RESUMEN
Using concentration-time data from the NEAT001/ARNS143 study (single sample at week 4 and 24), we determined raltegravir pharmacokinetic parameters using nonlinear mixed effects modelling (NONMEM v.7.3; 602 samples from 349 patients) and investigated the influence of demographics and SNPs (SLC22A6 and UGT1A1) on raltegravir pharmacokinetics and pharmacodynamics. Demographics and SNPs did not influence raltegravir pharmacokinetics and no significant pharmacokinetic/pharmacodynamic relationships were observed. At week 96, UGT1A1*28/*28 was associated with lower virological failure (p = 0.012), even after adjusting for baseline CD4 count (p = 0.048), but not when adjusted for baseline HIV-1 viral load (p = 0.082) or both (p = 0.089). This is the first study to our knowledge to assess the influence of SNPs on raltegravir pharmacodynamics. The lack of a pharmacokinetic/pharmacodynamic relationship is potentially an artefact of raltegravir's characteristic high inter and intra-patient variability and also suggesting single time point sampling schedules are inadequate to thoroughly assess the influence of SNPs on raltegravir pharmacokinetics.
Asunto(s)
Fármacos Anti-VIH , Infecciones por VIH , Humanos , Adulto , Raltegravir Potásico/uso terapéutico , Raltegravir Potásico/farmacología , Fármacos Anti-VIH/uso terapéutico , Fármacos Anti-VIH/farmacología , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/genética , Infecciones por VIH/epidemiología , Polimorfismo Genético , Carga Viral/genéticaRESUMEN
OBJECTIVES: We assessed the virologic efficacy of switching to co-formulated elvitegravir, cobicistat, emtricitabine, tenofovir disoproxil fumarate (E/C/F/TDF) in patients with controlled HIV infection. METHODS: We conducted a retrospective multicenter observational cohort study including adult patients with controlled HIV-1 infection on any stable antiretroviral (ART) regimen, who switched to E/C/F/TDF. Success was measured by the proportion of patients with plasma viral load < 50 copies/ml at W48 using the FDA snapshot algorithm. We also assessed risk factors associated with virological failure (VF). RESULTS: 382 patients with HIV RNA < 50 copies/mL who switched to E/C/F/TDF were included in the study. Most patients (69.9%) were male, with median age 44 years (IQR 38-51), who had been on ART for a median of 7 years (IQR 4-13). Median CD4 count was 614/mm3 and 24.6% of the patients had a history of previous virological failure. The reasons for switching were simplification (67.0%) and tolerance issues (22.0%). At week 48, 314 (82.0% [95% CI 78.4-86.0]) patients had HIV RNA < 50 copies/mL, 13 (3.5% [95% CI 3.64-8.41]) experienced virological failure. Genotype at failure was available in 6/13 patients with detection of resistance-associated mutations to integrase inhibitors and NRTIs in 5/6 (83.3%) patients. We found no predictive factor associated with virological failure except for a borderline significance with the duration of viral suppression before the switch. Tolerability of E/C/F/TDF was good with 23/382 (6.0%) patients experiencing mild adverse reactions. CONCLUSION: In our cohort, switching well-suppressed patients to E/C/F/TDF resulted in few virologic failures and was well tolerated. However, resistance to integrase inhibitors emerged in patients with virological failure.
Asunto(s)
Fármacos Anti-VIH , Infecciones por VIH , Adulto , Humanos , Masculino , Femenino , Infecciones por VIH/tratamiento farmacológico , Tenofovir/uso terapéutico , Tenofovir/efectos adversos , Emtricitabina/uso terapéutico , Emtricitabina/efectos adversos , Cobicistat/uso terapéutico , Cobicistat/efectos adversos , Fármacos Anti-VIH/efectos adversos , Inhibidores de Integrasa/uso terapéutico , Estudios de Cohortes , ARNRESUMEN
HIV-1 Gag p24 has long been identified as an informative biomarker of HIV replication, disease progression, and therapeutic efficacy, but the lower sensitivity of immunoassays in comparison to molecular tests and the interference with antibodies in chronic HIV infection limit its application for clinical monitoring. The development of ultrasensitive protein detection technologies may help in overcoming these limitations. Here, we evaluated whether immune complex dissociation combined with ultrasensitive digital enzyme-linked immunosorbent assay (ELISA) single-molecule array (Simoa) technology could be used to quantify p24 in plasma samples from people with HIV-1 infection. We found that, among different immune complex dissociation methods, only acid-mediated dissociation was compatible with ultrasensitive p24 quantification by digital ELISA, strongly enhancing p24 detection at different stages of HIV-1 infection. We show that ultrasensitive p24 levels correlated positively with plasma HIV RNA and HIV DNA and negatively with CD4-positive (CD4+) T cells in the samples from people with primary and chronic HIV-1 infection. In addition, p24 levels also correlated with plasma D-dimers and interferon alpha (IFN-α) levels. p24 levels sharply decreased to undetectable levels after initiation of combined antiretroviral treatment (cART). However, we identified a group of people who, 48 weeks after cART initiation, had detectable p24 levels despite most having undetectable viral loads. These people had different virological and immunological baseline characteristics compared with people who had undetectable p24 after cART. These results demonstrate that ultrasensitive p24 analysis provides an efficient and robust means to monitor p24 antigen in plasma samples from people with HIV-1 infection, including during antiretroviral treatment, and may provide complementary information to other commonly used biomarkers. IMPORTANCE The introduction of combined antiretroviral treatment has transformed HIV-1 infection into a manageable condition. In this context, there is a need for additional biomarkers to monitor HIV-1 residual disease or the outcome of new interventions, such as in the case of HIV cure strategies. The p24 antigen has a long half-life outside viral particles, and it is, therefore, a very promising marker to monitor episodes of viral replication or transient activation of the viral reservoir. However, the formation of immune complexes with anti-p24 antibodies makes its quantification difficult beyond acute HIV-1 infection. We show here that, upon immune complex dissociation, new technologies allow the ultrasensitive p24 quantification in plasma samples throughout HIV-1 infection at levels close to those of viral RNA and DNA determinations. Our results further indicate that ultrasensitive p24 quantification may have added value when used in combination with other classic clinical biomarkers.
Asunto(s)
Ensayo de Inmunoadsorción Enzimática/métodos , Proteína p24 del Núcleo del VIH/sangre , Infecciones por VIH/virología , Adulto , Fármacos Anti-VIH/uso terapéutico , Complejo Antígeno-Anticuerpo , Terapia Antirretroviral Altamente Activa , Biomarcadores/sangre , Enfermedad Crónica , Estudios de Cohortes , Femenino , Infecciones por VIH/sangre , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/inmunología , Humanos , Concentración de Iones de Hidrógeno , Masculino , Sensibilidad y EspecificidadRESUMEN
A 45-year-old female patient receiving rituximab for B cell non-Hodgkin follicular lymphoma presented unexplained recurrent fever, abdominal discomfort, and pollakiuria. We performed shotgun metagenomic sequencing from peri-kidney collection that identified a co-infection with Mycoplasma hominis and Ureaplasma urealyticum. The patient recovered with sequelae after appropriate antibiotic treatment was given.
Asunto(s)
Infecciones por Mycoplasma , Infecciones por Ureaplasma , Antibacterianos/uso terapéutico , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Persona de Mediana Edad , Infecciones por Mycoplasma/microbiología , Mycoplasma hominis , Rituximab/uso terapéutico , Ureaplasma , Infecciones por Ureaplasma/microbiología , Ureaplasma urealyticumRESUMEN
BACKGROUND: The Data Collection on Adverse Events of Anti-HIV Drugs (DAD) study has reported an increased risk of cardiovascular diseases in people with human immunodeficiency virus who were exposed to darunavir (DRV) but not to atazanavir (ATV). Our objective was to evaluate associations between ATV or DRV exposures and the risk of myocardial infarction (MI) in a nested case-control study within ANRS-CO4 French Hospital Database on HIV (FHDH). METHODS: Cases were individuals who had a first validated MI between 2006 and 2012. Up to 5 controls were selected at random with replacement among individuals with no history of MI, followed at the time of MI diagnosis, and matched for age and sex. Conditional logistic regression models were used to adjust for potential confounders (MI risk factors and HIV-related parameters) and for cumulative exposure to each antiretroviral drug (ARV). RESULTS: Overall, 408 MI cases and 1250 controls were included: 109 (27%) cases and 288 (23%) controls had been exposed to ATV, and 41 (10%) cases and 107 (9%) controls had been exposed to DRV. There was no significant association between exposure to ATV (adjusted odds ratio [OR] = 1.54; 95% confidence interval [CI], .87-2.73) or DRV (adjusted OR = 0.51; 95% CI, .11-2.32) and the risk of MI. CONCLUSIONS: In FHDH, exposures to ATV or to DRV were not significantly associated with the risk of MI, adjusting for complete ARV history, contrary to the analysis in DAD.
Asunto(s)
Sulfato de Atazanavir/efectos adversos , Sulfato de Atazanavir/uso terapéutico , Darunavir/efectos adversos , Darunavir/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Inhibidores de la Proteasa del VIH/efectos adversos , Inhibidores de la Proteasa del VIH/uso terapéutico , VIH-1 , Infarto del Miocardio/inducido químicamente , Adulto , Estudios de Casos y Controles , Estudios de Cohortes , Bases de Datos Factuales , Femenino , Infecciones por VIH/virología , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Resultado del TratamientoRESUMEN
Background: Risk factors for progressive multifocal leukoencephalopathy (PML) in individuals with human immunodeficiency virus (HIV) infection are poorly documented in the era of combination antiretroviral therapy (cART). Methods: We studied HIV-1-infected individuals aged ≥15 years who had no history of PML and were prospectively followed up between 1997 and 2011 in the French Hospital Database on HIV (FHDH-ANRS CO4) cohort. Cox models were used to calculate adjusted hazard ratios (HRs), focusing on sub-Saharan origin, suggested to be protective, and recent cART initiation, potentially associated with an increased risk of PML. Results: PML developed in 555 individuals, in 57 during the first 6 months of cART. From 1997-2000 to 2009-2011, the incidence fell from 1.15 (95% confidence interval [CI], .98-1.31) to 0.49 (.37-.61) per 1000 person-years. Sub-Saharan African origin had no clear influence (HR, 0.80; 95% CI, .58-1.11). Compared with men who have sex with men, injection drug users (IDUs) were at higher risk (HR, 1.80 [95% CI, 1.32-2.45] for male and 1.68 [1.13-2.48] for female IDUs). When IDUs were excluded, hepatitis C virus seropositivity was associated with an increased risk (HR, 1.40; 95% CI, 1.02-1.93). Compared with no cART initiation, initiation <6 months previously was associated with PML onset (HR, 4.91; 95% CI, 2.42-9.95). Conclusions: Recent cART initiation is associated with an increased risk of PML, as are injection drug use and hepatitis C virus seropositivity. Sub-Saharan African origin had no protective effect.
Asunto(s)
Fármacos Anti-VIH/efectos adversos , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Leucoencefalopatía Multifocal Progresiva/etiología , Adulto , Fármacos Anti-VIH/uso terapéutico , Bases de Datos Factuales , Quimioterapia Combinada , Femenino , Francia , VIH-1 , Hepatitis C/complicaciones , Homosexualidad Masculina , Hospitales , Humanos , Incidencia , Masculino , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Factores de Riesgo , Minorías Sexuales y de Género , Abuso de Sustancias por Vía Intravenosa/complicacionesRESUMEN
Background: Standard genotypic tests performed on HIV DNA from patients on suppressive ART, with previous resistance-associated mutations (RAMs) detected in their plasma, underestimate resistance. We thus compared ultra-deep sequencing (UDS) with bulk sequencing of DNA to detect RAMs previously identified in plasma. Methods: We sequenced the DNA of 169 highly treatment experienced patients with suppressed viraemia (ANRS 138-EASIER trial). Protease (PR) and reverse transcriptase (RT) genes from HIV DNA were sequenced by bulk sequencing and UDS, comparing 1% and 20% as thresholds of detection for UDS. Results: Patients were highly treatment experienced (13.6 years). UDS of DNA was successful for the RT and PR genes in 133 (79%) and 137 (81%) patients, respectively. The detection of RAMs was similar by bulk sequencing and UDS with a 20% cut-off. However, the detection of RAMs by UDS with a 1% cut-off was significantly higher than that of bulk sequencing for RT codons D67N (65.4% versus 52.3%), M184V (66.2% versus 52.3%), L210W (48.9% versus 36.4%) and T215Y (57.9% versus 42.1%) and PR codons M46I (46% versus 26%), I54L (12.4% versus 3.9%), V82A (44.5% versus 29.9%) and L90M (57.7% versus 42.5%). Conclusions: Genotypic resistance testing of cellular HIV DNA of well-controlled patients should use UDS technology with a sensitivity threshold of 1% to improve the detection of the resistant reservoir.
Asunto(s)
Terapia Antirretroviral Altamente Activa , Farmacorresistencia Viral/genética , VIH-1/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Viremia/tratamiento farmacológico , Adulto , Anciano , Fármacos Anti-VIH/uso terapéutico , ADN Viral/sangre , Femenino , Genotipo , Infecciones por VIH/tratamiento farmacológico , Proteasa del VIH/genética , VIH-1/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Mutación , ADN Polimerasa Dirigida por ARN/genética , Carga Viral/efectos de los fármacosRESUMEN
OBJECTIVES: Tuberculosis (TB) is a rare but life-threatening infection after solid organ transplant. The present study was undertaken to assess the clinical features, risk factors, and outcome of TB after kidney transplantation in a low-prevalence area. METHODS: We conducted a retrospective study, describing all kidney transplant recipients diagnosed with TB between 2005 and 2015 in 3 French centers. For each TB case, 2 controls without TB were identified and matched by center, age, transplant date, and birth country. Risk factors associated with TB were identified and survival estimated. RESULTS: Thirty-two cases and 64 control patients were included among 3974 transplantations. The prevalence of TB was 0.83%. Median age at the time of diagnosis was 64 years; 75% were born in a high TB prevalence country, but only 3 had received isoniazid prophylaxis for latent TB infection. TB occurred at a median of 22 months after transplantation. On diagnosis, 66% had disseminated infection. Median duration of treatment was 9 months. Immunosuppressive therapy changes were necessary in all patients because of drug-drug interactions. Among cases, 5 deaths occurred during follow-up (median duration: 41 months), one directly related with TB. Survival was significantly lower in transplant recipients with TB, as compared to controls (P = .001). No predictive factors of tuberculosis after transplantation were statistically significant in univariate analysis. CONCLUSION: TB in kidney transplant recipients is a rare and late event, but is associated with significantly reduced survival. Our results emphasize the need for systematic screening for LTBI, followed by IPT in high-risk patients.
Asunto(s)
Antituberculosos/uso terapéutico , Trasplante de Riñón/efectos adversos , Mycobacterium tuberculosis/aislamiento & purificación , Tuberculosis/epidemiología , Anciano , Estudios de Casos y Controles , Femenino , Estudios de Seguimiento , Rechazo de Injerto/epidemiología , Rechazo de Injerto/inmunología , Rechazo de Injerto/prevención & control , Humanos , Inmunosupresores/efectos adversos , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Retrospectivos , Factores de Riesgo , Análisis de Supervivencia , Receptores de Trasplantes/estadística & datos numéricos , Tuberculosis/microbiología , Tuberculosis/prevención & controlRESUMEN
BACKGROUND: In the ANRS EASIER trial where treatment-experienced patients switched from enfuvirtide (ENF) to raltegravir (RAL), a high incidence of transaminase elevation was reported in the RAL arm. METHODS: We compared the incidence of emergent liver enzyme elevations (LEE) of grade 2 or more among patients randomized to the maintenance ENF arm or the switch RAL arm up to W24. We also assessed the overall incidence of LEE over the 48-week duration of the trial and baseline risk factors for grade 2 or more alanine aminotransferase (ALT) elevation using univariate and multivariate analyses. RESULTS: During the first 24 weeks, 6/84 (7.1 %) and 2/85 patients (2.4 %) presented with ALT elevation of grade 2 or more in the RAL and ENF arms, respectively (p = 0.21). Grade 2 or more γGT and ALP elevations were seen in 18 and 11 % (p = 0.35), and 5 and 1 % (p = 0.14) of patients in the RAL and ENF arms, respectively. The 48-week incidence of grade 2 or more LEE was 11.6 per 100-pts-years for ALT, 24.5 per 100-pts-years for γ-GT and 4.5 per 100-pts-years for ALP, respectively. In the multivariate analysis, tipranavir/ritonavir use (OR 3.66; 95 % CI [1.20-11.1], p = 0.022) and elevated ALT at baseline (OR 10.3; 95 % CI [2.67-39.6], p < 10(-3)) were significantly associated with a grade 2 or more ALT elevation during follow-up. CONCLUSION: The incidence of LEE was relatively high in these highly treatment-experienced patients switching to a RAL-based regimen. Both tipranavir/ritonavir use and high baseline ALT levels were associated with an increased risk of ALT. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00454337.
Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Sustitución de Medicamentos/efectos adversos , Proteína gp41 de Envoltorio del VIH/efectos adversos , Inhibidores de Fusión de VIH/efectos adversos , Infecciones por VIH/tratamiento farmacológico , Inhibidores de Integrasa VIH/efectos adversos , Fragmentos de Péptidos/efectos adversos , Raltegravir Potásico/efectos adversos , Adulto , Alanina Transaminasa/sangre , Enfermedad Hepática Inducida por Sustancias y Drogas/epidemiología , Enfuvirtida , Femenino , Proteína gp41 de Envoltorio del VIH/uso terapéutico , Inhibidores de Fusión de VIH/uso terapéutico , Inhibidores de Integrasa VIH/uso terapéutico , Humanos , Incidencia , Pruebas de Función Hepática , Masculino , Persona de Mediana Edad , Fragmentos de Péptidos/uso terapéutico , Raltegravir Potásico/uso terapéutico , Factores de RiesgoRESUMEN
BACKGROUND: Before the advent of combination antiretroviral therapy (cART), roughly 50% of cases of invasive aspergillosis (IA) associated with human immunodeficiency virus (HIV) infection involved individuals without classical predisposing host factors, and the median survival time was <4 months after diagnosis. We examined if the situation evolved over time using the revised European Organisation for Research and Treatment of Cancer/National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC) definition and analyzed survival trends after diagnosis over 20 years. METHODS: A data review committee evaluated 342 medical records that mentioned IA in the French Hospital Database on HIV. Validated cases were classified as fulfilling the EORTC criteria or otherwise as "HIV-related IA." Three periods were analyzed: pre-cART (before 1996), cART era prevoriconazole (1996-2001), and 2002-2011. RESULTS: Among 242 validated cases of IA, 124 (51%) fulfilled the EORTC criteria (EORTC-IA) and 118 (49%) were classified as "HIV-related," with similarly low CD4 cell counts in both groups. The proportion of EORTC-IA cases remained stable across the 3 periods (50%, 48%, and 54%, respectively). The 3-month survival rate improved after the advent of cART (38% vs 69%), with no difference between EORTC-IA and HIV-related IA (hazard ratio [HR], 1.2 95% confidence interval [CI] {0.7-1.8}). Voriconazole exposure decreased mortality in 2002-2011 (HR, 0.1 95% CI [0.01-0.8]). CONCLUSIONS: In the cART era, EORTC criteria, developed for use in hematology/oncology, still applied to only half the cases diagnosed among HIV-infected patients. A rapid diagnosis of IA is paramount to improve survival. For patients who do not fulfill the EORTC definition, we suggest that the addition of "HIV infected with a CD4 count <100 cells/µL" to the EORTC host criteria be validated.
Asunto(s)
Aspergilosis/complicaciones , Aspergilosis/diagnóstico , Infecciones por VIH/complicaciones , Aspergilosis Pulmonar Invasiva/complicaciones , Aspergilosis Pulmonar Invasiva/diagnóstico , Adulto , Fármacos Anti-VIH/uso terapéutico , Antifúngicos/uso terapéutico , Aspergilosis/tratamiento farmacológico , Aspergilosis/epidemiología , Aspergilosis/mortalidad , Aspergillus/efectos de los fármacos , Aspergillus/patogenicidad , Recuento de Linfocito CD4 , Quimioterapia Combinada , Femenino , Francia/epidemiología , Infecciones por VIH/tratamiento farmacológico , Humanos , Aspergilosis Pulmonar Invasiva/tratamiento farmacológico , Aspergilosis Pulmonar Invasiva/mortalidad , Masculino , Registros Médicos , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Tasa de Supervivencia , Factores de Tiempo , Voriconazol/administración & dosificación , Voriconazol/uso terapéuticoRESUMEN
BACKGROUND: Rifampicin (RIF) induces UGT1A1, an enzyme involved in raltegravir (RAL) elimination, thereby potentially lowering RAL exposure. We examined the pharmacokinetics of RAL in human immunodeficiency virus (HIV)-infected patients on RIF-based antitubercular therapy in the French National Agency for HIV/AIDS and Viral Hepatitis Research 12 180 Reflate Tuberculosis trial. METHODS: Patients started RAL in combination with tenofovir disoproxil fumarate and lamivudine after initiation of RIF (10 mg/kg/day). In arm 1 (n = 21), they received 400 mg RAL twice daily; in arm 2 (n = 16), they received RAL 800 mg twice daily initially then 400 mg twice daily 4 weeks after RIF discontinuation. Pharmacokinetic sampling was performed over 12-hour periods, 4 weeks after initiation of RAL together with RIF (period 1), 4 weeks after RIF discontinuation (period 2), and after the RAL dose reduction in arm 2 (period 3). RESULTS: In arm 1, the geometric mean ratio (GMR) between period 1 and period 2 was 0.94 (90% confidence interval [CI], .64-1.37) for the 12-hour area under the time-concentration curve (AUC0-12), and 0.69 (90% CI, .42-1.13) for the concentration at 12 hours (C12). In arm 2, the corresponding GMRs were 0.75 (90% CI, .48-1.17) and 1.10 (90% CI, .61-2.00) for period 1 vs period 2, and 1.10 (90% CI, .78-1.55) and 1.68 (90% CI, .88-3.23) for period 1 vs period 3. CONCLUSIONS: The double dose of RAL overcompensated for RIF induction, but the standard dose was associated with only small decreases in AUC0-12 and C12 during RIF coadministration, warranting further evaluation in patients with HIV/tuberculosis coinfection. CLINICAL TRIALS REGISTRATION: NCT0082231.
Asunto(s)
Fármacos Anti-VIH/farmacocinética , Antibióticos Antituberculosos/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Raltegravir Potásico/farmacocinética , Rifampin/uso terapéutico , Tuberculosis/tratamiento farmacológico , Adulto , Fármacos Anti-VIH/administración & dosificación , Fármacos Anti-VIH/uso terapéutico , Coinfección , Esquema de Medicación , Quimioterapia Combinada , Femenino , Infecciones por VIH/complicaciones , VIH-1/efectos de los fármacos , Humanos , Lamivudine/administración & dosificación , Lamivudine/uso terapéutico , Masculino , Raltegravir Potásico/administración & dosificación , Tenofovir/administración & dosificación , Tenofovir/uso terapéuticoRESUMEN
Although the decline in cancer mortality rates with the advent of combination antiretroviral therapy (cART) in HIV-infected individuals can be mostly explained by a decrease in cancers incidence, we looked here if improved survival after cancer diagnosis could also contribute to this decline. Survival trends were analyzed for most frequent cancers in the HIV-infected population followed in the French Hospital Database on HIV: 979 and 2,760 cases of visceral and non-visceral Kaposi's sarcoma (KS), 2,339 and 461 cases of non-Hodgkin lymphoma (NHL) and Hodgkin's lymphoma (HL), 446 lung, 312 liver and 257 anal cancers. Five-year Kaplan-Meier survival rates were estimated for four periods: 1992-1996, 1997-2000, 2001-2004 and 2005-2009. Cox proportional hazard models were used to compare survival across the periods, after adjustment for confounding factors. For 2001-2004, survival was compared to the general population after standardization on age and sex. Between the pre-cART (1992-1996) and early-cART (1997-2000) periods, survival improved after KS, NHL, HL and anal cancer and remained stable after lung and liver cancers. During the cART era, 5-year survival improved after visceral and non-visceral KS, NHL, HL and liver cancer, being 83, 92, 65, 87 and 19% in 2005-2009, respectively, and remained stable after lung and anal cancers, being 16 and 65%, respectively. Compared with the general population, survival in HIV-infected individuals in 2001-2004 was poorer for hematological malignancies and similar for solid tumors. For hematological malignancies, survival continues to improve after 2004, suggesting that the gap between the HIV-infected and general populations will close in the future.
Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Neoplasias/mortalidad , Adulto , Terapia Antirretroviral Altamente Activa/métodos , Neoplasias del Ano/mortalidad , Femenino , Francia/epidemiología , Infecciones por VIH/mortalidad , Enfermedad de Hodgkin/mortalidad , Humanos , Neoplasias Hepáticas/mortalidad , Neoplasias Pulmonares/mortalidad , Linfoma no Hodgkin/mortalidad , Masculino , Persona de Mediana Edad , Mortalidad/tendencias , Sarcoma de Kaposi/mortalidad , Análisis de SupervivenciaRESUMEN
Due to the differences between bioavailability of efavirenz (EFV) and tenofovir (TDF), the single-tablet regimen of EFV/emtricitabine (FTC)/TDF is not approved as initial antiretroviral therapy (ART) in Europe by the European Medical Agency. To compare clinical, immunological, and virological outcomes between co-formulated TDF/FTC+EFV and the co-formulated EFV/FTC/TDF single-tablet regimen in patients infected with HIV-1 naive to ART, the data of patients (n = 231) who initiated either TDF/FTC+EFV (n = 155) or EFV/FTC/TDF (n = 76) between January 1, 2007 and June 1, 2010 were analyzed. Changes from baseline to week 48 (TDF/FTC+EFV vs. EFV/FTC/TDF) in HIV plasma load (- 3.25 log vs. -3.32 log) and CD4+ T cell count (+180 vs. +138 cells/mm3) were similar in the two groups. Treatment discontinuation was recorded in 50 (22%) patients (40 on TDF/FTC+EFV and 10 on EFV/FTC/TDF, P = 0.03) but time to discontinuation did not differ between the two groups. Only patients on TDF/FTC+EFV discontinued treatment because of neurological symptoms. Virological failure occurred in 11 (4.7%) patients (seven on TDF/FTC+EFV and four on EFV/FTC/TDF, P = 0.75) with new resistance-associated mutations in five among the six with successful resistance genotype tests. Only baseline resistance-associated mutations was a risk factor for virological failure (P = 0.0146). These data show comparable outcomes between TDF/FTC+EFV or EFV/FTC/TDF used in patients infected with HIV-1 and not treated previously, consistent with a low rate of virological failure in the absence of pretreatment resistance. This would suggest that the European Medical Agency should approve co-formulated EFV/FTC/TDF single-tablet regimen for patients naive to ART.
Asunto(s)
Adenina/análogos & derivados , Fármacos Anti-VIH/uso terapéutico , Benzoxazinas/uso terapéutico , Desoxicitidina/análogos & derivados , Infecciones por VIH/tratamiento farmacológico , Organofosfonatos/uso terapéutico , Adenina/efectos adversos , Adenina/uso terapéutico , Adulto , Alquinos , Fármacos Anti-VIH/efectos adversos , Benzoxazinas/efectos adversos , Recuento de Linfocito CD4 , Ciclopropanos , Desoxicitidina/efectos adversos , Desoxicitidina/uso terapéutico , Combinación de Medicamentos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/patología , Emtricitabina , Europa (Continente) , Femenino , Infecciones por VIH/virología , VIH-1/aislamiento & purificación , Humanos , Masculino , Persona de Mediana Edad , Organofosfonatos/efectos adversos , Plasma/virología , Comprimidos/efectos adversos , Comprimidos/uso terapéutico , Tenofovir , Resultado del Tratamiento , Carga ViralAsunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Tratamiento Farmacológico de COVID-19 , Complemento C5/antagonistas & inhibidores , Inactivadores del Complemento/uso terapéutico , SARS-CoV-2/efectos de los fármacos , COVID-19/inmunología , COVID-19/virología , Humanos , Pronóstico , SARS-CoV-2/inmunologíaRESUMEN
Stored plasma specimens from 164 participants in the ANRS 138 trial were analyzed to determine interleukin 6 (IL-6), high-sensitivity C-reactive protein (hsCRP), and D-dimer levels at baseline and weeks 24 and 48. These virologically suppressed, treatment-experienced patients were randomly assigned to undergo an immediate switch (IS) or a deferred switch (DS; at week 24) from an enfuvirtide-based antiretroviral therapy (ART) regimen to a raltegravir-based regimen. At week 24, a significant decrease from baseline was observed in the IS arm, compared with the DS arm, for IL-6 level (-30% vs +10%; P < .002), hsCRP level (-46% vs +15%; P < .0001), and D-dimer level (-40% vs +6%; P < .0001). At week 48, there was a reproducible decrease in levels of all biomarkers in the DS arm.
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Biomarcadores/sangre , Coagulación Sanguínea/efectos de los fármacos , Proteína gp41 de Envoltorio del VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Inflamación/sangre , Fragmentos de Péptidos/uso terapéutico , Pirrolidinonas/uso terapéutico , Adulto , Fármacos Anti-VIH/uso terapéutico , Proteína C-Reactiva/análisis , Recuento de Linfocito CD4 , Enfuvirtida , Femenino , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Infecciones por VIH/sangre , Infecciones por VIH/virología , VIH-1 , Humanos , Inflamación/virología , Interleucina-6/sangre , Masculino , Persona de Mediana Edad , ARN Viral/sangre , Raltegravir Potásico , Manejo de Especímenes , Carga ViralRESUMEN
We report the case of an allogeneic stem cell transplant recipient with nosocomial acquisition of SARS-CoV-2 infection who received antispike neutralizing monoclonal antibody bamlanivimab 2 days after diagnosis of SARS-CoV-2 infection but progressed to severe COVID-19 pneumonia and died with the selection of E484K/Q resistance mutations to bamlanivimab.
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Anticuerpos Monoclonales Humanizados , COVID-19 , Infección Hospitalaria , Trasplante de Células Madre Hematopoyéticas , Humanos , Infección Hospitalaria/tratamiento farmacológico , COVID-19/diagnóstico , SARS-CoV-2 , Anticuerpos Neutralizantes , Mutación , Trasplante de Células Madre , Trasplante de Células Madre Hematopoyéticas/efectos adversosRESUMEN
Background: The aim of this study was to assess the epidemiology, clinical manifestations, and outcome of mucormycosis over 15 years in a single center in France. Methods: We conducted a retrospective analysis of all mucormycosis cases in our institution from 1 January 2006 to 31 December 2020 and analyzed patients' medical records, laboratory results, and treatment to describe the epidemiology, clinical manifestations, diagnosis, treatment, and outcome. Mucorales quantitative polymerase chain reaction (qPCR) for the diagnosis was implemented in 2015. Results: Seventy-seven mucormycosis cases were analyzed in 77 patients, with a median age of 54 years (60% male). Identified risk factors were hematological diseases (46 cases [60%]), solid malignancies (2 cases), solid organ transplants (3), burns (18), diabetes only (7), and trauma (1). Sites of infection were lungs (42%), sinus (36%), skin (31%), central nervous system (9%), liver (8%), others (6%), and disseminated (12%). Diagnosis remained difficult and qPCR contributed to mucormycosis diagnosis in 30% of cases. Among hematology patients, serum qPCR was the only positive test in 15% of cases. A mixed mold infection was diagnosed in 24 of 77 (31%) patients. Surgical treatment was undertaken in 43 (56%) cases. Most patients received liposomal amphotericin B (89%), with a combination therapy in 18 of 77 cases (23%). Three-month survival rate was 40% (95% confidence interval [CI], .30-.53]). As for treatment, adjunction of surgery (hazard ratio, 0.47 [95%CI, .25-.91); P = 0.02) was associated with lower mortality. Conclusions: Mucormycosis remained associated with high mortality, especially in the hematological and burn populations. Surgery in combination with antifungal treatment was associated with improved survival.
RESUMEN
In a cohort of 72 consecutive virologically-suppressed patients with HIV-1 switching to long-acting cabotegravir and rilpivirine, we observed low cabotegravir trough concentrations 1 and 3 months after the first injection, with a significant association with no oral lead-in at 1 month [odds ratio (OR)â=â6.3 [95% confidence interval (CI) 1.7-29.5], Pâ=â0.01] and three months (ORâ=â5.6 [95% CI 1.3-29.7], Pâ=â0.03), and with high BMI at 1 month (ORâ=â1.3 [95% CI 1.1-1.6], Pâ=â0.007).
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Fármacos Anti-VIH , Infecciones por VIH , VIH-1 , Piridonas , Rilpivirina , Humanos , Piridonas/administración & dosificación , Rilpivirina/administración & dosificación , Rilpivirina/uso terapéutico , Rilpivirina/farmacocinética , Infecciones por VIH/tratamiento farmacológico , Masculino , Femenino , Fármacos Anti-VIH/administración & dosificación , Fármacos Anti-VIH/farmacocinética , Fármacos Anti-VIH/uso terapéutico , VIH-1/aislamiento & purificación , Persona de Mediana Edad , Adulto , Sustitución de Medicamentos , Administración Oral , Plasma/química , DicetopiperazinasRESUMEN
BACKGROUND: The combination of dolutegravir plus rilpivirine has been studied in people with virologically suppressed HIV with no previous history of treatment failure or resistance. We investigated the potential to maintain viral suppression with dolutegravir plus rilpivirine in people with Lys103Asn mutations whose HIV was previously managed with other treatment regimens. METHODS: In this open-label pilot trial at 32 clinical sites in seven European countries, virologically suppressed, HBsAg-negative adults aged 18 years or older with HIV-1 and Lys103Asn mutations were randomly assigned (2:1) to switch to 50 mg dolutegravir plus 25 mg rilpivirine (given as a single tablet) once daily or to continue their current antiretroviral therapy regimen (control group). After 48 weeks, participants in the control group also switched to dolutegravir plus rilpivirine. Randomisation was stratified by country, and a computer-generated randomisation list with permuted blocks within strata was used to assign participants to treatment groups. The primary endpoints were virological failure (ie, two consecutive measurements of 50 copies or more of HIV RNA per mL at least 2 weeks apart) and virological suppression (the proportion of participants with fewer than 50 copies of HIV RNA per mL) at week 48 (week 96 data will be reported separately). Analyses were done in the modified intention-to-treat population, which included all participants who received at least one dose of the study medication. This trial is registered with ClinicalTrials.gov, NCT05349838, and EudraCT, 2017-004040-38. FINDINGS: Between Nov 5, 2018, and Dec 9, 2020, 140 participants were enrolled and randomly assigned, 95 to the dolutegravir plus rilpivirine group and 45 to the control group. Virological failure was recorded in three participants (3·2%, 95% CI 0·7 to 9·0) in the the dolutegravir plus rilpivirine group and one (2·2%, 0·1 to 11·8) in the control group. The proportion of participants in whom virological suppression was maintained at week 48 was 88·4% (80·2 to 94·1) in the dolutegravir plus rilpivirine group versus 88·9% (75·9 to 96·3) in the control group (difference -0·5, -11·7 to 10·7). Significantly more adverse events were recorded in the dolutegravir plus rilpivirine group than in the control group (234 vs 72; p=0·0034), but the proportion of participants who reported at least one adverse event was similar between groups (76 [80%] of 95 vs 33 [73%] of 45; p=0·39). The frequency of serious adverse events was low and similar between groups. INTERPRETATION: Virological suppression was maintained at week 48 in most participants with Lys103Asn mutations when they switched from standard regimens to dolutegravir plus rilpivirine. The results of this pilot study, if maintained when the week 96 data are reported, support conduct of a large, well-powered trial of dolutegravir plus rilpivirine. FUNDING: ViiV Healthcare.
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Fármacos Anti-VIH , Infecciones por VIH , Seropositividad para VIH , VIH-1 , Oxazinas , Piperazinas , Piridonas , Adulto , Humanos , Infecciones por VIH/tratamiento farmacológico , VIH-1/genética , Proyectos Piloto , Resultado del Tratamiento , Rilpivirina/efectos adversos , Antirretrovirales/uso terapéutico , Compuestos Heterocíclicos con 3 Anillos/efectos adversos , Seropositividad para VIH/tratamiento farmacológico , ARN/uso terapéutico , Mutación , Carga Viral , Fármacos Anti-VIH/efectos adversosRESUMEN
Background: After antiretroviral therapy (ART) initiation, people with HIV (PWH) treated for tuberculosis (TB) may develop TB-associated immune reconstitution inflammatory syndrome (TB-IRIS). Integrase inhibitors, by providing a faster HIV-RNA decline than efavirenz, might increase the risk for this complication. We sought to assess incidence and determinants of TB-IRIS in PWH with TB on raltegravir- or efavirenz-based ART. Methods: We conducted a secondary analysis of the Reflate TB 2 trial, which randomized ART-naive PWH on standard TB treatment, to receive raltegravir- or efavirenz-based ART. The primary objective was to evaluate the incidence of TB-IRIS. Incidence rate ratio comparing TB-IRIS incidence in each arm was calculated. Kaplan-Meier curves were used to compare TB-IRIS-free survival probabilities by ART arm. Cox regression models were fitted to analyze baseline characteristics associated with TB-IRIS. Results: Of 460 trial participants, 453 from Brazil, Côte d'Ivoire, Mozambique, and Vietnam were included in this analysis. Baseline characteristics were median age 35 years (interquartile range [IQR], 29-43), 40% female, 69% pulmonary TB only, median CD4, 102 (IQR, 38-239) cells/mm³, and median HIV RNA, 5.5 (IQR, 5.0-5.8) log copies/mL. Forty-eight participants developed TB-IRIS (incidence rate, 24.7/100 PY), 19 cases in the raltegravir arm and 29 in the efavirenz arm (incidence rate ratio 0.62, 95% confidence interval .35-1.10). Factors associated with TB-IRIS were: CD4 ≤ 100 cells/µL, HIV RNA ≥500 000â copies/mL, and extrapulmonary/disseminated TB. Conclusions: We did not demonstrate that raltegravir-based ART increased the incidence of TB-IRIS compared with efavirenz-based ART. Low CD4 counts, high HIV RNA, and extrapulmonary/disseminated TB at ART initiation were associated with TB-IRIS.