RESUMO
BACKGROUND: Advanced kidney disease is an emerging problem in people living with HIV despite sustained viral suppression. METHODS: We performed a prospective cohort study to identify people living with HIV with advanced kidney disease according to the Kidney Disease Improving Global Outcomes criteria and to assess disease progression over a 48-week period following the offer of targeted multidisciplinary management. RESULTS: From our cohort of 3090 individuals, 55 (1.8%, 95% confidence interval [CI] 1.31-2.25) fulfilled the inclusion criteria. Most were male (83.6%), and the median (interquartile range [IQR]) age was 58 (53.25-66.75) years. Nadir CD4 T-cell count was 135.5 (IQR 43.5-262.75) cells/µl, current CD4 T-cell count was 574 (IQR 438.5-816) cells/µl, and 96% had maintained HIV viral suppression. The most frequent comorbidity was arterial hypertension (85.5%). Inadequate antiretroviral dose was detected in three individuals (5.5%), and drug-drug interactions were recorded in eight (14.5%), mainly involving the use of cobicistat (n = 5 [9%]). Four individuals (7%) required modification of their concomitant treatment. Seven (13%) had to start or resume follow-up with a nephrologist. Nine participants (16.4%) experienced an improvement in kidney disease stage, three individuals (5.5%) underwent renal transplantation, and one (2%) started haemodialysis. CONCLUSIONS: Our results show that a multidisciplinary approach, including a critical review of treatment and evaluation of specific requirements, could be useful for anticipating drug-drug interactions and toxicities and for reducing death and hospitalization in people living with HIV with advanced kidney disease.
Assuntos
Infecções por HIV , Insuficiência Renal Crônica , Idoso , Contagem de Linfócito CD4 , Cobicistat/uso terapêutico , Estudos de Coortes , Feminino , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/terapia , Carga ViralRESUMO
Optimal management of cardiovascular disease should start with the identification of subjects at subclinical stages. However, available tools are not always accurate or affordable. We assess the usefulness of ultrasound-guided measurement of abdominal fat layers as a surrogate marker of cardiovascular risk. We performed a cross-sectional, case-control, exploratory, pilot study in 10 people living with HIV (PLWH) and 10 HIV-uninfected subjects (control group) matched for age, sex, and body mass index. All participants were men 45-60 years of age, with no active disease or previous abdominal surgery; the PLWH group had been virologically suppressed for ≥2 years under stable antiretroviral therapy. The thickness of abdominal superficial and deep subcutaneous fat, preperitoneal fat, omental (periaortic) fat, and retroperitoneal (perirenal) fat was compared between both groups. Correlations between fat layers and traditional markers of cardiovascular risk were assessed. The thickness of most layers was always higher among PLWH. The differences were statistically significant for the preperitoneal fat layer (p = .04). The presence of atherosclerotic plaque was correlated with the preperitoneal fat layer in the PLWH group (odds ratio = 1.49, p = .02), and metabolic syndrome was correlated with superficial subcutaneous fat, although this was low (odds ratio = 0.54, p = .02). In the control group, several associations were found between carotid intima media thickness and abdominal fat layers. All abdominal fat layers were thicker in the PLWH group, especially preperitoneal fat, and several associations were found between specific fat layers and traditional cardiovascular risk markers. Our results suggest that the thickness of abdominal fat layers, assessed by ultrasound, could be a marker of cardiovascular risk. However, further studies with larger populations are required to confirm these findings.
Assuntos
Doenças Cardiovasculares , Infecções por HIV , Biomarcadores , Doenças Cardiovasculares/diagnóstico por imagem , Espessura Intima-Media Carotídea , Pré-Escolar , Estudos Transversais , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Fatores de Risco de Doenças Cardíacas , Humanos , Masculino , Projetos Piloto , Fatores de RiscoRESUMO
In an ongoing Mediterranean cohort, we compared age-related conditions between 208 HIV-infected persons and 104 matched controls. ≥3 comorbidities were found in 31.0% of HIV-infected patients and 8.7% of controls. Conditions significantly more frequent among the HIV-infected population were: lipid abnormalities, cancer, osteopenia/osteoporosis, liver disease, sexual dysfunction, hearing deficit, sleep disorders, falls, cognitive complaints, being single, living alone, and being elderly at risk. HIV-infected patients aged >70 years had a significantly higher number of cardiovascular risk factors (CVRF) and comorbidities than controls. HIV-infected persons who had never smoked had a higher prevalence of CVRFs, ≥3 comorbidities, liver disease, cancer, and cognitive complaints compared to controls. Factors associated with frailty were being a man who has sex with men, ≥3 CVRFs, nadir CD470 years. The multidisciplinary assessment also revealed concerning findings in social, cognitive, and functional variables among HIV-infected individuals, with a higher prevalence of elderly at risk than among controls.
Assuntos
Infecções por HIV , Idoso , Envelhecimento , Estudos de Coortes , Comorbidade , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Humanos , Masculino , Prevalência , Fatores de RiscoRESUMO
AIMS: To determine the prevalence of potential prescribing issues (PPI) in HIV-infected subjects aged ≥65 years according to the Beers and STOPP/START criteria and antiretroviral drug-drug interactions (Liverpool website). Secondary objectives were to assess the concordance between Beers and STOPP/START criteria in our population, and to identify the drugs most frequently involved in PPI. METHODS: Cross-sectional cohort study based on a systematic review of the electronic drug prescriptions confirmed by an interview of 91 HIV-infected patients aged ≥65 years. Discrepancies between prescription criteria were assessed using crosstabs and compared using the χ2 test or Fisher exact test. RESULTS: The mean age was 72.1 (5.6) years, 75.8% had ≥3 comorbidities and 59.3% polypharmacy. PPI were identified in 87.9%: 71.4% by STOPP/START and 45.1% by Beers. Comparing both criteria, 56.9% of PPI by STOPP/START were detected by Beers, while 92.5% of those detected by the Beers criteria were detected by STOPP/START (P < .001). Amber/red flag interactions between antiretrovirals and comedications were found in 45.1%: 3 severe (red) in 2 patients (2.2%). The most frequent drugs involved in PPI were benzodiazepines (>30%). Cobicistat was the drug most frequently involved in potential interactions (42.2%). CONCLUSION: The prevalence of PPI among older HIV-infected persons gives cause for concern, as it is almost 90%. Optimization strategies, including a critical review of the treatment plan, should be implemented in clinical routine by a multidisciplinary team, in particular in patients with multiple comorbidities and polypharmacy. The STOPP/START criteria seem to detect more PPI, mainly for European populations.
Assuntos
Infecções por HIV , Prescrição Inadequada , Idoso , Estudos Transversais , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Lista de Medicamentos Potencialmente Inapropriados , PrevalênciaRESUMO
Background: HIV infection is an increasingly complex chronic disease associated with numerous medical, psychological, and social problems. The life expectancy of affected patients has increased considerably. Medical apps could also play a role in prevention and management of comorbid conditions in the HIV-infected population. Objectives: To determine the usefulness of an app designed specifically for HIV-infected patients aged 60 years or older and to assess changes in patient satisfaction, adherence to treatment, and quality of health care. Methods: A randomized clinical trial was conducted, including 100 patients (50 per group): (1) an experimental group comprising patients using the app + routine medical care (app group) and (2) with routine medical care (control group). The usability of the app and patient satisfaction were evaluated in the app group at week 48. Quality of life, adherence to treatment, and clinical parameters were compared between both groups at 48 weeks, as well as the number of face-to-face visits. Results: We found that 52.2% and 73.8% of patients in the app group used the app at weeks 24 and 48, respectively. Patients used the app for a mean of 23.7 (±2.84) days over the 48 weeks. The most visited screens were health counseling and medical records (24.8% and 22.2%, respectively). At week 48, 85.2% of patients thought that the app was useful and 91.4% would recommend the app to friends or relatives. The app was well valued by participants (4.79 [±0.21] of 5.00) and 64.6% thought that the app improved their health care.
Assuntos
Infecções por HIV , Aplicativos Móveis , Telemedicina , Infecções por HIV/terapia , Humanos , Pessoa de Meia-Idade , Satisfação do Paciente , Qualidade de VidaRESUMO
OBJECTIVE: Optimization of antiretroviral therapy and anti-inflammatory treatments, such as statins, are among the strategies aimed at reducing metabolic disorders, inflammation and immune activation in people living with HIV (PLWH). We evaluated the potential benefit of combining both strategies. DESIGN: Forty-two PLWH aged ≥40 years receiving a protease inhibitor (PI)-based regimen were randomized (1:1) to switch from PI to Raltegravir (n = 20), or to remain on PI (n = 22). After 24 weeks, all patients received atorvastatin 20mg/day for 48 weeks. METHODS: We analyzed plasma inflammatory as well as T-cell maturation, activation, exhaustion and senescence markers at baseline, 24 and 72 weeks. RESULTS: Plasma inflammatory markers remained unchanged. Furthermore, no major changes on T-cell maturation subsets, immunoactivation, exhaustion or immunosenescence markers in both CD4 and CD8 T cell compartments were observed. Only a modest decrease in the frequency of CD38+ CD8 T cells and an increase in the frequency of CD28-CD57+ in both CD4 and CD8 T-cell compartments were noticed in the Raltegravir-switched group. CONCLUSIONS: The study combined antiretroviral switch to Raltegravir and Statin-based anti-inflammatory strategies to reduce inflammation and chronic immune activation in PLWH. Although this combination was safe and well tolerated, it had minimal impact on inflammatory and immunological markers. CLINICAL TRIALS REGISTRATION: NCT02577042.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Anticolesterolemiantes/uso terapêutico , Atorvastatina/uso terapêutico , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/uso terapêutico , Raltegravir Potássico/uso terapêutico , Adulto , Fármacos Anti-HIV/administração & dosagem , Anticolesterolemiantes/administração & dosagem , Atorvastatina/administração & dosagem , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/imunologia , Feminino , Infecções por HIV/sangue , Infecções por HIV/imunologia , Inibidores da Protease de HIV/administração & dosagem , Humanos , Imunossenescência/efeitos dos fármacos , Inflamação/sangue , Inflamação/tratamento farmacológico , Inflamação/imunologia , Ativação Linfocitária/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Raltegravir Potássico/administração & dosagemRESUMO
BACKGROUND: Sarcopenia is a geriatric syndrome that leads to a loss of functionality and mortality. METHODS: We assessed the prevalence of sarcopenia in HIV-infected patients attended in our HIV Unit who had at least two DXA scans from 2000 to 2016 (1,720 DXA scans from 860 individuals). Sarcopenia was determinate according to appendicular skeletal muscle mass index (ASM) calculated as the ratio between skeletal muscle mass index (SMI) by DXA and height2 (kg/m2). We stratified patients by gender and age (<40, 41-50, and >50 years) and according to the interval between DXAs (≤3, 3-7, 7-10, >10 years). The statistical analysis was performed using SPSS version 19. RESULTS: Median (IQR) age was 52 (47; 57) years, and 76% were male. The median (IQR) time with HIV infection was 8 (3; 15) years. The prevalence of sarcopenia was 25.7% (95% CI, 22.8-28.7), more prevalent in those aged >50 years (27.8%). Stratifying by gender, 43% of women aged >50 years presented sarcopenia compared with 8.8% of men. The frequency of sarcopenia increased from 37.6% to 49.4% when interval between DXA was 7-10 years (n=109), significantly higher in women than in men (p=0.016). In addition to the traditional risk factors, time with HIV infection was associated with sarcopenia [RR 1.780 (95% CI, 1.314-2.411), p=0.001]. CONCLUSION: The prevalence and progression of sarcopenia in HIV-infected patients were high, mainly among women. Further studies are necessary to assess the best approaches to prevent this condition and its consequences.
Assuntos
Infecções por HIV/complicações , Sarcopenia/complicações , Absorciometria de Fóton , Adulto , Idoso , Índice de Massa Corporal , Feminino , Força da Mão , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético , Prevalência , Sarcopenia/epidemiologiaRESUMO
Background: Osteoporotic fractures still remain very infrequent and physicians rarely evaluate bone health. We wanted to assess the magnitude of this problem in the near future by determining the risk and likelihood of progression to osteoporosis. Methods: We estimated the risk of progression to osteopenia/osteoporosis among HIV-infected patients with at least 2 DXA scans (3726 scans from 875 patients). Time-non-homogeneous bidirectional multistate models based on three states (normal bone mineral density, osteopenia and osteoporosis) were used to model the progression of bone mineral density as a function of age and to study the association between the risk of bone loss and antiretroviral use. Results: The HRs associated with age (>45 versus ≤45 years) were: (i) from normal bone mineral density to osteopenia, 0.71 (95% CI 0.45-1.11) for men and 1.06 (95% CI 0.55-2.05) for women; and (ii) from osteopenia to osteoporosis, 0.83 (95% CI 0.51-1.35) for men and 0.99 (95% CI 0.38-2.56) for women. The transition probabilities from osteopenia to osteoporosis over 10 years among men aged 30 and 50 years were 14.9% (95% CI 10.5%-20.4%) and 19% (95% CI 14.3%-24.3%), respectively; and for women, 6.9% (95% CI 3.1%-14.4%) and 30.1% (95% CI 19.8%-41.8%), respectively. An increased osteoporosis risk was observed for PIs and PIs + tenofovir disoproxil fumarate; darunavir was associated with a higher risk of osteoporosis among men (HR 3.9; 95% CI 2-7.5) and women (HR 4.5; 95% CI 1.4-14.7); and atazanavir was associated with a higher risk of osteoporosis among women (HR 4.2; 95% CI 1.3-14). Conclusions: Our results highlight the importance of monitoring bone mineral density given the high probability of progression to osteopenia/osteoporosis, especially in women. In the future, changes in antiretrovirals other than tenofovir, such as PIs, should be recommended to reduce the risk of fracture.
Assuntos
Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/efeitos adversos , Osteoporose/induzido quimicamente , Osteoporose/epidemiologia , Absorciometria de Fóton , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Densidade Óssea/efeitos dos fármacos , Feminino , Inibidores da Protease de HIV/administração & dosagem , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Fatores SexuaisRESUMO
Prevalence of kidney disease (KD) is increasing among human immunodeficiency virus (HIV)-infected population. Different factors have been related, varying on different published series.The objectives were to study prevalence of KD in those patients, its evolution, and associated risk factors.An observational cohort study of 1596 HIV-positive patients with cross-sectional data collection in 2008 and 2010 was conducted. We obtained clinical and laboratory markers, and registered previous or current treatment with tenofovir (TDF) and indinavir (IDV). The sample was divided according to estimated glomerular filtration rate (eGFR) by modification of diet in renal disease (MDRD) equation. Group 1: eGFR ≤60âmL/min/1.73âm; group 2: eGFR >60âmL/min/1.73âm.Among the patients, 76.4% were men, mean age (SD) 45â±â9 years, time since diagnose of HIV 14â±â7 years, and 47.2% of the patients received previous treatment with TDF and 39.1% with IDV. In 2008, eGFR ≤60: 4.9% (91.4% of them in chronic kidney disease [CKD] stage 3, eGFR 59-30âmL/min); this group was older, presented higher fibrinogen levels, and more patients were treated previously with TDF and IDV. In 2010, eGFR ≤60: 3.9% (87.1% stage 3 CKD). The 2.4% of cohort showed renal improvement and 1.3% decline of renal function over time. The absence of hypertension and treatment with TDF were associated with improvement in eGFR. Increased age, elevated fibrinogen, decreased albumin, diabetes mellitus, hyperTG, and worse virological control were risk factors for renal impairment.The HIV-positive patients in our area have a CKD prevalence of 4% to 5% (90% stage 3 CKD) associated with ageing, inflammation, worse immune control of HIV, TDF treatment, and metabolic syndrome.
Assuntos
Infecções por HIV/epidemiologia , Nefropatias/epidemiologia , Animais , Fármacos Anti-HIV/uso terapêutico , Estudos de Coortes , Estudos Transversais , Feminino , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/metabolismo , Humanos , Nefropatias/complicações , Nefropatias/metabolismo , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prevalência , Fatores de Risco , Espanha/epidemiologiaRESUMO
Background: Switching from PIs to dolutegravir in virologically suppressed HIV-infected individuals has not been assessed. Objectives: The principal aim was to assess the evolution of bone mineral density (BMD) when switching from a ritonavir-boosted PI to dolutegravir in HIV-infected patients with osteopenia or osteoporosis. The secondary objective was to assess the antiviral efficacy and safety of the switch therapy. Methods: This randomized, multicentre study assessed changes in BMD, bone turnover markers, and antiviral efficacy and safety in 73 virologically suppressed patients with osteopenia/osteoporosis taking a ritonavir-boosted PI plus abacavir/lamivudine who were randomized to switch from PI to dolutegravir (DOLU group, n = 37) or continue with a PI (PI group, n = 36). Clinical Trials: NCT02577042. Results: One and three patients from the DOLU and PI groups, respectively, withdrew prematurely (unrelated to treatment). At 48 weeks, 97.3% versus 91.7%, respectively, maintained viral suppression (snapshot analysis, ITT, M = F). No significant differences were seen between the groups in percentage change from baseline to week 48 in femoral ( P = 0.56) and lumbar spine ( P = 0.29) BMD, although lumbar spine BMD improved by 1.43% (-1.36; 2.92) in the DOLU group [0.12% (-2.83; 2.89) in the PI group]. Bone marker values did not vary significantly. At week 48, triglycerides were lower ( P < 0.001) and HDL cholesterol higher ( P = 0.027) in the DOLU group. Conclusions: Dolutegravir + Kivexa ® was safe and well-tolerated in virologically suppressed patients receiving a PI-based regimen. The lipid profile was better, albeit without significant changes in BMD, probably because of the short follow-up.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Didesoxinucleosídeos/uso terapêutico , Infecções por HIV/tratamento farmacológico , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Lamivudina/uso terapêutico , Ritonavir/uso terapêutico , Adulto , Fármacos Anti-HIV/administração & dosagem , Densidade Óssea/efeitos dos fármacos , Didesoxinucleosídeos/administração & dosagem , Didesoxinucleosídeos/efeitos adversos , Combinação de Medicamentos , Feminino , Infecções por HIV/complicações , Infecções por HIV/virologia , Inibidores da Protease de HIV/administração & dosagem , Inibidores da Protease de HIV/efeitos adversos , Inibidores da Protease de HIV/uso terapêutico , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Humanos , Lamivudina/administração & dosagem , Lamivudina/efeitos adversos , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Oxazinas , Piperazinas , Piridonas , Ritonavir/administração & dosagem , Ritonavir/efeitos adversos , Carga Viral/efeitos dos fármacosRESUMO
Kidney injury (defined as the presence of albuminuria, proteinuria, glycosuria [without hyperglycemia], hematuria, and/or renal hypophosphatemia) is an emerging problem in human immunodeficiency virus (HIV)-infected patients, although few data are available on the role of protease inhibitors (PIs) in this condition.To determine the time to kidney injury in a cohort of HIV-infected patients receiving a PI-containing regimen.We report the results of a subanalysis of a published cross-sectional study. The subanalysis included only patients receiving PI-containing regimens for more than 6 months (377 of the overall 970 patients). We determined associated factors and constructed receiver operating characteristic curves to estimate time to kidney injury depending on the PI used.The percentage of patients with kidney injury was 27.7% for darunavir, 27.9% for lopinavir, and 30% for atazanavir. Time to kidney injury was as follows: 229 days for atazanavir/ritonavir (area under the curve [AUC], 0.639; sensitivity, 0.89; specificity, 0.41); 332 days for atazanavir/ritonavir plus tenofovir (AUC, 0.603; sensitivity, 0.75; and specificity, 0.29); 318 days for nonboosted atazanavir (AUC, 0.581; sensitivity, 0.89; and specificity, 0.29); 478 days for lopinavir/ritonavir (AUC, 0.566; sensitivity, 0.864; and specificity, 0.44); 1339 days for lopinavir/ritonavir plus tenofovir (AUC, 0.667; sensitivity, 0.86; and specificity, 0.77); 283 days for darunavir/ritonavir (AUC, 0.523; sensitivity, 0.80; and specificity, 0.261); and 286 days for darunavir/ritonavir plus tenofovir (AUC, 0.446; sensitivity, 0.789; and specificity, 0.245). The use of lopinavir/ritonavir without tenofovir was a protective factor (odds ratioâ=â1.772; 95%CI, 1.070-2.93; Pâ=â0.026).For all PIs, the percentage of patients with kidney injury exceeded 27%, irrespective of tenofovir use. The longest time to kidney injury was recorded with lopinavir/ritonavir. These results demonstrate the need for renal monitoring, including urine samples, in patients receiving a PI-based regimen, even when tenofovir is not used concomitantly.
Assuntos
Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/efeitos adversos , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/urina , Adulto , Albuminúria/induzido quimicamente , Albuminúria/urina , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Sulfato de Atazanavir/efeitos adversos , Sulfato de Atazanavir/uso terapêutico , Biomarcadores/urina , Estudos Transversais , Darunavir/administração & dosagem , Darunavir/uso terapêutico , Feminino , Infecções por HIV/urina , Inibidores da Protease de HIV/uso terapêutico , Humanos , Lopinavir/efeitos adversos , Lopinavir/uso terapêutico , Masculino , Pessoa de Meia-Idade , Proteinúria/induzido quimicamente , Proteinúria/urina , Ritonavir/efeitos adversos , Ritonavir/uso terapêuticoRESUMO
Data on dolutegravir removal by hemodialysis are lacking. To study this, we measured dolutegravir plasma concentrations in samples of blood entering and leaving the dialyzer and of the resulting dialysate from 5 HIV-infected patients with end-stage renal disease. The median dolutegravir hemodialysis extraction ratio was 7%. The dolutegravir concentrations after the dialysis session remained far above the protein-binding-adjusted inhibitory concentration. Our results show minimal dolutegravir removal by hemodialysis, with no specific dolutegravir dosage adjustments required in this setting. (This study is registered at ClinicalTrials.gov under registration number NCT02487706.).
Assuntos
Fármacos Anti-HIV/farmacocinética , Soluções para Diálise/química , Infecções por HIV/tratamento farmacológico , Compostos Heterocíclicos com 3 Anéis/farmacocinética , Falência Renal Crônica/terapia , Diálise Renal , Adulto , Idoso , Fármacos Anti-HIV/farmacologia , Terapia Antirretroviral de Alta Atividade , Esquema de Medicação , Feminino , Infecções por HIV/complicações , Infecções por HIV/fisiopatologia , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , HIV-1/fisiologia , Compostos Heterocíclicos com 3 Anéis/farmacologia , Humanos , Falência Renal Crônica/complicações , Falência Renal Crônica/fisiopatologia , Falência Renal Crônica/virologia , Masculino , Pessoa de Meia-Idade , Oxazinas , Piperazinas , Piridonas , Resultado do TratamentoRESUMO
INTRODUCTION: Loss of bone mineral density is an emerging problem in persons living with HIV infection. Earlier and more rapid bone demineralization has been attributed not only to the high prevalence of traditional risk factors, but also to specific HIV-related factors. The aim of this guidance is to stimulate an appropriate management of osteoporosis in this population, to identify patients at risk and to better manage them. AREAS COVERED: Appropriate screening of HIV-infected subjects to identify those at risk for bone fractures is described, as well as the recommended interventions. American and European recommendations in HIV-infected and non-infected populations were considered. As the etiology of bone loss is multifactorial, many factors have to be addressed. Overall, recommendations on traditional risk factors are the same for HIV-infected and non-HIV-infected subjects. However, we should consider some specific factors in the HIV-infected population, including an appropriate antiretroviral therapy in patients with low bone mineral density, and probably novel strategies that could provide an additional benefit, such as anti-inflammatory drugs, although data supporting this approach are scant. EXPERT OPINION: Some personal opinions are highlighted on the management of bone health in HIV-infected subjects, mainly on the use of FRAX(®) score and DXA scans. In addition, the need to implement new strategies to delay demineralization is remarked upon.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Conservadores da Densidade Óssea/uso terapêutico , Densidade Óssea/efeitos dos fármacos , Infecções por HIV/tratamento farmacológico , Difosfonatos/uso terapêutico , Gerenciamento Clínico , Fraturas Ósseas/prevenção & controle , Infecções por HIV/complicações , Infecções por HIV/fisiopatologia , Humanos , Osteoporose/complicações , Osteoporose/tratamento farmacológico , Osteoporose/fisiopatologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de RiscoRESUMO
Background. Prospective studies about the reversibility of tenofovir disoproxil fumarate- (TDF-) related renal impairment remain scarce. Methods. This is an observational prospective study including all patients that presented at our HIV Unit who interrupted TDF owing to nephrotoxicity. We assessed the evolution of renal parameters after discontinuation of this drug. Results. We included 59 patients, who were followed up for 72 weeks. Most were male (41, 69.5%), median (IQR) age was 53 (44; 58) years, and median time receiving TDF-containing regimens was 55.4 (28; 87.7) months. Most patients were receiving PI-based treatments (67%). At the final visit, most of the subjects showed complete recovery (35, 59.3%) or improvement (13 subjects, 22%). Significant improvements were observed in creatinine levels (from 84.9 [73.8; 97.5] to 78 [69.6; 91] µmol/L, p = 0.013), estimated glomerular filtration rate (eGFR, CKD EPI equation, from 87.7 [67; 99] to 89.9 [73.6; 99.3] mL/min/1.73 m2, p = 0.017), and number of patients with eGFR <60 mL/min/1.73 m2 (from 9 [15.3%] to 1 [1.7%], p = 0.031). A trend toward significance was observed in abnormal urine proteinuria/creatinine ratio (from 22 [37%] to 8 [13.6%], p = 0.057). Conclusions. Our results corroborate the high frequency of complete or partial renal recovery in patients receiving TDF-containing regimens who discontinued therapy owing to nephrotoxicity.
Assuntos
Fármacos Anti-HIV/efeitos adversos , Infecções por HIV/tratamento farmacológico , Insuficiência Renal/tratamento farmacológico , Tenofovir/efeitos adversos , Adulto , Fármacos Anti-HIV/administração & dosagem , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Infecções por HIV/complicações , Infecções por HIV/patologia , Humanos , Estimativa de Kaplan-Meier , Rim/efeitos dos fármacos , Rim/patologia , Masculino , Pessoa de Meia-Idade , Insuficiência Renal/induzido quimicamente , Insuficiência Renal/patologia , Tenofovir/administração & dosagemRESUMO
Tenofovir disoproxil fumarate (TDF) is an adenine analogue reverse transcription inhibitor widely used in first-line treatment of human immunodeficiency virus (HIV) infection and also in hepatitis B virus infection. Its use has been linked to sporadic Fanconi syndrome, renal failure and bone disease. We present the clinical characteristics of tenofovir-induced osteomalacia, discuss bone biopsy findings, describe predisposing factors and compare our results with other reported cases. We describe five cases of hypophosphatemic osteomalacia induced by TDF and recorded at the rheumatology service of a university hospital between 2010 and 2014. We also report the characteristics of bone biopsies of this pathology, which have not been previously described. We include a review of published cases of proximal renal tubulopathy (PRT) and osteomalacia induced by TDF (PubMed 1995-2014; keywords: osteomalacia, tenofovir, Fanconi syndrome, hypophosphatemic osteomalacia, proximal renal tubulopathy, bone biopsy). Five HIV patients who developed hypophosphatemic osteomalacia under TDF treatment (>5 years) presented increasing bone pain and a progressive inability to walk without assistance as a result of multiple insufficiency fractures. Bone biopsy performed in three patients after tetracycline labelling showed increased osteoid thickness, confirming osteomalacia. A literature review retrieved 17 publications on this condition, including 53 cases: 26 patients developed isolated PRT, 25 presented PRT and with multiple insufficiency fractures and two presented isolated bone disease, including osteomalacia and osteoporosis. Rheumatologists should be alert to this complication in patients receiving tenofovir. The main complaint reported by these patients is diffuse pain, predominantly in the lower limbs, indicating multiple stress fractures. Serum phosphate and appropriate screening for abnormal proximal tubule function should be monitored. Bone scintigraphy should be carried out in cases of limb pain before the occurrence of more severe complications.
Assuntos
Fármacos Anti-HIV/efeitos adversos , Infecções por HIV/tratamento farmacológico , Hipofosfatemia/induzido quimicamente , Osteomalacia/induzido quimicamente , Tenofovir/efeitos adversos , Adulto , Fármacos Anti-HIV/uso terapêutico , Osso e Ossos/diagnóstico por imagem , Feminino , Humanos , Hipofosfatemia/diagnóstico por imagem , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Osteomalacia/diagnóstico por imagem , Tenofovir/uso terapêuticoRESUMO
Although some clinical trials have studied the impact of treatments on bone mineral density (BMD), scarce data are available about the impact of protease inhibitor (PI) monotherapies on BMD. The aim of this study was to evaluate changes in BMD in patients after one, two, or three years of a PI monotherapy. This study included 46 HIV-infected patients who switched from a conventional triple antiretroviral strategy to a monotherapy with lopinavir/ritonavir (LPV/r) or darunavir/ritonavir (DRV/r) for one (one-year group, n=16), two (two-year group, n=20), and three (three-year group, n=10) years. BMD was assessed by dual-energy X-ray absorptiometry (DXA). The median percentage of change in total femur BMD was 0.20% after one, 0.79% after two, and -0.31% after three years. The change in lumbar spine was -0.08%, -0.14%, and 0.50% % after the same years. No significant differences were found when patients were classified regarding the type of PI and whether or not had previously received PI or tenofovir. However, patients who interrupted tenofovir or those who started with DRV/r had a higher BMD increment. Patients who had taken non-nucleoside reverse transcriptase inhibitors previously decreased BMD when started PIs. Monotherapy treatment with ritonavir-boosted protease inhibitors (both LPV/r and DRV/r) during one, two, or three years leads to the stabilization of BMD in HIV-infected patients with long-term virological suppression. Larger studies are necessary to compare the effect of starting or withdrawing PIs on BMD.
Assuntos
Densidade Óssea/efeitos dos fármacos , Fêmur/efeitos dos fármacos , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/uso terapêutico , Adulto , Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/uso terapêutico , Feminino , Fêmur/química , Fêmur/crescimento & desenvolvimento , Infecções por HIV/fisiopatologia , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , HIV-1/fisiologia , Humanos , Estudos Longitudinais , Lopinavir/uso terapêutico , Masculino , Pessoa de Meia-Idade , Ritonavir/uso terapêutico , Fatores de Tempo , Carga Viral/efeitos dos fármacosRESUMO
Long-term results (>5 years) for synthetic substances used to repair facial lipoatrophy have not been published. We performed a cross-sectional study to evaluate the 10-year safety of polyacrylamide hydrogel (Aquamid) among the 751 patients from our unit who received facial infiltrations at least 10 years ago. Epidemiological and clinical data such as complications and patient satisfaction were collected. We also identified those patients who presented a facial infection at any time after infiltration. A total of 104 patients had received Aquamid at least 10 years ago. Before infiltrations, 24.0%, 41.3%, and 34.7% presented very severe, severe, and moderate facial lipoatrophy, respectively. After a mean (SD) of 10.3 (0.5) years since the infiltrations, 19.2%, 47.7%, and 31.7% of patients reported moderate, mild, and no signs of facial lipoatrophy. The values reported by physicians for the same categories were 1.9%, 10.6%, and 87.5%. Indurations were detected in 6.7% of patients and nodules in 3.8%. Five patients (4.8%) had a local infection. A further 15 patients with a shorter follow-up (less than 10 years) presented local infections (overall incidence considering the 751 patients who received infiltrations of Aquamid, 2.7%); the product had to be withdrawn in three cases. The majority of patients were highly satisfied (74.8%) or satisfied (23.4%) with the cosmetic results; among patients with severe or very severe lipoatrophy at baseline, 31.4% were satisfied and 65.7% were highly satisfied. Infiltrations with polyacrylamide hydrogel (Aquamid) are a safe strategy for the treatment of facial lipoatrophy in the long term. The rate of severe complications was low, and patient satisfaction with the cosmetic results was high. However, facial infections may appear in the long term. Therefore, HIV-infected patients who received synthetic substances should be carefully monitored over time.
Assuntos
Resinas Acrílicas/efeitos adversos , Resinas Acrílicas/uso terapêutico , Técnicas Cosméticas/efeitos adversos , Infecções por HIV/complicações , Síndrome de Lipodistrofia Associada ao HIV/cirurgia , Hidrogéis/efeitos adversos , Hidrogéis/uso terapêutico , Adulto , Estudos Transversais , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Infecção da Ferida Cirúrgica/epidemiologia , Resultado do TratamentoRESUMO
BACKGROUND: Tenofovir is involved in accelerated bone mineral density (BMD) loss. METHODS: We recently published a hip BMD improvement at week 48 [+2.1% (95% CI: -0.6, 4.7) (Pâ=â0.043)] in HIV-infected patients with osteopenia/osteoporosis randomized to switch from tenofovir to abacavir (nâ=â26), although without reaching statistical significance compared with those who maintained tenofovir (nâ=â28). Here, we present changes at week 48 in bone markers [C-terminal telopeptide of collagen type 1 (CTX), osteocalcin and procollagen type 1 N propeptide (P1NP)] as well as in circulating levels of three proteins involved in bone regulation [osteoprotegerin, receptor activator for NF-κB ligand (RANKL) and sclerostin, a selective regulator of bone formation through the Wnt pathway] in 44 of these patients. χ(2) or Fisher and Student t-tests were performed according to the distribution of the variables. RESULTS: Bone markers decreased only in the abacavir group [mean (SD) CTX changed from 0.543 (0.495) to 0.301 (0.306) ng/mL; mean (SD) osteocalcin changed from 23.72 (22.20) to 13.95 (12.40) ng/mL; and mean (SD) P1NP changed from 54.68 (54.52) to 28.65 (27.48) ng/mL (Pâ<â0.001 in all cases)], reaching statistical significance between the groups at week 48. Osteoprotegerin did not vary, but sclerostin significantly increased in the abacavir group [from 29.53 (27.91) to 35.56 (34.59) pmol/L, Pâ=â0.002]. No significant differences in osteoprotegerin and sclerostin were detected between the groups at week 48. RANKL values were below the limit of detection in all samples. CONCLUSIONS: The switch from tenofovir to abacavir seems to induce a positive effect on bone tissue, since bone turnover markers decreased. In addition, circulating sclerostin levels increased, a change associated with improved bone properties.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Densidade Óssea , Proteínas Morfogenéticas Ósseas/sangue , Remodelação Óssea , Didesoxinucleosídeos/uso terapêutico , Infecções por HIV/tratamento farmacológico , Tenofovir/uso terapêutico , Proteínas Adaptadoras de Transdução de Sinal , Adulto , Idoso , Fármacos Anti-HIV/efeitos adversos , Biomarcadores/análise , Didesoxinucleosídeos/efeitos adversos , Feminino , Marcadores Genéticos , Infecções por HIV/virologia , HIV-1/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Tenofovir/efeitos adversosRESUMO
Several studies have reported associations between lipid parameters and clinical progression of HIV infection. We performed a cross-sectional study including 468 antiretroviral-treated HIV-infected patients to investigate the impact of 13 polymorphisms of 9 genes affecting lipid metabolism and CD4 and CD8-T cell levels. Polymorphisms were identified in genes selected for their role in the development of atherogenic dyslipidemia, defined as triglycerides ⩾1.7mmol/L and high-density lipoprotein cholesterol (HDLc) <1.02 in women or 1.28mmol/L in men. Lipid and lipoprotein parameters were determined in all participants, as well as CD4 and CD8 T-cell counts. ANOVA was performed to compare the mean values of lipid and CD4 and CD8 T-cell count data. A Bonferroni correction for multiple comparisons was applied. 468 patients were included, 148 of them had a diagnosis of atherogenic dyslipidemia. The polymorphism rs3135506 in APOA5 was associated with a 9% increase in triglycerides (p=0.002), 10% and 21% decrease in HDLc (p=0.005), and CD4 T-cell count (p=0.024), respectively. APOA5 rs662799, was associated with a 19% increase in CD8 T-cell count (p=0.002). Carriers of LPL rs328 in the dyslipidemic group presented 11% higher levels of HDLc (p=0.015) and 14% higher levels of CD4 cells (p=0.038). In conclusion, polymorphisms in genes associated to the development of atherogenic dyslipidemia, especially variants in APOA5 gene (rs3135506 and rs662799), can influence the circulating CD4 T-cell levels in chronically HIV-infected patients. These data support previous reports on the effect of lipid metabolism on immunologic parameters in HIV+ individuals on antiretroviral therapy.
Assuntos
Contagem de Linfócito CD4 , Infecções por HIV/genética , Infecções por HIV/imunologia , Metabolismo dos Lipídeos/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Apolipoproteína A-V , Apolipoproteínas A/genética , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/virologia , HDL-Colesterol/sangue , Doença Crônica , Estudos Transversais , Feminino , Genótipo , Infecções por HIV/metabolismo , Humanos , Lipídeos/sangue , Lipoproteínas/sangue , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Triglicerídeos/sangue , Adulto JovemRESUMO
INTRODUCTION: Polymorphisms in some host genes have a significant impact on susceptibility to HIV-1 infection and rate of disease progression (1, 2). The purpose of the current sub-study was to find out the relationship between polymorphisms in genes involved in the lipid metabolism and the CD4/CD8 T-cell counts. METHODS: Sub-study of a cross-sectional, observational study conducted in 468 patients with HIV infection attended at the outpatient clinic to investigate individual genetic predisposition to atherogenic dyslipidemia (AD). All patients were genetically characterized and all polymorphisms were in Hardy-Weinberg equilibrium. Thirteen polymorphisms were selected from nine genes: APOA5 (rs662799 and rs3135506); APOC3 (rs5128 and rs4520); LPL (rs328 and rs268); CETP (rs708272); HL (rs1800588); MTP (rs1800591); APOE (rs7412 and rs429358); LRP5 (rs7116604); and VLDLR (rs1454626). Lipid and lipoprotein parameters, CD4 and CD8 T-cell counts and plasma HIV-RNA were determinate. The statistical analysis was performed using SPSS statistical software version 19 (SPSS Inc., Chicago, IL, USA). RESULTS: We studied 468 HIV-infected patients (men, 77%), with a mean (SD) age of 45.9 (19.7) years. The mean CD4 T-cell count and nadir CD4 was 547 (459) and 193 (159) cells/µL, respectively; 78.7% of participants were virologically suppressed. Patients carrying rs3135506 in the APOA5 gene presented a 9% increase in circulating TG levels (p=0.002) and 10% decrease in HDLc levels (p=0.005). Such association of APOA5 towards dyslipidemia was accompanied by a 21% decrease of the CD4 T-cell count (p=0.024) and a 19% increase in CD8 T-cell count (p=0.002) in carriers of the rare allele in the APOA5 rs662799 polymorphism adjusted by age and gender. Patients carrying the rare allele in rs5128 (APOC3) had a 16% decrease in circulating CD4 T cells (p=0.029); patients carrying rs1800591 (MTP) had a 29% decrease in CD4 T cells and 14% decrease in CD8 T cells (p=0.018 and p=0.008, respectively); patients carrying the rare allele rs1800588 in HL had a 11% increase in CD4 T cells (p=0.043); and carriers of the rs145626 in the VLDLR gene had 10% decrease in CD4 circulating T cells (p=0.013). CONCLUSION: Variants in genes involved in the development of AD may also influence the immunological host-virus equilibrium in chronically HIV-infected subjects (2, 3).