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1.
Niger Postgrad Med J ; 26(4): 195-198, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31621657

RESUMO

Background: The presence of human leukocyte antigen (HLA) B*57:01 allele predicts hypersensitivity reaction (HSR) to abacavir (ABC), a nucleoside reverse-transcriptase inhibitor used for human immunodeficiency virus (HIV) treatment. However, the prevalence of this allele amongst Nigerians with HIV is yet to be established. We aimed to determine the prevalence of HLA-B*57:01 allele amongst Nigerians with HIV infection. Methods: We conducted a multicentre cross-sectional epidemiologic survey. Between April 2016 and April 2017, patients were enrolled across five HIV treatment facilities in Nigeria. Participants' demographic information and their history of ABC exposure were obtained, and venous blood was obtained for HLA typing. Results: One thousand five hundred and four (1504) adults were enrolled, with a mean age of 44.6 ± 10.7 years, 1078 (71.7%) were female. 1463 (97.3%) were on antiretroviral therapy. ABC use was reported by 12 (0.8%) participants and none reported HSR. Of 1500 blood samples that were processed, 1458 (97.2%) were successfully typed. Of these, 132 (9.1%) were HLA-B*57 positive using non-specific low-resolution HLA-B*5701 primer mix. On further analysis, none of the 132 samples (0%) had the HLA-B*5701 allele. Conclusion: HLA-B*5701allele is rare amongst Nigerians.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Didesoxinucleosídeos/uso terapêutico , Hipersensibilidade a Drogas/imunologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Antígenos HLA-B/genética , Inibidores da Transcriptase Reversa/uso terapêutico , Adulto , Grupo com Ancestrais do Continente Africano/genética , Idoso , Estudos Transversais , Didesoxinucleosídeos/efeitos adversos , Hipersensibilidade a Drogas/epidemiologia , Hipersensibilidade a Drogas/genética , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/genética , Antígenos HLA-B/sangue , Antígenos HLA-B/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Nigéria/epidemiologia , Prevalência , Inibidores da Transcriptase Reversa/efeitos adversos
2.
Sensors (Basel) ; 19(16)2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31416185

RESUMO

Pre-treatment screening of individuals for human leukocyte antigens (HLA) HLA-B*57:01 is recommended for the prevention of life-threatening hypersensitivity reactions to abacavir, a drug widely prescribed for HIV treatment. However, the implementation of screening in clinical practice is hindered by the slow turnaround time and high cost of conventional HLA genotyping methods. We have developed a biosensor platform using interdigitated electrode (IDE) functionalized with a monoclonal antibody to detect cells expressing HLA-B*57:01. This platform was evaluated using cell lines and peripheral blood mononuclear cells expressing different HLA-B alleles. The functionalized IDE sensor was able to specifically capture HLA-B*57:01 cells, resulting in a significant change in the impedance magnitude in 20 min. This IDE platform has the potential to be further developed to enable point-of-care HLA-B*57:01 screening.


Assuntos
Técnicas Biossensoriais/métodos , Didesoxinucleosídeos/efeitos adversos , Hipersensibilidade a Drogas/prevenção & controle , Antígenos HLA-B/análise , Leucócitos Mononucleares/metabolismo , Alelos , Anticorpos Imobilizados/química , Anticorpos Imobilizados/imunologia , Anticorpos Monoclonais/química , Anticorpos Monoclonais/imunologia , Didesoxinucleosídeos/uso terapêutico , Hipersensibilidade a Drogas/etiologia , Técnicas Eletroquímicas , Eletrodos , Infecções por HIV/tratamento farmacológico , Antígenos HLA-B/genética , Antígenos HLA-B/imunologia , Humanos
3.
Braz J Infect Dis ; 23(4): 268-270, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31374183

RESUMO

Abacavir can cause a multi-systemic hypersensitivity reaction (HSR) in 5-8% of the patients, which is related to HLA-B*57-01 allele. In Brazil, the HLA-B*57-01 screening test became available only in March 2018, several years after abacavir was in use. In this retrospective study we reviewed medical charts of all patients receiving an abacavir-containing regimen to evaluate the frequency of HSR in patients followed at a referral center in Salvador, Brazil. A total of 192 patients who received abacavir were identified, most male (67.1%), black or racially mixed (77.8%), and having diagnosis of a previous AIDS defining conditions (83.7%). Only one patient developed HSR (incidence: 0.52%). The main reasons for abacavir-containing antiretroviral therapy discontinuation were virological failure (28%), adverse effects to other components of the regimen (25%), and simplification of therapy (16%). The low incidence of HSR to abacavir does not support the use of HLA-B*57-01 screening test, in Salvador, Brazil.


Assuntos
Fármacos Anti-HIV/efeitos adversos , Didesoxinucleosídeos/efeitos adversos , Hipersensibilidade a Drogas/epidemiologia , Hipersensibilidade a Drogas/etiologia , Infecções por HIV/tratamento farmacológico , Adulto , Brasil/epidemiologia , Feminino , Humanos , Incidência , Masculino , Estudos Retrospectivos
4.
BMC Infect Dis ; 19(1): 583, 2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-31277607

RESUMO

BACKGROUND: Human leukocyte antigen (HLA) alleles are implicated in drug-induced hypersensitivity, including by nevirapine and abacavir. The purpose of this meta-analysis was to evaluate the relationship between HLA polymorphisms and hypersensitivity to antiretroviral therapy in human immunodeficiency virus (HIV)-infected patients. METHODS: We conducted a systematic search of PubMed, Embase, Web of Science, and the Cochrane Library for studies that evaluated the associations of HLA polymorphisms with antiretroviral therapy-induced hypersensitivity published in April 2019. The summary odds ratios (ORs) with 95% confidence intervals (CIs) were considered as estimates of the effect. RESULTS: The meta-analysis included 17 studies that assessed a total of 4273 patients. First, carriers of HLA-A *24 were associated with an increased risk of hypersensitivity among patients with HIV who received antiretroviral therapy (OR: 12.12; P = 0.018). Second, five SNPs of HLA-B genotypes, including *18 (OR: 1.63; P = 0.028), *35 (OR: 2.31; P = 0.002), *39 (OR: 11.85; P = 0.040), *51 (OR: 1.66; P = 0.028), and *81 (OR: 8.11; P = 0.021), were associated with an increased risk of hypersensitivity. Conversely, carriers of HLA-B *15 were associated with a reduced risk of hypersensitivity (OR: 0.43; P < 0.001). Third, HLA-C *04 was associated with an increased risk of hypersensitivity (OR: 3.09; P < 0.001), whereas a lower risk for hypersensitivity was observed in patients who were carriers of HLA-C *02 (OR: 0.22; P = 0.030), *03 (OR: 0.53; P = 0.049), and *07 (OR: 0.61; P = 0.044). Finally, carriers of HLA-DRB1 *05 (OR: 0.18; P = 0.006) and *15 (OR: 0.23; P = 0.013) were associated with a reduced risk of hypersensitivity among patients receiving antiretroviral therapy. CONCLUSIONS: The findings of this meta-analysis indicated patients carrying HLA-A *24, HLA-B *18, *35, *39, *51, *81, HLA-C *04 were associated with a higher risk of hypersensitivity. Conversely, subjects carrying HLA-B *15, HLA-C *02, *03, *07, HLA-DRB1 *05, *15 were associated with a reduced risk of hypersensitivity.


Assuntos
Fármacos Anti-HIV/efeitos adversos , Hipersensibilidade a Drogas/genética , Antígenos HLA/genética , Polimorfismo de Nucleotídeo Único , Fármacos Anti-HIV/uso terapêutico , Didesoxinucleosídeos/efeitos adversos , Didesoxinucleosídeos/uso terapêutico , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , Nevirapina/efeitos adversos , Nevirapina/uso terapêutico , Razão de Chances
6.
Int J STD AIDS ; 30(5): 467-471, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30999834

RESUMO

Raltegravir (RAL) is an HIV-1 integrase strand transfer inhibitor that is well established as a component of highly active antiretroviral therapy regimens for the treatment of adults living with human immunodeficiency virus (HIV), due to its high virological efficacy and good tolerability profile. To date, limited data are available on the use of RAL with abacavir/lamivudine (ABC/3TC). We investigated retrospectively 62 HIV-1 infected patients managed by three Italian Infectious Diseases Outpatient Departments, including 57 treatment-experienced patients and 5 treatment-naïve patients, treated with ABC/3TC plus RAL. In all five naïve patients (100%), virological suppression was achieved and maintained , while 55 experienced patients (96.5%) maintained viral suppression at the most recent review. In the treatment-experienced patients, we observed a significant decrease in triglyceride levels (p < 0.01), while liver transaminases, renal function and cholesterol levels remained substantially stable. In the 34 treatment-experienced patients who switched from a protease inhibitor (PI)-based regimen, we observed a significant improvement of total cholesterol (p=0.03) and triglyceride (p < 0.01) levels. No significant alterations were found on renal and liver function and serum lipid profile of treatment-naïve patients. Despite the small number of participants, results support the efficacy and safety of ABC/3TC plus RAL, either in treatment-naïve or treatment-experienced patients.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Didesoxinucleosídeos/uso terapêutico , Infecções por HIV/tratamento farmacológico , Inibidores de Integrase de HIV/uso terapêutico , HIV-1/efeitos dos fármacos , Lamivudina/uso terapêutico , Raltegravir Potássico/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Fármacos Anti-HIV/efeitos adversos , Terapia Antirretroviral de Alta Atividade/métodos , Colesterol/sangue , Didesoxinucleosídeos/efeitos adversos , Combinação de Medicamentos , Quimioterapia Combinada , Feminino , Infecções por HIV/virologia , Inibidores de Integrase de HIV/efeitos adversos , Humanos , Testes de Função Renal , Lamivudina/efeitos adversos , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Raltegravir Potássico/efeitos adversos , Resultado do Tratamento , Triglicerídeos/sangue
7.
Medicine (Baltimore) ; 98(17): e15149, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31027057

RESUMO

RATIONALE: With the existence of the human immunodeficiency virus (HIV) infection as a chronic disease, more often adverse effects of its treatment with the various antiretroviral therapies (ARTs) available have been recognized. Going further, Triumeq has been associated with a myriad of adverse effects, of which rhabdomyolysis is rarely reported in the literature. PATIENT CONCERNS: The patient presented with muscle tenderness over the lower limbs and dark brown-to-red colored urine. DIAGNOSIS: Given the presenting symptoms, as well as the laboratory testing, including elevated serum creatine kinase and liver enzymes, the diagnosis of rhabdomyolysis was made. INTERVENTIONS: Improvement was achieved rapidly after starting intravenous fluid therapy and with discontinuation of Triumeq. OUTCOMES: After discharge, repeated creatine kinase levels in the clinic have been normal and decision was made to initiate another ART and until now, no further episodes of rhabdomyolysis have developed. Regular outpatient follow-up has been ongoing for over 1 year and no complications have been identified. LESSONS: This case aims to recognize rhabdomyolysis as a rare, but possible adverse effect associated with the use of Triumeq for HIV-infected patients and therefore clinicians prescribing this combination should be aware of this potential side effect and counsel their patients accordingly.


Assuntos
Fármacos Anti-HIV/efeitos adversos , Didesoxinucleosídeos/efeitos adversos , Infecções por HIV/tratamento farmacológico , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Lamivudina/efeitos adversos , Rabdomiólise/etiologia , Fármacos Anti-HIV/uso terapêutico , Didesoxinucleosídeos/uso terapêutico , Combinação de Medicamentos , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Humanos , Lamivudina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Rabdomiólise/diagnóstico , Rabdomiólise/terapia
8.
Chemosphere ; 225: 304-310, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30877924

RESUMO

Electrochemical degradation of antiviral drug abacavir was investigated by using a penetration flux porous Ti/SnO2-Sb anode prepared by sol-gel method. The effects of applied current density, initial pH, and inorganic anions on the degradation kinetics were systematically studied. Degradation efficiency more than 97% was performed in only 10 min at a current density of 0.2 mA cm-2. The corresponding degradation rate constant and the lowest electrical energy per order were calculated to be 0.36 min-1 and 6.5 mWh L-1, respectively. Extending the reaction duration to 5 h, 53.3% of TOC removal was observed. The results indicated that effective degradation of abacavir appeared in the penetration flux porous Ti/SnO2-Sb anode with a very low energy consumption. Furthermore, the electrochemical intermediate products and the reaction site during abacavir degradation were detected and recognized. The quantitative structure-activity relationship model revealed that the potential risks of abacavir to the aquatic organism, such as fish, greatly decreased after flowing through the penetration flux porous Ti/SnO2-Sb anode.


Assuntos
Didesoxinucleosídeos/química , Técnicas Eletroquímicas/métodos , Poluentes Químicos da Água/química , Antivirais/efeitos adversos , Antivirais/química , Organismos Aquáticos/efeitos dos fármacos , Didesoxinucleosídeos/efeitos adversos , Eletrodos , Cinética , Porosidade , Compostos de Estanho/química , Titânio/química , Poluentes Químicos da Água/efeitos adversos , Purificação da Água/métodos
9.
J. bras. nefrol ; 41(1): 48-54, Jan.-Mar. 2019. tab
Artigo em Inglês | LILACS | ID: biblio-1002416

RESUMO

ABSTRACT Aim: To determine the prevalence of chronic kidney disease (CKD) and the epidemiological, clinical, and laboratory factors associated with CKD in Mexican HIV-infected patients. Methods: Cross-sectional study. We included 274 patients with HIV/AIDS. CKD was defined by the estimated glomerular filtration rate (eGFR < 60 mL/min/1.73 m2 assessed by CKD-EPI) and albuminuria criteria from KDIGO guidelines. Clinical, epidemiological, and laboratory characteristics were compared between patients with and without CKD. The factors associated with CKD were assessed by logistic regression analysis. Results: The mean age was 41±11 years, and 72.3% of the patients were men. The global prevalence of CKD was 11.7% (n = 32); 7.2% (n = 20) were defined by eGFR criterion; 7.6% (n = 21), by the albuminuria criterion; and 3.2% (n = 9), by both CKD criteria. The most frequently observed stages of CKD were KDIGO G3A1 stage with 4.7% (n = 13), KDIGO G1A2 stage with 3.6% (n = 10) and KDIGO G3A2 stage with 1.7% (n = 5). The factors associated with CKD were use of abacavir/lamivudine (OR 3.2; 95% CI 1.1-8.9; p = 0.03), a CD4 lymphocyte count < 400 cells/µL (OR 2.6; 95% 1.03-6.4, p = 0.04), age (OR 1.1; 95% CI 1.04-1.2, p = 0.001) and albuminuria (OR 19.98; 95% CI: 5.5-72.2; p < 0.001). Conclusions: CKD was a frequent complication in HIV-infected patients. These findings confirm the importance of screening and the early detection of CKD, as well as the importance of identifying and treating traditional and non-traditional risk factors associated with CKD.


RESUMO Objetivo: Determinar a prevalência de doença renal crônica (DRC) e os fatores epidemiológicos, clínicos e laboratoriais associados à DRC em pacientes mexicanos infectados pelo HIV. Métodos: Estudo transversal. Incluímos 274 pacientes com HIV/AIDS. A DRC foi definida pela taxa de filtração glomerular estimada (TFGe < 60 mL/min/1,73 m2, avaliada pelo CKD-EPI) e pelos critérios de albuminúria das diretrizes do KDIGO. As características clínicas, epidemiológicas e laboratoriais foram comparadas entre pacientes com e sem DRC. Os fatores associados à DRC foram avaliados por análise de regressão logística. Resultados: A média da idade foi de 41 ± 11 anos e 72,3% dos pacientes eram homens. A prevalência global de DRC foi de 11,7% (n = 32); 7,2% (n = 20) foram definidos pelo critério TFGe; 7,6% (n = 21), pelo critério da albuminúria; e 3,2% (n = 9), pelos dois critérios para DRC. Os estágios mais frequentemente observados da DRC foram o estágio KDIGO G3A1 com 4,7% (n = 13); estágio KDIGO G1A2 com 3,6% (n = 10) e estágio KDIGO G3A2 com 1,7% (n = 5). Os fatores associados à DRC foram o uso de abacavir/lamivudina (OR 3,2; IC95% 1,1-8,9; p = 0,03), contagem de linfócitos CD4 < 400 células/µL (OR 2,6; 95% 1,03-6,4, p = 0,04), idade (OR 1,1; IC95% 1,04-1,2, p = 0,001) e albuminúria (OR 19,98; IC95%: 5,5-72,2; p < 0,001). Conclusões: A DRC foi uma complicação frequente em pacientes infectados pelo HIV. Esses achados confirmam a importância do rastreamento e da detecção precoce da DRC, bem como a importância de identificar e tratar os fatores de risco tradicionais e não tradicionais associados à DRC.


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Infecções por HIV/complicações , Insuficiência Renal Crônica/etiologia , Insuficiência Renal Crônica/epidemiologia , Didesoxinucleosídeos/efeitos adversos , Modelos Logísticos , Prevalência , Estudos Transversais , Estudos Retrospectivos , Fatores de Risco , Fatores Etários , Contagem de Linfócito CD4 , Lamivudina/efeitos adversos , Fármacos Anti-HIV/efeitos adversos , Complicações do Diabetes , Albuminúria , Taxa de Filtração Glomerular , Hipertensão/complicações , México/epidemiologia
10.
AIDS Res Ther ; 16(1): 1, 2019 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-30651100

RESUMO

BACKGROUND: HLA-B*57:01 screening was added to clinical care guidelines in 2008 to reduce the risk of hypersensitivity reaction from abacavir. The uptake of HLA-B*57:01 screening and incidence of hypersensitivity reaction were assessed in a prospective clinical cohort in the United States to evaluate the effectiveness of this intervention. METHODS: We included all patients initiating an abacavir-containing regimen for the first time in the pre-HLA-B*57:01 screening period (January 1, 1999 to June 14, 2008) or the post-HLA-B*57:01 screening period (June 15, 2008 to January 1, 2016). Yearly incidence of both HLA-B*57:01 screening and physician panel-adjudicated hypersensitivity reactions were calculated and compared. RESULTS: Of the 9619 patients eligible for the study, 33% initiated abacavir in the pre-screening period and 67% in the post-screening period. Incidence of HLA-B*57:01 screening prior to abacavir initiation increased from 43% in 2009 to 84% in 2015. The incidence of definite or probable hypersensitivity reactions decreased from 1.3% in the pre-screening period to 0.8% in 2009 and further to 0.2% in 2015 in the post-screening period. CONCLUSIONS: Frequency of HLA-B*57:01 screening increased steadily since its first inclusion in treatment guidelines in the United States. This increase in screening was accompanied by a decreasing incidence of definite or probable hypersensitivity reactions over the same period. However, a considerable proportion of patients initiating abacavir were not screened, representing a failed opportunity to prevent hypersensitivity reactions. Where HLA-B*57:01 screening is standard of care, patients should be confirmed negative for this allele before starting abacavir treatment.


Assuntos
Fármacos Anti-HIV/efeitos adversos , Didesoxinucleosídeos/efeitos adversos , Hipersensibilidade a Drogas/prevenção & controle , Infecções por HIV/epidemiologia , Antígenos HLA-B/genética , Adulto , Terapia Antirretroviral de Alta Atividade , Registros Eletrônicos de Saúde , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Estudos Prospectivos
11.
Int J STD AIDS ; 30(5): 447-452, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30630396

RESUMO

Hyperparathyroidism has been described in people living with HIV undergoing tenofovir disoproxil fumarate (TDF)-containing antiretroviral therapy (ART), but differences in calcium levels have never been investigated in detail. We aimed to compare the prevalence of hypocalcemia between patients with and without TDF-containing ART. The patients and methods were a retrospective cohort study in HIV-infected adult patients receiving dolutegravir and either abacavir (ABC)/lamivudine (3TC) or TDF/emtricitabine in a single center in Munich, Germany. Of 172 patients, 126 (73.3%) were male and the median age was 48.5 years (interquartile range 42-54). Average calcium levels were 2.24 (2.21-2.29) mmol/l and 2.21 (2.16-2.26) mmol/l (P < 0.001) with a prevalence of at least one episode of total calcium <2.12 mmol/l of 16.2 and 34.4% in the groups treated with ABC/3TC and TDF/emtricitabine, respectively (P = 0.006). TDF use was independently associated with the occurrence of albumin-corrected calcium levels of <2.12 mmol/l (odds ratio: 6.7 [1.3-35.6]; P = 0.025). Hypocalcemia seems to occur more often in TDF-treated patients. Further research into hypocalcemia with TDF and potential cardiovascular effects may be of benefit based on these findings.


Assuntos
Fármacos Anti-HIV/efeitos adversos , Terapia Antirretroviral de Alta Atividade/métodos , Didesoxinucleosídeos/efeitos adversos , Infecções por HIV/tratamento farmacológico , Inibidores de Integrase de HIV/efeitos adversos , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Hipocalcemia/induzido quimicamente , Lamivudina/efeitos adversos , Tenofovir/efeitos adversos , Adulto , Fármacos Anti-HIV/uso terapêutico , Cálcio/sangue , Estudos de Coortes , Didesoxinucleosídeos/uso terapêutico , Combinação de Medicamentos , Feminino , Infecções por HIV/virologia , Inibidores de Integrase de HIV/uso terapêutico , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Humanos , Hipocalcemia/diagnóstico , Hipocalcemia/epidemiologia , Lamivudina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Tenofovir/uso terapêutico , Resultado do Tratamento
12.
Pharmacotherapy ; 39(1): 40-54, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30414209

RESUMO

INTRODUCTION: Human leukocyte antigen (HLA)-B*5701 screening identifies patients at increased risk for abacavir (ABC) hypersensitivity reaction (HSR). Screening was adopted in GlaxoSmithKline and ViiV Healthcare clinical trials in 2007 and human immunodeficiency virus treatment guidelines in 2008. Company meta-analyses of trials pre-HLA-B*5701 screening reported HSR rates of 4-8%. We analyzed the effectiveness of HLA-B*5701 screening on reducing HSR rates using clinical trial, Observational Pharmaco-Epidemiology Research & Analysis (OPERA) cohort, and spontaneous reporting data. METHODS: A meta-analysis examined 12 trials in 3063 HLA-B*5701-negative patients receiving an ABC-containing regimen from April 9, 2007, to September 22, 2015. Potential cases were identified using prespecified Medical Dictionary for Regulatory Activities (MedDRA) preferred terms (drug hypersensitivity, hypersensitivity, anaphylactic reaction, anaphylaxis) and adjudicated against a Company ABC HSR case definition. Investigator-diagnosed cases were identified and rates were calculated. In the OPERA cohort, 9619 patients initiating their first ABC-containing regimen from January 1, 1999, to January 1, 2016, were identified. Patients were observed from regimen start until the earliest-following censoring event: ABC discontinuation, loss to follow-up, death, or study end (July 31, 2016). OPERA physicians evaluated events against OPERA definitions for definite/probable cases of ABC HSR; rates were calculated pre- and post-2008. The Company case definition was used to identify spontaneously reported cases for four marketed ABC-containing products; reporting rates were calculated using estimated exposure from sales data, through December 31, 2016. RESULTS: Suspected ABC HSR rates were 1.3% or less in the meta-analysis. In the OPERA cohort, the rate was 0.4% among patients initiating ABC post-2008 versus 1.3% pre-2008 (p<0.0001). Spontaneous reporting rates were low post-2008 (54 to 22 cases per 100,000 patient-years exposure [PYE]) versus pre-2008 (618 to 55 cases per 100,000 PYE). CONCLUSIONS: Clinically suspected ABC HSR rates were 1.3% or less in HLA-B*5701-negative patients. Recognizing their limitations, data from the OPERA cohort and spontaneous reporting indicate that HLA-B*5701 screening has reduced reporting rates of suspected HSR in clinical practice. Where screening for HLA-B*5701 is standard care, patients should be confirmed negative for this allele before starting ABC treatment.


Assuntos
Didesoxinucleosídeos/efeitos adversos , Hipersensibilidade a Drogas/etiologia , Antígenos HLA-B/genética , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/efeitos adversos , Didesoxinucleosídeos/administração & dosagem , Hipersensibilidade a Drogas/genética , Infecções por HIV/tratamento farmacológico , Humanos , Programas de Rastreamento/métodos
13.
J Antimicrob Chemother ; 74(1): 157-164, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30304447

RESUMO

Objectives: Abacavir use has been associated with an increased risk of cardiovascular disease (CVD) and metabolic events in HIV-infected patients, although this finding was not consistently found. It is unclear whether abacavir only increases this risk in subpopulations of HIV-infected patients. It may be hypothesized that inosine 5'-triphosphate pyrophosphohydrolase (ITPase), an enzyme involved in the metabolism of purine analogues used in HIV treatment, plays a role in the risk of CVD and metabolic events in HIV-infected patients. Methods: ITPase activity and ITPA genotype were determined in 393 HIV-infected patients. ITPase activity <4 mmol IMP/mmol Hb/h was considered decreased. ITPA polymorphisms tested were: c.94C>A (rs1127354) and c.124 + 21A>C (rs7270101). ORs were determined using generalized estimating equation models for developing CVD in patients who had ever been exposed to abacavir, tenofovir or didanosine and for developing metabolic events in patients currently using these drugs. Results: In patients using abacavir, metabolic events were associated with ITPase activity. No association was demonstrated for tenofovir or didanosine. The OR for metabolic events was 3.11 in patients using abacavir with normal ITPase activity (95% CI 1.34-7.21; P = 0.008) compared with patients with decreased ITPase activity [adjusted for age, BMI, cumulative duration of combination ART (cART) use and the use of PI and NNRTI]. CVD was not associated with ITPase activity or ITPA genotype. Conclusions: This study shows, for the first time, that ITPase activity is associated with the occurrence of metabolic events in patients using abacavir. Further studies are needed to confirm this association and to elucidate the possible mechanism.


Assuntos
Didesoxinucleosídeos/efeitos adversos , Eritrócitos/enzimologia , Infecções por HIV/tratamento farmacológico , Hipercolesterolemia/epidemiologia , Hipertensão/epidemiologia , Pirofosfatases/metabolismo , Inibidores da Transcriptase Reversa/efeitos adversos , Adulto , Idoso , Diabetes Mellitus/epidemiologia , Didanosina/efeitos adversos , Didanosina/uso terapêutico , Didesoxinucleosídeos/uso terapêutico , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Pirofosfatases/genética , Inibidores da Transcriptase Reversa/uso terapêutico , Tenofovir/efeitos adversos , Tenofovir/uso terapêutico
14.
Eur J Clin Microbiol Infect Dis ; 38(3): 423-426, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30443683
16.
J Bras Nefrol ; 41(1): 48-54, 2019.
Artigo em Inglês, Português | MEDLINE | ID: mdl-30010693

RESUMO

AIM: To determine the prevalence of chronic kidney disease (CKD) and the epidemiological, clinical, and laboratory factors associated with CKD in Mexican HIV-infected patients. METHODS: Cross-sectional study. We included 274 patients with HIV/AIDS. CKD was defined by the estimated glomerular filtration rate (eGFR < 60 mL/min/1.73 m2 assessed by CKD-EPI) and albuminuria criteria from KDIGO guidelines. Clinical, epidemiological, and laboratory characteristics were compared between patients with and without CKD. The factors associated with CKD were assessed by logistic regression analysis. RESULTS: The mean age was 41±11 years, and 72.3% of the patients were men. The global prevalence of CKD was 11.7% (n = 32); 7.2% (n = 20) were defined by eGFR criterion; 7.6% (n = 21), by the albuminuria criterion; and 3.2% (n = 9), by both CKD criteria. The most frequently observed stages of CKD were KDIGO G3A1 stage with 4.7% (n = 13), KDIGO G1A2 stage with 3.6% (n = 10) and KDIGO G3A2 stage with 1.7% (n = 5). The factors associated with CKD were use of abacavir/lamivudine (OR 3.2; 95% CI 1.1-8.9; p = 0.03), a CD4 lymphocyte count < 400 cells/µL (OR 2.6; 95% 1.03-6.4, p = 0.04), age (OR 1.1; 95% CI 1.04-1.2, p = 0.001) and albuminuria (OR 19.98; 95% CI: 5.5-72.2; p < 0.001). CONCLUSIONS: CKD was a frequent complication in HIV-infected patients. These findings confirm the importance of screening and the early detection of CKD, as well as the importance of identifying and treating traditional and non-traditional risk factors associated with CKD.


Assuntos
Infecções por HIV/complicações , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/etiologia , Adulto , Fatores Etários , Albuminúria , Fármacos Anti-HIV/efeitos adversos , Contagem de Linfócito CD4 , Estudos Transversais , Complicações do Diabetes , Didesoxinucleosídeos/efeitos adversos , Feminino , Taxa de Filtração Glomerular , Humanos , Hipertensão/complicações , Lamivudina/efeitos adversos , Modelos Logísticos , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Fatores de Risco
17.
J Allergy Clin Immunol ; 143(1): 66-73, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30573342

RESUMO

Controversies exist with regard to in vivo approaches to delayed immunologically mediated adverse drug reactions, such as exanthem (maculopapular eruption), drug reaction with eosinophilia and systemic symptoms, acute generalized exanthematous pustulosis, Stevens-Johnson syndrome/toxic epidermal necrolysis, and fixed drug eruptions. In particular, widespread differences exist between regions and practice on the availability and use of intradermal and patch testing, the standard drug concentrations used, the use of additional drugs in intradermal and patch testing to help determine cross-reactivity, the timing of testing in relation to the occurrence of the adverse drug reaction, the use of testing in specific phenotypes, and the use of oral challenge in conjunction with delayed intradermal and patch testing to ascertain drug tolerance. It was noted that there have been advances in the science of delayed T cell-mediated reactions that have shed light on immunopathogenesis and provided a mechanism of preprescription screening in the case of HLA-B*57:01 and abacavir hypersensitivity and HLA-B*15:02 and carbamazepine Stevens-Johnson syndrome/toxic epidermal necrolysis in Southeast Asian subjects. Future directions should include the collaboration of large international networks to develop and standardize in vivo diagnostic approaches, such as skin testing and patch testing, combined with ex vivo and in vitro laboratory approaches.


Assuntos
Antígenos HLA-B , Antígeno HLA-B15 , Síndrome de Stevens-Johnson , Animais , Grupo com Ancestrais do Continente Asiático , Carbamazepina/efeitos adversos , Carbamazepina/uso terapêutico , Didesoxinucleosídeos/efeitos adversos , Didesoxinucleosídeos/uso terapêutico , Antígenos HLA-B/genética , Antígenos HLA-B/imunologia , Antígeno HLA-B15/genética , Antígeno HLA-B15/imunologia , Humanos , Testes Cutâneos/normas , Síndrome de Stevens-Johnson/genética , Síndrome de Stevens-Johnson/imunologia , Síndrome de Stevens-Johnson/patologia
18.
Yonsei Med J ; 59(10): 1245-1252, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30450860

RESUMO

PURPOSE: A high risk of cardiovascular disease (CVD) is reported for HIV-infected individuals. While a link between abacavir and CVD risk is suggested, an association between abacavir and hypertension remains unclear. This study evaluated hypertension risk with abacavir use in comparison to non-abacavir antiretroviral treatment (ART). MATERIALS AND METHODS: From a nationwide cohort of HIV-infected individuals on their initial ART, 6493 who were free of hypertension at baseline were analyzed. The use of ART was treated as a time-varying covariate measured as a daily unit. Incidence rate of hypertension was calculated, and Cox proportional hazard models were used to estimate adjusted hazard ratios (HRs) with 95% confidence interval (CI) of incident hypertension overall and among subgroups. RESULTS: From the 6493 participants, 24072 person-years (PY) of follow-up were contributed during 2008-2016. The incidence rates of hypertension were 4.6 and 3.6 per 100 PY for abacavir and non-abacavir ART users, respectively. The population attributable fraction of abacavir use on hypertension was 12%. Abacavir exposure did not elevate the risk of hypertension among overall study population [HR, 1.2 (95% CI, 1.0-1.4), p=0.061]. However, those with poor ART adherence, defined as a medication possession ratio <50% [HR, 1.9 (95% CI, 1.5-2.4), p<0.0001] or requiring prophylactic antibiotics [HR, 1.2 (95% CI, 1.0-1.3), p=0.023], were at risk of hypertension induced by abacavir, as were men, individuals aged ≥40 years, and patients visiting tertiary hospitals in urban areas. CONCLUSION: When present, poor ART adherence, requiring prophylactic antibiotics, male sex, and older age may warrant additional concern for hypertension in patients treated with abacavir.


Assuntos
Fármacos Anti-HIV/efeitos adversos , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Didesoxinucleosídeos/efeitos adversos , Infecções por HIV/tratamento farmacológico , Hipertensão/induzido quimicamente , Adolescente , Adulto , Fármacos Anti-HIV/administração & dosagem , Terapia Antirretroviral de Alta Atividade/métodos , Estudos de Coortes , Didesoxinucleosídeos/administração & dosagem , Feminino , Humanos , Hipertensão/epidemiologia , Incidência , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , República da Coreia/epidemiologia , Fatores de Risco
19.
Ann Dermatol Venereol ; 145(12): 773-776, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30301570

RESUMO

BACKGROUND: Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are antiretroviral drugs often used in the first-line treatment regimen of HIV1 infection worldwide. We report a case of successive gynecomastia and Stevens-Johnson syndrome (SJS) respectively induced by efavirenz and nevirapine in a single patient. CASE REPORT: A 16-year-old boy, HIV1-infected since birth, was started on antiretroviral treatment (ART) in August 2015 and was taking a regimen comprising abacavir, lamivudine and efavirenz. In April 2016, when his weight reached 35kg, abacavir was replaced with tenofovir. Bilateral breast enlargement, previously hidden by the patient, was diagnosed two years after the start of ART. History-taking, physical examination and laboratory tests ruled out known causes of gynecomastia, and efavirenz was thus considered the most likely cause. This drug was then withdrawn and replaced with nevirapine in July 2017. Thirty-three days after the patient started nevirapine treatment, a skin rash appeared. Physical examination revealed erythematous macules and flaccid bullae with estimated skin detachment of 10%. There were also conjunctival, buccal and genital lesions. A diagnosis was made of SJS induced by nevirapine. Three months after withdrawal of efavirenz, breast size decreased by 3cm on the left breast and 2cm on the right breast; two months after the SJS, cutaneous sequelae alone persisted, such as diffuse hyperchromic macules. DISCUSSION: Recognition of gynecomastia as a side-effect of efavirenz is important to allow the condition to be treated while it is still potentially reversible. Moreover, when efavirenz is replaced, a protease inhibitor should be preferred to nevirapine.


Assuntos
Fármacos Anti-HIV/efeitos adversos , Ginecomastia/induzido quimicamente , Infecções por HIV/tratamento farmacológico , Nevirapina/efeitos adversos , Inibidores da Transcriptase Reversa/efeitos adversos , Síndrome de Stevens-Johnson/etiologia , Adolescente , Benzoxazinas/administração & dosagem , Benzoxazinas/efeitos adversos , Benzoxazinas/uso terapêutico , Didesoxinucleosídeos/administração & dosagem , Didesoxinucleosídeos/efeitos adversos , Didesoxinucleosídeos/uso terapêutico , Substituição de Medicamentos , Infecções por HIV/complicações , Humanos , Lamivudina/administração & dosagem , Lamivudina/efeitos adversos , Lamivudina/uso terapêutico , Masculino , Mucosite/induzido quimicamente , Nevirapina/administração & dosagem , Nevirapina/uso terapêutico
20.
Mol Immunol ; 101: 488-499, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30125869

RESUMO

Adverse drug reactions have been linked with genetic polymorphisms in HLA genes in numerous different studies. HLA proteins have an essential role in the presentation of self and non-self peptides, as part of the adaptive immune response. Amongst the associated drugs-allele combinations, anti-HIV drug Abacavir has been shown to be associated with the HLA-B*57:01 allele, and anti-epilepsy drug Carbamazepine with B*15:02, in both cases likely following the altered peptide repertoire model of interaction. Under this model, the drug binds directly to the antigen presentation region, causing different self peptides to be presented, which trigger an unwanted immune response. There is growing interest in searching for evidence supporting this model for other ADRs using bioinformatics techniques. In this study, in silico docking was used to assess the utility and reliability of well-known docking programs when addressing these challenging HLA-drug situations. The overall aim was to address the uncertainty of docking programs giving different results by completing a detailed comparative study of docking software, grounded in the MHC-ligand experimental structural data - for Abacavir and to a lesser extent Carbamazepine - in order to assess their performance. Four docking programs: SwissDock, ROSIE, AutoDock Vina and AutoDockFR, were used to investigate if each software could accurately dock the Abacavir back into the crystal structure for the protein arising from the known risk allele, and if they were able to distinguish between the HLA-associated and non-HLA-associated (control) alleles. The impact of using homology models on the docking performance and how using different parameters, such as including receptor flexibility, affected the docking performance were also investigated to simulate the approach where a crystal structure for a given HLA allele may be unavailable. The programs that were best able to predict the binding position of Abacavir were then used to recreate the docking seen for Carbamazepine with B*15:02 and controls alleles. It was found that the programs investigated were sometimes able to correctly predict the binding mode of Abacavir with B*57:01 but not always. Each of the software packages that were assessed could predict the binding of Abacavir and Carbamazepine within the correct sub-pocket and, with the exception of ROSIE, was able to correctly distinguish between risk and control alleles. We found that docking to homology models could produce poorer quality predictions, especially when sequence differences impact the architecture of predicted binding pockets. Caution must therefore be used as inaccurate structures may lead to erroneous docking predictions. Incorporating receptor flexibility was found to negatively affect the docking performance for the examples investigated. Taken together, our findings help characterise the potential but also the limitations of computational prediction of drug-HLA interactions. These docking techniques should therefore always be used with care and alongside other methods of investigation, in order to be able to draw strong conclusions from the given results.


Assuntos
Alelos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/genética , Antígenos HLA/química , Antígenos HLA/genética , Simulação de Acoplamento Molecular , Carbamazepina/efeitos adversos , Carbamazepina/química , Didesoxinucleosídeos/efeitos adversos , Didesoxinucleosídeos/química , Humanos , Peptídeos/química , Fatores de Risco , Software , Homologia Estrutural de Proteína
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