RESUMEN
OBJECTIVES: We aimed to investigate and compare the efficacy and safety of two dolutegravir-based two-drug regimens: dolutegravirâ+âlamivudine versus dolutegravirâ+ârilpivirine. METHODS: We analysed a cohort of people living with HIV (PLWHIV) switching to dolutegravirâ+âlamivudine or dolutegravirâ+ârilpivirine. We excluded from the analysis PLWHIV with no available pre-switch genotypic test or with a known resistance mutation to one of the study drugs. We evaluated incidence of virological failure (VF) and treatment discontinuation (TD), as well as changes in immunological and metabolic parameters. RESULTS: We enrolled 592 PLWHIV: 306 in the lamivudine group and 286 in the rilpivirine group. We observed nine VFs in the lamivudine group [1.4â VF per 100â patient-years of follow-up (PYFU)] and four VFs in the rilpivirine group (0.6â VF per 100â PYFU). Subsequent genotypic analysis showed no acquired resistance-associated mutations in those experiencing VF. Estimated probability of maintaining virological suppression at 144 and 240â weeks were 96.6% and 92.7%, respectively, in the lamivudine group and 98.7% and 98.7%, respectively, in the rilpivirine group (log-rank Pâ=â0.172). The estimated probability of maintaining study regimen at Week 240 was 82.3% in the lamivudine group and 85.9% in the rilpivirine group (log-rank Pâ=â0.018). We observed a significant improvement in CD4+ cell count at Week 240 in the lamivudine group (Pâ=â0.012); in the rilpivirine group we registered a significant increase in CD4/CD8 ratio (Pâ=â0.014). CONCLUSIONS: Both analysed strategies are effective and safe as switch strategies in clinical practice, with a low incidence of VF and a favourable immunological recovery, even in the long term.
Asunto(s)
Fármacos Anti-VIH , Infecciones por VIH , Humanos , Lamivudine/efectos adversos , Infecciones por VIH/tratamiento farmacológico , Fármacos Anti-VIH/efectos adversos , Rilpivirina/efectos adversos , Compuestos Heterocíclicos con 3 Anillos/efectos adversos , Piridonas/uso terapéutico , Oxazinas/uso terapéuticoAsunto(s)
COVID-19 , Anticuerpos Antivirales , Humanos , Huésped Inmunocomprometido , SARS-CoV-2 , SeroconversiónRESUMEN
OBJECTIVES: The aim of this study was to compare the tolerability and viro-immunological efficacy of dolutegravir-based regimens (DTG group) with regimens based on EVG, RAL, PI or NNRTI (NODTG group) in patients with acute HIV-1 infections (AHI). METHODS: All patients diagnosed with AHI and on antiretroviral therapy (ART) between January 2015 and December 2017 from five centers in Italy were included and followed-up to 30th April 2018. AHI was defined by the presence of the positive p24 antigen with negative or indeterminate western blot. RESULTS: Forty-three patients were enrolled: 20 in the DTG group, 23 in the NODTG group. Nine patients (20.9%; four in the DTG group, five in the NODTG group) were prescribed a four-drug regimen. In the cohort, 81.4% were Italian and 83.7% were male, with a median age of 41 years (interquartile range [IQR] 31-48). Median time between HIV diagnosis and ART initiation was 12 days (IQR 5-28). Seven patients harbored a virus with transmitted mutations at baseline (16.2%), all were in the DTG group (P=0.005). All patients had undetectable HIV-RNA at the end of follow-up except two patients, one of whom had 57 copies and one who was lost to follow-up. In Kaplan-Meier analysis, time to virological suppression was similar in the two groups (log rank: P= 0.7155). After achieving virological suppression, four patients stopped ART because of toxicity: two on DTG, two on EVG for neurological and gastrointestinal toxicity, respectively. CONCLUSION: In our setting, ART in AHI is started very early. DTG showed good viro-immunological efficacy even in the presence of NRTI-transmitted mutations. DTG interruptions were rare.
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Terapia Antirretroviral Altamente Activa/métodos , Infecciones por VIH/tratamiento farmacológico , Inhibidores de Integrasa VIH/uso terapéutico , Inhibidores de la Proteasa del VIH/uso terapéutico , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Adulto , Terapia Antirretroviral Altamente Activa/efectos adversos , Recuento de Linfocito CD4 , Femenino , Inhibidores de Integrasa VIH/efectos adversos , Inhibidores de la Proteasa del VIH/efectos adversos , Compuestos Heterocíclicos con 3 Anillos/efectos adversos , Humanos , Italia , Masculino , Persona de Mediana Edad , Oxazinas , Piperazinas , Piridonas , Inhibidores de la Transcriptasa Inversa/efectos adversos , Respuesta Virológica Sostenida , Resultado del TratamientoRESUMEN
OBJECTIVES: The aim of the study was to compare the efficacy and tolerability of switching antiretroviral therapy to dolutegravir + emtricitabine/tenofovir disoproxil fumarate (TDF) with those of switching to elvitegravir/cobicistat/emtricitabine/TDF in clinical practice. METHODS: In a multicentre real-life observational study, we analysed data for HIV-infected patients on antiretroviral treatment with viral load < 50 HIV-1 RNA copies/mL switching to dolutegravir + emtricitabine/TDF (dolutegravir group) or elvitegravir/cobicistat/emtricitabine/TDF (elvitegravir group). Follow-up was censored at 48 weeks. RESULTS: The 48-week estimated proportion maintaining virological efficacy was 96.1% with dolutegravir (n = 123) and 95.4% with elvitegravir (n = 186; P = 0.941). Patients in the dolutegravir group showed more treatment discontinuations, but these were mainly as a result of simplification. The elvitegravir group showed more discontinuations because of renal adverse events (2.7% versus 0% with dolutegravir). Interestingly, no difference was observed between the two regimens in central nervous system toxicity-related discontinuations. Switching to dolutegravir was associated with a better blood lipid profile. CONCLUSIONS: Switching to dolutegravir + emtricitabine/TDF was associated with similar efficacy and tolerability to switching to elvitegravir/cobicistat/emtricitabine/TDF in virologically suppressed patients in clinical practice, although reasons for discontinuation showed differences between regimens. These results should be interpreted with caution, as this is a nonrandomized comparison.
Asunto(s)
Cobicistat/uso terapéutico , Emtricitabina/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Quinolonas/uso terapéutico , Tenofovir/uso terapéutico , Adulto , Cobicistat/efectos adversos , Quimioterapia Combinada/efectos adversos , Emtricitabina/efectos adversos , Femenino , Infecciones por VIH/virología , VIH-1/genética , Compuestos Heterocíclicos con 3 Anillos/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Oxazinas , Piperazinas , Piridonas , Quinolonas/efectos adversos , ARN Viral/genética , Estudios Retrospectivos , Tenofovir/efectos adversos , Carga ViralRESUMEN
OBJECTIVES: We evaluated the efficacy and tolerability of lamivudine + dolutegravir in a cohort of HIV-1 infected, treatment-experienced patients with undetectable HIV-RNA. METHODS: Time to treatment discontinuation (TD) and virological failure (VF) and their predictors were assessed in a multicenter cohort of HIV-1 infected patients, starting lamivudine + dolutegravir after reaching viral suppression. Secondary objective was the evaluation of changes in lipid profile, renal and immunological functions at week 48. RESULTS: We enrolled 206 patients (72.8% male, with 51 years median age), who mainly switched their antiretroviral therapy for simplification (32.5%) or drug toxicity (54.5%). The estimated probability of maintaining virological suppression at 48 and 96 weeks was 98.2% and 95.1%, respectively. VF was independently predicted by cumulative time on antiretroviral therapy. The estimated probability of remaining on lamivudine plus dolutegravir was 86.7% and 80.5% at week 48 and 96, respectively. A significant improvement in immunological function (CD4 count and CD4/CD8 ratio) was evidenced at week 48, as well as a decrease in total cholesterol/HDL ratio, triglycerides and estimated glomerular filtration rate. CONCLUSIONS: Lamivudine plus dolutegravir was effective in maintaining viral suppression in our cohort and led to an improvement in metabolic and immunologic functions.
RESUMEN
We evaluated the efficacy of tenofovir (TDF) - and didanosine (ddI)-containing backbones in HIV-infected experienced subjects. We included in the study 245 subjects who started a TDF/ddI-containing HAART with HIV-RNA > 3 log(10) cp/ml and an available genotypic resistance test at baseline. At baseline, median CD4 counts and HIV-RNA were 278 cell/mmc and 4.32 log(10) cp/ml, respectively. Seventy-four subjects (30.2%) discontinued TDF and/or ddI, 23 of them for drug-related toxicities or intolerance. One-hundred and twenty-six (51.4%) subjects achieved virologic success (HIV-RNA < 50 copies/ml in two consecutive determinations) in a median time of 6.1 months; higher HIV-RNA levels (HR: 0.66, 95% CI: 0.54- 0.79, p < 0.001 for each additional log(10) copies/ml), and the total number of mutations either for PI and NNRTI at baseline (HR: 0.87, 95% CI: 0.81-0.92, p < 0.001 for each additional mutation) were both predictors of virologic success. M184V was marginally associated with virologic success (HR: 1.34, 95% CI: 0.94-1.90, p = 0.10 vs no M184V), whilst the number of TAMs was not associated. One-hundred-thirty-three (54.3%) subjects achieved immunologic success (increase of > or = 100 cells/mm(3) from baseline) in a median time of 7.5 months; immunologic success was associated with HIV-RNA levels at baseline (HR: 0.91, 95% CI: 0.79-0.98, p = 0.04 for each additional log(10) copies/ml), the total number of mutations either for PI or NNRTI (HR: 0.91, 95% CI: 0.85-0.98, p = 0.01 for each additional mutation) and CD4 count at baseline (HR: 1.11, 95% CI: 1.00-1.23, p = 0.05 for each additional 100 cells/mm(3)). Results obtained by the on-treatment analyses were comparable. In our study, HAART containing TDF/ddI seem associated with a virologic and immunologic response, when such regimens are chosen according to a genotypic resistance test.
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Adenina/análogos & derivados , Fármacos Anti-VIH/uso terapéutico , Terapia Antirretroviral Altamente Activa , Didanosina/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/inmunología , Organofosfonatos/uso terapéutico , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Adenina/administración & dosificación , Adenina/uso terapéutico , Adulto , Fármacos Anti-VIH/administración & dosificación , Recuento de Linfocito CD4 , ADN Viral/genética , Didanosina/administración & dosificación , Farmacorresistencia Viral , Quimioterapia Combinada , Femenino , VIH-1/genética , VIH-1/aislamiento & purificación , Humanos , Masculino , Persona de Mediana Edad , Mutación , Organofosfonatos/administración & dosificación , Estudios Retrospectivos , Inhibidores de la Transcriptasa Inversa/administración & dosificación , Análisis de Secuencia de ADN , Tenofovir , Resultado del TratamientoRESUMEN
BACKGROUND: Severe, intractable pruritus, often associated with erythematopapular skin lesions and hypereosinophilia, is a condition observed in some nonatopic, HIV-infected patients. We performed immunovirologic analyses of this condition. METHODS: Immunologic (mitogen-stimulated production of cytokines, tumor necrosis factor-alpha [TNF-alpha], and soluble CD23; serum levels of soluble CD23, ICAM-1, TNF-alpha, IgG, IgE, and IgA) and virologic (HIV viral load) parameters were analyzed in six patients with therapy-resistant pruritus. Hypereosinophilia was present in all these patients. Results were compared to those of seven HIV-seropositive individuals similar to the first one in terms of CD4 counts and clinical staging, but without pruritus. RESULTS: Hypereosinophilia; hyper-IgE and hyper-IgA; augmented interleukin (IL)-4, IL-5, and sCD23; and reduced interferon-gamma production by mitogen-stimulated peripheral blood mononuclear cells (PBMC) were detected when patients with pruritus were compared to HIV controls. HIV viral load was also augmented in patients in whom pruritus was present. CONCLUSIONS: The results suggest that therapy-resistant, intractable pruritus accompanied by hypereosinophilia may be used to define a subset of HIV-seropositive individuals showing prototypic hyperactivation of humoral immunity, and in whom augmented HIV viral load is present.
Asunto(s)
Infecciones por VIH/complicaciones , Infecciones por VIH/inmunología , Prurito/complicaciones , Prurito/inmunología , Adulto , Citocinas/biosíntesis , Eosinofilia , Femenino , VIH/fisiología , Infecciones por VIH/virología , Humanos , Inmunoglobulina A/sangre , Inmunoglobulina G/sangre , Molécula 1 de Adhesión Intercelular/sangre , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Prurito/patología , Prurito/virología , ARN Viral/sangre , Receptores de IgE/biosíntesis , Receptores de IgE/sangre , Piel/patología , Carga ViralRESUMEN
In the last three years basic science and clinical research have radically changed the therapeutical approach to HIV disease. Recent guidelines suggest that treatments to HIV disease should be early and aggressive, with the use of new potent antiretroviral drugs. This approach has been defined as HAART (highly active antiretroviral therapy). In this review we will discuss the main stages of antiretroviral therapy focusing on the acquisitions about results as well as problems of triple therapy.
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Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Inhibidores de la Proteasa del VIH/uso terapéutico , Fármacos Anti-VIH/efectos adversos , Interacciones Farmacológicas , Resistencia a Medicamentos , Quimioterapia Combinada , Inhibidores de la Proteasa del VIH/efectos adversos , HumanosAsunto(s)
Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Adulto , Estudios de Cohortes , Femenino , Inhibidores de la Proteasa del VIH/uso terapéutico , Humanos , Indinavir/uso terapéutico , Masculino , Persona de Mediana Edad , Ritonavir/uso terapéutico , Saquinavir/uso terapéutico , Insuficiencia del TratamientoRESUMEN
The effects of pentoxifylline on immunologic and virologic parameters were evaluated in 10 human immunodeficiency virus-infected patients not receiving antiretroviral treatment. Patients were asymptomatic, had 300-500 CD4 cells/microL, and received pentoxifylline (1200 mg/day orally) for 4 months. Peripheral blood mononuclear cells were tested before and at five time points during therapy. A transient increase in CD4 cells was observed in 8 of 9 patients, and CD8 cells increased in 7 of 9 patients. These increases were negatively correlated with susceptibility to in vitro mitogen-stimulated apoptotic cell death. Pentoxifylline had a temporary effect on mitogen-stimulated cytokine production; thus, interferon-gamma, interleukin (IL)-2, tumor necrosis factor-alpha, and lymphotoxin increased more than IL-10. Pentoxifylline also potentiated antigen-stimulated IL-2 production and proliferation in 8 of 9 patients and induced significant but transient decreases in plasma viremia in 7 of 9 patients. These preliminary findings suggest that pentoxifylline in vivo has an interesting but temporary influence on both immunologic and virologic parameters.
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Adyuvantes Inmunológicos/uso terapéutico , Fármacos Anti-VIH/uso terapéutico , Recuento de Linfocito CD4 , Citocinas/biosíntesis , Seropositividad para VIH/inmunología , Seropositividad para VIH/terapia , VIH-1/aislamiento & purificación , Linfocitos/inmunología , Pentoxifilina/uso terapéutico , Apoptosis , Quimioterapia Combinada , Seropositividad para VIH/sangre , Humanos , Inmunidad Celular , Activación de Linfocitos , Linfocitos/efectos de los fármacos , Reacción en Cadena de la Polimerasa/métodos , ARN Viral/sangre , Linfocitos T Colaboradores-Inductores/inmunología , Factores de Tiempo , Viremia/sangre , Viremia/tratamiento farmacológico , Viremia/inmunologíaAsunto(s)
Síndrome de Inmunodeficiencia Adquirida/complicaciones , Candidiasis/tratamiento farmacológico , Enfermedades del Esófago/tratamiento farmacológico , Factor Estimulante de Colonias de Granulocitos y Macrófagos/uso terapéutico , Infecciones Oportunistas Relacionadas con el SIDA/tratamiento farmacológico , Infecciones Oportunistas Relacionadas con el SIDA/inmunología , Síndrome de Inmunodeficiencia Adquirida/inmunología , Candidiasis/complicaciones , Candidiasis/inmunología , Enfermedades del Esófago/complicaciones , Enfermedades del Esófago/inmunología , Humanos , Proteínas Recombinantes/uso terapéuticoRESUMEN
Amphotericin B is the only antifungal drug which, despite its dose-limiting toxicity, can be given intravenously when an aggressive treatment is required. In an attempt to reduce the drug toxicity while retaining its therapeutic efficacy, new formulations of amphotericin B have been developed. The most promising have employed lipid vehicles such as liposomes. Three lipid-based amphotericin B formulations have been developed by pharmaceutical companies and are under active clinical investigation. Efficacy and safety data of these derivatives in animals and humans are reviewed, with particular concern to cryptococcal infection. The authors' experience with a small unilamellar liposomal amphotericin B formulation, AmBisome, in the primary therapy of cryptococcosis is reported. Nine AIDS patients affected with cryptococcosis, seven of whom had meningitis, were given AmBisome (3 mg/kg/day) for 3-6 weeks. Complete response was obtained in six patients, marked improvement in two, and failure in one. AmBisome was well tolerated and shortened the time to clinical and mycological response suggesting a further improvement in the management of cryptococcosis in AIDS patients.
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Infecciones Oportunistas Relacionadas con el SIDA/tratamiento farmacológico , Anfotericina B/administración & dosificación , Criptococosis/tratamiento farmacológico , Infecciones Oportunistas Relacionadas con el SIDA/sangre , Infecciones Oportunistas Relacionadas con el SIDA/diagnóstico , Adulto , Anfotericina B/farmacología , Anfotericina B/uso terapéutico , Linfocitos T CD4-Positivos , Química Farmacéutica , Criptococosis/sangre , Criptococosis/diagnóstico , Portadores de Fármacos , Evaluación de Medicamentos , Humanos , Recuento de Leucocitos , Liposomas , Masculino , Persona de Mediana Edad , Proyectos Piloto , Factores de Tiempo , Resultado del TratamientoRESUMEN
There is increasing evidence that cytokines contribute to the immunopathogenesis of human immunodeficiency virus (HIV) infection. It may be, therefore, that compensatory rises in circulating cytokine antagonists also occur in HIV infection and that such changes mark disease progression. To test this idea, plasma concentrations of the cytokine antagonists alpha-melanocyte-stimulating hormone (alpha-MSH), interleukin-1 receptor antagonist (IL-1ra), and soluble tumor necrosis factor receptor (sTNFr) were measured in patients of different Centers for Disease Control (CDC) categories of HIV infection and in seronegative controls. Plasma levels of all these cytokine antagonists were higher in HIV-infected patients. IL-1ra and sTNFr concentrations were correlated with indicators of disease activity: positively with plasma neopterin and negatively with CD4+ T lymphocyte counts. alpha-MSH and sTNF r were greater in CDC groups III and IV, whereas IL-1ra was elevated only in the latter group. Because cytokines activate the hypothalamic-pituitary-adrenal axis and adrenal steroids inhibit cytokine production, we measured circulating adrenocorticotropic hormone (ACTH) and cortisol in HIV-infected patients and investigated relations among these hormones, cytokine antagonists, and markers of disease progression. It appears that these physiological modulators of cytokine activity are not closely linked to sTNFr, IL-1ra and alpha-MSH: there were no significant correlations between plasma concentrations of ACTH or cortisol and those of cytokine antagonists, nor were there correlations between hormones and markers of disease progression such as neopterin or CD4+ T cell counts. It is notable that severe adrenal insufficiency was extremely rare (3%) in HIV-infected patients; it was confined to the AIDS group and was consistently secondary to ACTH deficiency.(ABSTRACT TRUNCATED AT 250 WORDS)