Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.990
Filtrar
2.
Zhonghua Jie He He Hu Xi Za Zhi ; 43(3): 170-172, 2020 Mar 12.
Artigo em Chinês | MEDLINE | ID: mdl-32164080

RESUMO

The recent outbreak of respiratory illness in Wuhan, China is caused by a novel coronavirus, named 2019-nCoV, which is genetically close to a bat-derived coronavirus. 2019-nCoV is categorized as beta genus coronavirus, same as the two other strains-severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). Antiviral drugs commonly used in clinical practice, including neuraminidase inhibitors (oseltamivir, paramivir, zanamivir, etc.), ganciclovir, acyclovir and ribavirin, are invalid for 2019-nCoV and not recommended. Drugs are possibly effective for 2019-nCoV include: remdesivir, lopinavir/ritonavir, lopinavir/ritonavir combined with interferon-ß, convalescent plasma, and monoclonal antibodies. But the efficacy and safety of these drugs for 2019-nCoV pneumonia patients need to be assessed by further clinical trials.


Assuntos
Antivirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Anticorpos Monoclonais/uso terapêutico , China , Inibidores do Citocromo P-450 CYP3A/uso terapêutico , Humanos , Interferon beta , Lopinavir/uso terapêutico , Coronavírus da Síndrome Respiratória do Oriente Médio , Ritonavir/uso terapêutico , Síndrome Respiratória Aguda Grave/tratamento farmacológico
3.
Zhonghua Jie He He Hu Xi Za Zhi ; 43(3): 173-176, 2020 Mar 12.
Artigo em Chinês | MEDLINE | ID: mdl-32164081

RESUMO

The new coronavirus pneumonia (NCP), also named as COVID-19 by WHO on Feb 11 2020, is now causing a severe public health emergency in China since. The number of diagnosed cases is more than 40,000 until the submission of this manuscript. Coronavirus has caused several epidemic situations world widely, but the present contagious disease caused by 2019 new coronavirus is unprecedentedly fulminating. The published cohorts of 2019 new coronavirus (n-Cov) are single-center studies, or retrospective studies. We here share the therapeutic experiences of NCP treatment with literature review. Combination of Ribavirin and interferon-α is recommended by the 5(th) edition National Health Commission's Regimen (Revised Edition) because of the effect on Middle East respiratory syndrome (MERS), and the effectiveness of Lopinavir/Ritonavir and Remdisivir needs to be confirmed by randomized controlled trial (RCT), given the situation of no specific antivirus drug on NCP is unavailable. Systemic glucocorticosteroid is recommended as a short term use (1~2 mg·kg(-1)·d(-1), 3~5 d) by the 5(th) edition National Health Commission's Regimen (Revised Edition) yet RCTs are expected to confirm the effectiveness. Inappropriate application of antibiotics should be avoided, especially the combination of broad-spectrum antibiotics, for the NCP is not often complicated with bacterial infection.


Assuntos
Adenosina/análogos & derivados , Alanina/análogos & derivados , Antivirais , Infecções por Coronavirus/tratamento farmacológico , Inibidores do Citocromo P-450 CYP3A/uso terapêutico , Lopinavir/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Ribonucleotídeos/uso terapêutico , Ritonavir/uso terapêutico , Adenosina/uso terapêutico , Alanina/uso terapêutico , Antibacterianos/uso terapêutico , China , Quimioterapia Combinada , Humanos , Estudos Retrospectivos
5.
Biosci Trends ; 14(1): 64-68, 2020 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-32037389

RESUMO

Pneumonia associated with the 2019 novel coronavirus (2019-nCoV) is continuously and rapidly circulating at present. No effective antiviral treatment has been verified thus far. We report here the clinical characteristics and therapeutic procedure for four patients with mild or severe 2019-nCoV pneumonia admitted to Shanghai Public Health Clinical Center. All the patients were given antiviral treatment including lopinavir/ritonavir (Kaletra®), arbidol, and Shufeng Jiedu Capsule (SFJDC, a traditional Chinese medicine) and other necessary support care. After treatment, three patients gained significant improvement in pneumonia associated symptoms, two of whom were confirmed 2019-nCoV negative and discharged, and one of whom was virus negative at the first test. The remaining patient with severe pneumonia had shown signs of improvement by the cutoff date for data collection. Results obtained in the current study may provide clues for treatment of 2019-nCoV pneumonia. The efficacy of antiviral treatment including lopinavir/ritonavir, arbidol, and SFJDC warrants further verification in future study.


Assuntos
Antivirais/uso terapêutico , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Indóis/uso terapêutico , Lopinavir/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Ritonavir/uso terapêutico , Adulto , China , Combinação de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
6.
J Korean Med Sci ; 35(6): e79, 2020 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-32056407

RESUMO

Since mid-December of 2019, coronavirus disease 2019 (COVID-19) infection has been spreading from Wuhan, China. The confirmed COVID-19 patients in South Korea are those who came from or visited China. As secondary transmissions have occurred and the speed of transmission is accelerating, there are rising concerns about community infections. The 54-year old male is the third patient diagnosed with COVID-19 infection in Korea. He is a worker for a clothing business and had mild respiratory symptoms and intermittent fever in the beginning of hospitalization, and pneumonia symptoms on chest computerized tomography scan on day 6 of admission. This patient caused one case of secondary transmission and three cases of tertiary transmission. Hereby, we report the clinical findings of the index patient who was the first to cause tertiary transmission outside China. Interestingly, after lopinavir/ritonavir (Kaletra, AbbVie) was administered, ß-coronavirus viral loads significantly decreased and no or little coronavirus titers were observed.


Assuntos
Infecções por Coronavirus , Inibidores do Citocromo P-450 CYP3A , Lopinavir , Pneumonia Viral , Pneumonia , Ritonavir , Betacoronavirus/genética , China , Infecções por Coronavirus/complicações , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/transmissão , Inibidores do Citocromo P-450 CYP3A/uso terapêutico , Combinação de Medicamentos , Humanos , Lopinavir/uso terapêutico , Masculino , Pessoa de Meia-Idade , Pneumonia/diagnóstico , Pneumonia/tratamento farmacológico , Pneumonia/etiologia , Pneumonia Viral/complicações , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/transmissão , Reação em Cadeia da Polimerase em Tempo Real , República da Coreia , Ritonavir/uso terapêutico , Carga Viral
7.
Nat Commun ; 11(1): 222, 2020 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-31924756

RESUMO

Middle East respiratory syndrome coronavirus (MERS-CoV) is the causative agent of a severe respiratory disease associated with more than 2468 human infections and over 851 deaths in 27 countries since 2012. There are no approved treatments for MERS-CoV infection although a combination of lopinavir, ritonavir and interferon beta (LPV/RTV-IFNb) is currently being evaluated in humans in the Kingdom of Saudi Arabia. Here, we show that remdesivir (RDV) and IFNb have superior antiviral activity to LPV and RTV in vitro. In mice, both prophylactic and therapeutic RDV improve pulmonary function and reduce lung viral loads and severe lung pathology. In contrast, prophylactic LPV/RTV-IFNb slightly reduces viral loads without impacting other disease parameters. Therapeutic LPV/RTV-IFNb improves pulmonary function but does not reduce virus replication or severe lung pathology. Thus, we provide in vivo evidence of the potential for RDV to treat MERS-CoV infections.


Assuntos
Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Infecções por Coronavirus/tratamento farmacológico , Interferon beta/uso terapêutico , Lopinavir/uso terapêutico , Coronavírus da Síndrome Respiratória do Oriente Médio/efeitos dos fármacos , Ritonavir/uso terapêutico , Monofosfato de Adenosina/uso terapêutico , Alanina/uso terapêutico , Animais , Antivirais/uso terapêutico , Carboxilesterase/genética , Infecções por Coronavirus/patologia , Combinação de Medicamentos , Desenvolvimento de Medicamentos , Feminino , Humanos , Lesão Pulmonar/patologia , Masculino , Camundongos , Camundongos Knockout , Carga Viral , Replicação Viral/efeitos dos fármacos
8.
Biosci Trends ; 14(1): 69-71, 2020 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-31996494

RESUMO

As of January 22, 2020, a total of 571 cases of the 2019-new coronavirus (2019-nCoV) have been reported in 25 provinces (districts and cities) in China. At present, there is no vaccine or antiviral treatment for human and animal coronavirus, so that identifying the drug treatment options as soon as possible is critical for the response to the 2019-nCoV outbreak. Three general methods, which include existing broad-spectrum antiviral drugs using standard assays, screening of a chemical library containing many existing compounds or databases, and the redevelopment of new specific drugs based on the genome and biophysical understanding of individual coronaviruses, are used to discover the potential antiviral treatment of human pathogen coronavirus. Lopinavir /Ritonavir, Nucleoside analogues, Neuraminidase inhibitors, Remdesivir, peptide (EK1), abidol, RNA synthesis inhibitors (such as TDF, 3TC), anti-inflammatory drugs (such as hormones and other molecules), Chinese traditional medicine, such ShuFengJieDu Capsules and Lianhuaqingwen Capsule, could be the drug treatment options for 2019-nCoV. However, the efficacy and safety of these drugs for 2019- nCoV still need to be further confirmed by clinical experiments.


Assuntos
Antivirais/uso terapêutico , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Alanina/análogos & derivados , Alanina/uso terapêutico , Combinação de Medicamentos , Descoberta de Drogas , Humanos , Lopinavir/uso terapêutico , Neuraminidase/antagonistas & inibidores , Nucleosídeos/uso terapêutico , Ribonucleotídeos/uso terapêutico , Ritonavir/uso terapêutico
10.
S Afr Med J ; 109(12): 919-926, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31865953

RESUMO

BACKGROUND: World Health Organization guidelines recommend that HIV patients who do not achieve viral suppression on efavirenz-based first-line antiretroviral therapy (ART) should be changed to a protease inhibitor (PI)-based regimen. In South Africa (SA), ~200 000 people are on second-line treatment, but little is known about these patients. OBJECTIVES: To describe second-line black African patients in a large urban area. METHODS: A quantitative retrospective study of 825 second-line patients in central Johannesburg, SA (subdistrict F), was performed with data extracted from government databases. Demographic characteristics, treatment status and laboratory information were gathered, then analysed with CD4+ cell count, viral load (VL) and retention-in-care data as outcome variables. RESULTS: The average recorded time to VL measurement after the switch to a PI-based ART regimen was 20 months, and 83.1% (570/686) of patients with a recent VL achieved viral suppression while on second-line treatment. The most recent median CD4+ cell count for the cohort was 286 cells/µL (interquartile range 160 - 478), which represented a 177 cells/µL increase from the baseline count at the start of first-line ART. Slightly less than three-quarters (72.4%) of the population remained active in care in the study clinics from initiation on first-line ART. Demographic characteristics such as being <25 years of age, male sex and geographical transfer (started initial treatment in a different region) independently predicted low CD4+ cell counts and virological failure on second-line treatment. Patients with virological failure were most likely (odds ratio (OR) 3.13, 95% confidence interval (CI) 1.50 - 6.56) to be lost to follow-up after the switch, while patients from Hillbrow Community Health Centre (OR 0.27, 95% CI 0.16 - 0.44), South Rand Hospital (OR 0.24, 95% CI 0.12 - 0.47) and Jeppe Clinic (OR 0.38, 95% CI 0.16 - 0.88), three larger sites, were most likely to remain active in care. CONCLUSIONS: VL suppression was high in patients on second-line treatment, but one-fifth of patients were lost to follow-up. Younger age, male sex and transfer from other treatment sites predicted poor treatment outcomes, highlighting opportunities for prioritisation of adherence interventions.


Assuntos
Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/uso terapêutico , Adesão à Medicação/estatística & dados numéricos , Carga Viral , Adulto , Fatores Etários , Contagem de Linfócito CD4 , Bases de Dados Factuais , Quimioterapia Combinada , Feminino , Infecções por HIV/imunologia , Humanos , Lamivudina/uso terapêutico , Lopinavir/uso terapêutico , Perda de Seguimento , Masculino , Pessoa de Meia-Idade , Retratamento , Estudos Retrospectivos , Inibidores da Transcriptase Reversa/uso terapêutico , Ritonavir/uso terapêutico , Fatores Sexuais , Tenofovir/uso terapêutico , Falha de Tratamento , Organização Mundial da Saúde , Zidovudina/uso terapêutico
11.
Infect Dis (Lond) ; 51(8): 593-601, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31219362

RESUMO

Background: The ritonavir-boosted protease inhibitor (PI/r) use has been associated with several metabolic abnormalities, and the non-alcoholic fatty liver disease (NAFLD) is becoming a very frequent comorbidity among HIV-infected patients. Methods: We performed an observational, prospective study of HIV-infected patients with NAFLD, receiving one PI/r plus two nucleoside analogues, who switched from the PI/r to raltegravir or were treated only with lifestyle modification, maintaining antiretroviral therapy unchanged. Changes in liver steatosis after 12 months were evaluated by transient elastography and measurement of controlled attenuation parameter (CAP). Results: As a whole, 61 patients (46 males; median age, 55.4 years) were enrolled, and 32 of them have been switched from PI/r to raltegravir. At baseline, median CAP was 259 dB/m, 28 (45.9%) subjects had a moderate-to-severe hepatic steatosis (CAP ≥260 dB/m), and 19 patients (31.1%) had elevated aminotransferases. Type-2 diabetes mellitus was present in 5 persons, and chronic HCV coinfection in 4. At month 12, the median decrease in CAP values was -27 dB/m in patients switched to raltegravir and -11 dB/m in those with unchanged cART (p = .021). The number of patients with CAP ≥260 dB/m decreased from 16 to 6 (-62.5%) in patients switched to raltegravir and from 12 to 8 (-33.3%) in the other group (p = .037). Conclusion: After 12 months, HIV-infected patients with NAFLD switching from a PI/r to raltegravir showed a significantly greater decrease in the hepatic steatosis degreee in comparison with those with unchanged cART and treated only with lifestyle modification.


Assuntos
Fígado Gorduroso/virologia , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/uso terapêutico , Hepatopatia Gordurosa não Alcoólica/virologia , Raltegravir Potássico/uso terapêutico , Ritonavir/uso terapêutico , Substituição de Medicamentos , Feminino , Infecções por HIV/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Estudos Prospectivos , Resultado do Tratamento
12.
Travel Med Infect Dis ; 30: 9-18, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31252170

RESUMO

BACKGROUND: The Middle East Respiratory Syndrome Coronavirus (MERS-CoV) was first described in 2012 and attracted a great international attention due to multiple healthcare associated outbreaks. The disease carries a high case fatality rate of 34.5%, and there is no internationally or nationally recommended therapy. METHOD: We searched MEDLINE, Science Direct, Embase and Scopus databases for relevant papers published till March 2019 describing in vitro, in vivo or human therapy of MERS. RESULTS: Initial search identified 62 articles: 52 articles were from Medline, 6 from Embase, and 4 from Science Direct. Based on the inclusions and exclusions criteria, 30 articles were included in the final review and comprised: 22 in vitro studies, 8 studies utilizing animal models, 13 studies in humans, and one study included both in vitro and animal model. There are a few promising therapeutic agents on the horizon. The combination of lopinavir/ritonavir and interferon-beta- 1b showed excellent results in common marmosets and currently is in a randomized control trial. Ribavirin and interferon were the most widely used combination and experience comes from a number of observational studies. Although, the data are heterogenous, this combination might be of potential benefit and deserve further investigation. There were no randomized clinical trials to recommend specific therapy for the treatment of MERS-CoV infection. Only one such study is planned for randomization and is pending completion. The study is based on a combination of lopinavir/ritonavir and interferon-beta- 1b. A fully human polyclonal IgG antibody (SAB-301) was safe and well tolerated in healthy individuals and this agent may deserve further testing for efficacy. CONCLUSION: Despite multiple studies in humans there is no consensus on the optimal therapy for MERS-CoV. Randomized clinical trials are needed and potential therapies should be evaluated only in such clinical trials. In order to further enhance the therapeutic aroma for MERS-CoV infection, repurposing old drugs against MERS-CoV is an interesting strategy and deserves further consideration and use in clinical settings.


Assuntos
Antivirais/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Coronavírus da Síndrome Respiratória do Oriente Médio , Animais , Combinação de Medicamentos , Humanos , Imunoglobulina G/uso terapêutico , Interferon beta/uso terapêutico , Lopinavir/uso terapêutico , Ritonavir/uso terapêutico
13.
BMC Infect Dis ; 19(1): 484, 2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-31146698

RESUMO

BACKGROUND: Network meta-analyses (NMAs) provide comparative treatment effects estimates in the absence of head-to-head randomized controlled trials (RCTs). This NMA compared the efficacy and safety of dolutegravir (DTG) with other recommended or commonly used core antiretroviral agents. METHODS: A systematic review identified phase 3/4 RCTs in treatment-naïve patients with HIV-1 receiving core agents: ritonavir-boosted protease inhibitors (PIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), or integrase strand inhibitors (INSTIs). Efficacy (virologic suppression [VS], CD4+ cell count change from baseline) and safety (adverse events [AEs], discontinuations, discontinuation due to AEs, lipid changes) were analyzed at Week 48 using Bayesian NMA methodology, which allowed calculation of probabilistic results. Subgroup analyses were conducted for VS (baseline viral load [VL] ≤/> 100,000copies/mL, ≤/> 500,000copies/mL; baseline CD4+ ≤/>200cells/µL). Results were adjusted for the nucleoside/nucleotide reverse transcriptase inhibitors (NRTI) combined with the core agent (except subgroup analyses). RESULTS: The NMA included 36 studies; 2 additional studies were included in subgroup analyses only. Odds of achieving VS with DTG were statistically superior to PIs (odds ratios [ORs] 1.78-2.59) and NNRTIs (ORs 1.51-1.86), and similar but numerically higher than other INSTIs. CD4+ count increase was significantly greater with DTG than PIs (difference: 23.63-31.47 cells/µL) and efavirenz (difference: 34.54 cells/µL), and similar to other core agents. INSTIs were more likely to result in patients achieving VS versus PIs (probability: 76-100%) and NNRTIs (probability: 50-100%), and a greater CD4+ count increase versus PIs (probability: 72-100%) and NNRTIs (probability: 60-100%). DTG was more likely to result in patients achieving VS (probability: 94-100%), and a greater CD4+ count increase (probability: 53-100%) versus other core agents, including INSTIs (probability: 94-97% and 53-93%, respectively). Safety outcomes with DTG were generally similar to other core agents. In patients with baseline VL > 100,000copies/mL or ≤ 200 CD4+cells/µL (18 studies), odds of achieving VS with DTG were superior or similar to other core agents. CONCLUSION: INSTI core agents had superior efficacy and similar safety to PIs and NNRTIs at Week 48 in treatment-naïve patients with HIV-1, with DTG being among the most efficacious, including in patients with baseline VL > 100,000copies/mL or ≤ 200 CD4+cells/µL, who can be difficult to treat.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Adolescente , Adulto , Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/classificação , Teorema de Bayes , Benzoxazinas/uso terapêutico , Contagem de Linfócito CD4 , Ensaios Clínicos Fase III como Assunto/estatística & dados numéricos , Ensaios Clínicos Fase IV como Assunto/estatística & dados numéricos , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Humanos , Masculino , Meta-Análise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Inibidores da Transcriptase Reversa/uso terapêutico , Ritonavir/uso terapêutico , Resultado do Tratamento , Carga Viral/efeitos dos fármacos , Adulto Jovem
14.
Georgian Med News ; (288): 77-81, 2019 Mar.
Artigo em Russo | MEDLINE | ID: mdl-31101781

RESUMO

The aim of this study was to investigate the efficacy and safety of the ombitasvir/ paritaprevir/ ritonavir and dasabuvir in patients with HCV, genotype-1b, in real clinical practice in Ukraine. The study included a total of 50 HCV infection genotype 1b patients receiving ombitasvir/ paritaprevir/ ritonavir and dasabuvir for 12 weeks. The patients were evaluated in respect of demographic, clinical and virological data, sustained virologic response (SVR) and adverse events. The mean age of patients was 52 years (40-60), 42% men, 20% treatment experienced, 42% with compensated cirrhosis. The SVR12 rate of all HCV genotype 1b patients was 96% (95%CI:86,3-99,5%). The most common adverse events were fatigue in 14 (28%) patients, diarrhea in 10 (20%) and headache in 12 (24%). In our study, the real world clinical practice data shows that ombitasvir/ paritaprevir/ ritonavir and dasabuvir for 12 weeks in HCV genotype 1b patients was well tolerated and resulted in 96% SVR12 regardless of previous treatment status and liver fibrosis stage.


Assuntos
Antivirais , Hepatite C Crônica , Adulto , Anilidas/uso terapêutico , Antivirais/uso terapêutico , Carbamatos/uso terapêutico , Quimioterapia Combinada , Feminino , Genótipo , Hepacivirus , Hepatite C Crônica/tratamento farmacológico , Humanos , Compostos Macrocíclicos/uso terapêutico , Masculino , Pessoa de Meia-Idade , Ribavirina , Ritonavir/uso terapêutico , Sulfonamidas/uso terapêutico , Resultado do Tratamento , Ucrânia , Uracila/análogos & derivados , Uracila/uso terapêutico
15.
Int J STD AIDS ; 30(7): 718-722, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30975070

RESUMO

The potential for drug-drug interactions (DDIs) between direct oral anticoagulants and antiretroviral therapy (ART) is vast. Ritonavir and cobicistat are used as pharmacokinetic enhancers with either concurrent protease inhibitors or the integrase strand transfer inhibitor, elvitegravir, to optimize therapeutic concentrations by cytochrome P450 (CYP) inhibition. To date, only rivaroxaban and dabigatran have reported cases of use with ritonavir-boosted ART. Apixaban is metabolized similarly to rivaroxaban, but offers a dose reduction in the case of major DDIs. We report the successful use of reduced-dose apixaban to treat and prevent thromboembolic complications in six persons living with human immunodeficiency virus (HIV) on ritonavir- or cobicistat-boosted ART. This case series and available literature support the use of apixaban or dabigatran, depending on the boosted ART regimen.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Cobicistat/uso terapêutico , Pirazóis/uso terapêutico , Piridonas/uso terapêutico , Ritonavir/uso terapêutico , Tromboembolia/tratamento farmacológico , Idoso , Interações de Medicamentos , Inibidores do Fator Xa , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Tromboembolia/prevenção & controle , Resultado do Tratamento
16.
J Acquir Immune Defic Syndr ; 81(4): 463-472, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-30985556

RESUMO

BACKGROUND: Doravirine is a novel, nonnucleoside reverse transcriptase inhibitor with demonstrated efficacy in treatment-naive adults with HIV-1. METHODS: In this open-label, active-controlled, noninferiority trial, adults with HIV-1 virologically suppressed for ≥6 months on 2 nucleoside reverse transcriptase inhibitors plus a boosted protease inhibitor, boosted elvitegravir, or a non-nucleoside reverse transcriptase inhibitor were randomized (2:1) to switch to once-daily, single-tablet doravirine 100 mg with lamivudine 300 mg and tenofovir disoproxil fumarate 300 mg (DOR/3TC/TDF) or to continue their current therapy (Baseline Regimen) for 24 weeks. The primary endpoint was the proportion of participants with HIV-1 RNA <50 copies/mL (defined by the FDA Snapshot approach), with the primary comparison between DOR/3TC/TDF at week 48 and Baseline Regimen at week 24 and a secondary comparison between the groups at week 24 (noninferiority margin, -8%). RESULTS: Six hundred seventy participants (447 DOR/3TC/TDF, 223 Baseline Regimen) were treated and included in the analyses. At week 24, 93.7% on DOR/3TC/TDF vs 94.6% on Baseline Regimen had HIV-1 RNA <50 copies/mL [difference -0.9 (-4.7 to 3.0)]. At week 48, 90.8% on DOR/3TC/TDF had HIV-1 RNA <50 copies/mL, demonstrating noninferiority vs Baseline Regimen at week 24 [difference -3.8 (-7.9 to 0.3)]. In participants on ritonavir-boosted protease inhibitor at entry, mean reductions in fasting LDL-C and non-HDL-C at week 24 were significantly greater for DOR/3TC/TDF vs Baseline Regimen (P < 0.0001). Adverse events occurred in 68.9% on DOR/3TC/TDF and 52.5% on Baseline Regimen by week 24, leading to treatment discontinuation in 2.5% and 0.4%, respectively. CONCLUSIONS: Switching to once-daily DOR/3TC/TDF is a generally well-tolerated option for maintaining viral suppression in patients considering a change in therapy. REGISTRATION: ClinicalTrials.gov NCT02397096.


Assuntos
Antirretrovirais/uso terapêutico , HIV-1/efeitos dos fármacos , Lamivudina/uso terapêutico , Piridonas/uso terapêutico , Tenofovir/uso terapêutico , Triazóis/uso terapêutico , Adulto , Idoso , Antirretrovirais/administração & dosagem , Estudos de Equivalência como Asunto , Feminino , Humanos , Lamivudina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Inibidores de Proteases/uso terapêutico , Piridonas/administração & dosagem , Quinolonas/uso terapêutico , Ritonavir/uso terapêutico , Tenofovir/administração & dosagem , Resultado do Tratamento , Triazóis/administração & dosagem , Adulto Jovem
17.
Int J STD AIDS ; 30(7): 710-714, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30961466

RESUMO

Organ transplantation among people living with human immunodeficiency virus (PLHIV) is increasing. Guidelines recommend any changes in antiretroviral therapy (ART) prior to transplantation, but there are limited data regarding ART changes post transplantation. We report a case where an ART switch from a protease inhibitor-based regimen to dolutegravir plus emtricitabine/tenofovir alafenamide in a renal transplant recipient led to subtherapeutic tacrolimus concentrations and an increased serum creatinine (SCr). A workup for graft rejection was performed (including kidney biopsy and cytomegalovirus and BK virus polymerase chain reaction) following the rise in SCr, which was higher than expected from dolutegravir initiation (via organ cation transporter 2 inhibition). This case highlights the potential challenges of switching ART regimens in PLHIV post transplantation.


Assuntos
Fármacos Anti-HIV/efeitos adversos , Antirretrovirais/efeitos adversos , Interações de Medicamentos , Substituição de Medicamentos , Infecções por HIV/tratamento farmacológico , Fármacos Anti-HIV/uso terapêutico , Antirretrovirais/administração & dosagem , Antirretrovirais/uso terapêutico , Creatinina/sangue , Compostos Heterocíclicos com 3 Anéis , Humanos , Rim/patologia , Falência Renal Crônica/cirurgia , Transplante de Rim , Masculino , Pessoa de Meia-Idade , Ritonavir/uso terapêutico , Resultado do Tratamento
18.
J Clin Pharm Ther ; 44(4): 640-643, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30830975

RESUMO

WHAT IS KNOWN AND OBJECTIVE: Treatment of tacrolimus toxicity includes holding tacrolimus and supportive care. The objective is to describe considerations for pharmacologic induction of tacrolimus metabolism. CASE DESCRIPTION: A 52-year-old male with a failed renal transplant on chronic haemodialysis developed tacrolimus toxicity due to a drug-drug interaction with darunavir/ritonavir. Tacrolimus concentrations were >60 ng/mL for 10 days despite holding tacrolimus and darunavir/ritonavir. Development of encephalopathy prompted initiation of phenytoin to induce tacrolimus metabolism. Tacrolimus concentration was <2 ng/mL within 4 days and mental status normalized. WHAT IS NEW AND CONCLUSION: Phenytoin metabolic induction is a therapeutic option for prolonged tacrolimus toxicity.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/tratamento farmacológico , Imunossupressores/efeitos adversos , Fenitoína/uso terapêutico , Tacrolimo/efeitos adversos , Darunavir/uso terapêutico , Interações de Medicamentos , Humanos , Masculino , Pessoa de Meia-Idade , Diálise Renal/métodos , Ritonavir/uso terapêutico
19.
BMC Infect Dis ; 19(1): 280, 2019 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-30909871

RESUMO

BACKGROUND: The World Health Organisation approved boosted atazanavir as a preferred second line protease inhibitor in 2010. This is as an alternative to the current boosted lopinavir. Atazanavir has a lower genetic barrier than lopinavir. We compared the virological outcomes of patients during the roll out of routine viral load monitoring, who had switched to boosted second- line regimens of either atazanavir or lopinavir. METHODS: This was a cross-sectional study involving adult patients at the Infectious Diseases Institute Kampala, Uganda started on a standard WHO recommended second-line regimen containing either boosted atazanavir or boosted lopinavir between 1 Dec 2014 and 31 July 2015.. Mantel -Haenszel chi square was used to test for the statistical significance of the odds of being suppressed (VL < 400 copies/ml) when on boosted atazanavir compared to boosted lopinavir after stratifying by duration on antiretroviral therapy (ART). Multivariate logistic regression analysis used to determine if the type of boosted protease inhibitor (bPI) was associated with virological outcome. RESULTS: Ninety (90) % on ATV/r and 83% on LPV/r had a VL less than 1000 copies/ml. The odds of being suppressed using the same viral load cut-off while on boosted atazanavir compared to boosted lopinavir was not statistically significant after stratifying for duration on ART (p = 0.09). In a multivariate analysis the type of bPI used was not a predictor of virological outcome (p = 0.60). CONCLUSIONS: Patients using the WHO recommended second-line of boosted atazanavir have comparable virological suppression to those on boosted lopinavir.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Sulfato de Atazanavir/uso terapêutico , Infecções por HIV/tratamento farmacológico , Lopinavir/uso terapêutico , Ritonavir/uso terapêutico , Adulto , Instituições de Assistência Ambulatorial , Estudos Transversais , Quimioterapia Combinada , Feminino , Inibidores da Protease de HIV/uso terapêutico , Humanos , Masculino , Uganda , Carga Viral/efeitos dos fármacos
20.
Indian J Tuberc ; 66(1): 129-133, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30797270

RESUMO

BACKGROUND & OBJECTIVE: Rifabutin (RBT) is the rifamycin that is recommended to treat tuberculosis (TB) in HIV-infected individuals during combination antiretroviral therapy (ART) containing HIV protease inhibitors (PIs). We studied the pharmacokinetics of rifabutin at doses of 300 mg thrice weekly and 150 mg daily during concomitant atazanavir/ritonavir (ATZ/r) administration in adult HIV-infected TB patients treated in the Revised National TB Control Programme (RNTCP) in India. METHODS: This was a multi-centric study conducted in 45 adult HIV-infected TB patients, who were being treated for TB with a RBT-containing regimen and an antiretroviral treatment regimen with ATZ/r, at doses of 300 mg thrice-weekly (n = 36) or 150 mg daily (n = 9). Serial blood draws at pre-dosing and at 1, 2, 4, 6, 8, 12 and 24 hours after drug administration were done. Plasma RBT was estimated by high pressure liquid chromatography (HPLC). RESULTS: The peak concentration (Cmax) of both doses were within the therapeutic range (0.45-0.90 µg/ml) of RBT. Proportion of patients having Cmax above or below the therapeutic range and trough concentration (Cmin) below the minimum inhibitory concentration of RBT did not significantly differ between the two doses. TB treatment outcomes were also similar at both doses. CONCLUSIONS: This is the first and only study from India reporting on the pharmacokinetics of RBT at 300 mg thrice weekly and 150 mg daily doses. Both doses yielded similar plasma RBT concentrations, outcomes and were well tolerated. RBT can be administered at either doses during ATZ/r co-administration in HIV-infected patients with TB.


Assuntos
Antibióticos Antituberculose/farmacocinética , Sulfato de Atazanavir/uso terapêutico , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/uso terapêutico , Rifabutina/farmacocinética , Ritonavir/uso terapêutico , Tuberculose/tratamento farmacológico , Adulto , Antibióticos Antituberculose/administração & dosagem , Interações de Medicamentos , Feminino , Infecções por HIV/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Rifabutina/administração & dosagem , Tuberculose/complicações
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA