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In this update, antiretroviral therapy (ART) is recommended for all patients infected by type 1 human immunodeficiency virus (HIV-1). The strength and grade of the recommendation vary depending on the CD4+ T-lymphocyte count, the presence of opportunistic infections or comorbid conditions, age, and the efforts to prevent the transmission of HIV. The objective of ART is to achieve an undetectable plasma viral load (PVL). Initial ART should comprise three drugs, namely, two nucleoside reverse transcriptase inhibitors (NRTI) and one drug from another family. Three of the recommended regimens, all of which have an integrase strand transfer inhibitor (INSTI) as the third drug, are considered a preferred regimen; a further seven regimens, which are based on an INSTI, an non-nucleoside reverse transcriptase inhibitor (NNRTI), or a protease inhibitor boosted with ritonavir (PI/r), are considered alternatives. The reasons and criteria for switching ART are presented both for patients with an undetectable PVL and for patients who experience virological failure, in which case the rescue regimen should include three (or at least two) drugs that are fully active against HIV. The specific criteria for ART in special situations (acute infection, HIV-2 infection, pregnancy) and comorbid conditions (tuberculosis and other opportunistic infections, kidney disease, liver disease, and cancer) are updated.
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Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , VIH-1 , Infecciones Oportunistas Relacionadas con el SIDA , Adulto , Fármacos Anti-VIH/administración & dosificación , Fármacos Anti-VIH/efectos adversos , Terapia Antirretroviral Altamente Activa , Lactancia Materna , Recuento de Linfocito CD4 , Comorbilidad , Contraindicaciones , Farmacorresistencia Viral , Sustitución de Medicamentos , Quimioterapia Combinada , Femenino , Infecciones por VIH/inmunología , VIH-1/efectos de los fármacos , VIH-2 , Humanos , Embarazo , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Carga Viral , Viremia/tratamiento farmacológicoRESUMEN
There are clear sex-related biological differences between men and women. Diseases that affect the two sexes differently are studied separately. However, some diseases affect both men and women, but their incidence or outcome are clearly different. In human immunodeficiency virus infection, the potential differences in the effects of antiretroviral therapy are poorly characterized and few studies have been designed to elucidate these differences. Moreover, women are usually poorly represented in clinical trials of antiretroviral drugs.
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Infecciones por VIH/tratamiento farmacológico , Inhibidores de la Proteasa del VIH/uso terapéutico , Lopinavir/uso terapéutico , Ritonavir/uso terapéutico , Fármacos Anti-VIH/efectos adversos , Fármacos Anti-VIH/uso terapéutico , Tamaño Corporal , Combinación de Medicamentos , Femenino , Infecciones por VIH/epidemiología , Inhibidores de Integrasa VIH/administración & dosificación , Inhibidores de Integrasa VIH/uso terapéutico , Inhibidores de la Proteasa del VIH/efectos adversos , Síndrome de Lipodistrofia Asociada a VIH/inducido químicamente , Humanos , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Lopinavir/efectos adversos , Metaanálisis como Asunto , Estudios Multicéntricos como Asunto , Selección de Paciente , Embarazo , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como Asunto , Inhibidores de la Transcriptasa Inversa/administración & dosificación , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Ritonavir/efectos adversos , Caracteres SexualesRESUMEN
BACKGROUND: Ribavirin (RBV) exposure seems to be critical to maximize treatment response in human immunodeficiency virus (HIV)-positive patients with chronic hepatitis C virus (HCV) infection. METHODS: HIV/HCV-coinfected individuals naive to interferon were prospectively randomized to receive peginterferon-α-2a (180 µg/d) plus either RBV standard dosing (1000 or 1200 mg/d if <75 or ≥ 75 kg, respectively) or RBV induction (2000 mg/d) along with subcutaneous erythropoietin ß (450 IU/kg/wk), both during the first 4 weeks, followed by standard RBV dosing until completion of therapy. Early stopping rules at weeks 12 and 24 were applied in patients with suboptimal virological response. RESULTS: A total of 357 patients received ≥ 1 dose of the study medication. No differences in main baseline characteristics were found when comparing treatment arms. Sustained virological response (SVR) was attained by 160 (45%) patients, with no significant differences between RBV induction and standard treatment arms (SVR in 72 of 169 patients [43%] vs 88 of 188 [47%], respectively). At week 4, undetectable HCV RNA (29% vs 25%) and mean RBV trough concentration (2.48 vs 2.14 µg/mL) were comparable in both arms, whereas mean hemoglobin decay was less pronounced in the RBV induction plus erythropoietin arm than in the RBV standard dosing arm (-1.7 vs -2.3 mg/dL; P < .005). Treatment discontinuation occurred in 91 (25%) patients owing to nonresponse and in 29 (8%) owing to adverse events. HCV relapse occurred in 34 patients (10%). Univariate and multivariate analyses identified HCV genotype 2 or 3 (odds ratio [OR], 10.3; 95% confidence interval [CI], 2.08-50.2; P = .004), IL28B CC variants (OR, 2.92; 95% CI, 1.33-6.41; P = .007), nonadvanced liver fibrosis (OR, 2.27; 95% CI, 1.06-5.01; P = .03), and rapid virological response (OR, 40.3; 95% CI, 5.1-314.1; P < .001) as predictors of SVR. CONCLUSIONS: A 4-week course of induction therapy with high RBV dosing along with erythropoietin does not improve SVR rates in HIV/HCV-coinfected patients. Preemptive erythropoietin might blunt the benefit of RBV overdosing by enhancing erythrocyte uptake of plasma RBV.
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Antivirales/uso terapéutico , Infecciones por VIH/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Polietilenglicoles/uso terapéutico , Ribavirina/uso terapéutico , Adulto , Terapia Antirretroviral Altamente Activa , Antivirales/administración & dosificación , Antivirales/efectos adversos , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada , Femenino , Hepacivirus/genética , Hepatitis C Crónica/complicaciones , Humanos , Interferón-alfa/administración & dosificación , Interferón-alfa/efectos adversos , Masculino , Persona de Mediana Edad , Polietilenglicoles/administración & dosificación , Polietilenglicoles/efectos adversos , ARN Viral/sangre , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/efectos adversos , Proteínas Recombinantes/uso terapéutico , Ribavirina/administración & dosificación , Ribavirina/efectos adversosRESUMEN
OBJECTIVE: There are a lack of consistency among articles in regards to the evolution of peripheral immune biomarkers after HCV therapy. We aimed to detect the most relevant changes in peripheral immune biomarkers among HIV/HCV-coinfected patients who achieved sustained virologic response (SVR) following peg-IFN-α/ribavirin therapy and to evaluate its normalization with respect to an HIV-monoinfected control group. METHODS: We performed a prospective cohort study in 99 HIV/HCV-coinfected patients with samples at baseline (HIV/HCV-b-group) and at week 24 after SVR (HIV/HCV-f-group). We also used a control group of 39 HIV-monoinfected patients (HIV-group) negative for HCV and HBV infections, and who had undetectable HIV viral load and CD4+ >500 cells/mm3. Peripheral T cell subsets were assessed by flow cytometry and plasma biomarkers by immunoassays. RESULTS: HIV/HCV-coinfected patients had higher values of in IL-10, IL-4, IP-10, IL-8, IL-1ß, IL-18, IL-6, IFN-γ, IL-12p70, TNF-α, sVCAM-1, sICAM-1, and sTNFR-1 than HIV control subjects, both at the beginning and at the end of follow-up. Moreover, three biomarkers (CD4+CD38+, telomere length, and IL-1RA) were normalized in relation to the control group at the end of follow-up (the HIV/HCV-b group had higher values and the HIV/HCV-f group had similar values as the HIV-group). Additionally, LPS, IL-2, and IL-17A levels were higher in the HIV/HCV-f group than the HIV-group (24 weeks after SVR). During the follow-up, HIV/HCV-coinfected patients had a significant decrease by the end of follow-up in CD8+CD45RA-CD28+, CD4+CD38+, CD4+CD25+CD127-/low, CD4+CD25+CD127-/low CD45RA-, FABP2, LBP, IP-10, sVCAM1. Only CD4+CD38+ was normalized. CONCLUSION: HIV/HCV-patients showed a slight improvement in the overall profile of immune biomarkers after achieving SVR.
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Coinfección , Infecciones por VIH , Hepatitis C Crónica , Hepatitis C , Antivirales/uso terapéutico , Biomarcadores , Coinfección/tratamiento farmacológico , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Hepatitis C/complicaciones , Hepatitis C/tratamiento farmacológico , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Estudios Prospectivos , Ribavirina/uso terapéuticoRESUMEN
BACKGROUND: The efficacy of licensed direct-acting antiviral (DAA) regimens is assumed to be the same for hepatitis C virus (HCV)-monoinfected patients (HCV-Mono) and HIV/HCV-coinfected patients (HCV-Co). However, the high sustained viral response (SVR) rates of DAA regimens and the small number of HIV-infected patients included in registration trials have made it difficult to identify predictors of treatment failure, including the presence of HIV. METHODS: We compared treatment outcomes for ledipasvir/sofosbuvir (LDV/SOF) against HCV G1 in treatment-naïve HCV-Mono and HCV-Co without cirrhosis in a prospective registry of individuals receiving DAAs for HCV. RESULTS: Up to September 2017, a total of 17 269 patients were registered, and 1358 patients (1055 HCV-Mono/303 HCV-Co) met the inclusion criteria. Significant differences between HCV-Mono and HCV-Co were observed for age, gender, and G1 subtype distribution. Among HCV-Co, 99.0% were receiving antiretroviral therapy. SVR rates for LDV/SOF at 8 weeks did not differ significantly between HCV-Mono and HCV-Co (96.9% vs 94.0%; P = .199). However, the SVR rate for LDV/SOF at 12 weeks was significantly higher for HCV-Mono than HCV-Co (97.2% vs 91.8%; P = .001). A multivariable logistic regression model including age, sex, liver stiffness, G1 subtype, HCV-RNA, HIV, and treatment duration showed the factors associated with treatment failure to be male sex (adjusted odds ratio [aOR], 2.49; 95% confidence interval [CI], 1.27-4.91; P = .008) and HIV infection (aOR, 2.23; 95% CI, 1.13-4.38; P = .020). CONCLUSIONS: The results of this large prospective study analyzing outcomes for LDV/SOF against HCV G1 in treatment-naïve noncirrhotic patients suggest that HIV infection is a predictor of treatment failure in patients with chronic hepatitis C.
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The magnitude of sexualized drug use (SDU), also known as chemsex, and its association with sexually transmitted infections (STI) has not been systematically explored in HIV-positive patients. This study aimed to calculate the prevalence of SDU and associated factors in a sample of HIV-positive men who have sex with men (MSM) in Spain. We calculated the frequency of SDU in a sample of HIV-positive MSM who responded to an anonymous online survey on sexual behavior and recreational drug use. We also analyzed differences between those who responded and those who did not (data taken from the physician's registry). The association between SDU, sexual risk behaviors, and STI was evaluated using a univariate and a multivariate analysis. Data were collected and managed using Research Electronic Data Capture (REDCap). The survey was completed by 742 HIV-positive MSM, of whom 60% had had unprotected anal intercourse (UAI), 62% had been diagnosed with a STI, and 216 (29.1%) reported recent SDU (slamsex in 16% of cases). In the multivariate analysis, patients who engaged in SDU were more likely to have had high-risk sexual behaviors and a diagnosis of STI than participants who did not engage in SDU. A diagnosis of hepatitis C was independently associated with slamsex (5.2 [95% confidence interval (CI), 2.06-13.13]; p < 0.001), chemsex (2.51 [95% CI, 1.28-4.91]; p = 0.007), and UAI (1.82 [95% CI, 0.90-3.70]; p = 0.094). The magnitude of SDU or chemsex in our sample is relatively high. We found a clear association between SDU, high-risk sexual behaviors, and STI including hepatitis C.
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Consumidores de Drogas/estadística & datos numéricos , Infecciones por VIH/epidemiología , Homosexualidad Masculina/estadística & datos numéricos , Asunción de Riesgos , Conducta Sexual/estadística & datos numéricos , Enfermedades de Transmisión Sexual/epidemiología , Sexo Inseguro/estadística & datos numéricos , Adulto , Estudios Transversales , Seropositividad para VIH , Hepatitis C/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Enfermedades de Transmisión Sexual/microbiología , España/epidemiología , Trastornos Relacionados con Sustancias/epidemiología , Encuestas y Cuestionarios , Adulto JovenRESUMEN
Transmission of HIV through transfusion occurred in a 78-year-old male after receiving red blood cells from a 27-year-old woman, who was negative for HIV antibodies and p24 antigen at the time of donation, but seroconverted thereafter. Plasma viral load at donation was 2538 HIV RNA copies/ml. Phylogenetic analyses demonstrated that viruses from both patients clustered tightly together, belonged to subtype B clade, and had no primary drug resistance mutations. This case highlights the residual risk of HIV transmission from donors in the window period, and supports the implementation of nucleic acid testing in blood banks.
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Donantes de Sangre , Transfusión Sanguínea , Infecciones por VIH/transmisión , VIH-1/aislamiento & purificación , ARN Viral/sangre , Adulto , Anciano , Femenino , Anticuerpos Anti-VIH/sangre , Proteína p24 del Núcleo del VIH/sangre , Infecciones por VIH/virología , VIH-1/clasificación , VIH-1/genética , Humanos , MasculinoRESUMEN
INTRODUCTION: Nucleoside reverse transcriptase inhibitors (NRTI)-sparing regimens have been studied in antiretroviral therapy (ART)-naïve patients but data with ART-experienced are scarce. NRTI-sparing regimens may be an option in patients with toxicities and for simplification reasons. METHODS: Retrospective multicentre analysis including ART-experienced patients starting treatment with darunavir/ritonavir and etravirine (DRV/r 800 mg/100 mg QD or 600 mg/100 mg BID and ETV 400 mg QD or 200 mg BID) with at least six months of follow-up. Primary endpoint was proportion of patients with VL<50 copies/mL at 48 weeks with an ITT analysis (missing or switch equals failure). Secondary endpoints were safety, CD4 count and lipid changes over 48 weeks. RESULTS: Seventy-five patients were included of whom 44 (58.6%) had HIV RNA<50 copies/mL. Baseline characteristics: median age 50 years (IQR 34-65), 72% males, 93% Caucasians, 38.6% hepatitis C, and 45.4% with CDC C stage. Median HIV duration and time on ART were 20 (IQR 7-28) and 14 years (IQR 5-21) respectively. Reasons for switching were virologic failure in 27 (36%), simplification in 25 (33.3%), toxicity in 20 (26.6%) and other 3 (4.1%). Most of them received DRV/r and ETV QD. Thirty-nine patients had NNRTI resistance mutations [28 K103N (37.3%), 6 Y181I/C (8%), 3 G190A (4%)] and 29 patients had ≥1 primary PI mutations. Main analysis (ITT) showed that 67 (89.3%) had a VL undetectable at 24 weeks (95% CI 83.1-95.5) and 57 (76%) at 48 weeks (95% CI 68.4-83.6). On treatment analysis showed that 94.3% and 89% had a viral load<50 copies at 24 and 48 weeks, respectively. 11 (14.6%) patients discontinued the regimen (three virologic failures, three switching to darunavir/ritonavir monotherapy, two to salvage regimen and three due to toxicity). No significant changes in CD4+ count and lipid changes were observed at 48 weeks. CONCLUSIONS: Dual therapy with Darunavir/ritonavir and etravirine is an efficacious and safety option in ART-experienced HIV patients even in patients on virologic failure.
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BACKGROUND: It is uncertain whether a 4-week induction period of pegylated interferon and ribavirin increases early virological response (EVR) in HIV-HCV-coinfected patients. METHODS: HIV and HCV genotype 1- and 4-coinfected subjects were randomized to receive pegylated interferon-α2a 270 µg/week plus ribavirin 1,600 mg daily and epoetin-ß for 4 weeks, followed by pegylated interferon-α2a at standard dosages plus weight-based ribavirin (WBR) dosage for 8 weeks (induction arm [IA]), or pegylated interferon-α2a plus WBR for 12 weeks (standard therapy arm [SA]). HCV RNA was determined at weeks 0, 1, 2, 3, 4, 8 and 12. Ribavirin plasma trough concentrations were determined at weeks 4 (RBV-C(4)) and 12 (RBV-C(12)). RESULTS: A total of 67 patients were included; 33 in the SA and 34 in the IA. Overall, 25% received nucleoside reverse transcriptase inhibitor (NRTI)-sparing regimens. More patients achieved an HCV RNA decrease ≥1 log(10) at week 4 in the IA than in the SA (62% versus 38%; P=0.017), but EVR rates were similar in the two groups (74% versus 59% in the IA and SA, respectively; P=0.15). Independent predictors of faster HCV RNA decrease at 12 weeks were higher RBV-C(4) and younger age. RBV-C(4) were higher in patients allocated in the IA and in those receiving NRTIs (P=0.039). CONCLUSIONS: A 4-week induction with pegylated interferon-α2a plus ribavirin was associated with a greater decrease in HCV RNA at week 4; however, this did not translate into higher EVR rates. Higher RBV doses and avoidance of NRTI-sparing antiretroviral regimens might improve HCV treatment efficacy.
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Antivirales/uso terapéutico , Coinfección/tratamiento farmacológico , Infecciones por VIH/complicaciones , Hepatitis C/complicaciones , Hepatitis C/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Polietilenglicoles/uso terapéutico , Ribavirina/uso terapéutico , Adulto , Antivirales/efectos adversos , Coinfección/virología , Femenino , VIH/genética , Hepacivirus/genética , Hepatitis C/virología , Humanos , Interferón-alfa/efectos adversos , Masculino , Persona de Mediana Edad , Polietilenglicoles/efectos adversos , Proteínas Recombinantes/efectos adversos , Proteínas Recombinantes/uso terapéutico , Ribavirina/efectos adversos , Resultado del Tratamiento , Carga ViralRESUMEN
BACKGROUND AND OBJECTIVE: AIDS-related Burkitt's lymphoma or leukemia (BLL) is increasingly treated with specific and intensive multiagent schedules. This retrospective study aimed to compare the results of CHOP with those from two protocols (PETHEMA-LAL3/97 and BURKIMAB) of specific therapy in Spain. PATIENTS AND METHODS: Patients from Group A (n=31) received 6 standard CHOP cycles every 3 weeks. Patients from group B (n=44) received six multiagent cycles including high-dose methotrexate and high-dose cytarabine. The response to therapy, disease-free survival and overall survival (OS) were compared in the two groups. RESULTS: Both groups were comparable for the main clinical and biological parameters at diagnosis except for risk activity, previous HAART, bone marrow involvement, bulky disease and extranodal involved sites. Complete remission (CR) was achieved in 10 out of 31 (32%) patients in group A and 28 out of 44 (67%) patients in group B (P=.005). After a median (range) follow-up of 70 (26-139) and 17 (1-134) months, the 5-year (95% CI) DFS probability was 87% (64%-100%) for group A and 70% (51%-89%) for group B (P=.374), and the 5-year (95% CI) OS was 27% (10%-43%) for Group A and 57% (40%-74%) for group B (P=.028). Multivariate analyses showed that specific therapy was associated with an improved CR and OS. CONCLUSIONS: In AIDS-related BLL short intensive specific chemotherapy is feasible, with higher remission rate and improved survival than that obtained with CHOP-based regimens.
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Protocolos de Quimioterapia Combinada Antineoplásica , Linfoma de Burkitt/tratamiento farmacológico , Linfoma Relacionado con SIDA/tratamiento farmacológico , Adulto , Anciano , Ciclofosfamida , Doxorrubicina , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prednisona , Estudios Retrospectivos , Vincristina , Adulto JovenRESUMEN
No disponible
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Adulto , Humanos , Masculino , Lepra Lepromatosa/complicaciones , Lepra Lepromatosa/diagnóstico , Lepra Lepromatosa/inmunología , Autoinmunidad/inmunología , Nervios Periféricos/patología , Lepra Multibacilar/diagnóstico , Lepra Multibacilar/tratamiento farmacológico , Lepra Multibacilar/inmunología , Artralgia/tratamiento farmacológico , Artralgia/etiología , Extremidad Inferior/patología , Nervios Periféricos/inmunología , Dapsona/uso terapéutico , Talidomida/uso terapéuticoRESUMEN
Existen claras diferencias biológicas entre varones y mujeres determinadas por razón de sexo; las enfermedades que inciden de manera diferenciada en varones y mujeres se estudian por separado. Sin embargo hay enfermedades que afectan a ambos sexos, pero cuya incidencia o evolución es marcadamente diferente. En la infección por el virus de la inmunodeficiencia humana, las potenciales diferencias en cuanto a los efectos del tratamiento antirretroviral no están bien estudiadas y hay pocos estudios diseñados con este fin; además, las mujeres, en general, están poco representadas en los ensayos clínicos de fármacos antirretrovirales (AU)
There are clear sex-related biological differences between men and women. Diseases that affect the two sexes differently are studied separately. However, some diseases affect both men and women, but their incidence or outcome are clearly different. In human immunodeficiency virus infection, the potential differences in the effects of antiretroviral therapy are poorly characterized and few studies have been designed to elucidate these differences. Moreover, women are usually poorly represented in clinical trials of antiretroviral drugs (AU)
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Humanos , Femenino , Embarazo , Infecciones por VIH/tratamiento farmacológico , Inhibidores de la Proteasa del VIH/uso terapéutico , Lopinavir/uso terapéutico , Ritonavir/uso terapéutico , Fármacos Anti-VIH/uso terapéutico , Combinación de Medicamentos , Inhibidores de Integrasa VIH/uso terapéutico , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Síndrome de Lipodistrofia Asociada a VIH/inducido químicamente , Transmisión Vertical de Enfermedad Infecciosa/prevención & controlRESUMEN
OBJECTIVES: We analyzed survival, therapeutic response, and prognostic factors in patients with HIV-related Hodgkin lymphoma (HL) treated or not with highly active antiretroviral therapy (HAART). METHODS: This study included 104 patients with HL, treated (n = 83) or not (n = 21) with HAART. Outcomes and prognostic factors of complete remission (CR), overall survival (OS), and disease-free survival (DFS) were assessed by an intention-to-treat analysis of all patients who received at least 1 chemotherapy course. RESULTS: No differences were found between groups at baseline in the specific characteristics of HIV and HL. The proportion of patients receiving appropriate-for-stage therapy for HL was similar for both groups. The CR rates in the HAART (-) and HAART (+) groups were 14 (70%) of 20 versus 71 (91%) of 78 (P = 0.023). The median OS in the HAART (-) group was 39 months (95% confidence interval [CI]: 0 to 89) and was not reached in the HAART (+) group (P = 0.0089). The median DFS in the HAART (-) group was 85 months (95% CI: 73 to 97) and was not reached in the HAART (+) group (P = 0.129). Factors independently associated with CR by logistic regression analysis were appropriate-for-stage therapy of HL, HAART, and baseline CD4 count > or =100 cells/microL. CR was the only factor independently associated with OS by Cox regression analysis. CONCLUSIONS: The achievement of CR was independently associated with appropriate-for-stage therapy for HL, with HAART, and with a baseline CD4 count > or =100 cells/microL. The only variable independently associated with OS was the achievement of CR.
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Terapia Antirretroviral Altamente Activa , Infecciones por VIH/tratamiento farmacológico , Enfermedad de Hodgkin/tratamiento farmacológico , Linfoma Relacionado con SIDA/tratamiento farmacológico , Adulto , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Pronóstico , Sistema de Registros/estadística & datos numéricos , Inducción de Remisión , España , Factores de Tiempo , Resultado del TratamientoRESUMEN
OBJECTIVES: To assess complete remission (CR) and survival in patients with systemic AIDS-related non-Hodgkin lymphoma (ARL) receiving highly active antiretroviral therapy (HAART). METHODS: We analyzed the Grupo de Estudio del SIDA register of systemic ARL, which started in Jan 1994, to collect cases diagnosed at 15 institutions prospectively and with active follow-up every 6 months. The date of censorship for this study was March 2005. RESULTS: During the study period, 210 consecutive patients were diagnosed with ARL, with a median age 39 of years, 75.7% of whom were male, and with a median baseline CD4 count of 160 cells/microL. Histologic subtypes were diffuse large B-cell lymphoma (DLCL; n = 153 [72.9%]), Burkitt and atypical Burkitt/Burkitt-like lymphoma (BL; n = 40 [19.0%]), T-cell lymphoma (TC; n = 8 [3.8%]), and miscellaneous (n = 9 [4.3%]). Chemotherapy with or without other modalities was administered to 186 (88.6%) patients. In an intent-to-treat analysis of 184 patients who received at least 1 chemotherapy course with adequate follow-up to assess their response, 119 (64.7%) achieved CR, and the median length of survival (Kaplan-Meier analysis) was 52 months (95% confidence interval [CI]: 23 to 82 months). Factors independently associated with CR were histologic subtype and International Prognostic Index (IPI) score. Factors independently associated with improved overall length of survival (OS) were CR, low IPI score, and histologic subtype. The single factor independently associated with disease-free survival was Ann Arbor stage. CONCLUSIONS: In patients with ARL treated with HAART, CR was associated exclusively with tumor-related factors. The CR rate was poorer in patients with BL and TC subtypes and was inversely correlated with IPI score. OS was independently associated with CR, IPI score, and the histologic subtype.
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Fármacos Anti-VIH/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica , Terapia Antirretroviral Altamente Activa , Linfoma Relacionado con SIDA/tratamiento farmacológico , Linfoma Relacionado con SIDA/patología , Adulto , Linfoma de Burkitt/tratamiento farmacológico , Linfoma de Burkitt/patología , Terapia Combinada , Supervivencia sin Enfermedad , Femenino , Humanos , Estudios Longitudinales , Linfoma Relacionado con SIDA/terapia , Linfoma de Células B/tratamiento farmacológico , Linfoma de Células B/patología , Linfoma de Células T/tratamiento farmacológico , Linfoma de Células T/patología , Masculino , Persona de Mediana Edad , Pronóstico , Inducción de Remisión , Estadística como Asunto , Análisis de SupervivenciaRESUMEN
BACKGROUND: Metabolic disturbances and fat maldistribution are main features of the antiretroviral-related lipodystrophy syndrome (LDS). Different phenotypes of fat distribution abnormalities can be observed: fat loss, fat accumulation, or a mixed pattern. In patients with predominant loss of fat, the roles of leptin, lipids, and glucose homeostasis disturbances have not yet been clearly established. METHODS: The study comprised 34 HIV-infected male patients receiving antiretroviral treatment that included protease inhibitors. A lipoatrophic phenotype, defined as fat loss in face or extremities, both normal weight and waist:hip ratio, and absence of fat accumulation elsewhere, was present in all cases. Fat distribution disturbances were confirmed by abdominal and midthigh computed tomography-calculated adipose tissue content. Fasting plasma glucose, insulin, proinsulin, total leptin, testosterone, and lipid profiles were measured. After 2 hours, 75-g oral glucose tolerance test (OGTT), glucose, insulin, and proinsulin levels were also obtained. Insulin resistance was calculated using the homeostasis model assessment for insulin resistance (HOMA-r) method. Both healthy study subjects ( n = 385) and antiretroviral-naive HIV-positive patients ( n = 13) were used as controls. RESULTS: Of these LDS patients, 5.8% showed diagnostic criteria for diabetes and 17.8% for impaired glucose tolerance. A lipid pattern characterized by high total cholesterol and high low density lipoprotein (LDL) plasma levels, hypertriglyceridemia, and normal high density lipoprotein (HDL) levels was observed. Fasting insulin and 2-hour post OGTT insulin levels, and insulin resistance index were significantly higher in LDS patients than in antiretroviral-naive HIV-positive patients. Plasma leptin levels were significantly lower in lipoatrophic patients than in healthy control individuals. Patients with LDS presented with significant midthigh fat reduction and visceral fat accumulation compared with findings in antiretroviral-naive HIV-positive patients. A significant correlation was found between plasma leptin levels and midthigh fat content. CONCLUSION: Peripheral fat loss in extremities in LDS patients with lipoatrophic phenotype is also associated with low plasma leptin levels, visceral fat accumulation, and metabolic disturbances related to an increased cardiovascular risk. In LDS patients, plasma leptin levels could be a marker of subcutaneous adipose tissue content.
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Tejido Adiposo/metabolismo , Fármacos Anti-VIH/efectos adversos , Infecciones por VIH/tratamiento farmacológico , VIH-1 , Leptina/metabolismo , Lipodistrofia/inducido químicamente , Adulto , Anciano , Composición Corporal/efectos de los fármacos , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Ayuno , Infecciones por VIH/sangre , Humanos , Insulina/sangre , Leptina/sangre , Lipodistrofia/sangre , Masculino , Persona de Mediana Edad , Proinsulina/sangreRESUMEN
Fundamento y objetivo: En pacientes con infección por el VIH el tratamiento de la leucemia/linfoma de Burkitt con esquemas intensivos y específicos es cada vez más frecuente. Este estudio retrospectivo comparó los resultados del tratamiento con CHOP con el de dos protocolos de quimioterapia específica (PETHEMA-LAL3/97 and BURKIMAB) en España. Pacientes y método: Los pacientes del grupo A (n=31) recibieron 6 ciclos de CHOP estándar cada tres semanas. Los pacientes del grupo B (n=44) 6 ciclos de poliquimioterapia que incluía metotrexato y citarabina a altas dosis. Se comparó la respuesta al tratamiento, la supervivencia libre de enfermedad y la supervivencia global (SG) en ambos grupos. Resultados: Ambos grupos fueron comparables en las principales características clínicas al diagnóstico excepto en la actividad de riesgo, tratamiento previo con TARGA, afección de médula ósea, enfermedad voluminosa y afección extranodal. Se obtuvo la remisión completa (RC) en 10 de 31 (32%) pacientes en el grupo A y 28 de 44 (67%) pacientes en el grupo B (p=0,005). Tras una mediana (extremos) de seguimiento de 70 (26-139) y 17 (1-134) meses, la probabilidad de SG a los 5 años (IC 95%) fue del 87% (64%-100%) en el grupo A y 70% (51%-89%) en el grupo B (p=0,374), y la SG a los 5 años (IC 95%) fue del 27% (10%-43%) en el grupo A y 57% (40%-74%) en el grupo B (p=0,028). El análisis multivariable demostró que el empleo de tratamientos específicos se asoció a una mayor probabilidad de RC y SG. Conclusiones:En la leucemia/linfoma de Burkitt asociada a la infección por el VIH el tratamiento intensivo específico es factible, con unas mejores tasas de RC y SG que la obtenida con los regímenes tipo CHOP (AU)
Background and objective: AIDS-related Burkitts lymphoma or leukemia (BLL) is increasingly treated with specific and intensive multiagent schedules. This retrospective study aimed to compare the results of CHOP with those from two protocols (PETHEMA-LAL3/97 and BURKIMAB) of specific therapy in Spain.Patients and methods: Patients from Group A (n = 31) received 6 standard CHOP cycles every 3 weeks. Patients from group B (n = 44) received six multiagent cycles including high-dose methotrexate and high-dose cytarabine. The response to therapy, disease-free survival and overall survival (OS) werecompared in the two groups. Results: Both groups were comparable for the main clinical and biological parameters at diagnosis except for risk activity, previous HAART, bone marrow involvement, bulky disease and extranodal involved sites. Complete remission (CR) was achieved in 10 out of 31 (32%) patients in group A and 28 out of 44 (67%) patients in group B (P = .005). After a median (range) follow-up of 70 (26-139) and 17 (1-134)months, the 5-year (95% CI) DFS probability was 87% (64%-100%) for group A and 70% (51%-89%) for group B (P = .374), and the 5-year (95% CI) OS was 27% (10%-43%) for Group A and 57% (40%-74%) for group B (P = .028). Multivariate analyses showed that specific therapy was associated with an improved CR and OS. Conclusions: In AIDS-related BLL short intensive specific emotherapy is feasible, with higher remissionrate and improved survival than that obtained with CHOP-based regimens (AU)