BACKGROUND:We evaluated whether switching to bictegravir/tenofovir alafenamide/emtrictabine (BIC/TAF/FTC) or dolutegravir (DTG)/tenofovir disoproxil fumarate (TDF)/FTC in people with human immunodeficiency virus (PWH) with virological success increased risks of virological failure (VF), and if VF was driven by tenofovir resistance. METHODS:Analysis embedded in the French national Dat'AIDS cohort (NCT02898987) of all PWH followed after 1 January 2014, with no history of DTG and BIC exposure or resistance, and with a viral load <50 copies/mL for more than 12 months. Switchers changed their antiretroviral regimen to BIC/TAF/FTC or DTG + TDF/FTC. VF defined as 1 value >200 copies/mL. Marginal structural models compared VF in switchers and nonswitchers, emulating a target trial. A multivariate Cox model assessed tenofovir resistance with VF in switchers only. RESULTS:There was a total of 9827 PWH, of whom 1393 (14.2%) switched to BIC/TAF/FTC or DTG + TDF/FTC. We observed 75 (5.4%) VF in switchers and 523 (6.2%) in nonswitchers. After weighing, switching was associated with a nonsignificant risk of VF (hazard ratio [HR] 1.29; 95% CI: .97-1.7) (P = .08). Presence of possible resistance and resistance to tenofovir (ANRS resistance algorithm) was not associated with VF (HR 1.12; 95% CI: .82-1.5; P = .47) In switchers only, tenofovir resistance was not associated with VF (HR 1.04; 95% CI: .47-2.33), nor was M184V or M184I mutations (HR 0.98; 95% CI: .5-2.1). CONCLUSIONS:In a real-world setting, switching to BIC/TAF/FTC or DTG + TDF/FTC in PWH with virological success was associated with a nonsignificant risk of VF, but M184V or M184I mutations and tenofovir resistance had no effect on VF. Most VF were blips or related to unmeasured adherence issues.

BACKGROUND:Doravirine is a non-nucleoside reverse transcriptase inhibitor (NNRTI) with moderate plasma protein binding and good potential for anatomical sanctuary penetration. MATERIALS AND METHODS:Adding doravirine to existing antiretroviral therapy (ART) regimens has led to virological success in two groups of people living with HIV (PLWHIV): those with recent virological rebound (n = 84) and those with prolonged low-level viremia (LLV, n = 39). Doravirine was added without any modification to the other ART drugs. RESULTS:After 6 months, 88% of PLWHIV in the recent failure group had achieved virological success, compared to 33% of those in the LLV group. Efficacy was closely tied to the genotypic susceptibility score (GSS), with higher success rates in patients whose regimens retained two or more active drugs. Doravirine resistance mutations were uncommon but occurred more frequently in the LLV group. No significant associations were found between treatment response and CD4 count, nadir, VL zenith or duration of suppression. CONCLUSIONS:These findings support the use of doravirine add-on strategies to rescue virological control without changing the full regimen, particularly when a full regimen change is not feasible and when GSS is favourable. The study highlights the potential of doravirine in tailored salvage therapy strategies.

ABSTRACT There is limited data on lenacapavir (LEN) use, the newest capsid inhibitor, in observational settings. We describe population characteristics and pharmaco-virological outcomes of people with HIV-1 (PWH) who initiated LEN-based treatment. We conducted a national retrospective observational study of PWH initiating LEN-based treatment in France after its approval (December 2022). Virological failure (VF) was defined as two consecutive viral loads (VLs) ≥50 c/mL, and a non-virological response as a VL decrease of <1 log 10 c/mL or still >50 c/mL at W24. Ninety-six PWH were included; 49 were virologically suppressed at initiation. Median follow-up on LEN was 12 months (IQR = 8–17). Genotypic susceptibility score was <1 in 59 cases (61%). Twelve participants (12.5%) discontinued LEN-based treatment. Among the virologically suppressed and viremic PWH at initiation, 94% and 64% had VL <50 c/mL at the last follow-up visit, respectively. VF occurred in 8 PWH (3 in virological success and 5 viremic at baseline), and a non-virological response was observed in 12 PWH. Capsid sequence at VF was available for eight subjects, showing the emergence of N74D mutation in one. LEN plasma concentrations were available for 13 of the 20 PWH presenting with VF or non-response with adequate concentrations in 90% of cases. Twenty-four participants received cabotegravir + LEN, 18 having VL <50 c/mL at the last follow-up visit. Our observational findings confirm that LEN-based regimens are effective among heavily treatment-experienced individuals with advanced resistance. In this population, LEN-based treatments were associated with high rates of sustained virological suppression and a low incidence of capsid emergent resistance.

The majority of SARS-CoV-2 genomes obtained during the pandemic were derived by amplifying overlapping windows of the genome (‘tiled amplicons’), reconstructing their sequences and fitting them together. This leads to systematic errors in genomes unless the software is both aware of the amplicon scheme and of the error modes of amplicon sequencing. Additionally, over time, amplicon schemes need to be updated as new mutations in the virus interfere with the primer binding sites at the end of amplicons. Thus, waves of variants swept the world during the pandemic and were followed by waves of systematic errors in the genomes, which had significant impacts on the inferred phylogenetic tree. Here we reconstruct the genomes from all public data as of June 2024 using an assembly tool called Viridian ( https://github.com/iqbal-lab-org/viridian ), developed to rigorously process amplicon sequence data. With these high-quality consensus sequences we provide a global phylogenetic tree of 4,471,579 samples, viewable at https://viridian.taxonium.org . We provide simulation and empirical validation of the methodology, and quantify the improvement in the phylogeny.

BACKGROUND:The S147G mutation is associated with high-level resistance to the integrase strand transfer inhibitor (INSTI) elvitegravir. In several poorly documented cases, it was also selected in patients on dolutegravir. Given the widespread use of dolutegravir, further studies of S147G are required. METHODS:We consulted the HIV-1 resistance databases of French laboratories to identify all cases of S147G emergence. We collected immunological and virological parameters, history of treatment and INSTI resistance mutations. Mann-Whitney and Fisher's exact tests were performed. RESULTS:We retrospectively identified 88 cases of S147G selection, from 2015 to 2022, in 22 laboratories. The most frequent HIV-1 subtypes were Clade B (55.7%) and CRF02_AG (21.6%). At the time of resistance genotyping, the median viral load was 5860 copies/mL (IQR 1011-24  525) and the median CD4 cell count was 412 cells/mm3 (228-560). S147G emerged on dolutegravir (48%), elvitegravir (36%) and raltegravir (10%) treatments. S147G was associated with a larger median number of other INSTI mutations on dolutegravir than on elvitegravir [3.0 (2.0-4.0) versus 2.0 (1.0-2.0); P = 0.0002] and was never observed with Q148H or G118R. On dolutegravir, S147G was associated principally with T97A (62%), N155H (59%), E138K (50%), L74I/M (38%) and Q148R (33%). CONCLUSIONS:In this French study, S147G emerged principally in patients on dolutegravir regimens, in association with up to five other INSTI resistance mutations. This accumulation of mutations suggests a replicative advantage on HIV strains under dolutegravir selection pressure, suggesting that caution is required when interpreting dolutegravir resistance in the presence of such S147G resistance patterns, even in patients prescribed dolutegravir twice daily.

OBJECTIVES:The effect of the M184I/V mutation on the rate of virological failure in people with HIV (PWH) with plasma HIV RNA viral load less than 50 copies/ml switching to a triple-therapy regimen of doravirine+lamivudine+ tenofovir or abacavir has not been evaluated. DESIGN:A retrospective national study of antiretroviral-experienced PWH who were switched to a doravirine plus lamivudine and abacavir or tenofovir regimen in the context of maintenance (viral load <50 copies/ml) was conducted. Virological failure was characterized by either two consecutive plasma viral loads at least 50 copies/ml or a single viral load at least 200 copies/ml. Viral blip was defined as an isolated viral load 50_200 copies/ml at any time up to month 6 after switching to the doravirine-containing regimen. RESULTS:Among the 338 PWH, doravirine was mainly associated with tenofovir+lamivudine (311/338, 92.0%). Of these, 45 had a M184I/V mutation before switching. Virological failure at M6 was 14.0 and 17.8% in the absence and presence of M184I/V, respectively, with an adjusted odds ratio (aOR) of 2.409, 95% confidence interval (95% CI) 0.574-10.113, P  = 0.21. The risk of virological failure at M6 was associated with the level of zenith plasma HIV viral load, with an aOR of 1.646, 95% CI 1.163-2.328, P  = 0.0049, per additional log 10 unit. The proportion of viral blip at M6 was 2.4 and 6.7% in PWH in the absence and presence of M184I/V, respectively, with an aOR of 0.818, 95% CI 0.187-3.587, P  = 0.7897. CONCLUSION:Among PWH with antiretroviral experience, there was no evidence that switching to doravirine + lamivudine plus tenofovir affected short-term treatment response in individuals harboring HIV M184I/V mutations.

Background Doravirine is the latest NNRTI to be approved for the treatment of HIV-1 and has a different resistance profile from first-generation NNRTIs. Our aim was to investigate the virological efficacy of antiretroviral treatment including doravirine in people living with HIV-1 (PLWHIV), the factors associated with virological failure (VF) and those associated with the emergence of reverse transcriptase (RT) mutations in the case of VF.Methods A retrospective national survey of PLWHIV who were either naive or experienced on antiretroviral treatment including doravirine was conducted. VF was defined as two consecutive plasma viral loads (VLs) of >= 50 copies/mL or one VL of >= 200 copies/mL. Genotypic resistance tests were interpreted using the Stanford (v9.4.1) and ANRS (v33) algorithms.Results Of the 589 PLWHIV treated with a doravirine-containing regimen, 8.5% were naive and 91.5% had prior antiretroviral experience; 56.9% were infected with HIV-1 B subtype. Overall, 88.3% and 85.1% of participants were virologically controlled at Month (M)3 and M6 of doravirine treatment, respectively. In multivariable analysis, CRF02_AG subtype, higher zenith plasma HIV-1 RNA VL, doravirine initiation in the context of failure and baseline V179D mutation presence were associated with VF. Among 88 PLWHIV who experienced virological failure at M6, 15.9% had a median of 2 (IQR 1-3) HIV RT mutations. In multivariable analysis, the only factor associated with the occurrence of mutations was a genotypic sensitivity score that was not fully sensitive.Conclusions This study is one of the largest to characterize the virological efficacy of doravirine-containing regimens in clinical practice and to identify factors associated with VF or emergence of resistance mutations that should be considered in clinical management.

Objectives As many disparities in the clinical use of HIV DNA sequencing are observed, a DELPHI-type consensus was initiated in France to homogenize use, techniques and interpretation of results.Methods Based on a literature review and clinical experience, a steering committee (SC) of eight virologists and one infectious disease specialist formulated statements. Statements were submitted to an independent and anonymous electronic vote of virologists and HIV clinicians in France, between October 2022 and December 2022.Results The SC developed 20 statements grouped into six categories: clinical situations for the use of HIV DNA genotyping; techniques for performing HIV DNA genotyping; consideration of apolipoprotein B mRNA editing enzyme (APOBEC) mutations; genotyping results reporting; recycling of antiretrovirals; and availability of HIV DNA genotyping tests and delays. Twenty-one virologists and 47 clinicians participated in two voting rounds and 18/20 (90%) assertions reached a 'strong' consensus. For example, that prior genotyping on HIV DNA is useful for clinical decision-making when considering switching to some long-acting regimens or to reduce the number of antiretroviral agents in virologically suppressed patients for whom RNA data are unavailable/not exploitable/not sufficiently informative. Two statements achieved no consensus: reporting any detected viral minority population for discussion in multidisciplinary meetings (virologists), and possible risk of virological failure when using a second-generation InSTI plus lamivudine or emtricitabine regimen in patients with undetectable viral load within >= 1 year and in the presence of a documented M184V mutation within the last 5 years (clinicians).Conclusions This DELPHI-type consensus will facilitate the strengthening and harmonization of good practice when performing HIV DNA sequencing.

The SARS-CoV-2 genome occupies a unique place in infection biology - it is the most highly sequenced genome on earth (making up over 20% of public sequencing datasets) with fine scale information on sampling date and geography, and has been subject to unprecedented intense analysis. As a result, these phylogenetic data are an incredibly valuable resource for science and public health. However, the vast majority of the data was sequenced by tiling amplicons across the full genome, with amplicon schemes that changed over the pandemic as mutations in the viral genome interacted with primer binding sites. In combination with the disparate set of genome assembly workflows and lack of consistent quality control (QC) processes, the current genomes have many systematic errors that have evolved with the virus and amplicon schemes. These errors have significant impacts on the phylogeny, and therefore over the last few years, many thousands of hours of researchers time has been spent in "eyeballing" trees, looking for artefacts, and then patching the tree. Given the huge value of this dataset, we therefore set out to reprocess the complete set of public raw sequence data in a rigorous amplicon-aware manner, and build a cleaner phylogeny. Here we provide a global tree of 4,471,579 samples, built from a consistently assembled set of high quality consensus sequences from all available public data as of June 2024, viewable at https://viridian.taxonium.org. Each genome was constructed using a novel assembly tool called Viridian (https://github.com/iqbal-lab-org/viridian), developed specifically to process amplicon sequence data, eliminating artefactual errors and mask the genome at low quality positions. We provide simulation and empirical validation of the methodology, and quantify the improvement in the phylogeny. We hope the tree, consensus sequences and Viridian will be a valuable resource for researchers.

Dans certaines situations cliniques, le séquençage de l'ADN VIH est réalisé pour rechercher les mutations de résistances aux antirétroviraux (ARV). De nombreuses disparités dans les pratiques étant observées, un consensus national de type DELPHI a été initié dans l'objectif de faciliter l'homogénéisation des situations de recours et l'interprétation des résultats obtenus. Après analyse de la littérature et partage d'expériences, un Comité de Pilotage (CP) composé de 8 virologues et 1 infectiologue a formulé des assertions soumises au vote électronique, indépendant et anonyme de virologues et de cliniciens en France, sélectionnés pour leur expertise dans le suivi clinique des PVVIH, entre octobre et décembre 2022. Les votes étaient recueillis à l'aide d'une échelle de 1 «Pas du tout d'accord» à 9 «Tout à fait d'accord». Un fort ou un bon consensus était atteint lorsque plus de 75% des scores étaient ≥7 et/ou que le score médian était ≥8. Les assertions n'ayant pas satisfait à ces critères étaient reformulées par le CP puis soumises à un 2nd tour de vote. Le CP a formulé initialement 21 assertions regroupées en 6 catégories: situations cliniques de recours au génotypage sur ADN VIH, techniques de réalisation, prise en considération des mutations APOBEC, rendu des résultats, recyclage des ARV et disponibilité des tests. Vingt et un virologues et 47 cliniciens ont participé à chacun des 2 tours de votes. Au 1er tour, 14/21 assertions ont recueilli un bon ou fort consensus et 7/21 une absence de consensus. Le CP a reformulé 5 assertions avec bon consensus et les 7 avec absence de consensus, dont 2 ont été fusionnées. Au 2nd tour, 2/20 assertions sont restées sans consensus. Au final, 18/20 (90%) assertions ont atteint un consensus fort (après les 2 tours), notamment: la réalisation préalable d'un génotypage sur ADN VIH est utile à la décision clinique en cas de volonté d'allégement/simplification vers un traitement en «long acting» ou par diminution du nombre d'ARV chez un patient en succès virologique pour qui les données ARN à disposition ne sont pas exploitables ou suffisamment informatives; il n'est pas indispensable pour passer au traitement 4 ou 5 jours/7 sans changement de molécule; les mutations de résistance attribuables à APOBEC détectées lors du test doivent être mentionnées dans l'analyse du résultat. En revanche, le panel de virologues n'a pas validé de manière unanime l'intérêt de signaler toute population minoritaire détectée afin de la discuter en réunion de concertation pluridisciplinaire. De même, le panel de cliniciens était partagé sur le risque virologique possible de l'utilisation d'une association INI + XTC chez un patient présentant une charge virale indétectable ≥1 an et en présence d'une mutation M184V documentée <5 ans. Ce consensus de type DELPHI permettra de renforcer et d'harmoniser les bonnes pratiques de réalisation du génotypage sur ADN VIH, notamment vis-à-vis de la réduction du nombre d'ARV et de l'utilisation des «long acting». E. A-G: ViiV, Gilead et MSD

Analysing 92,598 variant screening tests performed on SARS-CoV-2 positive samples collected in France between 1 July and 31 August 2021 shows an increase of Kappa-like infections. Full genome sequencing reveals that these correspond to Delta variants bearing the S:E484Q mutation. Most of these sequences belong to a phylogenetic cluster and also bear the S:T95I mutation. Further monitoring is needed to determine if this trend is driven by undocumented superspreading events or an early signal of future viral evolutionary dynamics

The implementation of rapid diagnostic tests (RDTs) may enhance the efficiency of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) testing, as RDTs are widely accessible and easy to use. The aim of this study was to evaluate the performance of a diagnosis strategy based on a combination of antigen and immunoglobulin M (IgM) or immunoglobulin G (IgG) serological RDTs. Plasma and nasopharyngeal samples were collected between 14 March and 11 April 2020 at hospital admission from 45 patients with reverse transcription polymerase chain reaction (RT‐PCR) confirmed COVID‐19 and 20 negative controls. SARS‐CoV‐2 antigen (Ag) was assessed in nasopharyngeal swabs using the Coris Respi‐Strip. For IgM/IgG detection, SureScreen Diagnostics and Szybio Biotech RDTs were used in addition to laboratory assays (Abbott Alinity i SARS‐CoV‐2 IgG and Theradiag COVID‐19 IgM enzyme‐linked immunosorbent assay). Using the Ag RDT, 13 out of 45 (29.0%) specimens tested positive, the sensitivity was 87.0% for cycle threshold (Ct) values ≤25% and 0% for Ct values greater than 25. IgG detection was associated with high Ct values and the amount of time after the onset of symptoms. The profile of isolated IgM on RDTs was more frequently observed during the first and second week after the onset of symptoms. The combination of Ag and IgM/IgG RDTs enabled the detection of up to 84.0% of COVID‐19 confirmed cases at hospital admission. Antigen and antibody‐based RDTs showed suboptimal performances when used alone. However when used in combination, they are able to identify most COVID‐19 patients admitted in an emergency department.

The characterization of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral kinetics in hospitalized patients and its association with mortality is unknown. We analyzed death and nasopharyngeal viral kinetics in 655 hospitalized patients from the prospective French COVID cohort. The model predicted a median peak viral load that coincided with symptom onset. Patients with age >= 65 y had a smaller loss rate of infected cells, leading to a delayed median time to viral clearance occurring 16 d after symptom onset as compared to 13 d in younger patients (P < 10(-4)). In multivariate analysis, the risk factors associated with mortality were age >= 65 y, male gender, and presence of chronic pulmonary disease (hazard ratio [HR] > 2.0). Using a joint model, viral dynamics after hospital admission was an independent predictor of mortality (HR = 1.31, P < 10-3). Finally, we used our model to simulate the effects of effective pharmacological interventions on time to viral clearance and mortality. A treatment able to reduce viral production by 90% upon hospital admission would shorten the time to viral clearance by 2.0 and 2.9 d in patients of age <65 y and >= 65 y, respectively. Assuming that the association between viral dynamics and mortality would remain similar to that observed in our population, this could translate into a reduction of mortality from 19 to 14% in patients of age >= 65 y with risk factors. Our results show that viral dynamics is associated with mortality in hospitalized patients. Strategies aiming to reduce viral load could have an effect on mortality rate in this population.

Human immunodeficiency virus (HIV) infection is a chronic disease that can be treated with antiretroviral (ARV) therapy. However, the success of this treatment has been jeopardized by the emergence of HIV infections resistant to ARV drugs. In low-to middle-income countries (LMICs), where transmission of resistant viruses has increased over the past decade, there is an urgent need to improve access to HIV drug resistance testing. Here, we present a proof-of-concept study of a rapid and simple molecular method to detect two major mutations (K103 N, Y181C) conferring resistance to first-line nonnucleoside reverse transcriptase inhibitor regimens. Our near-pointof-care (near-POC) diagnostic test, combining a sequence-specific primer extension and a lateral flow DNA microarray strip, allows visual detection of HIV drug resistance mutations (DRM) in a short turnaround time (4 h 30). The assay has a limit of detection of 100 copies of plasmid DNA and has a higher sensitivity than standard Sanger sequencing. The analytical performance was assessed by use of 16 plasma samples from individuals living with HIV-1 and results demonstrated the specificity and the sensitivity of this approach for multiplex detection of the two DRMs in a single test. Furthermore, this near-POC assay could be easily taylored to detect either new DRMs or DRM of from various HIV clades and might be useful for pre-therapy screening in LMICs with high levels of transmitted drug resistance.

BACKGROUND Successful 2-drug regimens (2DRs) for HIV were made possible by the availability of drugs combining potency and tolerability with a high genetic barrier to resistance. How these deal with resistance development/re-emergence, compared with 3DRs, is thus of paramount importance. MATERIALS AND METHODS A national survey including patients who were either naive or experienced with any 2DR or 3DR but failing integrase strand transfer inhibitor (INSTI)-containing regimens [two consecutive plasma viral load (VL) values >50 copies/mL] was conducted between 2014 and 2019. Genotypic resistance tests were interpreted with the v28 ANRS algorithm. RESULTS Overall, 1104 patients failing any INSTI-containing regimen (2DRs, n = 207; 3DRs, n = 897) were analysed. Five hundred and seventy-seven (52.3%) patients were infected with a B subtype and 527 (47.3%) with non-B subtypes. Overall, 644 (58%) patients showed no known integrase resistance mutations at failure. In multivariate analysis, factors associated with the emergence of at least one integrase mutation were: high VL at failure (OR = 1.24 per 1 log10 copies/mL increase); non-B versus B subtype (OR = 1.75); low genotypic sensitivity score (GSS) (OR = 0.10 for GSS = 2 versus GSS = 0-0.5); and dolutegravir versus raltegravir (OR = 0.46). Although 3DRs versus 2DRs reached statistical significance in univariate analysis (OR = 0.59, P = 0.007), the variable is not retained in the final model. CONCLUSIONS This study is one of the largest studies characterizing integrase resistance in patients failing any INSTI-containing 2DR or 3DR in routine clinical care and reveals factors associated with emergence of integrase resistance that should be taken into consideration in clinical management. No difference was evidenced between patients receiving a 2DR or a 3DR.

L'infection par le virus de l'immunodéficience humaine (VIH) est une maladie chronique qui peut être traitée par des traitements antirétroviraux (ARV). Cependant, le succès de ces traitements a été compromis par l'émergence croissante d'infections au VIH résistantes aux ARV notamment dans les pays à ressources limitées. La détection de ces mutations avant traitement aux ARV permettrait d'améliorer la prise en charge des patients. Nous présentons une étude de preuve de concept d'un test moléculaire rapide et simple pour détecter deux mutations majeures (K103 N, Y181 C) conférant une résistance aux traitements antirétroviraux de première ligne comportant un inhibiteur non nucléosidique de la transcriptase inverse (INNTI). Notre test de diagnostic combine une amplification moléculaire des génomes viraux, une étape d'extension d'amorce spécifique des mutations et une migration sur bandelette permettant de détecter visuellement des mutations de résistance aux traitements du VIH (DRM). Le test, réalisé en 4 h 30, a une limite de détection de 100 copies d'ADN plasmidique par réaction et une sensibilité supérieure au séquençage standard de type Sanger. La performance analytique a été évaluée à l'aide de 16 échantillons de plasma provenant d'individus vivant avec le VIH-1 et les résultats ont démontré la pertinence de cette approche pour la détection multiplexée des deux DRM en un seul test. Ce test évitant le recours au séquençage pourrait être facilement adapté pour la détection de nouvelles DRMs en vue d'un dépistage pré-thérapeutique. Cette approche diagnostique originale ouvre de nouvelles possibilités d'applications en infectiologie.

Background Limited information exists on nursing home (NH) residents regarding BNT162b2/Pfizer vaccine efficacy in preventing SARS-CoV-2 and severe Covid-19, and its association with post-vaccine humoral response. Methods 396 residents from seven NHs suffering a SARS-CoV-2 B.1.1.7 (VOC-α) outbreak at least 14 days after a vaccine campaign were repeatedly tested using SARS-CoV-2 real-time reverse-transcriptase polymerase chain reaction on nasopharyngeal swab test (RT-PCR). SARS-CoV-2 Receptor-Binding Domain (RBD) of the S1 subunit (RBD-IgG) was measured in all residents. Nucleocapsid antigenemia (N-Ag) was measured in RT-PCR-positive residents, and serum neutralizing antibodies in vaccinated residents from one NH. Results The incidence of positive RT-PCR was lower in residents vaccinated by two doses (22.7%) vs one dose (32.3%) or non-vaccinated residents (43.7%)(p<0.01). Covid-19-induced deaths were observed in 10.4% of the non-vaccinated residents, in 6.4% of those who had received one dose, and in 0.9% with two doses (p=0.0007). Severe symptoms were more common in infected non-vaccinated (21.0%) vs vaccinated residents (47.6%, p=0.002). Higher levels of RBD-IgG (n=325) were associated with a lower SARS-CoV-2 incidence. No in vitro serum neutralization activity was found for RBD-IgG levels below 1,050 AU/mL. RBD-IgG levels were inversely associated with N-Ag levels, found as a risk factor of severe Covid-19. Conclusions Two BNT162b2/Pfizer doses are associated with a 48% reduction of SARS-CoV-2 incidence and a 91.3% reduction of death risk in residents from NHs facing a VOC-α outbreak. BNT162b2/Pfizer efficacy was partly predicted by post-vaccine RBD-IgG levels.

Background: The ANRS-163 ETRAL trial, a switch study to an etravirine 200 mg/raltegravir 400 mg twice-daily regimen in 165 patients with HIV-1 infection, showed durable efficacy until Week 96. The aim of this work was to investigate in detail the virological rebounds (VRs), defined as at least one plasma HIV viral load (VL) >50 copies/mL. Methods: Quantification of HIV-DNA level was assessed at baseline, Week 48 and Week 96 (n=157). VLs were measured in seminal plasma at Week 48 (n=26). Genotypic resistance testing by ultra-deep sequencing (UDS) for reverse transcriptase (RT) and integrase regions was performed at baseline and at the time of VR. Results: In this study, 19 patients experienced VR, with 2 patients having virological failure (VF; two consecutive VLs >50 copies/mL). For the first patient with VF, UDS detected minority resistant variants only in RT (K103N, 9.6%; Y181C, 4.9%) at baseline. Some RT variants became dominant at VF (K101E, 86.3%; Y181C, 100.0%; G190A, 100.0%) and others emerged in integrase (Y143C, 2.4%; Q148R, 6.2%; N155H, 18.8%). For the second patient with VF, neither RT nor integrase mutations were detected at baseline and VF. Median HIV-DNA level was similar at baseline, Week 48 and Week 96 (2.17, 2.06 and 2.11 log(10) copies/10(6) cells, respectively). Only one patient had a detectable seminal HIV VL (505 copies/mL). Conclusions: The dual etravirine/raltegravir regimen as maintenance therapy was effective and the emergence of mutations in cases of VF was similar to that seen in other dual-regimen studies. No HIV-DNA level modification was evidenced by Week 96.

Objectives Patients with primary HIV-1 infection (PHI) are a particular population, giving important insight about ongoing evolution of transmitted drug resistance-associated mutation (TDRAM) prevalence, HIV diversity and clustering patterns. We describe these evolutions of PHI patients diagnosed in France from 2014 to 2016. Methods A total of 1121 PHI patients were included. TDRAMs were characterized using the 2009 Stanford list and the French ANRS algorithm. Viral subtypes and recent transmission clusters (RTCs) were also determined. Results Patients were mainly MSM (70%) living in the Paris area (42%). TDRAMs were identified among 10.8% of patients and rose to 18.6% when including etravirine and rilpivirine TDRAMs. Prevalences of PI-, NRTI-, first-generation NNRTI-, second-generation NNRTI- and integrase inhibitor-associated TDRAMs were 2.9%, 5.0%, 4.0%, 9.4% and 5.4%, respectively. In a multivariable analysis, age >40 years and non-R5 tropic viruses were associated with a >2-fold increased risk of TDRAMs. Regarding HIV diversity, subtype B and CRF02_AG (where CRF stands for circulating recombinant form) were the two main lineages (56% and 20%, respectively). CRF02_AG was associated with higher viral load than subtype B (5.83 versus 5.40 log10 copies/mL, P = 0.004). We identified 138 RTCs ranging from 2 to 14 patients and including overall 41% from the global population. Patients in RTCs were younger, more frequently born in France and more frequently MSM. Conclusions Since 2007, the proportion of TDRAMs has been stable among French PHI patients. Non-B lineages are increasing and may be associated with more virulent CRF02_AG strains. The presence of large RTCs highlights the need for real-time cluster identification to trigger specific prevention action to achieve better control of the epidemic.