exceptional genetic variability of hepatitis B virus indicates that Rwanda is east of an emerging African genotype E/A1 divide.

In Western Africa, hepatitis B virus (HBV) genotype E predominates throughout a vast crescent spanning from Senegal to Namibia and at least to the Central African Republic to the East. Although from most of the eastern parts of sub-Saharan Africa only limited sets of strains have been characterized, these belong predominantly to genotype A. To study how far the genotype E crescent extends to the East, a larger number of HBV strains from Rwanda were analyzed. Phylogenetic analysis of 45 S fragment sequences revealed strains of genotypes A (n = 30), D (n = 10), C (n = 4), and B (n = 1). Twelve genotype A sequences formed a new cluster clearly separated from the reference strains of the known sub-genotypes. Thus, with four genotypes and at least six sub-genotypes and a new cluster of genotype A strains, HBV shows an exceptional genetic variability in this small country, unprecedented in sub-Saharan Africa. Despite this exceptional genetic variability, not a single genotype E virus was found indicating that this country does not belong to the genotype E crescent, but is east of an emerging African genotype E/A1 divide.

Access to treatment of hepatitis C in prison inmates.

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.

Injection of cocaine is associated with a recent HIV outbreak in people who inject drugs in Luxembourg.

BACKGROUND: An outbreak of HIV infections among people who inject drugs (PWID) started in 2014 in Luxembourg. OBJECTIVES: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: Injecting cocaine is a new trend of drug use in Luxembourg associated with HIV infection in this recent outbreak among PWID.

Predominance of the heterozygous CCR5 delta-24 deletion in African individuals resistant to HIV infection might be related to a defect in CCR5 addressing at the cell surface.

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.

Hepatitis C virus genotypes distribution and transmission risk factors in Luxembourg from 1991 to 2006.

AIM: To analyze the Hepatitis C virus (HCV) genotype distribution and transmission risk factors in a population of unselected patients in Luxembourg. METHODS: Epidemiological information (gender, age and transmission risks) were collected from 802 patients newly diagnosed for hepatitis C and living in Luxembourg, among whom 228 patients referred from prison. Genotyping using 5'noncoding (5'NC) sequencing was performed. We compared categorical data using the Fisher's exact F-test and odds ratios (OR) were calculated for evaluating association of HCV genotype and risk factors. RESULTS: The sex ratio was predominantly male (2.2) and individuals aged less than 40 years represented 49.6% of the population. Genotype 1 was predominant (53.4%) followed by genotype 3 (33%). Among risk factors, intravenous drug usage (IVDU) was the most frequently reported (71.4%) followed by medical-related transmission (17.6%) including haemophilia, transfusion recipients and other nosocomial reasons. Genotype 3 was significantly associated to IVDU (OR = 4.84, P < 0.0001) whereas genotype 1 was significantly associated with a medical procedure (OR = 2.42, P < 0.001). The HCV genotype distribution from inmate patients differed significantly from the rest of the population (Chi-square test with four degrees of freedom, P < 0.0001) with a higher frequency of genotype 3 (46.5% vs 27.5%) and a lower frequency of genotype 1 and 4 (44.7% vs 56.8% and 5.3% vs 9.6%, respectively). IVDU was nearly exclusively reported as a risk factor in prison. CONCLUSION: We report the first description of the HCV genotype distribution in Luxembourg. The repartition is similar to other European countries, with one of the highest European prevalence rates of genotype 3 (33%). Since serology screening became available in 1991, IVDU remains the most common way of HCV transmission in Luxembourg.

A new recombinant virus system for the study of HIV-1 entry and inhibition.

The construction is described of a HIV-1 proviral, eGFP-tagged plasmid that allows for the recombination of any selected env gene without the use of restriction enzymes and for the quantitation of the infection by the recombinant virus using flow cytometry. The system was tested showing that an isoleucine to valine substitution at residue position 37 of the HIV-1 gp41 impairs the fitness of the virus but does not lead by itself to T-20 resistance.

Missed opportunities of inclusion in a cohort of HIV-infected children to initiate antiretroviral treatment before the age of two in West Africa, 2011 to 2013.

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.

HPLC analysis of generic antiretroviral drugs purchased in Rwanda.

A reversed phase HPLC method using photo diode array detection for the simultaneous quantification of lamivudine, stavudine, nevirapine, zidovudine, methyl paraben and propyl paraben in solid and liquid drug formulations was developed and validated. The separation was achieved using a Waters Symmetry C8 column, using a mobile phase gradient comprising 50 mM NaH2PO4 (pH 3.8) and acetonitrile (95:5 to 45:55, v/v) and a flow gradient (0.5 to 1.0 ml/min). The limits of detection and quantification were below 19 ng/ml and 55 ng/ml respectively. The intra- and inter-day assay precisions were within 4.4% relative standard deviations. The developed method was applied to 12 different generic antiretroviral medications, consisting of tablets, capsules and solutions, produced by two Indian manufacturers and purchased by the Central Agency of Essential Drug Procurement of Rwanda for the ESTHER project in Rwanda. The average content of the antiretroviral agent(s) compared to the labeled amount(s) was 101.4%. Methyl paraben and propyl paraben, added to solutions as preservatives, were within the FDA recommended limits.

HIV-1 subtypes in Luxembourg, 1983-2000.

OBJECTIVES: To study the prevalence of HIV-1 subtypes in Luxembourg between 1983 and 2000. To compare the drug susceptibility of non-B and B clade viruses and the prevalence of resistance-associated mutations and polymorphisms before antiretroviral treatment. DESIGN: A retrospective study on plasma samples of HIV-infected patients registered at the National Service of Infectious Diseases, Luxembourg, between 1983 and 2000. METHODS: Genotyping was performed by sequencing of the reverse transcriptase (RT) and protease coding region of the pol gene. Drug susceptibility was assessed in a recombinant virus assay. RESULTS: A total of 20.1% of the HIV-positive patients were infected with non-B subtypes, and since 1990 the proportion of non-B viruses has increased ninefold. Eleven out of 14 F1 subtypes occurred in patients native to Luxembourg. Major resistance mutations related to protease inhibitors (PI), nucleoside reverse transcriptase inhibitors (NRTI) and non-nucleoside reverse transcriptase inhibitors (NNRTI) occurred in less than 3% of treatment-naive viruses; however, 87% of the viruses had at least one PI-associated mutation. Natural polymorphism of the protease and RT coding region was observed more frequently among non-B than B viruses. Significantly more B viruses displayed resistance to the tested PI, NRTI and NNRTI (P = 0.044). CONCLUSION: The proportion of non-B viruses has increased dramatically since 1990. Non-B subtypes showed no decreased susceptibility to antiretroviral drugs, but displayed minor mutations and polymorphisms at higher frequency in their protease and RT coding region. In contrast, a significantly higher proportion of B viruses showed resistance to a range of antiretroviral drugs.

Rare and new V3 loop variants in HIV-1-positive long-term non-progressors from Rwanda.

We identified uncommon amino acid substitutions in the V3 loop regions of HIV-1 strains infecting patients from Rwanda. Their frequency was greater in long-term non-progressors (LTNP) compared with late-stage patients (P = 0.006), particularly in a sequence region that has crucial interactions with the cell surface, and is highly relevant for the host's immune response. These variants might reflect a viral response to a strong immune pressure, or represent attenuated HIV-1 strains infecting LTNP in Rwanda.

HIV type 1 pol gene diversity and archived nevirapine resistance mutation in pregnant women in Rwanda.

This study aimed to find out whether genetic polymorphisms were present in positions potentially affecting susceptibility to antiretrovirals in non-B subtypes from HIV-1-infected patients in Rwanda. Viral pol gene diversity was investigated by direct sequencing in 43 treatment-naive women. In addition, 10 DNA sequences from uncultured peripheral blood mononuclear cells were analyzed 6 weeks after a single dose of nevirapine (prevention of mother-to-child transmission program). Phylogenetic analyses have shown 34 subtype A1, 6 subtype C, and 2 subtype D strains. In addition, an A/C recombinant between the protease (PR) (subtype A1) and the reverse transcriptase (RT) (subtype C) was identified. In the PR coding region, high numbers of polymorphisms were found, including substitutions in secondary PR resistance sites. PR 35D, 36I, and 37N were always present within subtype A as were PR 93L in subtype C strains. PR 10I/V, 20R, 33F, and 77V were found in subtype A whereas PR 36I was highly prevalent in subtype C strains. The A/C recombinant displayed substitutions related to resistance (PR 10, 33, 36 and RT 118). One nevirapine resistance mutation (RT 181Y/C) was found in proviral DNA after 6 weeks. In conclusion, subtypes A and C are predominant in this cohort in Rwanda. Substitutions similar to secondary protease inhibitor resistance mutations are common before treatment whereas major resistance mutation may be archived after a single dose of nevirapine. Accordingly, the hypothesis of a genetic background effect in non-B strains has to be further addressed in programs of introduction of antivirals in Africa.

Resistance testing in children changing human immunodeficiency virus type 1 protease inhibitor.

OBJECTIVE: To assess genotypic and phenotypic resistance testing in HIV-1-infected children failing a first protease inhibitor (PI) therapy. METHODS: In a multicenter observational study 21 children, ages 3 to 16 years, were given two reverse transcriptase inhibitors and one PI (mainly ritonavir, n = 18). They were subsequently treated with single or dual PI-based therapy (predominantly nelfinavir, n = 10, or ritonavir-saquinavir, n = 7). Resistance testing was performed at the time of therapy switch via direct sequencing and a recombinant virus susceptibility assay. RESULTS: A total of 21 genotypic and 15 phenotypic resistance profiles were obtained. Most viruses displayed several reverse transcriptase mutations; however, 7 isolates maintained a wild-type protease. Ritonavir targeted the well-known pathway containing 82, 54, 46 and other secondary (nonactive site) mutations including T74A. No in vitro cross-resistance, i.e. > or = 8-fold resistance to saquinavir or amprenavir, was encountered. Secondary mutations enhanced the prediction of ritonavir resistance (i.e. L10I) and in vitro nelfinavir cross-resistance (i.e. K20R/I) conferred by primary (active site) resistance mutations. Either the 82, 54, 46 mutational genotype or the phenotype showing > or = 8-fold nelfinavir cross-resistance predicted a poorer virologic response to nelfinavir salvage therapy. CONCLUSION: In a small cohort of heavily pretreated pediatric patients, resistance testing appears to predict the response to nelfinavir as salvage for a ritonavir-based therapy. This is further supported by the correlation between ritonavir-selected mutations and in vitro nelfinavir cross-resistance. Prospective studies should assess clinical outcome in children undergoing regimen changes based on resistance testing.

[Prevalence of transmission of methicillin resistant Staphylococcus in home care patients]. / Prévalence du portage de Staphylocoque doré résistant a la Méthicilline chez des patients soignés a domicile.

Methicilline-resistant Staphylococcus aureus (MRSA) is among the most important causes of hospital-acquired infections. The aim of the present study was to investigate the prevalence of MRSA carriage among home care patients as well as among the health care personnel taking care of those patients. 93 patients and 30 staff members of the team of a home care sector in the western part of Luxembourg were screened for MRSA carriage and factors associated with carriage were investigated among the patients.