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1.
N Engl J Med ; 384(5): 417-427, 2021 02 04.
Article in English | MEDLINE | ID: mdl-33289973

ABSTRACT

BACKGROUND: Current strategies for preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are limited to nonpharmacologic interventions. Hydroxychloroquine has been proposed as a postexposure therapy to prevent coronavirus disease 2019 (Covid-19), but definitive evidence is lacking. METHODS: We conducted an open-label, cluster-randomized trial involving asymptomatic contacts of patients with polymerase-chain-reaction (PCR)-confirmed Covid-19 in Catalonia, Spain. We randomly assigned clusters of contacts to the hydroxychloroquine group (which received the drug at a dose of 800 mg once, followed by 400 mg daily for 6 days) or to the usual-care group (which received no specific therapy). The primary outcome was PCR-confirmed, symptomatic Covid-19 within 14 days. The secondary outcome was SARS-CoV-2 infection, defined by symptoms compatible with Covid-19 or a positive PCR test regardless of symptoms. Adverse events were assessed for up to 28 days. RESULTS: The analysis included 2314 healthy contacts of 672 index case patients with Covid-19 who were identified between March 17 and April 28, 2020. A total of 1116 contacts were randomly assigned to receive hydroxychloroquine and 1198 to receive usual care. Results were similar in the hydroxychloroquine and usual-care groups with respect to the incidence of PCR-confirmed, symptomatic Covid-19 (5.7% and 6.2%, respectively; risk ratio, 0.86 [95% confidence interval, 0.52 to 1.42]). In addition, hydroxychloroquine was not associated with a lower incidence of SARS-CoV-2 transmission than usual care (18.7% and 17.8%, respectively). The incidence of adverse events was higher in the hydroxychloroquine group than in the usual-care group (56.1% vs. 5.9%), but no treatment-related serious adverse events were reported. CONCLUSIONS: Postexposure therapy with hydroxychloroquine did not prevent SARS-CoV-2 infection or symptomatic Covid-19 in healthy persons exposed to a PCR-positive case patient. (Funded by the crowdfunding campaign YoMeCorono and others; BCN-PEP-CoV2 ClinicalTrials.gov number, NCT04304053.).


Subject(s)
Anti-Infective Agents/therapeutic use , COVID-19/prevention & control , Hydroxychloroquine/therapeutic use , SARS-CoV-2 , Adult , Anti-Infective Agents/adverse effects , COVID-19/transmission , COVID-19/virology , Disease Transmission, Infectious/prevention & control , Double-Blind Method , Female , Humans , Hydroxychloroquine/adverse effects , Male , Middle Aged , Patient Compliance , Treatment Failure , Viral Load
2.
HIV Med ; 23(10): 1078-1084, 2022 11.
Article in English | MEDLINE | ID: mdl-35470944

ABSTRACT

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.


Subject(s)
HIV Infections , Renal Insufficiency, Chronic , Aged , CD4 Lymphocyte Count , Cobicistat/therapeutic use , Cohort Studies , Female , HIV Infections/complications , HIV Infections/drug therapy , HIV Infections/epidemiology , Humans , Male , Middle Aged , Prevalence , Prospective Studies , Renal Insufficiency, Chronic/epidemiology , Renal Insufficiency, Chronic/therapy , Viral Load
3.
AIDS Care ; 34(2): 155-162, 2022 02.
Article in English | MEDLINE | ID: mdl-34743624

ABSTRACT

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.


Subject(s)
HIV Infections , Aged , Aging , Cohort Studies , Comorbidity , HIV Infections/complications , HIV Infections/epidemiology , Humans , Male , Prevalence , Risk Factors
4.
Gastroenterol Hepatol ; 45(1): 77-81, 2022 Jan.
Article in English, Spanish | MEDLINE | ID: mdl-34052398

ABSTRACT

Over recent years, ultrasonography has been used increasingly in various medical specialties and is now an indispensable diagnostic tool. In gastroenterology, bedside or point-of-care ultrasound allows the early diagnosis and monitoring of multiple intraabdominal conditions. Ultrasound guidance is also highly useful in certain therapeutic procedures, increasing procedural safety. Ultrasound is a non-invasive technique but has the drawback of being very operator dependent. Therefore, it is necessary to ensure that the professionals who perform ultrasonography have a sufficient level of training in the technique. In Catalonia, abdominal ultrasound is usually carried out by radiologists and has not yet been incorporated as an investigation performed by gastroenterologists. In view of this, the Societat Catalana de Radiologia and the Societat Catalana de Digestologia judged it necessary to develop a consensus framework document on ultrasound use and training for gastroenterologists. The document establishes the suggested format for training, the appropriate indications, the minimum material requirements and appropriate documentation of the procedure to ensure that gastroenterologist-performed ultrasound is useful and safe.


Subject(s)
Consensus , Gastroenterologists/education , Gastroenterology/education , Ultrasonics/education , Clinical Competence , Humans , Point-of-Care Systems , Societies, Medical , Spain , Ultrasonography , Ultrasonography, Interventional
5.
Clin Infect Dis ; 73(11): e4073-e4081, 2021 12 06.
Article in English | MEDLINE | ID: mdl-32674126

ABSTRACT

BACKGROUND: No effective treatments for coronavirus disease 2019 (COVID-19) exist. We aimed to determine whether early treatment with hydroxychloroquine (HCQ) would be efficacious for outpatients with COVID-19. METHODS: Multicenter open-label, randomized, controlled trial conducted in Catalonia, Spain, between 17 March and 26 May 2020. Patients recently diagnosed with <5-day of symptom onset were assigned to receive HCQ (800 mg on day 1 followed by 400 mg once daily for 6 days) or usual care. Outcomes were reduction of viral load in nasopharyngeal swabs up to 7 days after treatment start, disease progression up to 28 days, and time to complete resolution of symptoms. Adverse events were assessed up to 28 days. RESULTS: A total of 293 patients were eligible for intention-to-treat analysis: 157 in the control arm and 136 in the intervention arm. The mean age was 41.6 years (SD, 12.6), mean viral load at baseline was 7.90 log10 copies/mL (SD, 1.82), and median time from symptom onset to randomization was 3 days. No differences were found in the mean reduction of viral load at day 3 (-1.41 vs -1.41 log10 copies/mL in the control and intervention arm, respectively) or at day 7 (-3.37 vs -3.44). Treatment did not reduce risk of hospitalization (7.1% control vs 5.9% intervention) nor shorten the time to complete resolution of symptoms (12 days, control vs 10 days, intervention). No relevant adverse events were reported. CONCLUSIONS: In patients with mild COVID-19, no benefit was observed with HCQ beyond the usual care.


Subject(s)
COVID-19 Drug Treatment , Hydroxychloroquine , Adult , Humans , Hydroxychloroquine/therapeutic use , SARS-CoV-2 , Treatment Outcome
6.
Br J Clin Pharmacol ; 87(3): 1310-1317, 2021 03.
Article in English | MEDLINE | ID: mdl-32852102

ABSTRACT

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.


Subject(s)
HIV Infections , Inappropriate Prescribing , Aged , Cross-Sectional Studies , HIV Infections/drug therapy , HIV Infections/epidemiology , Humans , Potentially Inappropriate Medication List , Prevalence
7.
Telemed J E Health ; 27(4): 432-440, 2021 04.
Article in English | MEDLINE | ID: mdl-32667858

ABSTRACT

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.


Subject(s)
HIV Infections , Mobile Applications , Telemedicine , HIV Infections/therapy , Humans , Middle Aged , Patient Satisfaction , Quality of Life
8.
Clin Infect Dis ; 71(2): 390-399, 2020 07 11.
Article in English | MEDLINE | ID: mdl-31504329

ABSTRACT

BACKGROUND: The efficacy of screening programs to prevent anal cancer in persons with human immunodeficiency virus 1 (HIV-1) is unclear. METHODS: To examine the impact of a screening program to detect anal cancer precursors on the incidence of cases of invasive anal squamous-cell carcinoma (IASCC) in persons with HIV-1, we performed a single-center, retrospective analysis of a prospective cohort of outpatients with HIV-1 attending a reference HIV unit from January 2005 onward. All participants were invited to participate in a continued structured screening program for anal cancer prevention. We estimated the incidence of IASCC and performed a comparative analysis between subjects enrolled in the screening program (screening group) and those who declined to participate (nonscreening group). To reduce any selection bias, a propensity score analysis was applied. RESULTS: We included 3111 persons with HIV-1 (1596 men-who-have-sex-with-men [MSM], 888 men-who-have-sex-with-women [MSW], 627 women; mean age, 41 years), with a median follow-up of 4.7 years (14 595 patient-years of follow-up); 1691 (54%) participated in the screening program. Ten patients were diagnosed with IASCC: 2 (MSM) in the screening group and 8 (4 MSM, 2 MSW, and 2 women) in the nonscreening group. The incidence rates of IASCC were 21.9 (95% confidence interval [CI], 2.7-70.3) and 107.0 (95% CI, 46.2-202.0) per 100 000 person-years, respectively. After a propensity score adjustment, the difference was significant in favor of the screening group (hazard ratio, 0.17; 95% CI, .03-.86). CONCLUSIONS: The number of cases of IASCC was significantly lower in persons with HIV engaged in an anal cytology screening program. These results should be validated in a randomized clinical trial.


Subject(s)
Anus Neoplasms , HIV Infections , Sexual and Gender Minorities , Adult , Anus Neoplasms/diagnosis , Anus Neoplasms/epidemiology , Cohort Studies , Early Detection of Cancer , Female , HIV Infections/complications , Homosexuality, Male , Humans , Male , Prospective Studies , Retrospective Studies
9.
J Am Anim Hosp Assoc ; 56(2): e56203, 2020.
Article in English | MEDLINE | ID: mdl-31961213

ABSTRACT

A 12 yr old intact female Siberian husky was referred with a 2 wk history of progressive weakness, paraparesis, anorexia, and panting. A 4 cm diameter grade 3 mammary solid carcinoma involving the fifth right mammary gland had been removed 2 days prior to the current visit. While hospitalized, the dog was diagnosed with Addison's disease based on electrolyte disturbances and low serum cortisol levels following adrenocorticotropic hormone stimulation test. An abdominal ultrasound revealed adrenal glands at the upper limit of normal size. Despite treatment, the dog deteriorated and died 4 days after presentation. A postmortem examination revealed a neoplastic infiltrate of epithelial malignant cells in both adrenal glands, popliteal lymph nodes, vertebral bodies, and paralumbar musculature, compatible with metastasis from mammary carcinoma. To our knowledge, this is the first reported case of Addison's disease secondary to metastatic mammary carcinoma in a dog.


Subject(s)
Addison Disease/veterinary , Adrenal Gland Neoplasms/veterinary , Dog Diseases/pathology , Mammary Neoplasms, Animal/pathology , Addison Disease/etiology , Adrenal Gland Neoplasms/secondary , Animals , Dog Diseases/etiology , Dogs , Fatal Outcome , Female
10.
J Vet Med Educ ; 46(4): 523-532, 2019.
Article in English | MEDLINE | ID: mdl-30418815

ABSTRACT

Vertebral fractures and luxations are common causes of neurological emergencies in small-animal patients. The objective of this study was to evaluate the impact of three-dimensional printing (3Dp) models on how veterinary students understand and learn to identify canine spinal fractures and to compare 3Dp models to computed tomography (CT) images and three-dimensional CT (3D-CT) reconstructions. Three spinal fracture models were generated by 3Dp. Sixty first-year veterinary students were randomized into three teaching module groups (CT, 3D-CT, or 3Dp) and asked to answer a multiple-choice questionnaire with 12 questions that covered normal spinal anatomy and the identification of vertebral fractures. We used four additional questions to evaluate the overall learning experience and knowledge acquisition. Results showed that students in the 3Dp group performed significantly better than those in the CT (p < .001) and the 3D-CT (p < .001) groups. Students in the 3Dp and 3D-CT groups answered all questions more quickly than the CT group (3Dp versus CT, p < .001; 3D-CTversus CT, p < .001), with no significant differences between the 3Dp and 3D-CT groups (p = .051). Only the degree of knowledge acquisition that the students considered they had acquired during the session showed significant differences between groups (p = .01). In conclusion, across first-year veterinary students, 3Dp models facilitated learning about normal canine vertebral anatomy and markedly improved the identification of canine spinal fractures. Three-dimensional printing models are an easy and inexpensive teaching method that could be incorporated into veterinary neuroanatomy classes to improve learning in undergraduate students.


Subject(s)
Education, Veterinary , Printing, Three-Dimensional , Spinal Fractures , Animals , Dogs , Education, Veterinary/methods , Educational Measurement , Humans , Imaging, Three-Dimensional/veterinary , Spinal Fractures/diagnostic imaging , Spinal Fractures/veterinary
11.
J Antimicrob Chemother ; 73(9): 2452-2459, 2018 09 01.
Article in English | MEDLINE | ID: mdl-29860519

ABSTRACT

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.


Subject(s)
HIV Infections/drug therapy , HIV Protease Inhibitors/adverse effects , Osteoporosis/chemically induced , Osteoporosis/epidemiology , Absorptiometry, Photon , Adult , Age Factors , Aged , Aged, 80 and over , Bone Density/drug effects , Female , HIV Protease Inhibitors/administration & dosage , Humans , Longitudinal Studies , Male , Middle Aged , Retrospective Studies , Risk Assessment , Sex Factors
12.
J Antimicrob Chemother ; 72(3): 844-849, 2017 03 01.
Article in English | MEDLINE | ID: mdl-27999056

ABSTRACT

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.


Subject(s)
Anti-HIV Agents/therapeutic use , Antiretroviral Therapy, Highly Active , Dideoxynucleosides/therapeutic use , HIV Infections/drug therapy , Heterocyclic Compounds, 3-Ring/therapeutic use , Lamivudine/therapeutic use , Ritonavir/therapeutic use , Adult , Anti-HIV Agents/administration & dosage , Bone Density/drug effects , Dideoxynucleosides/administration & dosage , Dideoxynucleosides/adverse effects , Drug Combinations , Female , HIV Infections/complications , HIV Infections/virology , HIV Protease Inhibitors/administration & dosage , HIV Protease Inhibitors/adverse effects , HIV Protease Inhibitors/therapeutic use , Heterocyclic Compounds, 3-Ring/administration & dosage , Heterocyclic Compounds, 3-Ring/adverse effects , Humans , Lamivudine/administration & dosage , Lamivudine/adverse effects , Lipids/blood , Male , Middle Aged , Oxazines , Piperazines , Pyridones , Ritonavir/administration & dosage , Ritonavir/adverse effects , Viral Load/drug effects
13.
J Antimicrob Chemother ; 70(7): 2104-7, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25769303

ABSTRACT

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) (P = 0.043)] in HIV-infected patients with osteopenia/osteoporosis randomized to switch from tenofovir to abacavir (n = 26), although without reaching statistical significance compared with those who maintained tenofovir (n = 28). 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 (P < 0.001 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, P = 0.002]. 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.


Subject(s)
Anti-HIV Agents/therapeutic use , Bone Density , Bone Morphogenetic Proteins/blood , Bone Remodeling , Dideoxynucleosides/therapeutic use , HIV Infections/drug therapy , Tenofovir/therapeutic use , Adaptor Proteins, Signal Transducing , Adult , Aged , Anti-HIV Agents/adverse effects , Biomarkers/analysis , Dideoxynucleosides/adverse effects , Female , Genetic Markers , HIV Infections/virology , HIV-1/isolation & purification , Humans , Male , Middle Aged , Tenofovir/adverse effects
14.
J Transl Med ; 13: 230, 2015 Jul 17.
Article in English | MEDLINE | ID: mdl-26183947

ABSTRACT

BACKGROUND: High levels of ex vivo CD4 T-cell death and the accumulation of highly differentiated and/or immunosenescent T cells have been associated with poor CD4 T-cell recovery in treated HIV-infected individuals. However, the relationship between cell death and T-cell differentiation is still unclear. METHODS: We have analyzed cell death, immunosenescence and differentiation parameters in HAART-treated subjects (VL <50 copies/mL for more than 2 years) with CD4 T-cell count <350 cells/µL (immunodiscordant, n = 23) or >400 cells/µL (immunoconcordant, n = 33). We included 11 healthy individuals as reference. RESULTS: As expected, suboptimal CD4 T-cell recovery was associated with low frequencies of naïve cells, high frequencies of transitional and effector memory cells and a subsequent low ratio of central/transitional memory cells in the CD4 compartment. These alterations correlated with spontaneous CD4 T-cell death. A deeper analysis of cell death in CD4 T-cell subsets showed increased cell death in memory cells of immunodiscordant individuals, mainly affecting central memory cells. Immunosenescence was also higher in immunodiscordant individuals albeit unrelated to cell death. The CD8 compartment was similar in both HIV-infected groups, except for an underrepresentation of naïve cells in immunodiscordant individuals. CONCLUSION: Immunodiscordant individuals show alterations in memory CD4 T-cell differentiation associated with a short ex vivo lifespan of central memory cells and an in vivo low central/transitional memory cell ratio. These alterations may contribute to poor CD4 T-cell repopulation.


Subject(s)
Antiretroviral Therapy, Highly Active , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/pathology , HIV Infections/drug therapy , HIV Infections/immunology , Immunologic Memory , Adult , CD4 Lymphocyte Count , CD57 Antigens/metabolism , CD8-Positive T-Lymphocytes/immunology , Cell Compartmentation , Cell Death , Cell Differentiation/immunology , Female , HIV Infections/pathology , Humans , Male , Middle Aged , T-Lymphocyte Subsets/immunology
15.
New Microbiol ; 38(2): 193-9, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25938744

ABSTRACT

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.


Subject(s)
Bone Density/drug effects , Femur/drug effects , HIV Infections/drug therapy , HIV Protease Inhibitors/therapeutic use , Adult , Anti-HIV Agents/adverse effects , Anti-HIV Agents/therapeutic use , Female , Femur/chemistry , Femur/growth & development , HIV Infections/physiopathology , HIV Infections/virology , HIV-1/drug effects , HIV-1/physiology , Humans , Longitudinal Studies , Lopinavir/therapeutic use , Male , Middle Aged , Ritonavir/therapeutic use , Time Factors , Viral Load/drug effects
16.
J Antimicrob Chemother ; 69(12): 3368-71, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25125679

ABSTRACT

BACKGROUND: Tenofovir has been associated with a decrease in bone mineral density (BMD). However, data on changes in BMD after discontinuing tenofovir are lacking. METHODS: We performed a two-centre randomized pilot study in virologically suppressed HIV-infected patients receiving tenofovir with osteopenia/osteoporosis (OsteoTDF study, ClinicalTrials.gov number NCT 01153217). Fifty-four patients were randomly assigned to switch from tenofovir to abacavir (n = 26) or to continue with tenofovir (n = 28). Changes in lumbar and total hip BMD were evaluated at Week 48 from baseline. RESULTS: Five patients discontinued the study (three from the tenofovir group and two from the abacavir group). No significant differences were detected between the groups at Week 48 (P = 0.229 for total hip and P = 0.312 for lumbar spine). However, hip BMD improved by 2.1% (95% CI -0.6 to 4.7) (P = 0.043) in the abacavir group and 0.7% (95% CI -0.9 to 2.4) (P = 0.372) in the tenofovir group. Lumbar spine BMD varied by -0.7% (95% CI -3.8 to 3.3) (P ≤ 0.001) in the abacavir group and -1.2% (95% CI -3.8 to 0.4) (P < 0.001) in the tenofovir group. CONCLUSIONS: Switching from tenofovir to abacavir led to a slight improvement in femoral BMD although no differences were detected between groups. Larger studies are necessary before firm recommendations can be made on the discontinuation of tenofovir in patients with a low BMD.


Subject(s)
Adenine/analogs & derivatives , Anti-HIV Agents/therapeutic use , Bone Density , Dideoxynucleosides/therapeutic use , HIV Infections/complications , HIV Infections/drug therapy , Organophosphonates/therapeutic use , Osteoporosis/chemically induced , Adenine/adverse effects , Adenine/therapeutic use , Adult , Anti-HIV Agents/adverse effects , Dideoxynucleosides/adverse effects , Female , Humans , Male , Middle Aged , Organophosphonates/adverse effects , Osteoporosis/pathology , Pilot Projects , Tenofovir , Treatment Outcome
17.
AIDS Behav ; 18(4): 676-685, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24077971

ABSTRACT

Long-term diagnosed and treated HIV-infected patients have to cope with a wide range of challenges that threaten their ability to age successfully. We report the results of a randomized controlled trial testing the effects of a mindfulness-based cognitive therapy (MBCT) program on quality of life (QoL), emotional status, and immune status over a 3-month period. Forty HIV-infected patients diagnosed prior to 1996 and on cART for a minimum of 5 years were randomized to follow an MBCT program (n = 20) or remain as controls (routine follow-up) (n = 20). A regression analysis was performed, and the measurement of effect size was estimated using Cohen's d. QoL, psychological stress, depressive symptoms, and anxiety symptoms improved in the MBCT group compared with the control group. During follow-up, patients in the MBCT group had a significantly increased CD4 cell count. Effect sizes for MBCT on the variables assessed were large (d = 0.8). The findings suggest that this program may help to promote successful aging in these patients.

18.
Curr HIV Res ; 2024 Aug 28.
Article in English | MEDLINE | ID: mdl-39206476

ABSTRACT

INTRODUCTION: People with the human immunodeficiency virus (PWH) who were diagnosed long ago are more prone to age-related conditions and comorbidities than the general population. We hypothesized that older PWH have endocrine abnormalities that may influence the patient's health status. METHODS: Mean hormonal values across the thyrotropic, somatotropic, corticotropic, and gonadal axis, and percentage of subjects with abnormal values, were compared between PWH aged ≥50 years (n=30) and people without HIV (n=30) (Over50 cohort). Clinical factors were also analyzed as independent variables. RESULTS: PWH had a higher prevalence of comorbidities (36.67% PWH and 20.69% controls had ≥3 comorbidities). Male PWH exhibited lower estradiol levels than male controls (29.75±7.68 pg/mL vs. 35.45±10.04 pg/mL; p=0.0041). Abnormal concentrations of testosterone were found in 35% of male PWH compared to 55% of male controls (mostly above reference values). Cortisol levels were significantly lower among PWH (9.97±4.33 µg/dL vs. 13.56±3.39 µg/dL; p=0.002); 16.6% of PWH exhibited abnormally low levels (<5 µg/dL), compared to 0% of controls, and 3 PWH met criteria for a definitive diagnosis of adrenal insufficiency (<3.6 µg/dL). For the somatotropic axis, growth hormone (GH) levels were significantly lower in male PWH than in controls (p=0.0394). No significant differences were found in relation to the thyroid axis. CONCLUSION: Hormones are generally similar between the chronic PWH who are receiving ART treatment and the general control population, except for cortisol in both sexes and testosterone and estradiol in men. Some special attention should be given to cortisol in PWH due to a presumably higher risk of adrenal complications.

19.
Pediatr Infect Dis J ; 43(3): 278-285, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38113520

ABSTRACT

BACKGROUND: Diagnosis of nontuberculous mycobacteria (NTM) infections remains a challenge. In this study, we describe the evaluation of an immunological NTM-interferon (IFN)-γ release assay (IGRA) that we developed using glycopeptidolipids (GPLs) as NTM-specific antigens. METHODS: We tested the NTM-IGRA in 99 samples from pediatric patients. Seventy-five were patients with lymphadenitis: 25 were NTM confirmed, 45 were of unknown etiology but compatible with mycobacterial infection and 5 had lymphadenitis caused by an etiologic agent other than NTM. The remaining 24 samples were from control individuals without lymphadenitis (latently infected with M. tuberculosis , uninfected controls and active tuberculosis patients). Peripheral blood mononuclear cells were stimulated overnight with GPLs. Detection of IFN-γ producing cells was evaluated by enzyme-linked immunospot assay. RESULTS: NTM culture-confirmed lymphadenitis patient samples had a significantly higher response to GPLs than the patients with lymphadenitis of unknown etiology but compatible with mycobacterial infection ( P < 0.001) and lymphadenitis not caused by NTM ( P < 0.01). We analyzed the response against GPLs in samples from unknown etiology lymphadenitis but compatible with mycobacterial infection cases according to the tuberculin skin test (TST) response, and although not statistically significant, those with a TST ≥5 mm had a higher response to GPLs when compared with the TST <5 mm group. CONCLUSIONS: Stimulation with GPLs yielded promising results in detecting NTM infection in pediatric patients with lymphadenitis. Our results indicate that the test could be useful to guide the diagnosis of pediatric lymphadenitis. This new NTM-IGRA could improve the clinical handling of NTM-infected patients and avoid unnecessary misdiagnosis and treatments.


Subject(s)
Lymphadenitis , Mycobacterium Infections, Nontuberculous , Mycobacterium tuberculosis , Tuberculosis , Humans , Child , Interferon-gamma Release Tests/methods , Leukocytes, Mononuclear , Tuberculosis/diagnosis , Tuberculin Test , Mycobacterium Infections, Nontuberculous/diagnosis , Lymphadenitis/diagnosis
20.
J Antimicrob Chemother ; 68(6): 1382-7, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23354282

ABSTRACT

OBJECTIVES: To evaluate the safety and efficacy of switching the third drug of antiretroviral treatment to maraviroc in aviraemic subjects infected with R5 HIV. PATIENTS AND METHODS: This is a pilot, prospective, randomized clinical trial (ClinicalTrials ID: NCT00966329). Eighty HIV-1-infected aviraemic adults on stable antiretroviral treatment for ≥1 year and no antiretroviral drug resistance were screened for the presence of non-R5 HIV by triplicate proviral V3 population sequencing. From them, 30 subjects with R5 HIV-1 were randomized 1 : 1 to switch the non-nucleoside reverse transcriptase inhibitor or ritonavir-boosted protease inhibitor to maraviroc (n = 15) or to continue the same antiretroviral treatment (controls, n = 15). The principal endpoint was the proportion of subjects with HIV-1 RNA <50 copies/mL at week 48. Ultrasensitive proviral HIV-1 tropism testing (454 sequencing) was performed retrospectively at weeks 0, 4, 12, 24, 36 and 48. RESULTS: One subject in the maraviroc arm and one control had non-R5 HIV in proviral DNA by retrospective 454 sequencing. The subject receiving maraviroc was the only individual to develop virological failure. However, plasma HIV at failure was R5. Switching to maraviroc was well tolerated and associated with small, but statistically significant, declines in total, high-density lipoprotein and low-density lipoprotein cholesterol. Median (IQR) triglyceride [1 (0.67-1.22) versus 1.6 (1.4-3.1) mmol/L, P = 0.003] and total cholesterol [4.3 (4.1-4.72) versus 5.4 (4-5.7) mmol/L, P = 0.059] values were lower in the maraviroc arm than in controls at week 48. CONCLUSIONS: In this pilot, prospective, randomized clinical trial, switching the third drug to maraviroc was safe, efficacious and improved lipid parameters.


Subject(s)
Antiretroviral Therapy, Highly Active/methods , Cyclohexanes/therapeutic use , HIV Fusion Inhibitors/therapeutic use , HIV Infections/drug therapy , HIV Infections/virology , Triazoles/therapeutic use , Adult , CD4 Lymphocyte Count , Dyslipidemias/blood , Dyslipidemias/complications , Female , HIV-1/drug effects , Humans , Hypolipidemic Agents/therapeutic use , Intention to Treat Analysis , Male , Maraviroc , Middle Aged , Pilot Projects , Prospective Studies , Triglycerides/blood , Viral Tropism/drug effects
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