RESUMO
We evaluated Ibalizumab (IBA)-containing standardized optimized salvage regimen (with or without a 4-week foscarnet induction) in individuals harboring multidrug-resistant human immunodeficiency virus type 2 (HIV-2). Nine were included; 2 achieved virological suppression after foscarnet induction with a sustained suppression at Week 24 after IBA initiation, and an additional individual at Week 24 after Ibalizumab initiation.
Assuntos
Fármacos Anti-HIV , Anticorpos Monoclonais , Infecções por HIV , Humanos , Foscarnet/uso terapêutico , HIV-2 , Fármacos Anti-HIV/uso terapêutico , Terapia de Salvação , Infecções por HIV/tratamento farmacológicoRESUMO
OBJECTIVES: HIV pre-exposure prophylaxis (PrEP) is effective in preventing HIV, but some seroconversions occur due to poor adherence or PrEP discontinuation. Our objective was to estimate the incidence of PrEP discontinuation and describe the reasons and factors associated with discontinuations. METHODS: A retrospective cohort was conducted in three French hospitals between January 2016 and June 2022. PrEP users who attended at least twice within 6â months during study period were included and followed up until December 2022. The incidence rate of PrEP discontinuation was estimated by censoring lost to follow up individuals. Factors associated with PrEP discontinuations were identified using a multivariate Cox model. RESULTS: A total of 2785 PrEP users were included, with 94% men and 5% transgender people. Median age was 35â years. By December 2022, 653 users had stopped PrEP (24%). The incidence rate was 10.8 PrEP discontinuations for 100 person-years (PY). The main causes of discontinuation were being in a stable relationship (32%), and not judging the treatment useful anymore (12%). Individuals who discontinued PrEP were younger [<29, HRâ=â1.45 (1.17-1.80)], and more likely to be women [HRâ=â2.44 (1.50-3.96)] or sex workers [HRâ=â1.53 (0.96-2.44)]. They were more likely to report PrEP side effects [HRâ=â2.25 (1.83-2.77)] or ≥2 sexually transmitted infections [HRâ=â1.87 (1.53-2.27)] during the last year. CONCLUSION: The incidence of PrEP discontinuations was quite low compared to rates observed in other cohorts. Users who stopped PrEP were sometimes still exposed to HIV, emphasizing the need for targeted interventions to prepare and support PrEP discontinuations and limit seroconversion risk.
Assuntos
Fármacos Anti-HIV , Infecções por HIV , Profilaxia Pré-Exposição , Humanos , França/epidemiologia , Feminino , Masculino , Adulto , Infecções por HIV/prevenção & controle , Infecções por HIV/epidemiologia , Profilaxia Pré-Exposição/estatística & dados numéricos , Estudos Retrospectivos , Incidência , Fármacos Anti-HIV/uso terapêutico , Fármacos Anti-HIV/administração & dosagem , Adesão à Medicação/estatística & dados numéricos , Pessoa de Meia-Idade , Adulto JovemRESUMO
BACKGROUND: Initiating same-day ART for newly HIV-diagnosed individuals reduces secondary HIV transmissions and the risk of them being lost to follow-up between diagnosis and initiation of ART. METHODS: The FAST study was a national, prospective, single-arm study assessing the efficacy, safety and feasibility of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) in a same-day initiation model. ART had to be started on the first medical appointment, before any laboratory results were available. Participants completed a self-administered questionnaire at each visit including a HIV anxiety 5-point Likert scale. The primary outcome was the proportion of participants in the ITT population with plasma HIV RNA (pVL)â<â50 copies/mL at Week (W) 24 using the FDA Snapshot algorithm. RESULTS: Overall, 112 participants were included in the ITT population. During follow-up, seven participants discontinued the study drug but remained on the study, and seven others discontinued follow-up. According to FDA Snapshot analysis, at W24 and W48, 90/112, (80.4%; 95% CI: 71.8-87.3) and 95/112 (84.8%; 95% CI: 76.8-90.9) of participants achieved pVLâ<â50 copies/mL, respectively. The protocol-defined virological failure (PDVF, 2 consecutive pVLâ≥â50 copies/mL as of W24) was observed in 11/112 (9.8%) at W24 and 14/112 (12.5%) at W48. No emergent resistance-associated mutation was detected in those with PDVF at W24 and W48. BIC/FTC/TAF was well tolerated through to W48, with a low incidence of grade 3-4 adverse events (15/100 person-years). Patient opinion of same-day treatment initiation and continuing BIC/FTC/TAF was very favourable. CONCLUSIONS: These results suggest that BIC/FTC/TAF is safe, effective and well accepted for same-day initiation.
Assuntos
Fármacos Anti-HIV , Infecções por HIV , Humanos , Infecções por HIV/tratamento farmacológico , Emtricitabina/uso terapêutico , Estudos Prospectivos , Adenina , Alanina/uso terapêutico , Piridonas/uso terapêutico , Combinação de Medicamentos , Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico , Fármacos Anti-HIV/uso terapêuticoRESUMO
BACKGROUND: HIV-2 resistance to integrase strand-transfer inhibitors (INSTIs) is characterized by two main pathways: (i) mutations at codons 143, 148 and155; and (ii) amino acid insertion after integrase codon 231 (231ins). OBJECTIVES: To complete INSTI resistance data on HIV-2 by determining the viral replicative capacity and INSTI phenotypic susceptibility of integrase mutants obtained through site-directed mutagenesis. METHODS: Site-directed mutants (SDMs) were constructed and viral stocks produced. Viral replicative capacity was assessed by measuring HIV-2 viral load at days 3, 7 and 14. In vitro phenotypic susceptibility was measured using the ANRS PBMC assay. RESULTS: Viruses bearing 231ins did not present impaired replicative capacity, except the 231ins GIRGK mutant. A 231ins GK SDM was resistant to raltegravir and cabotegravir, but remained susceptible to dolutegravir and bictegravir. SDMs harbouring a 5 amino acid insertion (GYKGK or SREGK) were both resistant to all INSTIs. The SDM with T97A+N155H, with or without E92Q, was resistant to all INSTIs, except bictegravir. CONCLUSIONS: These first data on the newly described resistance pathway 231ins, using site-directed mutagenesis, showed no measurable impact on viral fitness and confirmed the decreased susceptibility to a first-generation INSTI (raltegravir) and cabotegravir. Resistance to second-generation INSTIs (dolutegravir and bictegravir) occurred for mutants with a 5 amino acid 231ins.
Assuntos
Infecções por HIV , Inibidores de Integrase de HIV , Integrase de HIV , HIV-1 , Farmacorresistência Viral/genética , Infecções por HIV/tratamento farmacológico , Integrase de HIV/metabolismo , Inibidores de Integrase de HIV/farmacologia , Inibidores de Integrase de HIV/uso terapêutico , HIV-1/genética , HIV-2/genética , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Humanos , Leucócitos Mononucleares/metabolismo , Piridonas/farmacologia , Piridonas/uso terapêutico , Raltegravir Potássico/uso terapêuticoAssuntos
Infecções por HIV , Minorias Sexuais e de Gênero , Infecções Sexualmente Transmissíveis , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Homossexualidade Masculina , Humanos , Masculino , Monkeypox virus , Paris/epidemiologia , Prevalência , Infecções Sexualmente Transmissíveis/diagnóstico , Infecções Sexualmente Transmissíveis/epidemiologiaRESUMO
Paget's disease of bone (PDB) has rarely been reported in people with HIV (PWH). We describe the prevalence and characteristics of patients with PDB in the French multicenter Dat'AIDS cohort. Among 49 698 PWH actively followed in 2022, 9 had a diagnosis of PDB. The overall prevalence of PDB was 0.02% [95% confidence interval (CI) 0.01-0.03]. The prevalence of PDB in PWH is very low and does not appear to differ from the non-HIV population.
Assuntos
Adenocarcinoma , Infecções por HIV , Osteíte Deformante , Humanos , Osteíte Deformante/epidemiologia , Osteíte Deformante/diagnóstico , Infecções por HIV/complicações , Infecções por HIV/epidemiologiaRESUMO
INTRODUCTION: Our objective was to determine the risk factors of a "severe/critical" form of COVID-19 in a cohort of people living with HIV-1 (PLWH1) followed in the Bichat University Hospital center in PARIS, FRANCE. METHODS: This study was an observational retrospective monocentric cohort of PLWH1 diagnosed with COVID-19 between February 1 st and November 31 st, 2020. Risk factors associated with "severe/critical" forms were determined using stepwise forward selection. RESULTS: One-hundred-and-twenty-nine PLWH1 with COVID-19 were included. COVID-19 diagnosis was confirmed in 98 cases (75.9%) and deemed probable according to the association of clinical criteria and contact case in 31 cases (24.1%). Clinical presentation of COVID-19 was "asymptomatic/mild/moderate" in 95 (73.6%), "severe" in 26 (21.7%) and "critical" in eight (6%). Patients with "severe/critical" COVID-19 tended to be older (median 54 year old), have a higher BMI (median 28.8 kg/m²) and were likely to have diabetes (9 versus 5) or chronic kidney disease (5 versus 2). Transgender women had higher risk too (OR: 4.9 (IC95: 1.35-24.0)). No association was observed between severity of COVID-19 and viral suppression or CD4 rates. CONCLUSION: Risk factors for severe COVID-19 were similar in PLWH1 than in the general population and PLWH1 transgender women were at higher risk.
Assuntos
COVID-19 , Soropositividade para HIV , HIV-1 , COVID-19/complicações , Teste para COVID-19 , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2RESUMO
OBJECTIVE: Treatment of multidrug-resistant HIV-2 is an emerging issue, because of the rapid selection of mutations at time of virological failure and the low number of antiretrovirals active on HIV-2. The aim of this study was to determine the susceptibility of HIV-2 primary isolates to ibalizumab, a long-acting monoclonal antibody that binds to CD4 that is approved for the treatment of MDR HIV-1. METHODS: In-vitro phenotypic susceptibility of 16 HIV-2 primary isolates was measured using a modified version of the ANRS peripheral blood mononuclear cells (PBMC) assay. Susceptibility to ibalizumab was assessed through 50% inhibitory concentrations and maximum percentage inhibitions (MPI), and gp105 was sequenced to look for determinants of reduced susceptibility. RESULTS: Ibalizumab inhibited viral replication of all 16 isolates, with a median IC 50 value of 0.027âµg/ml (range = 0.001-0.506âµg/ml), and a median MPI of 93%. Although two isolates presented higher IC 50 (above 0.1âµg/ml), they did not exhibit a loss of potential N-linked glycosylation sites in V5 loop, as reported in HIV-1 strains with reduced susceptibility. However, both presented shorter V1 and V2 loops than the HIV-2 reference strain. CONCLUSION: Ibalizumab inhibits HIV-2 replication, with IC 50 and MPI in the range of those reported for HIV-1. These in vitro data support the use of ibalizumab in patients with MDR HIV-2, in combination with an optimized background regimen.
Assuntos
Fármacos Anti-HIV , Infecções por HIV , HIV-1 , Fármacos Anti-HIV/uso terapêutico , Anticorpos Monoclonais/efeitos adversos , Infecções por HIV/tratamento farmacológico , HIV-2 , Humanos , Leucócitos MononuclearesRESUMO
INTRODUCTION: An acute respiratory disease caused by a novel coronavirus (SARSCOV2) is spreading from China since January 2020. Surprisingly, few cases of Covid-19 have been reported in people living with HIV (PLWHIV). METHODS: Here we present a series of 30 PLWHIV diagnosed for SARS-COV2 infection. The principal outcome was to describe clinical characteristics of this population. RESULTS: Eighteen (60%) patients were men, 10/30 (33,3%) women and 2/30 (6,7%) transgender women. Median age was 53,7 years (range 30-80 years) and 23/30 patients (76,7%) were born in a foreign country (out of France). The most common comorbidities were cardiovascular disease (11/30, 36,7%), hypertension (11/30, 36,7%), diabetes (9/30,30%) obesity (7/30, 23%) and chronic renal disease (5/30, 16,7%). Twenty (66,7%) patients presented overweight. Five patients (16,7%) had a Charlson comorbidity (Quan et al., 2011) score ≥3. Twenty-seven (90%) patients were virologically suppressed.CD4 count was >500cell/mm 3 in 23/30 (76,6%) patients. An antiviral treatment for SARS-COV2 was administered, in addition to HIV treatment, in 5/30 patients (16,3%). Twenty-four patients (80%) recovered from covid-19, 3/30 (10%) required invasive mechanical ventilation, 2/30 (6,7%) patients died and 4/30 (13,3%) patients were still hospitalized. CONCLUSIONS: Most of the patients were virologically suppressed with CD4>500 mm3. Risk factors were the same as those described in other SARS-COV2 series, suggesting that HIV infection is probably not an independent risk factor for covid-19.
Assuntos
COVID-19/etiologia , Infecções por HIV/complicações , SARS-CoV-2 , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Hospitais Universitários , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Injecting drug use is a major driver of hepatitis C virus (HCV) spread worldwide, and the World Health Organization (WHO) has identified people who inject drugs (PWID) as a key population to target for HCV screening and care. Point-of-care (POC) hepatitis C tests and dried blood spot (DBS) sampling offer benefits for the management of patients with HCV infection by increasing HCV testing and linkage to care in different nonclinical settings. The aims of this prospective study were to evaluate the feasibility and the acceptability of use HCV ribonucleic acid (RNA) POC and fingerstick DBS testing in social-medical risk-reduction centers and to describe the cascade of care among PWID in France. METHODS: Between June 2018 and February 2019, 89 consecutive HCV-seropositive PWID attending 2 drug treatment services and 1 supervised consumption room in inner Paris were invited to participate in further evaluation, undergoing a clinical review with a liver assessment and blood tests including fingerstick capillary whole blood POC HCV RNA testing and fingerstick DBS sampling. RESULTS: Of the 89 participants enrolled, HCV RNA was detected in 34 (38.6%) participants. Fingerstick whole blood POC RNA testing and HCV RNA detection from DBS sample were feasible and acceptable among PWID with no major difference in terms of HCV RNA detection rate. Overall, 16 participants received pan-genotypic antiviral treatment. The proportion of PWID with sustained virologic response at 12 weeks was 81.2%, with data for 3 patients still pending. CONCLUSIONS: One-step screening strategy based on the detection of HCV RNA would engage people in care for treatment scale-up and HCV elimination.