RESUMEN
The SARS-CoV-2 Omicron variant was first identified in November 2021 in Botswana and South Africa1-3. It has since spread to many countries and is expected to rapidly become dominant worldwide. The lineage is characterized by the presence of around 32 mutations in spike-located mostly in the N-terminal domain and the receptor-binding domain-that may enhance viral fitness and enable antibody evasion. Here we isolated an infectious Omicron virus in Belgium from a traveller returning from Egypt. We examined its sensitivity to nine monoclonal antibodies that have been clinically approved or are in development4, and to antibodies present in 115 serum samples from COVID-19 vaccine recipients or individuals who have recovered from COVID-19. Omicron was completely or partially resistant to neutralization by all monoclonal antibodies tested. Sera from recipients of the Pfizer or AstraZeneca vaccine, sampled five months after complete vaccination, barely inhibited Omicron. Sera from COVID-19-convalescent patients collected 6 or 12 months after symptoms displayed low or no neutralizing activity against Omicron. Administration of a booster Pfizer dose as well as vaccination of previously infected individuals generated an anti-Omicron neutralizing response, with titres 6-fold to 23-fold lower against Omicron compared with those against Delta. Thus, Omicron escapes most therapeutic monoclonal antibodies and, to a large extent, vaccine-elicited antibodies. However, Omicron is neutralized by antibodies generated by a booster vaccine dose.
Asunto(s)
Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , COVID-19/virología , Evasión Inmune/inmunología , Inmunización Secundaria , SARS-CoV-2/inmunología , Adulto , Anticuerpos Monoclonales/inmunología , Vacuna BNT162/administración & dosificación , Vacuna BNT162/inmunología , Bélgica , COVID-19/inmunología , COVID-19/transmisión , ChAdOx1 nCoV-19/administración & dosificación , ChAdOx1 nCoV-19/inmunología , Convalecencia , Femenino , Humanos , Masculino , Mutación , Pruebas de Neutralización , Filogenia , SARS-CoV-2/clasificación , SARS-CoV-2/genética , SARS-CoV-2/aislamiento & purificación , ViajeRESUMEN
The SARS-CoV-2 B.1.617 lineage was identified in October 2020 in India1-5. Since then, it has become dominant in some regions of India and in the UK, and has spread to many other countries6. The lineage includes three main subtypes (B1.617.1, B.1.617.2 and B.1.617.3), which contain diverse mutations in the N-terminal domain (NTD) and the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein that may increase the immune evasion potential of these variants. B.1.617.2-also termed the Delta variant-is believed to spread faster than other variants. Here we isolated an infectious strain of the Delta variant from an individual with COVID-19 who had returned to France from India. We examined the sensitivity of this strain to monoclonal antibodies and to antibodies present in sera from individuals who had recovered from COVID-19 (hereafter referred to as convalescent individuals) or who had received a COVID-19 vaccine, and then compared this strain with other strains of SARS-CoV-2. The Delta variant was resistant to neutralization by some anti-NTD and anti-RBD monoclonal antibodies, including bamlanivimab, and these antibodies showed impaired binding to the spike protein. Sera collected from convalescent individuals up to 12 months after the onset of symptoms were fourfold less potent against the Delta variant relative to the Alpha variant (B.1.1.7). Sera from individuals who had received one dose of the Pfizer or the AstraZeneca vaccine had a barely discernible inhibitory effect on the Delta variant. Administration of two doses of the vaccine generated a neutralizing response in 95% of individuals, with titres three- to fivefold lower against the Delta variant than against the Alpha variant. Thus, the spread of the Delta variant is associated with an escape from antibodies that target non-RBD and RBD epitopes of the spike protein.
Asunto(s)
Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , Vacunas contra la COVID-19/inmunología , COVID-19/inmunología , COVID-19/virología , Convalecencia , Evasión Inmune/inmunología , Glicoproteína de la Espiga del Coronavirus/inmunología , Anticuerpos Monoclonales Humanizados/inmunología , Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/sangre , COVID-19/epidemiología , Vacunas contra la COVID-19/administración & dosificación , Epítopos/química , Epítopos/genética , Epítopos/inmunología , Francia , Humanos , India/epidemiología , Masculino , Persona de Mediana Edad , Pruebas de Neutralización , Glicoproteína de la Espiga del Coronavirus/química , Glicoproteína de la Espiga del Coronavirus/genéticaRESUMEN
SARS-CoV-2 variants with undetermined properties have emerged intermittently throughout the COVID-19 pandemic. Some variants possess unique phenotypes and mutations which allow further characterization of viral evolution and Spike functions. Around 1,100 cases of the B.1.640.1 variant were reported in Africa and Europe between 2021 and 2022, before the expansion of Omicron. Here, we analyzed the biological properties of a B.1.640.1 isolate and its Spike. Compared to the ancestral Spike, B.1.640.1 carried 14 amino acid substitutions and deletions. B.1.640.1 escaped binding by some anti-N-terminal domain and anti-receptor-binding domain monoclonal antibodies, and neutralization by sera from convalescent and vaccinated individuals. In cell lines, infection generated large syncytia and a high cytopathic effect. In primary airway cells, B.1.640.1 replicated less than Omicron BA.1 and triggered more syncytia and cell death than other variants. The B.1.640.1 Spike was highly fusogenic when expressed alone. This was mediated by two poorly characterized and infrequent mutations located in the Spike S2 domain, T859N and D936H. Altogether, our results highlight the cytopathy of a hyper-fusogenic SARS-CoV-2 variant, supplanted upon the emergence of Omicron BA.1. (This study has been registered at ClinicalTrials.gov under registration no. NCT04750720.)IMPORTANCEOur results highlight the plasticity of SARS-CoV-2 Spike to generate highly fusogenic and cytopathic strains with the causative mutations being uncharacterized in previous variants. We describe mechanisms regulating the formation of syncytia and the subsequent consequences in a primary culture model, which are poorly understood.
Asunto(s)
COVID-19 , SARS-CoV-2 , Humanos , África , COVID-19/virología , Pandemias , SARS-CoV-2/fisiología , Glicoproteína de la Espiga del Coronavirus/fisiología , Células Gigantes/virologíaRESUMEN
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 ≥1â year and in the presence of a documented M184V mutation within the last 5â years (clinicians). CONCLUSIONS: This DELPHI-type consensus will facilitate the strengthening and harmonization of good practice when performing HIV DNA sequencing.
Asunto(s)
Fármacos Anti-VIH , Infecciones por VIH , Humanos , Fármacos Anti-VIH/uso terapéutico , Antirretrovirales/uso terapéutico , Consenso , ADN/uso terapéutico , Genotipo , Infecciones por VIH/diagnóstico , Infecciones por VIH/tratamiento farmacológicoRESUMEN
OBJECTIVES: The impact of the systematic screening of Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) in men having sex with men (MSM) on these pathogens' epidemiology remains unclear. We conducted a modelling study to analyse this impact in French MSM. METHODS: We modelled NG and CT transmission using a site-specific deterministic compartmental model. We calibrated NG and CT prevalence at baseline using results from MSM enrolled in the Dat'AIDS cohort. The baseline scenario was based on 1 million MSM, 40 000 of whom were tested every 90 days and 960 000 every 200 days. Incidence rate ratios (IRRs) at steady state were simulated for NG, CT, NG and/or CT infections, for different combinations of tested sites, testing frequency and numbers of frequently tested patients. RESULTS: The observed prevalence rate was 11.0%, 10.5% and 19.1% for NG, CT and NG and/or CT infections. The baseline incidence rate was estimated at 138.2 per year per 100 individuals (/100PY), 86.8/100PY and 225.0/100PY for NG, CT and NG and/or CT infections. Systematically testing anal, pharyngeal and urethral sites at the same time reduced incidence by 14%, 23% and 18% (IRR: 0.86, 0.77 and 0.82) for NG, CT and NG and/or CT infections. Reducing the screening interval to 60 days in frequently tested patients reduced incidence by 20%, 29% and 24% (IRR: 0.80, 0.71 and 0.76) for NG, CT and NG and/or CT infections. Increasing the number of frequently tested patients to 200 000 reduced incidence by 29%, 40% and 33% (IRR: 0.71, 0.60 and 0.67) for NG, CT and NG and/or CT infections. No realistic scenario could decrease pathogens' incidence by more than 50%. CONCLUSIONS: To curb the epidemic of NG and CT in MSM, it would not only be necessary to drastically increase screening, but also to add other combined interventions.
Asunto(s)
Infecciones por Chlamydia , Chlamydia trachomatis , Gonorrea , Homosexualidad Masculina , Tamizaje Masivo , Neisseria gonorrhoeae , Humanos , Masculino , Gonorrea/epidemiología , Gonorrea/diagnóstico , Homosexualidad Masculina/estadística & datos numéricos , Chlamydia trachomatis/aislamiento & purificación , Infecciones por Chlamydia/epidemiología , Infecciones por Chlamydia/diagnóstico , Neisseria gonorrhoeae/aislamiento & purificación , Prevalencia , Incidencia , Tamizaje Masivo/estadística & datos numéricos , Adulto , Francia/epidemiología , Adulto JovenRESUMEN
Because SARS-CoV-2 constantly mutates to escape from the immune response, there is a reduction of neutralizing capacity of antibodies initially targeting the historical strain against emerging Variants of Concern (VoC)s. That is why the measure of the protection conferred by vaccination cannot solely rely on the antibody levels, but also requires to measure their neutralization capacity. Here we used a mathematical model to follow the humoral response in 26 individuals that received up to three vaccination doses of Bnt162b2 vaccine, and for whom both anti-S IgG and neutralization capacity was measured longitudinally against all main VoCs. Our model could identify two independent mechanisms that led to a marked increase in measured humoral response over the successive vaccination doses. In addition to the already known increase in IgG levels after each dose, we identified that the neutralization capacity was significantly increased after the third vaccine administration against all VoCs, despite large inter-individual variability. Consequently, the model projects that the mean duration of detectable neutralizing capacity against non-Omicron VoC is between 348 days (Beta variant, 95% Prediction Intervals PI [307; 389]) and 587 days (Alpha variant, 95% PI [537; 636]). Despite the low neutralization levels after three doses, the mean duration of detectable neutralizing capacity against Omicron variants varies between 173 days (BA.5 variant, 95% PI [142; 200]) and 256 days (BA.1 variant, 95% PI [227; 286]). Our model shows the benefit of incorporating the neutralization capacity in the follow-up of patients to better inform on their level of protection against the different SARS-CoV-2 variants. Trial registration: This clinical trial is registered with ClinicalTrials.gov, Trial IDs NCT04750720 and NCT05315583.
Asunto(s)
Anticuerpos Neutralizantes , COVID-19 , Humanos , Anticuerpos Antivirales , Vacuna BNT162 , COVID-19/prevención & control , Inmunoglobulina G , SARS-CoV-2/genética , VacunaciónRESUMEN
BACKGROUND: In TANGO, switching to dolutegravir/lamivudine (DTG/3TC) demonstrated long-term noninferior efficacy vs continuing tenofovir alafenamide-based regimens in treatment-experienced adults with HIV-1. The phase 3 SALSA study evaluated efficacy and safety of switching to DTG/3TC compared with continuing various 3-/4-drug current antiretroviral regimens (CARs). METHODS: Adults with HIV-1 RNA <50 copies/mL and no previous virologic failure were randomized (1:1, stratified by baseline third agent class) to switch to once-daily fixed-dose combination DTG/3TC or continue CAR (primary endpoint: proportion of participants with HIV-1 RNA ≥50 copies/mL at week 48; Snapshot, intention-to-treat-exposed population, 5% noninferiority margin). RESULTS: Overall, 493 adults (39% women; 39% aged ≥50 years; 19% African American/African heritage; 14% Asian) were randomized to switch to DTG/3TC (nâ =â 246) or continue CAR (nâ =â 247). At week 48, 1 (0.4%) participant in the DTG/3TC group and 3 (1.2%) in the CAR group had HIV-1 RNA ≥50 copies/mL (Snapshot), demonstrating noninferiority (adjusted difference, -0.8%; 95% CI, -2.4%, .8%). Zero participants met confirmed virologic withdrawal criteria; therefore, no resistance testing was performed. Drug-related adverse events were more frequent with DTG/3TC (20%) than CAR (6%) through week 48 but comparable post-week 24 (5% vs 2%, respectively). Proximal tubular renal function and bone turnover biomarkers improved with DTG/3TC. Both groups had generally minimal changes in lipids and inflammatory biomarkers. CONCLUSIONS: Switching to DTG/3TC was noninferior to continuing CAR for maintaining virologic suppression at week 48 with no observed resistance, supporting the efficacy, good safety, and high barrier to resistance of DTG/3TC. CLINICAL TRIALS REGISTRATION: www.clinicaltrials.gov, NCT04021290.
Asunto(s)
Fármacos Anti-VIH , Infecciones por VIH , VIH-1 , Adulto , Humanos , Femenino , Masculino , Lamivudine/uso terapéutico , Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , ARN Viral , BiomarcadoresRESUMEN
OBJECTIVES: To minimize confounding factors, we aimed to describe the changes in weight and body mass index (BMI) following the single substitution of tenofovir disoproxil fumarate (TDF) by tenofovir alafenamide (TAF) in people living with HIV (PLWH). METHODS: We designed a retrospective study in a large French cohort. We included all HIV-suppressed adults under TDF + emtricitabine + rilpivirine or elvitegravir/cobistat, who experienced a first switch from TDF to TAF, while other antiretrovirals remained unchanged (Switch group). We compared this population to a propensity score-matched Control group (1:1) who stayed on the same TDF-based regimen. Changes were evaluated after 6 (M6) and 12 months (M12). RESULTS: Some 1260 and 468 PLWH were evaluable per group at M6 and M12, respectively. In the Switch group, there was a mean (95% confidence interval [95% CI]) weight gain of +1014 g (+826 to +1201) at M6 (p < 0.0001) and +1365 g (+910 to +1820) at M12 (p < 0.0001), as compared with baseline. Meanwhile, there was no significant weight gain at M6 (+139 g [-50 to +328]) and M12 (-32 g [-413 to +350]) in the matched Control group. Similarly, mean BMI increased significantly in the Switch group at M6 (+0.35, 95% CI: +0.29 to +0.41, p < 0.0001) and M12 (+0.49, 95% CI: +0.32 to +0.65, p < 0.0001), while it was stable at M6 (+0.05, 95% CI: -0.01 to +0.12, p = 0.11) and M12 (+0.01, 95% CI: -0.12 to +0.14, p = 0.89) in the No Switch group. CONCLUSIONS: Although modest, there is a significant weight gain following the substitution of TDF by TAF. This should be anticipated in certain at-risk populations.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida , Fármacos Anti-VIH , Infecciones por VIH , Adulto , Humanos , Tenofovir/efectos adversos , Fármacos Anti-VIH/efectos adversos , Infecciones por VIH/tratamiento farmacológico , Estudios Retrospectivos , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Puntaje de Propensión , Adenina/uso terapéutico , Emtricitabina/uso terapéutico , Aumento de PesoRESUMEN
BACKGROUND: Crushing or dissolving bictegravir/tenofovir alafenamide/emtricitabine (BIC/TAF/FTC) tablets is not recommended because there are no data supporting this practice. METHODS: A crossover, randomized trial in healthy adults (NCT04244448) investigated the bioavailability of two off-label uses of BIC/TAF/FTC (50/200/25â mg), dissolved in water or crushed in apple compote, compared with the solid tablet. Pharmacokinetic (PK) parameters were estimated from sequential intensive plasma antiretroviral concentrations over a 72â h period post dose. Bioequivalence was met if the 90% CIs of the geometric least-squares means ratios comparing BIC/TAF/FTC exposures (AUC and Cmax) from the experimental phases were within 80%-125% of the reference. RESULTS: Eighteen subjects participated in each of the three phases. Dissolved tablet Cmax geometric mean ratio (90% CI) for BIC/TAF/FTC was 105% (93-119)/97% (87-108)/96% (74-124), respectively. Dissolved tablet AUC geometric mean ratio (90% CI) for BIC/TAF/FTC was 111% (100-122)/100% (94 to 105)/99% (81 to 120), respectively. Crushed tablet Cmax geometric mean ratio (90%) CI for BIC/TAF/FTC was 110% (97 to 124)/70% (63-78)/66% (51-85), respectively. Crushed tablet AUC geometric mean ratio (90%) CI for BIC/TAF/FTC was 107% (96-118)/86% (82-91)/84% (69-103), respectively. CONCLUSIONS: Crushing BIC/TAF/FTC tablets may lead to suboptimal emtricitabine and tenofovir alafenamide drug exposures. Dissolving BIC/TAF/FTC in water may be acceptable if the tablet cannot be swallowed whole.
Asunto(s)
Fármacos Anti-VIH , Infecciones por VIH , Humanos , Adulto , Emtricitabina/uso terapéutico , Tenofovir/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Disponibilidad Biológica , Estudios Cruzados , Adenina/farmacocinética , Comprimidos , Fármacos Anti-VIH/uso terapéutico , Alanina/uso terapéuticoRESUMEN
The control of the COVID-19 epidemics has been one global health priorities for the last 2 years. To that end, more reliable and easy-to-use, regardless of age, diagnostic tests are necessary. Considering that, we evaluated an innovative two-step self-test, the AAZ COVID-VIRO ALL IN®, switching from the classic nasal swab to a nasal sponge. We performed a multicenter study, on 124 adults and children, in a point-of-care setting. Sensitivity, specificity and overall acceptance of the COVID-VIRO ALL IN® self-test compared to reverse transcriptase polymerase chain reaction (RT-PCR) on nasopharyngeal samples were of 93.0%, 100%, and 97.5%, respectively. We then performed a multicenter, usability study to evaluate the ease of use of COVID-VIRO ALL IN® on 68 laypersons adults. A vast majority of participants correctly executed and interpreted the test. The usability was then specifically investigated on 40 children and teenagers, comparing COVID-VIRO® first generation to the new COVID-VIRO ALL IN®. They all found COVID-VIRO ALL IN® more comfortable and easier to use. For young children, the new self-test seems safer (less risk of trauma and no liquid exposure), and faster than saliva-based RT-PCR. Moreover, the COVID-VIRO ALL IN® can easily be adapted as a multiplex self-test for other respiratory viruses, opening new perspectives of simultaneous, rapid and massive detection of respiratory infections, especially among vulnerable populations like children and elderly people.
Asunto(s)
COVID-19 , SARS-CoV-2 , Adolescente , Adulto , Anciano , COVID-19/diagnóstico , Niño , Preescolar , Pruebas Diagnósticas de Rutina , Humanos , Nasofaringe , SARS-CoV-2/genética , Autoevaluación , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Raltegravir (RAL) has favorable tolerability and safety profile, with few and manageable drug interactions. The use of RAL 1200 mg once daily (qd) for first-line therapy is well established. We assessed efficacy and safety of RAL 1200 mg qd, as part of triple combined antiretroviral therapy (cART), for maintenance strategy. METHODS: The QDISS trial (NCT03195452) was a 48-week multicenter, single-arm, open-label study designed to evaluate the ability of 2 NRTIs + RAL 1200 mg qd to maintain virological suppression in HIV-1 infected subjects on a stable cART with 2 NRTIs and a third agent for at least 6 months. The primary endpoint was the proportion of participants with HIV-1 RNA < 50 copies/mL at week 24, by the FDA snapshot algorithm. RESULTS: Of 100 participants 91% maintained viral suppression (95% CI: 83.6-95.8) at week 24 and 89% (81.2-94.4) at week 48. At week 24, there was one virological failure, without emergence of resistance-associated mutation and 10 participants had discontinued, 4 because of adverse events (AEs). Over 48 weeks, 7 AEs of grade 3-4 were reported, one possibly study-drug related (spontaneous abortion). BMI remained stable regardless of previous therapy or baseline BMI category. Over 48 weeks, total cholesterol (p = 0.023) and LDL-cholesterol (p = 0.009) decreased, lifestyle and ease subscale significantly improved (p = 0.04). The quality of life and Patients Reported Outcomes (PROs) also improved at W12 (p = 0.007). CONCLUSION: RAL 1200 mg qd as part of a maintenance triple therapy showed a high efficacy in virologically suppressed HIV-1 infected subjects, with good safety profile and improved lipid profile and patient reported outcomes. TRIAL REGISTRATION: Clinical trials.gov NCT03195452 and EudraCT 2016-003702-13.
Asunto(s)
Infecciones por VIH , Seropositividad para VIH , VIH-1 , Adulto , Infecciones por VIH/tratamiento farmacológico , Humanos , Calidad de Vida , Raltegravir Potásico/efectos adversos , Resultado del Tratamiento , Carga ViralRESUMEN
BACKGROUND: The arrival of highly effective, well-tolerated, direct-acting antiviral agents (DAA) led to a dramatic decrease in hepatitis C virus (HCV) prevalence. Human immunodeficiency virus (HIV)-HCV-coinfected patients are deemed a priority population for HCV elimination, while a rise in recently acquired HCV infections in men who have sex with men (MSM) has been described. We describe the variations in HIV-HCV epidemiology in the French Dat'AIDS cohort. METHODS: This was a retrospective analysis of a prospective cohort of persons living with HIV (PLWH) from 2012 to 2018. We determined HCV prevalence, HCV incidence, proportion of viremic patients, treatment uptake, and mortality rate in the full cohort and by HIV risk factors. RESULTS: From 2012 to 2018, 50â 861 PLWH with a known HCV status were followed up. During the period, HCV prevalence decreased from 15.4% to 13.5%. HCV prevalence among new HIV cases increased from 1.9% to 3.5% in MSM but remained stable in other groups. Recently acquired HCV incidence increased from 0.36/100 person-years to 1.25/100 person-years in MSM. The proportion of viremic patients decreased from 67.0% to 8.9%. MSM became the first group of viremic patients in 2018 (37.9%). Recently acquired hepatitis represented 59.2% of viremic MSM in 2018. DAA treatment uptake increased from 11.4% to 61.5%. More treatments were initiated in MSM in 2018 (41.2%) than in intravenous drug users (35.6%). In MSM, treatment at the acute phase represented 30.0% of treatments in 2018. CONCLUSIONS: A major shift in HCV epidemiology was observed in PLWH in France from 2012 to 2018, leading to a unique situation in which the major group of HCV transmission in 2018 was MSM. Clinical Trials Registration. NCT02898987.
Asunto(s)
Coinfección , Infecciones por VIH , Hepatitis C Crónica , Hepatitis C , Minorías Sexuales y de Género , Antivirales/uso terapéutico , Coinfección/tratamiento farmacológico , Coinfección/epidemiología , Francia/epidemiología , VIH , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Hepacivirus , Hepatitis C/complicaciones , Hepatitis C/tratamiento farmacológico , Hepatitis C/epidemiología , Hepatitis C Crónica/tratamiento farmacológico , Homosexualidad Masculina , Humanos , Masculino , Estudios Prospectivos , Estudios RetrospectivosRESUMEN
BACKGROUND: Maintenance ART with dolutegravir-based dual regimens have proved their efficacy among HIV-1-infected subjects in randomized trials. However, real-life data are scarce, with limited populations and follow-up. OBJECTIVES: We assessed virological failure (VF) and resistance-associated mutations (RAMs) on dolutegravir maintenance regimens in combination with rilpivirine or with lamivudine or emtricitabine (xTC) and analysed the factors associated with VF. METHODS: Between 2014 and 2018, all HIV-1-infected adults included in the Dat'AIDS cohort and starting dolutegravir/rilpivirine or dolutegravir/xTC as a maintenance dolutegravir-based dual regimen were selected. VF was defined as two consecutive HIV RNA values >50 copies/mL or a single value >400 copies/mL. We compared cumulative genotypes before initiation of a maintenance dolutegravir-based dual regimen with genotype at VF. RESULTS: We analysed 1374 subjects (799 on dolutegravir/rilpivirine and 575 on dolutegravir/xTC) with a median follow-up of 20 months (IQR = 11-31) and 19 months (IQR = 11-31), respectively. VF occurred in 3.8% (n = 30) of dolutegravir/rilpivirine subjects and 2.6% (n = 15) of dolutegravir/xTC subjects. Among subjects receiving dolutegravir/rilpivirine, two genotypes harboured emerging RAMs at VF: E138K on NNRTI (n = 1); and E138K+K101E on NNRTI and N155H on INSTI (n = 1). Among subjects receiving dolutegravir/xTC, no new RAM was detected. The only predictive factor of VF on dolutegravir/rilpivirine was the history of failure on an NNRTI-based regimen (adjusted HR = 2.97, 95% CI = 1.28-6.93). No factor was associated with VF on dolutegravir/xTC. CONCLUSIONS: In this large real-life cohort, dolutegravir/rilpivirine and dolutegravir/xTC sustained virological suppression and were associated with a low rate of VF and RAM emergence. Careful virological screening is essential before switching to dolutegravir/rilpivirine in virologically suppressed patients with a history of NNRTI therapy.
Asunto(s)
Fármacos Anti-VIH , Infecciones por VIH , Fármacos Anti-VIH/uso terapéutico , Emtricitabina/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Compuestos Heterocíclicos con 3 Anillos/efectos adversos , Humanos , Lamivudine/uso terapéutico , Oxazinas/uso terapéutico , Piperazinas , Piridonas/uso terapéutico , Rilpivirina/uso terapéutico , Carga ViralRESUMEN
OBJECTIVES: Low HIV reservoirs may be associated with viral suppression under a lower number of antiretroviral drugs. We investigated tenofovir disoproxil fumarate/emtricitabine as a maintenance strategy in people living with HIV (PLHIV) with low HIV-DNA. METHODS: TRULIGHT (NCT02302547) was a multicentre, open-label, randomized trial comparing a simplification to tenofovir disoproxil fumarate/emtricitabine versus a triple regimen continuation (tenofovir disoproxil fumarate/emtricitabine with a third agent, control arm) in virologically suppressed adults with HIV-DNA <2.7 log10 copies/106 PBMCs and no prior virological failure (VF). The primary endpoint (non-inferiority margin 12%) was the percentage of participants with a plasma viral load (pVL) <50 copies/mL in ITT (Snapshot approach) and PP analyses at Week 48 (W48). RESULTS: Of the 326 participants screened, 223 (68%) were randomized to the tenofovir disoproxil fumarate/emtricitabine arm (n = 113) or control arm (n = 110). At W48, the tenofovir disoproxil fumarate/emtricitabine and control arms maintained a pVL < 50 copies/mL in 100/113 (88.5%) and 100/110 (90.9%) participants, respectively (ITT difference 2.4%, 95% CI -5.9 to 10.7; PP difference 3.4%, 95% CI -4.2 to 11.0). Six VFs occurred in the tenofovir disoproxil fumarate/emtricitabine arm (two with emerging mutations M184V and K65R) versus two in the control arm (ITT difference 3.5%, 95% CI -1.9 to 9.4). All VFs were resuppressed after treatment modification. CONCLUSIONS: Although non-inferiority was shown, simplification to tenofovir disoproxil fumarate/emtricitabine should not be used for most PLHIV because of a low risk of VF with resistance.
Asunto(s)
Fármacos Anti-VIH , Infecciones por VIH , VIH-1 , Adenina/uso terapéutico , Adulto , Fármacos Anti-VIH/uso terapéutico , ADN , Emtricitabina/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , VIH-1/genética , Humanos , Tenofovir/uso terapéutico , Resultado del Tratamiento , Carga ViralRESUMEN
To control the spread of the coronavirus disease 2019 (COVID-19) epidemics, it is necessary to have easy-to-use, reliable diagnostic tests available. The nasopharyngeal sampling method being often uncomfortable, nasal sampling could prove to be a viable alternative to the reference sampling method. We performed a multicentre, prospective validation study of the COVID-VIRO® test, using a nasal swab sampling method, in a point-of-care setting. In addition, we performed a multicentre, prospective, and usability study to validate the use of the rapid antigen nasal diagnostic test by laypersons. In March 2021, 239 asymptomatic and symptomatic patients were included in the validation study. Compared with reverse-transcription polymerase chain reaction on nasopharyngeal samples, the sensitivity and specificity of the COVID-VIRO® Antigen test combined with a nasal sampling method were evaluated as 96.88% and 100%, respectively. A total of 101 individuals were included in the usability study. Among these, 99% of the participants rated the instructions material as good, 98% of the subjects executed the test procedure well, and 98% of the participants were able to correctly interpret the test results. This study validates the relevance of COVID-VIRO® as a diagnostic tool from nasal specimens as well as its usability in the general population. COVID-VIRO® diagnostic performances and ease of use make it suitable for widespread utilization.
Asunto(s)
Prueba de COVID-19/métodos , Pruebas Diagnósticas de Rutina/métodos , Autoevaluación , Adulto , Antígenos Virales/sangre , Humanos , Masculino , Pruebas en el Punto de Atención , Estudios Prospectivos , SARS-CoV-2/inmunología , Sensibilidad y EspecificidadRESUMEN
Optimal management of patients experiencing persistent low-level viremia (LLV) remains challenging and poorly understood. This study aimed to assess the association between poor antiretroviral treatment (ARV) adherence and persistent LLV. ADHELOW is a sub-study of the ECHEC cohort comprising HIV-infected adults with virological failure (viral load>50 copies/mL). Patients were recruited in 2013-2015 from 4 French university hospitals. Those with LLV (i.e., ≥2 viral load measurements between 50 and 500 copies/mL) were selected and matched on age and sex to 3 controls with virological suppression. The adherence rate was estimated using pharmacy-delivered prescription refills over one year. Overall, 60 patients were included (15 LLV and 45 controls). Mean age was 50.20 years, M/F sex ratio was 14 and mean EPICES (social deprivation) score was 42.90. In univariable analyses, LLV patients had significantly lower adherence (<80%: 53.30% vs. 6.67%, p < 0.01) and were more likely to have an EPICES score >40.2 (60.00% vs. 24.44%, p < 0.01). In multivariable analysis, these two variables remained significantly associated with LLV (OR 31.49, CI 95% [4.54-218.70]) and OR 11.00 (CI 95% [1.87-218.70], respectively). Poor long-term treatment adherence, estimated by prescription refills, was strongly associated with LLV. This reinforces the message that adherence counseling should be the primary intervention to overcome LLV.
Asunto(s)
Fármacos Anti-VIH , Infecciones por VIH , Adulto , Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Humanos , Persona de Mediana Edad , Prescripciones , Carga Viral , Viremia/tratamiento farmacológicoRESUMEN
BACKGROUND: Increasingly, people living with human immunodeficiency virus (HIV) benefit from lower drug regimens (LDRs). Exploring viral genital shedding during LDRs is crucial to ensure their safety. METHODS: We pooled genital sub-studies from 2 clinical trials in this area. Patients were randomized 1:1 to continue abacavir/lamivudine/dolutegravir or switch to dolutegravir (MONCAY trial), or to continue tenofovir/emtricitabine + a third agent or switch to tenofovir/emtricitabine (TRULIGHT trial). Participants whose plasma HIV-RNA remained <50 copies/mL had sperm or cervicovaginal lavage collected between Weeks 24 and 48. HIV-RNA and HIV-DNA were amplified by ultrasensitive polymerase chain reaction. The main objective was to measure the proportion of participants who had no detectable HIV in genital fluids, both according to each strategy and then in an aggregated analysis (LDR versus triple therapies). RESULTS: There were 64 participants (35 males, 29 females) included: 16 received dual therapies and 16 received triple therapies in TRULIGHT; and 16 received monotherapies and 16 received triple therapies in MONCAY. In TRULIGHT, 13/15 (87%) of evaluable participants on dual therapy had no detectable HIV in their genital fluid, versus 14/15 (93%) under triple therapy (P = 1.0). In MONCAY, these figures were 12/15 (80%) on monotherapy versus 13/16 (81%) on triple therapy (P = 1.0). In the pooled analysis, a similar proportion of participants in the LDR and triple therapy groups had no detectable HIV: 25/30 (83%) and 27/31 (87%), respectively (P = .73). CONCLUSIONS: There was no evidence of increased HIV-RNA and/or -DNA shedding in the genital fluids of people who maintained undetectable plasma HIV-RNA during LDRs. CLINICAL TRIALS REGISTRATION: NCT02302547 and NCT02596334.
Asunto(s)
Fármacos Anti-VIH , Infecciones por VIH , VIH-1 , Fármacos Anti-VIH/uso terapéutico , ADN/uso terapéutico , Emtricitabina/uso terapéutico , Femenino , Genitales , Infecciones por VIH/tratamiento farmacológico , VIH-1/genética , Humanos , Lamivudine/uso terapéutico , Masculino , ARN/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Carga ViralRESUMEN
BACKGROUND: We assessed prevalence of multimorbidity (MM) according to year of human immunodeficiency virus (HIV) diagnosis in elderly people living with HIV (PLWH). METHODS: This was a cross-sectional study of MM in PLWH aged ≥70 years from the Dat'AIDS French multicenter cohort. MM was defined as at least 3 coexistent morbidities of high blood pressure, diabetes mellitus, osteoporosis, non-AIDS cancer, chronic renal failure, cardiovascular and cerebrovascular disease, obesity, undernutrition, or hypercholesterolemia. Logistic regression models evaluated the association between MM and calendar periods of HIV diagnosis (1983-1996, 1997-2006, and 2007-2018). The secondary analysis evaluated MM as a continuous outcome, and a sensitivity analysis excluded PLWH with nadir CD4 count <200 cells/µL. RESULTS: Between January 2017 and September 2018, 2476 PLWH were included. Median age was 73 years, 75% were men, median CD4 count was 578 cells/µL, and 94% had controlled viremia. MM prevalence was 71%. HBP and hypercholesterolemia were the most prevalent comorbidities. After adjustment for age, gender, smoking status, hepatitis C and hepatitis B virus coinfection, group of exposure, nadir CD4 count, CD4:CD8 ratio, and last CD4 level, calendar period of diagnosis was not associated with MM (Pâ =â .169). MM was associated with older age, CD4/CD8 ratio <0.8, and nadir CD4 count <200 cells/µL. Similar results were found with secondary and sensitivity analyses. CONCLUSIONS: MM prevalence was high and increased with age, low CD4/CD8 ratio, and nadir CD4 count <200 cells/µL but was not associated with calendar periods of HIV diagnosis. Known duration of HIV diagnosis does not seem to be a criterion for selecting elderly PLWH at risk of MM.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida , Infecciones por VIH , Anciano , Recuento de Linfocito CD4 , Estudios de Cohortes , Estudios Transversales , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/diagnóstico , Infecciones por VIH/epidemiología , Humanos , Masculino , MultimorbilidadRESUMEN
HIV-1 infection is associated with B cell dysregulation and dysfunction. In HIV-1-infected patients, we previously reported preservation of intestinal lymphoid structures and dendritic cell maturation pathways after early combination antiretroviral therapy (e-ART), started during the acute phase of the infection, compared with late combination antiretroviral therapy started during the chronic phase. In this study, we investigated whether the timing of combination antiretroviral therapy initiation was associated with the development of the HIV-1-specific humoral response in the gut. The results showed that e-ART was associated with higher frequencies of functional resting memory B cells in the gut. These frequencies correlated strongly with those of follicular Th cells in the gut. Importantly, frequencies of HIV-1 Env gp140-reactive B cells were higher in patients given e-ART, in whom gp140-reactive IgG production by mucosal B cells increased after stimulation. Moreover, IL-21 release by PBMCs stimulated with HIV-1 peptide pools was greater with e-ART than with late combination antiretroviral therapy. Thus, early treatment initiation helps to maintain HIV-1-reactive memory B cells in the gut as well as follicular Th cells, whose role is crucial in the development of potent affinity-matured and broadly neutralizing Abs.
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Antirretrovirales/uso terapéutico , Linfocitos B/efectos de los fármacos , Infecciones por VIH/tratamiento farmacológico , VIH-1/efectos de los fármacos , Mucosa Intestinal/efectos de los fármacos , Intestinos/efectos de los fármacos , Linfocitos T Colaboradores-Inductores/efectos de los fármacos , Adulto , Anciano , Linfocitos B/virología , Femenino , Humanos , Memoria Inmunológica/efectos de los fármacos , Interleucinas/metabolismo , Mucosa Intestinal/virología , Intestinos/virología , Masculino , Persona de Mediana Edad , Linfocitos T Colaboradores-Inductores/virología , Productos del Gen env del Virus de la Inmunodeficiencia Humana/metabolismoRESUMEN
We report a case of sexual transmission of human immunodeficiency virus (HIV) that occurred during treatment discontinuation in a therapeutic vaccine trial, following oral sex. Transmission occurred even though the index participant was an HIV/AIDS activist, particularly well informed about the risks and modalities of transmission. This case report highlights the risk of secondary transmission of HIV during cessation of treatment in HIV cure-related trials.