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OBJECTIVES: To evaluate polypharmacy, anticholinergic burden (ACB) and drug-drug interactions (DDIs) in people with four-class-resistant HIV (4DR-PWH). METHODS: We performed a cross-sectional study, including 4DR-PWH from the PRESTIGIO Registry taking at least one non-antiretroviral drug. Polypharmacy was defined as taking five or more non-antiretroviral drugs. ACB was calculated using the ACB scale: 0â=âno AC effect, 1-2â=âlow/moderate risk, ≥3â=âhigh AC risk. Participants' characteristics by ACB score were compared using the Kruskal-Wallis test, and Spearman's correlation coefficient was used to assess linear relationships. DDIs were evaluated using the Liverpool database. RESULTS: Overall, 172 4DR-PLWH were evaluated: 75.6% males, median age 49.9â years (IQRâ=â45.6-56), 62 (27.1%) on polypharmacy, 124 (72.1%) using a boosting agent and 72 (41.8%) with four or more antiretrovirals. Based on ACB, 128 (74.45%), 33 (19.2%) and 11 (6.4%) had a no, low/moderate and high AC risk, respectively. The most common AC drugs were ß-blockers (12.2%), diuretics (8.7%) and antidepressants (8.7%). The high ACB was significantly related to the number of drugs/person (râ=â0.33, Pâ<â0.0001) and the number of clinical events (râ=â0.222, Pâ=â0.004). Overall, 258 DDIs were found between antiretrovirals and co-medications in 115 (66.8%) PWH, and 14 (8.1%) PWH received contraindicated drug combinations. CONCLUSIONS: In 4DR-PWH, polypharmacy, DDIs and the proportion of people with moderate/high AC burden were high. In 4DR-PWH undetectability achievement and maintenance is the priority and use of boosted PIs is common. A strict collaboration (infectious diseases specialists, virologists, pharmacologists) is needed to limit the risk of ACB and DDIs and to explore the advantages of new antiretrovirals.
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Síndrome de Inmunodeficiencia Adquirida/complicaciones , Anticuerpos Monoclonales Humanizados/uso terapéutico , Psoriasis/tratamiento farmacológico , Infecciones Oportunistas Relacionadas con el SIDA , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Terapia Antirretroviral Altamente Activa , Candidiasis/etiología , Esquema de Medicación , Esofagitis/microbiología , Femenino , Seropositividad para VIH/complicaciones , Humanos , Persona de Mediana Edad , Psoriasis/complicaciones , Inducción de Remisión , Índice de Severidad de la Enfermedad , Carga ViralRESUMEN
Few data are available on the safety and efficacy of sorafenib in HIV-infected patients with unresectable hepatocellular carcinoma (HIV-u-HCC) and concomitant highly active antiretroviral therapy (HAART). Between July 2007 and October 2010, 27 consecutive HIV-u-HCC patients were treated with sorafenib and concomitant HAART within the Gruppo Italiano Cooperativo AIDS e Tumori (GICAT). Three patients achieved a partial response, 12 achieved a stable disease, and 12 showed progression. The median time to progression and overall survival was 5.1 (range 0.5-13.3) and 12.8 (range 1.1-23.5) months, respectively. Grades 3-4 toxicities included diarrhea (four patients, 14.8%), hypertension (three patients, 11%), and hand-and-foot skin reaction (four patients, 14.9%). Most drug-related side effects were low grade and manageable. This retrospective study shows favorable survival data among HIV-u-HCC patients treated with sorafenib together with a reasonable safety profile.
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Antineoplásicos/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/virología , Infecciones por VIH/complicaciones , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/virología , Niacinamida/análogos & derivados , Compuestos de Fenilurea/uso terapéutico , Adulto , Anciano , Antineoplásicos/efectos adversos , Terapia Antirretroviral Altamente Activa/métodos , Progresión de la Enfermedad , Femenino , Infecciones por VIH/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Niacinamida/efectos adversos , Niacinamida/uso terapéutico , Compuestos de Fenilurea/efectos adversos , Estudios Retrospectivos , Sorafenib , Resultado del TratamientoRESUMEN
BACKGROUND: Human immunodeficiency virus (HIV)-infected patients may have a greater risk of noninfectious comorbidities (NICMs) compared with the general population. We assessed the prevalence and risk factors for NICMs in a large cohort of HIV-infected adults and compared these findings with data from matched control subjects. METHODS: We performed a case-control study involving antiretroviral therapy (ART)-experienced HIV-infected patients treated at Modena University, Italy, from 2002 through 2009. These patients were compared with age-, sex-, and race-matched adults (control subjects) from the general population included in the CINECA ARNO database. NICMs included cardiovascular disease, hypertension, diabetes mellitus, bone fractures, and renal failure. Polypathology (Pp) was defined as the concurrent presence of ≥2 NICMs. Logistic regression models were constructed to evaluate associated predictors of NICMs and Pp. RESULTS: There were 2854 patients and 8562 control subjects. The mean age was 46 years, and 37% were women. Individual NICM and Pp prevalences in each age stratum were higher among patients than among controls (all P <.001). Pp prevalence among patients aged 41-50 years was similar to that among controls aged 51-60 years (P value was not statistically significant); diabetes mellitus, cardiovascular disease, bone fractures, and renal failure were statistically independent after adjustment for sex, age, and hypertension. Logistic regression models showed that independent predictors of Pp in the overall cohort were (all P < .001) age (odds ratio [OR], 1.11), male sex (OR, 1.77), nadir CD4 cell count <200 cells/µL (OR, 4.46), and ART exposure (OR, 1.01). CONCLUSIONS: Specific age-related NICMs and Pp were more common among HIV-infected patients than in the general population. The prevalence of Pp in HIV-infected persons anticipated Pp prevalence observed in the general population among persons who were 10 years older, and HIV-specific cofactors (lower nadir CD4 cell count and more prolonged ART exposure) were identified as risk factors. These data support the need for earlier screening for NICMs in HIV-infected patients.
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Infecciones por VIH/complicaciones , Adulto , Factores de Edad , Fármacos Anti-VIH/administración & dosificación , Terapia Antirretroviral Altamente Activa , Enfermedades Cardiovasculares/epidemiología , Estudios de Casos y Controles , Comorbilidad , Diabetes Mellitus/epidemiología , Femenino , Fracturas Óseas/epidemiología , Infecciones por VIH/tratamiento farmacológico , Humanos , Hipertensión/epidemiología , Italia/epidemiología , Masculino , Persona de Mediana Edad , Prevalencia , Insuficiencia Renal/epidemiología , Factores de RiesgoRESUMEN
PURPOSE: Hepatocellular carcinoma (HCC) is an increasing cause of mortality in HIV-infected patients in the highly active antiretroviral therapy (HAART) era. The aims of this study were to describe HCC tumor characteristics and different therapeutic approaches, to evaluate patient survival time from HCC diagnosis, and to identify clinical prognostic predictors in patients with and without HIV infection. PATIENTS AND METHODS: A multicenter observational retrospective comparison of 104 HIV-infected patients and 484 uninfected patients was performed in four Italian centers. HCC was staged according to the Barcelona Clinic Liver Cancer (BCLC) criteria. RESULTS: Tumor characteristics of patients with and without HIV were significantly different for age, Eastern Cooperative Oncology Group performance status (PS) score ≤1, and etiology of chronic liver disease. Despite the similar potentially curative option rate and better BCLC stage at diagnosis, the median survival time was significantly shorter in HIV(+) patients. HIV(+) patients were less frequently retreated at relapse. Independent predictors of survival were: BCLC stage, potentially effective HCC therapy, tumor dimension ≤3 cm, HCC diagnosis under a screening program, HCC recurrence, and portal vein thrombosis. Restricting the analysis to HIV(+) patients only, all positive prognostic factors were confirmed together with HAART exposure. CONCLUSION: This study confirms a significantly shorter survival time in HIV(+) HCC patients. The less aggressive retreatment at recurrence approach does not balance the benefit of younger age and better BCLC stage and PS score of HIV(+) patients. Thus, considering the prognosis of HIV(+) HCC patients, effective screening techniques, programs, and specific management guidelines are urgently needed.
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Carcinoma Hepatocelular/virología , Infecciones por VIH/complicaciones , VIH , Neoplasias Hepáticas/virología , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/terapia , Femenino , Infecciones por VIH/patología , Humanos , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/terapia , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Currently, no data are available on the burden of morbidity and mortality in people with HIV-1 (PWH) harboring a 4-class drug-resistant (4DR) virus (nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors, integrase strand transfer inhibitors). The study aimed to assess the incidence of clinical events and death in this population. METHODS: This was a cohort study on PWH from the PRESTIGIO Registry with a documented 4DR virus. Burden of disease was defined as the occurrence of any new event including an AIDS-defining event (ADE) or non-AIDS-defining event (NADE) or death from any cause after 4DR evidence (baseline). Cox regression models evaluated factors associated with the risk of new clinical events/death. RESULTS: Among 148 PWH followed for a median (interquartile range) of 47 (32-84) months after 4DR evidence, 38 PWH had 62 new events or died from any cause (incidence rate, 9.12/100 person-years of follow-up; 95% CI = 6.85-11.39): 12 deaths (6 AIDS-related and 6 non-AIDS-related), 18 ADEs, 32 NADEs; 20 of the 38 NADEs (45%) of the incident clinical events were malignancies. The 4-year cumulative incidence of death was 6% (95% CI, 3%-13%), and that of ≥1 event or death was 22% (95% CI, 16%-31%). A higher risk of new clinical events/death was more likely in PWH with previous clinical events (adjusted hazard ratio [aHR], 2.67; 95% CI, 1.07-6.67) and marginally associated with lower baseline CD4+/CD8+ ratio (aHR, 0.82; 95% CI, 0.65-1.02). CONCLUSIONS: PWH harboring 4DR have a high burden of disease with a worrying incidence of malignancies, strongly advising for close prevention and monitoring interventions as well as access to innovative therapeutic strategies, especially in people with a history of clinical events and low CD4+/CD8+ ratio.
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Morphological changes induced by HIV-related lipodystrophy profoundly affect body image and influence health-related quality of life. Measurements of health-related quality of life in patients with lipodystrophy are complex due to a lack of consensus on the definition of lipodystrophy, a lack of appropriate methods to capture the impact of body fat changes, and the subjective perception of those changes by patients. This review describes the different tools that have been used to assess quality of life in patients with lipodystrophy, and critically analyzes published papers on health-related quality of life. With regard to facial lipoatrophy, the most stigmatizing condition of lipodystrophy, we have analyzed the impact of reconstructive plastic surgery on patient-related outcomes and health-related quality of life. A better knowledge of the associations between lipodystrophy and health-related quality of life will allow us to understand the burden of long-term toxicities of antiretroviral therapies as well as to identify novel patient-related endpoints useful in assessing the efficacy of lipodystrophy treating programs.
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Infecciones por VIH/complicaciones , Síndrome de Lipodistrofia Asociada a VIH/psicología , Calidad de Vida , Fármacos Anti-VIH/uso terapéutico , Distribución de la Grasa Corporal , Imagen Corporal , Infecciones por VIH/psicología , Síndrome de Lipodistrofia Asociada a VIH/etiología , Síndrome de Lipodistrofia Asociada a VIH/terapia , HumanosRESUMEN
BACKGROUND: HIV-related Burkitt's lymphoma with initial oropharyngeal presentation is rarely reported. The aim of this paper is to report the clinical findings of an unusual case of a patient with extranodal oropharyngeal Burkitt's lymphoma as presenting disease of an unknown HIV positivity and acquired immunodeficiency syndrome. METHODS: We reported the case of a hispanic patient with extranodal oropharyngeal Burkitt's lymphoma as presenting disease of an unknown HIV positivity and acquired immunodeficiency syndrome. We describe the diagnostic work-up and treatment of this rare case of extranodal oropharyngeal Burkitt's lymphoma. RESULTS: Histological exam on oropharyngeal incision biopsy documented a Burkitt's lymphoma. The patient underwent highly active antiretroviral therapy and chemotherapy. After two years of follow-up the patient shows no signs of recurrence from disease. CONCLUSIONS: HIV-related Burkitt's lymphoma presenting with primary oropharyngeal involvement is rare, with rapidly progressing dysphagia, and does not respond to antibiotherapy. Patients should undergo incision biopsy to rule out a malignancy. In young adults, diagnosis of Burkitt's lymphoma should suggest HIV infection. The importance of a prompt diagnosis in such cases is essential to correctly adequately staging the disease to start highly active antiretroviral therapy and chemotherapy as soon as possible.
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Linfoma de Burkitt/diagnóstico , Linfoma de Burkitt/virología , Infecciones por VIH/complicaciones , Infecciones por VIH/diagnóstico , Neoplasias Orofaríngeas/diagnóstico , Neoplasias Orofaríngeas/virología , Linfoma de Burkitt/terapia , Infecciones por VIH/terapia , Humanos , Masculino , Neoplasias Orofaríngeas/terapia , Adulto JovenRESUMEN
The case report is a description of a single case of hepatic myelolipoma, a very rare benign hepatic tumor, evaluated with contrast sonography, in a 72-year-old female. It was previously reported as hyperechoic lesions at sonography. CEUS features of the lesion were: homogeneous hyperenhancement in the arterial phase and a slight hyperenhancement in the portal venous phase typical of benign tumors. The case report shows CEUS may help in differential diagnosis between benign and malignant lesions, but only the biopsy of the tumor and the pathological evaluation allows the diagnosis.
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Neoplasias Hepáticas/diagnóstico por imagen , Mielolipoma/diagnóstico por imagen , Anciano , Medios de Contraste , Diagnóstico Diferencial , Femenino , Humanos , Biopsia Guiada por Imagen , Hallazgos Incidentales , Neoplasias Hepáticas/patología , Imagen por Resonancia Magnética , Mielolipoma/patología , Fosfolípidos , Hexafluoruro de Azufre , Tomografía Computarizada por Rayos X , UltrasonografíaRESUMEN
Coinfection of blood-borne hepatitis B and hepatitis C viruses (HBV and HCV, respectively) in human immunodeficiency virus type 1 (HIV-1)-positive individuals frequently occurs in inmate population and peculiar viral strains and patterns of virological markers may be observed.Plasma from 69 HIV-1-positive inmates was obtained from 7 clinical centers connected with correctional centers in different towns in Italy. HIV, HBV, and HCV markers were tested by commercial assays. Virus genotyping was carried out by sequencing the protease and reverse transcriptase-encoding region (PR-RT region) for HIV and a region encompassing the NS5B gene for HCV and subsequent phylogenetic analysis.Twelve over 14 HIV-subtyped inmates were infected with HIV-1 subtype B strains. The 2 non-B strains belonged to subtype G and CRF02_AG, in an Italian and a Gambian patient, respectively. Variants carrying the K103N and Y181C resistance mutations to non-nucleoside reverse transcriptase inhibitors (NNRTIs) were found in 2 out of 9 patients naive for combined antiretroviral therapy (cART) (22.2%). Most HIV-positive patients (92.8%) showed evidence of past or present HBV and/or HCV infection. Prevalence of HBV and HCV was 81.2% for both viruses, whereas prevalence of HBV/HCV coinfection was 69.6%. A significantly higher presence of HCV infection was found in Italians [odds ratio (OR) 11.0; interval 1.7-80.9] and in drug users (OR 27.8; interval 4.9-186.0). HCV subtypes were determined in 42 HCV or HBV/HCV-coinfected individuals. HCV subtypes 1a, 3a, 4d, and 1b were found in 42.9%, 40.5%, 14.3%, and 2.4% of inmates, respectively. Low titers of HBV DNA in HBV DNA positive subjects precluded HBV subtyping.The high prevalence of HBV and HCV coinfections in HIV-infected inmates, as well as the heterogeneity of HIV and HCV subtypes suggest the need to adopt systematic controls in prisons to monitor both the burden and the genetic forms of blood-borne viral infections, in order to apply targeted therapeutic interventions.
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Patógenos Transmitidos por la Sangre , Infecciones por VIH/sangre , VIH-1/genética , Hepacivirus/genética , Virus de la Hepatitis B/genética , Hepatitis B/sangre , Hepatitis C/sangre , Adulto , Anciano , Estudios Transversales , Femenino , Infecciones por VIH/diagnóstico , Infecciones por VIH/epidemiología , Infecciones por VIH/virología , Hepatitis B/diagnóstico , Hepatitis B/epidemiología , Hepatitis B/virología , Hepatitis C/diagnóstico , Hepatitis C/epidemiología , Hepatitis C/virología , Humanos , Italia , Masculino , Persona de Mediana Edad , PrevalenciaAsunto(s)
Neumonía Lipoidea/diagnóstico , Fumar/efectos adversos , Estreñimiento/inducido químicamente , Estreñimiento/terapia , Humanos , Masculino , Metadona/efectos adversos , Persona de Mediana Edad , Aceite Mineral/efectos adversos , Neumonía Lipoidea/diagnóstico por imagen , Neumonía Lipoidea/etiología , Tomografía Computarizada por Rayos XRESUMEN
PURPOSE: To prospectively evaluate the prevalence of the embolization of the spleen in patients with definite left-sided infective endocarditis (IE) using a contrast-enhanced ultrasound (CEUS). METHODS: From March 2012 through September 2013, 18 consecutive patients (9 females and 9 males, aged 21-83 years) evaluated at our hospital and with definite left-sided IE according to the revised Duke criteria were enrolled. All of the patients gave informed written consent and the study was performed in conformity with the ethical guidelines of the Declaration of Helsinki. All of the patients were submitted to a CEUS of the spleen within 10 days after the definite diagnosis of IE. For the CEUS, a blood pool second-generation contrast agent and an ultrasound machine with a contrast harmonic imaging technology were used. RESULTS: The splenic CEUS showed infarctions in 11 patients (61 %) and resulted positive in the 2 patients with negative echocardiography. CONCLUSIONS: In this study, CEUS of the spleen, a repeatable and low-cost imaging technique, easily allowed the bedside detection of asymptomatic and even tiny infarctions and showed a high rate of embolization in patients with definite left-sided IE. Therefore, in the setting of IE (possible or definite), CEUS of the spleen has the potential to better define or accelerate the diagnosis itself.
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Changes in body fat distribution and bone mass in HIV-infected patients may be associated with long-term use of nucleoside reverse transcriptase inhibitors (NRTIs). The Monarch trial recruited 30 patients receiving non-nucleoside reverse transcriptase inhibitor or protease inhibitor-based highly active antiretroviral therapy, with HIV RNA <40 copies/mL. Patients were randomized to either darunavir/ritonavir 800/100 mg once daily monotherapy or darunavir/ritonavir 800/100 mg once daily + two NRTIs. Bone mass, peripheral lipoatrophy and central fat accumulation were assessed using dual-energy X-ray absorptiometry scanning, supplemented by computed tomography scans. Median age was 43 years, 77% were men. Visceral adipose tissue remained stable from baseline to Week 48 in the whole group (p = 0.261) with no significant difference between arms (p = 0.56). There was a significant reduction in insulin resistance (HOMA-IR, p = 0.013) over 48 weeks in the whole group, but not of body mass index (p = 0.24). In the darunavir/ritonavir monotherapy arm, there was a small but significant increase in both lumbar and femur bone mineral density at 48 weeks and was observed after correction for baseline values. The absolute change in lumbar bone mineral density at 48 weeks was more pronounced in the darunavir/ritonavir arm compared with the darunavir/ritonavir + 2NRTIs arm. In this study, discontinuing nucleoside analogues and switching to darunavir/ritonavir monotherapy was associated with a small but statistically significant increase in bone mineral density, but stable levels of limb fat and visceral adipose tissue.
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Distribución de la Grasa Corporal , Densidad Ósea/efectos de los fármacos , Infecciones por VIH/tratamiento farmacológico , Inhibidores de la Proteasa del VIH/administración & dosificación , Síndrome de Lipodistrofia Asociada a VIH/inducido químicamente , Ritonavir/administración & dosificación , Sulfonamidas/administración & dosificación , Adulto , Terapia Antirretroviral Altamente Activa , Darunavir , Femenino , Infecciones por VIH/fisiopatología , Inhibidores de la Proteasa del VIH/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Inhibidores de la Transcriptasa Inversa/administración & dosificación , Ritonavir/efectos adversos , Sulfonamidas/efectos adversos , Resultado del TratamientoRESUMEN
INTRODUCTION: National cohort and intercohort studies have been set to describe the differences of life expectancy (LE) of HIV-infected individuals. OBJECTIVE: The aim of this study was to assess the impact of immune recovery (IR) on LE of patients with HIV undergoing combination antiretroviral therapy. METHODS: In this retrospective observational study, outcome measure was LE of patients with HIV compared with LE of northern Italian population. Group categorizations were as follows: patients with no immune recovery (nIR), patients with IR, patients who are immune maintained, and pre-highly active antiretroviral therapy (HAART) and post-HAART. Abridged life tables were constructed from age-specific mortality rates (per 1000 person years) to estimate LE from the age of 20-55 years. RESULTS: A total of 9671 patients, 71% men, were included. After 2005, we assisted to a rapid increase in the overall rate of patients attaining IR in the community coupled with a progressive decrease of AIDS death, but not of non-AIDS deaths. In a 40-year-old patient, LE was 38.10 years [standard error (SE) = 2.60], 30.08 years (SE = 0.98), and 22.9 (SE = 0.69) in the IR, post-HAART group and nIR, respectively, compared with 41.38 years of the general Italian population. An approximately 5-year gap in LE was observed in IR patients. DISCUSSION: We describe IR at a "community" level, related to calendar year and apparent 10 years after HAART introduction. HAART community IR is significantly influencing LE and is associated with the changing clinical picture of HIV disease. An increasing gradient of LE exists between nIR, post-HAART, and IR groups, with the latter, above the age of 40 years only, reaching LE of general population.
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Antirretrovirales/uso terapéutico , Epidemias , Infecciones por VIH/inmunología , Infecciones por VIH/mortalidad , Esperanza de Vida , Adulto , Femenino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Humanos , Italia/epidemiología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto JovenRESUMEN
The most striking effect of increased survival and improved quality of life in HIV-infected women undergoing antiretroviral therapy is the feasibility of motherhood-desire satisfaction. However, such advantages are often associated with drug-related metabolic toxicities, particularly relevant in the pregnancy context. Recent guidelines provide recommendations and trends for the use of antiretroviral therapy in pregnant women, but current literature falls short of providing specific insights on the need for metabolic monitoring and treatment in HIV-infected pregnant women. In this review we provide specific insight into the state-of-the-art of: detection, evaluation, and management of metabolic alterations in this special population. Pregnancy is in fact a metabolic transition process, potentially associated with specific diseases in the mother, in the newborn, and in the adulthood of the child. We will not simply discuss antiretroviral therapy metabolic toxicities, but rather their interaction with the physiological metabolic changes occurring during pregnancy. Close monitoring is needed to diagnose metabolic alterations that can lead to adverse outcomes in the mother, in the newborn, and potentially in adulthood. Lifestyle interventions and an appropriate metabolic tailoring of antiretroviral therapy drugs need to be considered in the prevention and treatment of metabolic alteration during pregnancy.
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Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/metabolismo , Femenino , Humanos , Recién Nacido , EmbarazoRESUMEN
OBJECTIVES: To determine whether for a given waist circumference (WC), a larger hip circumference (HC) was associated with a reduced risk of insulin resistance, type 2 diabetes (T2D), hypertension and cardiovascular disease (CVD) in HIV-infected patients. A second objective was to determine whether, for a given WC, the addition of HC improved upon estimates of abdominal adiposity, in particular visceral adipose tissue (VAT), compared to those obtained by WC alone. METHODS: HIV-infected men (Nâ=â1481) and women (Nâ=â841) were recruited between 2005 and 2009. WC and HC were obtained using standard techniques and abdominal adiposity was measured using computed tomography. RESULTS: After control for WC and covariates, HC was negatively associated with risk of insulin resistance (p<0.05) and T2D [Men: ORâ=â0.91 (95% CI: 0.86-0.96); Women: ORâ=â0.91 (95% CI: 0.84-0.98)]. For a given WC, HC was also negatively associated with a lower risk of hypertension (p<0.05) and CVD [ORâ=â0.94 (95% CI: 0.88-0.99)] in men, but not women. Although HC was negatively associated with VAT in men and women after control for WC (p<0.05), the addition of HC did not substantially improve upon the prediction of VAT compared to WC alone. CONCLUSIONS: The identification of HIV-infected individuals at increased health risk by WC alone is substantially improved by the addition of HC. Estimates of visceral adipose tissue by WC are not substantially improved by the addition of HC and thus variation in visceral adiposity may not be the conduit by which HC identifies increased health risk.
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Infecciones por VIH/patología , Obesidad Abdominal/diagnóstico , Circunferencia de la Cintura , Adulto , Índice de Masa Corporal , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiología , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/epidemiología , Cadera/patología , Humanos , Hipertensión/complicaciones , Hipertensión/diagnóstico , Hipertensión/epidemiología , Resistencia a la Insulina , Grasa Intraabdominal/patología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Obesidad Abdominal/complicaciones , Obesidad Abdominal/epidemiología , Factores de RiesgoRESUMEN
OBJECTIVE: HIV-infected patients receiving antiretroviral treatment frequently accumulate fat at the abdominal level. It is unknown whether T-cell activation and immune phenotypes are associated with fat accumulation. Thus, the aim of the study was to search for an association between the presence of clinical lipodystrophy (LD), visceral and subcutaneous abdominal adipose tissue amount (VAT and SAT), and peripheral T-cell immune phenotypes. DESIGN: Cross-sectional study including 87 HIV-infected antiretroviral therapy-treated virologically suppressed and immune-reconstituted patients. METHODS: The patients were evaluated for clinical LD, VAT, SAT, homeostasis model of insulin resistance, and coronary artery calcium score (>10). T-cell activation (CD8/CD38), differentiation (CD4/CD8/CCR7/CD45RA), and expression/activation of the interleukin-7 (IL-7)/IL-7R system (CD4/CD8/CD127, IL-7, and CD4/CD8/pStat-5) were assessed by cytometry. RESULTS: In multivariable analyses, CD8 T-cell activation (CD38) was associated with lipoatrophy and central fat accumulation (respectively, ß = 5.63, P = 0.005, and ß = 4.19, P = 0.020). This was also the case for IL-7R expressing CD8⺠T cells (CD127âº) for lipoatrophy ß = 12.8, P = 0.003, and for central fat accumulation ß = 9.45, P = 0.016. CD8⺠T-cell activation was also associated with VAT/total adipose tissue (ß = 0.01, P = 0.002) and SAT/VAT ratios (ß = -0.014, P = 0.015). As expected, VAT/total adipose tissue was an independent risk factor for homeostasis model of insulin resistance (r = 0.364, P = 0.028) and cardiovascular risk (coronary artery calcium, r = 0.406, P = 0.002). CONCLUSIONS: CD8⺠T-cell activation was associated with LD and the relative amount of VAT in antiretroviral therapy-controlled, virologically suppressed, HIV-infected patients. We propose that CD8 activation may be involved in the accumulation of central fat frequently observed in these patients, with resulting increased cardiometabolic risk.
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Fármacos Anti-VIH/uso terapéutico , Linfocitos T CD8-positivos/fisiología , Infecciones por VIH/tratamiento farmacológico , Síndrome de Lipodistrofia Asociada a VIH/metabolismo , Activación de Linfocitos/fisiología , Tejido Adiposo , Adulto , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fosforilación , Factor de Transcripción STAT5/genética , Factor de Transcripción STAT5/metabolismo , Carga Viral , ViremiaRESUMEN
BACKGROUND: Morphological abnormalities (lipoatrophy and central fat accumulation) and metabolic changes (dyslipidaemia and glucose regulation impairment) have emerged as components of lipodystrophy and as major tolerability issues with long-term use of highly active antiretroviral therapy (HAART) in HIV-positive patients. Protease inhibitors (PIs) are recognized as having the greatest impact in terms of metabolic complications, followed by nucleoside reverse transcriptase inhibitors, while the non-nucleoside reverse transcriptase inhibitors (NNRTIs) have the least impact. In particular, regimens based on the NNRTI nevirapine have been shown to achieve significant metabolic benefits and may help to improve dyslipidaemia. Improvements in body shape changes associated with lipodystrophy have also been reported when nevirapine replaced a PI in long-term triple therapy. OBJECTIVE: The objective of this cross-sectional observational ('real-world') study was to investigate the effect of three HAART regimens plus stable nevirapine therapy on morphological and metabolic components of lipodystrophy in HIV-infected patients. METHODS: Consecutive patients (aged >18 years) with serologically documented HIV infection, who had received HAART for at least 2 years and who had been diagnosed with lipodystrophy, were followed up as outpatients at the metabolic clinic of the University of Modena and Reggio Emilia, Modena, Italy. Patients received stable nevirapine therapy plus fixed-dose combinations of tenofovir disoproxil fumarate plus emtricitabine (Truvada(®); TVD), zidovudine plus lamivudine (3TC) [Combivir(®); CBV], or abacavir plus lamivudine (Kivexa(®); KVX). Multivariate regression analyses were performed to analyse predictors of four components of lipodystrophy: lipoatrophy using leg fat mass measured by dual-emission x-ray absorptiometry (DXA), fat accumulation using waist circumference, dyslipidaemia using apolipoprotein (Apo)B/ApoA1 ratio, and glucose intolerance using the Homeostasis Model Assessment for Insulin Resistance (HOMA-IR). RESULTS: Overall, 101 patients were enrolled (TVD group = 61, CBV group = 20, KVX group = 20); 191 observations were analysed. Male sex was associated with reduced leg fat mass, while age and body mass index (BMI) were associated with increased leg fat mass (all p < 0.05). Leg fat mass and male sex were associated with increased waist circumference (p < 0.001 for both). Leg fat mass predicted reduced ApoB/ApoA1 ratio, while age and BMI predicted increased ApoB/ApoA1 ratio (all p < 0.05). BMI predicted HOMA-IR increase (p = 0.0017). No differences in lipoatrophy, central fat accumulation, dyslipidaemia or glucose metabolism were observed among any of the three different nevirapine plus nucleoside backbone groups (TVD, CBV or KVX). CONCLUSION: HAART including nevirapine has a limited impact on components of lipodystrophy in patients with HIV infection. Further studies are needed to verify if nevirapine overcomes the expected distinct lipodystrophy risk profile associated with different nucleoside backbone therapies.
Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Lipodistrofia/tratamiento farmacológico , Nevirapina/uso terapéutico , Adulto , Anciano , Fármacos Anti-VIH/efectos adversos , Fármacos Anti-VIH/farmacología , Terapia Antirretroviral Altamente Activa/efectos adversos , Composición Corporal/efectos de los fármacos , Distribución de la Grasa Corporal , Estudios Transversales , Combinación de Medicamentos , Dislipidemias/complicaciones , Dislipidemias/tratamiento farmacológico , Dislipidemias/metabolismo , Dislipidemias/patología , Femenino , Infecciones por VIH/epidemiología , Infecciones por VIH/metabolismo , VIH-1/efectos de los fármacos , Humanos , Resistencia a la Insulina/fisiología , Italia , Lipodistrofia/epidemiología , Lipodistrofia/metabolismo , Lipodistrofia/patología , Masculino , Persona de Mediana Edad , Nevirapina/efectos adversos , Nevirapina/farmacología , Pacientes Ambulatorios , Inhibidores de Proteasas/efectos adversos , Inhibidores de Proteasas/farmacología , Inhibidores de Proteasas/uso terapéutico , Inhibidores de la Transcriptasa Inversa/efectos adversos , Inhibidores de la Transcriptasa Inversa/farmacología , Inhibidores de la Transcriptasa Inversa/uso terapéutico , UniversidadesRESUMEN
BACKGROUND: Although FOLFOX4 is considered the standard chemotherapy regimen for colorectal cancer (CRC), few data are available on its results in human immunodeficiency (HIV)-related CRC. The results were analyzed to evaluate feasibility and activity of FOLFOX4 plus highly active antiretroviral therapy (HAART) in metastatic CRC (mCRC) HIV-seropositive patients. PATIENTS AND METHODS: From January 2002 to March 2007, 24 patients were selected among the CRC HIV-seropositive patients treated with FOLFOX4 and concomitant HAART within the Italian Cooperative Group on AIDS and Tumors (GICAT). RESULTS: Four median cycles of chemotherapy were administered; the most common severe toxicity was neutropenia (37.5%). An overall response rate of 50% was observed; 4.2% of patients achieved complete response and 45.8% partial response. No opportunistic infections occurred during or immediately after chemotherapy. The median CD4+ count was 380 (range 220-570) at diagnosis. CONCLUSIONS: To our knowledge, this is the largest study describing activity and tolerability of FOLFOX4 and HAART, in this setting. FOLFOX4 plus concomitant HAART resulted feasible and active also in HIV-seropositive patients. Moreover, the concomitant use of HAART did not to seem to increase the FOLFOX4 toxicity. This study suggests the good tolerability of the FOLFOX4, making it a reasonable option for combination with HAART.