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1.
BMC Infect Dis ; 20(1): 532, 2020 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-32698772

RESUMO

BACKGROUND: The World Health Organisation recommends the use of tenofovir-containing pre-exposure prophylaxis (PrEP) as an additional Human Immunodeficiency Virus (HIV) prevention choice for men and women at substantial risk of HIV infection. PrEP could fill an important HIV prevention gap, especially for sexually active young women who are limited in their ability to negotiate mutual monogamy or condom use. As PrEP is scaled up in high HIV incidence settings, it is crucial to consider the importance of early identification of HIV infection during PrEP use, to allow for rapid discontinuation of PrEP to reduce the risk of antiretroviral (ARV) resistance. The purpose of this case study is to provide this critical evidence. CASE PRESENTATION: This report describes a 20-year-old woman in a HIV sero-discordant relationship who initiated oral PrEP (tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC)) through a demonstration project (CAPRISA 084) in October 2017. Despite good adherence throughout her PrEP use, she tested HIV antibody positive at month nine of study participation. Retrospective testing showed increasing HIV viral load over time, and retrospective use of fourth-generation rapid HIV tests showed HIV detection (positive antigen/antibody) at month one. Sequencing confirmed a dominant wild type at month one with dual therapy resistance patterns emerging by month three (M184V and K65R mutations), which is suggestive of protracted PrEP use during an undetected HIV infection. The participant was referred to infectious diseases for further management of her HIV infection and was initiated on a first line, tenofovir-sparing regimen. At the time of this report (January 2020), the participant had been on ARV- therapy (ART) for 13 months and had no signs of either clinical, immunologic or virologic failure. CONCLUSIONS: This case report highlights the importance of appropriate HIV screening during wider oral PrEP scale-up in high HIV incidence settings to circumvent the consequences of prolonged dual therapy in an undiagnosed HIV infection and in turn prevent ARV resistance.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Combinação Emtricitabina e Fumarato de Tenofovir Desoproxila/uso terapêutico , Epidemias/prevenção & controle , Soropositividade para HIV/tratamento farmacológico , HIV-1/imunologia , Profilaxia Pré-Exposição/métodos , Administração Oral , Benzoxazinas/uso terapêutico , Combinação de Medicamentos , Farmacorresistência Viral/efeitos dos fármacos , Farmacorresistência Viral/genética , Combinação Emtricitabina e Fumarato de Tenofovir Desoproxila/administração & dosagem , Combinação Emtricitabina e Fumarato de Tenofovir Desoproxila/efeitos adversos , Feminino , HIV-1/genética , Humanos , Lamivudina/uso terapêutico , Estudos Retrospectivos , África do Sul , Resultado do Tratamento , Carga Viral/efeitos dos fármacos , Adulto Jovem , Zidovudina/uso terapêutico
2.
Lancet HIV ; 7(5): e332-e339, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32386721

RESUMO

BACKGROUND: Late initiation of HIV antiretroviral therapy (ART) in pregnancy is associated with not achieving viral suppression before giving birth and increased mother-to-child transmission of HIV. We aimed to investigate virological suppression before giving birth with dolutegravir compared with efavirenz, when initiated during the third trimester. METHODS: In this randomised, open-label trial, DolPHIN-2, we recruited pregnant women in South Africa and Uganda aged at least 18 years, with untreated but confirmed HIV infection and an estimated gestation of at least 28 weeks, initiating ART in third trimester. Participants were randomly assigned (1:1) to dolutegravir-based or efavirenz-based therapy. HIV viral load was measured 7 days and 28 days after antiretroviral initiation, at 36 weeks' gestation, and at the post-partum visit (0-14 days post partum). The primary efficacy outcome was a viral load of less than 50 copies per mL at the first post-partum visit, and the primary safety outcome was the occurrence of drug-related adverse events in mothers and infants until the post-partum visit. Longer-term follow-up of mothers and infants continues. This study is registered with ClinicalTrials.gov, NCT03249181. FINDINGS: Between Jan 23, and Aug 15, 2018, we randomly assigned 268 mothers to dolutegravir (135) or efavirenz (133). All mothers and their infants were included in the safety analysis, and 250 mothers (125 in the dolutegravir group, 125 in the efavirenz group) and their infants in efficacy analyses, by intention-to-treat analyses. The median duration of maternal therapy at birth was 55 days (IQR 33-77). 89 (74%) of 120 in the dolutegravir group had viral loads less than 50 copies per mL, compared with 50 (43%) of 117 in the efavirenz group (risk ratio 1·64, 95% CI 1·31-2·06). 30 (22%) of 137 mothers in the dolutegravir group reported serious adverse events compared with 14 (11%) of 131 in the efavirenz group (p=0·013), particularly surrounding pregnancy and puerperium. We found no differences in births less than 37 weeks and less than 34 weeks gestation (16·4% vs 3·3%, across both groups). Three stillbirths in the dolutegravir group and one in the efavirenz group were considered unrelated to treatment. Three infant HIV infections were detected, all in the dolutegravir group, and were considered likely to be in-utero transmissions. INTERPRETATION: Our data support the revision to WHO guidelines recommending the transition to dolutegravir in first-line ART for all adults, regardless of pregnancy or child-bearing potential. FUNDING: Unitaid.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Benzoxazinas/uso terapêutico , Infecções por HIV/tratamento farmacológico , Inibidores de Integrase de HIV/uso terapêutico , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Adulto , Fármacos Anti-HIV/efeitos adversos , Benzoxazinas/efeitos adversos , Feminino , Infecções por HIV/mortalidade , Inibidores de Integrase de HIV/efeitos adversos , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Humanos , Recém-Nascido , Transmissão Vertical de Doença Infecciosa/prevenção & controle , Avaliação de Resultados em Cuidados de Saúde , Gravidez , Resultado da Gravidez , Terceiro Trimestre da Gravidez , Carga Viral/efeitos dos fármacos
3.
Lancet HIV ; 7(5): e322-e331, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32386720

RESUMO

BACKGROUND: Although antiretroviral regimens containing integrase inhibitors rapidly suppress HIV viral load in non-pregnant adults, few published data from randomised controlled trials have compared the safety and efficacy of any integrase inhibitor to efavirenz when initiated during pregnancy. We compared safety and efficacy of antiretroviral therapy with either raltegravir or efavirenz in late pregnancy. METHODS: An open-label, randomised controlled trial was done at 19 hospitals and clinics in Argentina, Brazil, South Africa, Tanzania, Thailand, and the USA. Antiretroviral-naive pregnant women (20-<37 weeks gestation) living with HIV were assigned to antiretroviral regimens containing either raltegravir (400 mg twice daily) or efavirenz (600 mg each night) plus lamivudine 150 mg and zidovudine 300 mg twice daily (or approved alternative backbone regimen), using a web-based, permuted-block randomisation stratified by gestational age and backbone regimen. The primary efficacy outcome was plasma HIV viral load below 200 copies per mL at (or near) delivery. The primary efficacy analysis included all women with a viral load measurement at (or near) delivery who had viral load of at least 200 copies per mL before treatment and no genotypic resistance to any study drugs; secondary analyses eliminated these exclusion criteria. The primary safety analyses included all women who received study drug, and their infants. This trial is registered with Clinicaltrials.gov, number NCT01618305. FINDINGS: From Sep 5, 2013, to Dec 11, 2018, 408 women were enrolled (206 raltegravir, 202 efavirenz) and 394 delivered on-study (200 raltegravir, 194 efavirenz); 307 were included in the primary efficacy analysis (153 raltegravir, 154 efavirenz). 144 (94%) women in the raltegravir group and 129 (84%) in the efavirenz group met the primary efficacy outcome (absolute difference 10%, 95% CI 3-18; p=0·0015); the difference primarily occurred among women enrolling later in pregnancy (interaction p=0·040). Frequencies of severe or life-threatening adverse events were similar among mothers (30% in each group; 61 raltegravir, 59 efavirenz) and infants (25% in each group; 50 raltegravir, 48 efavirenz), with no treatment-related deaths. INTERPRETATION: Our findings support major guidelines. The integrase inhibitor dolutegravir is currently a preferred regimen for the prevention of perinatal HIV transmission with raltegravir recommended as a preferred or alternative integrase inhibitor for pregnant women living with HIV. FUNDING: Eunice Kennedy Shriver National Institute of Child Health and Human Development and National Institute of Allergy and Infectious Diseases.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Benzoxazinas/uso terapêutico , Infecções por HIV/tratamento farmacológico , Inibidores de Integrase de HIV/uso terapêutico , Complicações Infecciosas na Gravidez/tratamento farmacológico , Raltegravir Potássico/uso terapêutico , Adulto , Fármacos Anti-HIV/efeitos adversos , Benzoxazinas/efeitos adversos , Quimioterapia Combinada , Feminino , Infecções por HIV/prevenção & controle , Humanos , Recém-Nascido , Transmissão Vertical de Doença Infecciosa/prevenção & controle , Lamivudina/uso terapêutico , Avaliação de Resultados em Cuidados de Saúde , Gravidez , Raltegravir Potássico/efeitos adversos , Carga Viral/efeitos dos fármacos , Adulto Jovem , Zidovudina/uso terapêutico
4.
Medicine (Baltimore) ; 99(16): e19789, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32311990

RESUMO

BACKGROUND: Combinations of long-acting bronchodilators with different mechanisms of action are recommended to improve prognosis and reduce risk of adverse events of chronic obstructive pulmonary disease (COPD). It is unclear whether the new combination therapy with long-acting muscarinic antagonist (LAMA) tiotropium (TIO) and long acting beta-agonists (LABA) olodaterol (OLO) was superior to tiotropium alone. METHODS: We measured the efficacy of the TIO/OLO combination vsTIO alone for COPD patients based on electronic databases up to February 2019. After rigorous quality review, data was extracted from eligible trials. All the main outcomes were pooled analysis using RevMan software. RESULTS: A total of 6 randomized controlled trials (RCTs) were identified. The pooled results of our meta-analysis demonstrated that FEV1 [MD = 0.03, 95% CI (-0.01,0.07), P = .18], FVC [MD = -0.03, 95%CI (-0.06,0.00), P = .09] and FEV1%pred [MD = 0.35, 95%CI (-0.30, 0.99), P = .29] all showed no significant difference between the 2 groups. The overall incidence of adverse effects (AEs) [OR = 1.01,95%CI (0.93,1.09), P = .87] and serious AEs [OR = 1.04,95% CI (0.82, 1.32), P = .72] in the combination group was similar to that of the TIO alone group, without statistical significance. CONCLUSION: These studies reported that the TIO/OLO combination did not show superior effects than tiotropium alone for COPD. Additionally, both therapies were well tolerated.


Assuntos
Benzoxazinas/uso terapêutico , Broncodilatadores/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Brometo de Tiotrópio/uso terapêutico , Combinação de Medicamentos , Volume Expiratório Forçado , Humanos , Capacidade Vital
5.
Pharmacogenet Genomics ; 30(3): 45-53, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32106141

RESUMO

OBJECTIVE: In AIDS Clinical Trials Group study A5316, efavirenz lowered plasma concentrations of etonogestrel and ethinyl estradiol, given as a vaginal ring, while atazanavir/ritonavir increased etonogestrel and lowered ethinyl estradiol concentrations. We characterized the pharmacogenetics of these interactions. METHODS: In A5316, women with HIV enrolled into control (no antiretrovirals), efavirenz [600 mg daily with nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs)], and atazanavir/ritonavir (300/100 mg daily with NRTIs) groups. On day 0, a vaginal ring was inserted, releasing etonogestrel/ethinyl estradiol 120/15 µg/day. Intensive plasma sampling for antiretrovirals was obtained on days 0 and 21, and single samples for etonogestrel and ethinyl estradiol on days 7, 14, and 21. Seventeen genetic polymorphisms were analyzed. RESULTS: The 72 participants in this analysis included 25, 24 and 23 in the control, efavirenz, and atazanavir/ritonavir groups, respectively. At day 21 in the efavirenz group, CYP2B6 genotype was associated with increased plasma efavirenz exposure (P = 3.2 × 10), decreased plasma concentrations of etonogestrel (P = 1.7 × 10), and decreased ethinyl estradiol (P = 6.7 × 10). Compared to controls, efavirenz reduced median etonogestrel concentrations by at least 93% in CYP2B6 slow metabolizers versus approximately 75% in normal and intermediate metabolizers. Efavirenz reduced median ethinyl estradiol concentrations by 75% in CYP2B6 slow metabolizers versus approximately 41% in normal and intermediate metabolizers. CONCLUSION: CYP2B6 slow metabolizer genotype worsens the pharmacokinetic interaction of efavirenz with hormonal contraceptives administered by vaginal ring. Efavirenz dose reduction in CYP2B6 slow metabolizers may reduce, but will likely not eliminate, this interaction.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Sulfato de Atazanavir/uso terapêutico , Benzoxazinas/uso terapêutico , Anticoncepcionais Femininos/sangue , Contraceptivos Hormonais/sangue , Ritonavir/uso terapêutico , Adulto , Sulfato de Atazanavir/farmacocinética , Benzoxazinas/farmacocinética , Anticoncepcionais Femininos/administração & dosagem , Anticoncepcionais Femininos/farmacocinética , Contraceptivos Hormonais/administração & dosagem , Contraceptivos Hormonais/farmacocinética , Dispositivos Anticoncepcionais Femininos , Citocromo P-450 CYP2B6/genética , Desogestrel/sangue , Desogestrel/farmacocinética , Interações Medicamentosas , Etinilestradiol/sangue , Etinilestradiol/farmacocinética , Feminino , Estudos de Associação Genética , Genótipo , Infecções por HIV/tratamento farmacológico , Infecções por HIV/genética , Humanos , Pessoa de Meia-Idade , Farmacogenética , Polimorfismo Genético , Polimorfismo de Nucleotídeo Único , Ritonavir/farmacocinética , Vagina
6.
BMC Infect Dis ; 20(1): 158, 2020 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-32075584

RESUMO

BACKGROUND: Although the global human immunodeficiency virus (HIV) epidemic has improved significantly due to antiretroviral treatment (ART), ART-related adverse events (AEs) remain an issue. Therefore, investigating the factors associated with ART-related AEs may provide vital information for monitoring risks. METHODS: A prospective cohort study was conducted among adult patients (aged 18 years or older) with HIV who received Tenofovir (TDF) + Lamivudine (3TC) + Efavirenz (EFV) as first-line ART regimens. All AEs during the first 12 months of therapy were recorded. Logistic regression analysis was used to identify variables associated with AEs. RESULTS: Four hundred seventy-four patients receiving TDF+ 3TC+ EFV ART regimens between March 2017 and October 2017 were included in the study analysis. Among them, 472 (99.6%) experienced at least one AE, 436 (92.0%) patients experienced at least one AE within 1 month of treatment, 33 (7.0%) between one and 3 months of treatment, and three (0.6%) patients after 3 months of treatment. The most commonly reported AE was nervous system (95.6%) related, followed by dyslipidemia (79.3%), and impaired liver function (48.1%). Patients with baseline body mass index (BMI) greater than 24 kg/m2 (adjusted OR 1.77, 95%CI 1.03-3.02), pre-existing multiple AEs (adjusted OR 2.72, 95%CI 1.59-4.64), and pre-existing severe AEs (adjusted OR 5.58, 95%CI 2.65-11.73) were at increased odds of developing a severe AE. Patients with baseline BMI greater than 24 kg/m2 (adjusted OR 2.72, 95%CI 1.25-5.89) were more likely to develop multiple AEs. CONCLUSION: The incidence of ART-related adverse events over a 12-month period in China was high. Baseline BMI greater than 24 kg/m2, pre-existing multiple AEs, and pre-existing severe AEs were shown to be independent risk factors for developing a severe AE.


Assuntos
Fármacos Anti-HIV/efeitos adversos , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Infecções por HIV/tratamento farmacológico , Adolescente , Adulto , Fármacos Anti-HIV/uso terapêutico , Benzoxazinas/efeitos adversos , Benzoxazinas/uso terapêutico , Índice de Massa Corporal , China/epidemiologia , Dislipidemias/induzido quimicamente , Dislipidemias/epidemiologia , Feminino , Humanos , Incidência , Lamivudina/efeitos adversos , Lamivudina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Cobertura de Condição Pré-Existente , Estudos Prospectivos , Tenofovir/efeitos adversos , Tenofovir/uso terapêutico , Adulto Jovem
7.
Medwave ; 20(1): e7767, 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31999679

RESUMO

Elephantiasis nostras verrucosa, a rare manifestation of Kaposis sarcoma, is a progressive cutaneous hypertrophy caused by chronic non-filarial lymphedema secondary to obstruction of the lymphatic system that can lead to severe disfigurement of parts of the body that have gravity-dependent blood flow, due to edema, fibrosis, and hyperkeratosis, especially lower extremities. Among the various conditions that can induce chronic lymphedema are tumors, trauma, radiotherapy, obesity, hypothyroidism, chronic venous stasis, and AIDS-related Kaposis sarcoma. Kaposis sarcoma is a vascular tumor associated with the presence of human gammaherpesvirus 8 that is predominantly cutaneous, locally aggressive, with metastasis, and is associated with the production of factors that favor inflammation, lymphatic obstruction, and lymphedema.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/complicações , Elefantíase/diagnóstico , Sarcoma de Kaposi/complicações , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/patologia , Fármacos Anti-HIV/uso terapêutico , Benzoxazinas/uso terapêutico , Didanosina/uso terapêutico , Quimioterapia Combinada , Elefantíase/etiologia , Elefantíase/patologia , Humanos , Lamivudina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Sarcoma de Kaposi/tratamento farmacológico , Sarcoma de Kaposi/patologia
8.
Sci Rep ; 10(1): 586, 2020 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-31953521

RESUMO

To characterize the use of olodaterol and indacaterol in clinical practice and to quantify the off-label use in asthma. Drug utilization study of new users of olodaterol or indacaterol between 2014 and 2017 in the PHARMO Database Network in the Netherlands, the Danish population registers, and the IMS Real-World Evidence Longitudinal Patient Database panels in France. On-label use was defined as use among adults with a recorded diagnosis of COPD. Off-label use was defined as use among adults with a recorded diagnosis of asthma without a recorded diagnosis of COPD or as use among patients aged ≤18 years. Potential off-label use was defined as no recorded diagnosis of either COPD or asthma. The study included 4,158 new users of olodaterol and 9,966 new users of indacaterol. Prevalence of off-label use ranged from 3.5% for both drugs to 12.4% for olodaterol and 11.9% for indacaterol. Prevalence of on-label use ranged from 47.8% to 77.7% for olodaterol and from 28.7% to 70.1% for indacaterol. The remaining new users of olodaterol and indacaterol were classified as potential off-label users, with prevalence ranging from 17.3% to 48.6% for olodaterol and from 20.5% to 66.6% for indacaterol. This study provides no evidence of a major concern in Europe for olodaterol or indacaterol for off-label use in asthma or for pediatric use.


Assuntos
Asma/tratamento farmacológico , Benzoxazinas/uso terapêutico , Broncodilatadores/uso terapêutico , Indanos/uso terapêutico , Uso Off-Label/estatística & dados numéricos , Quinolonas/uso terapêutico , Adulto , Idoso , Estudos Transversais , Dinamarca , Uso de Medicamentos , Feminino , França , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos , Prevalência , Adulto Jovem
9.
BMC Infect Dis ; 20(1): 68, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31964348

RESUMO

BACKGROUND: Cryptococcal meningitis (CCM) is a common and deadly disease among HIV-infected patients. Notable about CCM is its association with the immune reconstitution inflammatory syndrome (IRIS). Though it has been posited a switch from first to second-line antiretroviral therapy (ART) can induce CCM IRIS, a case presentation of CCM IRIS has not been published. CASE PRESENTATION: A 10-year-old, HIV-infected girl who initially presented with severe headache and new-onset seizures, with cerebrospinal fluid that returned antigen, India Ink, and culture positive for Cryptococcus neoformans. Notably, 8 weeks prior to seizures, she had switched from first line to second-line ART (abacavir-lamivudine-efavirenz to zidovudine-lamivudine-lopinavir/ritonavir) due to virologic failure, with a viral load of 224,000 copies/milliliter. At time of seizures and 8 weeks on second-line ART, her viral load had reduced to 262 copies/milliliter. Her hospital course was prolonged, as she had ongoing headaches and developed bilateral cranial nerve VI palsies despite clearance of Cryptococcus from cerebrospinal fluid on antifungal therapy and therapeutic lumbar punctures. However, symptoms stabilized, and she was discharged with oral fluconazole. Cranial nerve palsies resolved 10 weeks post discharge and she has remained disease free. CONCLUSIONS: We describe a case of CCM IRIS in a 10-year-old HIV infected child after changing to second-line ART. This case provides evidence that screening for cryptococcal antigenaemia prior to switch from first-line to second-line ART could be an important measure to prevent cryptococcal disease.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Fármacos Anti-HIV/uso terapêutico , Cryptococcus neoformans/isolamento & purificação , HIV/efeitos dos fármacos , Síndrome Inflamatória da Reconstituição Imune/diagnóstico , Lamivudina/uso terapêutico , Lopinavir/uso terapêutico , Meningite Criptocócica/diagnóstico , Ritonavir/uso terapêutico , Zidovudina/uso terapêutico , Infecções Oportunistas Relacionadas com a AIDS/complicações , Antifúngicos/uso terapêutico , Antígenos de Fungos/sangue , Benzoxazinas/uso terapêutico , Criança , Didesoxinucleosídeos/uso terapêutico , Combinação de Medicamentos , Feminino , Fluconazol/uso terapêutico , HIV/isolamento & purificação , Humanos , Síndrome Inflamatória da Reconstituição Imune/etiologia , Lamivudina/efeitos adversos , Meningite Criptocócica/tratamento farmacológico , Meningite Criptocócica/etiologia , Ritonavir/efeitos adversos , Resultado do Tratamento , Carga Viral , Zidovudina/efeitos adversos
10.
J Med Chem ; 63(12): 6474-6476, 2020 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-31845585

RESUMO

Cytochrome P450 46A1 (CYP46A1) or cholesterol-24-hydroxylase is responsible for cholesterol metabolism and homeostasis in the human brain. More recently its activity has been linked to brain function and disease. The anti-HIV drug efavirenz activates CYP46A1 at low drug levels while inhibiting the enzyme activity at the high dose used in clinical practice. Synthetic analogs and hydroxylated metabolites of efavirenz enhance CYP46A1 activity, with reduced unwanted enzyme inhibition at higher concentrations. These observations provide a platform for structural modifications of efavirenz to modulate CYP46A1 activity as a therapeutic target of brain disorders such as Alzheimer's disease, for which currently no treatment is available.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Benzoxazinas/uso terapêutico , Encéfalo/efeitos dos fármacos , Colesterol 24-Hidroxilase/metabolismo , Indutores do Citocromo P-450 CYP3A/uso terapêutico , Doença de Alzheimer/patologia , Animais , Benzoxazinas/química , Colesterol 24-Hidroxilase/química , Indutores do Citocromo P-450 CYP3A/química , Humanos
11.
AIDS Care ; 32(1): 12-20, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31142146

RESUMO

This study was to compare global and domain-specific neurocognitive performance between older people living with HIV (PLWH) taking/not taking efavirenz (EFV) and HIV-negative controls. A cross-sectional study was conducted in Yongzhou city, China. All PLWH older than 50 years listed on the registry of Centres for Disease Control and Prevention were invited to join the study. Frequency matching was used to sample HIV-negative controls according to the distribution of age, sex, and years of formal education of older PLWH. A total of 308 older PLWH and 350 HIV-negative controls completed the face-to-face interview and neurocognitive assessment using the comprehensive neuropsychological test battery. After adjusting for significant confounders, older PLWH taking EFV showed poorer performance in memory (p = 0.020), verbal fluency (p = 0.002), and poorer global neurocognitive performance (p = 0.032) than those without EFV use. Compared to HIV-negative controls, older PLWH taking EFV had poorer performance in all neurocognitive domains (p values: <0.001-0.003) and poorer global neurocognitive performance (p < 0.001). Similar trends were observed when comparing older PLWH without using EFV versus HIV-negative controls, with the exception of verbal fluency (p = 0.560). Health care workers should monitor the neuropsychological performance of older PLWH, epically those who were taking EFV. Longitudinal studies are warranted.


Assuntos
Benzoxazinas/uso terapêutico , Infecções por HIV/tratamento farmacológico , Testes Neuropsicológicos , Inibidores da Transcriptase Reversa/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , China , Estudos Transversais , Feminino , Infecções por HIV/psicologia , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade
12.
Sci Rep ; 9(1): 19923, 2019 12 27.
Artigo em Inglês | MEDLINE | ID: mdl-31882645

RESUMO

In 2007, HIV treatment services were established in five main governorates out of twenty-two which resulted in low access to services and poor treatment outcomes. The main goal of this study was to evaluate and analyse the selected treatment outcomes of eight cohorts of PLHIV who were treated with cART during 2007-2014. The method used was a retrospective descriptive study of 1,703 PLHIV who initiated cART at five public health facilities. The results: Retention rate was less than 80%, male: female ratio 1.661, with a mean age of 35 years (±9.2 SD), 85% had been infected with HIV via heterosexual contact. 65% of patients presented with clinical stages 3 and 4, and 52% of them were initiated cART at a CD4 T-cell count ≤200 cells/mm. 61% of cART included Tenofovir and Efavirenz. TB treatment started for 5% of PLHIV, and 22% developed HIV-related clinical manifestations after cART initiation. 67% of PLHIV had experienced cART substitution. The mean AIDS-mortality rate was 15% and the mean LTFU rate was 16%. Conclusion: Although cART showed effectiveness in public health, mobilization of resources and formulation of better health policies are important steps toward improving access to cART and achieving the desired treatment outcomes.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Antirretrovirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , Adulto , Terapia Antirretroviral de Alta Atividade/métodos , Benzoxazinas/uso terapêutico , Contagem de Linfócito CD4 , Quimioterapia Combinada/métodos , Feminino , Humanos , Masculino , Estudos Retrospectivos , Tenofovir/uso terapêutico , Resultado do Tratamento , Iêmen , Adulto Jovem
13.
S Afr Med J ; 110(1): 10-15, 2019 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-31865936

RESUMO

BACKGROUND: Effective combination antiretroviral therapy (cART) has tremendously reduced HIV-associated morbidity, mortality and mother-to-child transmission. However, the benefits of cART are threatened by comorbidities, adverse drug reactions and virus resistance to existing treatment regimens. One of the most occurring comorbidities is cytomegalovirus (CMV) infection. OBJECTIVES: To investigate the effects of cART on the occurrence of CMV infection among pregnant women. METHODS: Using a cross-sectional study design, 175 HIV-infected pregnant women were recruited, and data were obtained from their clinical records. Blood samples were collected for host DNA, CMV DNA and plasma efavirenz (EFV) measurement. CMV DNA was measured using real-time polymerase chain reaction (PCR). CYP2B6 c.516G>T and CYP2B6 c.983T>C single nucleotide polymorphisms were characterised using PCR/restriction fragment length polymorphism and TaqMan assays, respectively. Plasma EFV concentrations were determined using high-performance liquid chromatography. RESULTS: There was an inverse association between plasma EFV concentration and CMV DNA. Participants with lower plasma EFV concentrations were significantly (p<0.001) more likely to be CMV DNA positive than those with higher plasma concentrations. This result is also supported by the observation that carriers of CYP2B6 poor-metaboliser genotypes (CYP2B6 c.516T/T and CYP2B6 c.983T/C) were less likely to be positive for CMV DNA. Furthermore, poor metabolism as denoted by CYP2B6 c.516T/T and CYP2B6 c.983T/C genotypes was significantly associated with lower CMV viral load. CONCLUSIONS: HIV treatment disrupts the balance between host and co-infecting microbes. Reduced or subtherapeutic levels of antiretroviral drugs, which could be exacerbated by genetic polymorphisms in drug metabolism genes and non-adherence, predispose infected individuals to an increased risk of CMV infection in pregnancy.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/etiologia , Benzoxazinas/farmacocinética , Coinfecção/etiologia , Infecções por Citomegalovirus/etiologia , Complicações Infecciosas na Gravidez/etiologia , Inibidores da Transcriptase Reversa/farmacocinética , Infecções Oportunistas Relacionadas com a AIDS/sangue , Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/prevenção & controle , Adulto , Benzoxazinas/sangue , Benzoxazinas/uso terapêutico , Coinfecção/sangue , Coinfecção/diagnóstico , Coinfecção/prevenção & controle , Estudos Transversais , Infecções por Citomegalovirus/sangue , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/prevenção & controle , Feminino , Humanos , Gravidez , Complicações Infecciosas na Gravidez/sangue , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/prevenção & controle , Inibidores da Transcriptase Reversa/sangue , Inibidores da Transcriptase Reversa/uso terapêutico , Fatores de Risco
14.
Zhonghua Jie He He Hu Xi Za Zhi ; 42(11): 838-844, 2019 Nov 12.
Artigo em Chinês | MEDLINE | ID: mdl-31694094

RESUMO

Objective: To compare the efficacy and safety profiles of tiotropium/olodaterol with the mono-components in Chinese and total study population from TONADO trial. Methods: In the replicate, double-blind, parallel-group, active-controlled, randomized, 52-week, Phase Ⅲ TONADO studies (TONADO 1+2), patients received tiotropium/olodaterol, tiotropium, or olodaterol via the Respimat(®) Inhaler (Boehringer Ingelheim, Germany). Primary end points were forced expiratory volume in 1 second (FEV(1)) area under the curve from 0 to 3 hours (AUC(0-3h)) response and trough FEV(1) response, and St George's respiratory questionnaire (SGRQ) total score at 24 weeks. Adverse events were also collected. This subgroup analysis only focused on the efficacy and safety of the drug at the approved dose in China. Results: 548 Chinese patients were randomized, aged 41 to 82 years [mean age, (63±8) years] and most were male (526, 96%), 111 received tiotropium/olodaterol 5/5 µg, and 127 received tiotropium 5 µg and 95 received olodaterol 5 µg. The baseline characteristics of these groups were similar. After 24 weeks, treatment with tiotropium/olodaterol 5/5 µg, tiotropium 5 µg and olodaterol 5 µg resulted in an adjusted mean FEV(1) AUC(0-3h) response of 0.240, 0.157 and 0.079 L, and trough FEV(1) response of 0.117, 0.068 and-0.001 L, respectively. Tiotropium/olodaterol 5/5 µg significantly improved SGRQ scores in Chinese patients compared with olodaterol 5 µg (32.729 and 37.202, respectively). Generally, the safety profile of tiotropium/olodaterol was comparable with mono-components in 52 weeks. Conclusion: Compared with tiotropium or olodaterol, tiotropium/olodaterol in Chinese patients provided significant improvement in lung function and quality of life, and the safety profiles were similar.


Assuntos
Benzoxazinas/administração & dosagem , Broncodilatadores/administração & dosagem , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Qualidade de Vida , Brometo de Tiotrópio/administração & dosagem , Administração por Inalação , Agonistas de Receptores Adrenérgicos beta 2 , Adulto , Idoso , Idoso de 80 Anos ou mais , Benzoxazinas/uso terapêutico , Broncodilatadores/uso terapêutico , China/epidemiologia , Método Duplo-Cego , Volume Expiratório Forçado , Humanos , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/etnologia , Doença Pulmonar Obstrutiva Crônica/psicologia , Brometo de Tiotrópio/uso terapêutico , Resultado do Tratamento
15.
Medicina (B Aires) ; 79(5): 345-348, 2019.
Artigo em Espanhol | MEDLINE | ID: mdl-31671383

RESUMO

Hypovitaminosis D is frequent worldwide. In Argentina, according to studies conducted between 1987 and 2015, prevalence was > 40% in the general population. In people living with HIV it may vary between 20 and 90%, but the prevalence in our environment is not known. Our objective was to determine the prevalence of hypovitaminosis D in a cohort of adults with HIV infection in the city of Buenos Aires. We analyzed retrospectively medical records of 814 HIV positive subjects older than 18 years with at least one determination of vitamin D. The median age was 44 years (interquartile range 21-80), 746 (91.6%) were men, and 813 (99.9%) were on antiretroviral treatment. Univariate and multivariate analyses were performed to determine the association of hypovitaminosis D with CD4 values, viral load for HIV, and antiretroviral therapy. The present study shows that, in our environment, hypovitaminosis D is very common in people with HIV infection. Although it does not reveal evidence of a relationship with viral load for HIV, immune status, or antiretroviral treatment, the systematic search for hypovitaminosis D is mandatory in this population, taking into account its high frequency and the increased risk of osteopenia, osteoporosis and fractures, as described in people with HIV.


Assuntos
Instituições de Assistência Ambulatorial/estatística & dados numéricos , Infecções por HIV/epidemiologia , Deficiência de Vitamina D/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antirreumáticos/uso terapêutico , Argentina/epidemiologia , Benzoxazinas/uso terapêutico , Contagem de Linfócito CD4 , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Inibidores da Transcriptase Reversa/uso terapêutico , Fatores de Risco , Carga Viral , Deficiência de Vitamina D/etiologia , Adulto Jovem
16.
Int J Chron Obstruct Pulmon Dis ; 14: 2343-2354, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31632003

RESUMO

Background: Reduced physical activity is associated with increased morbidity and mortality in patients with COPD. Studies suggest that treatment with the long-acting muscarinic antagonist tiotropium and the long-acting ß2-agonist olodaterol increases exercise capacity. This study assessed the effects of a fixed-dose combination (FDC) of tiotropium/olodaterol (delivered via Respimat®) on physical functioning in patients with stable COPD in a "real-world setting". Methods: An international, open-label, single-arm, non-interventional study conducted in nine countries measuring changes in self-reported physical functioning in COPD patients treated with tiotropium/olodaterol 5/5 µg FDC for approximately 6 weeks. The primary endpoint was therapeutic success, defined as a minimum 10-point increase in the 10-question Physical Functioning Questionnaire (PF-10) score. Secondary endpoints included absolute change in PF-10 from Visit 1 to Visit 2, patient general condition (measured by Physician's Global Evaluation score) and patient satisfaction with the treatment and device (assessed by Patient Satisfaction Questionnaire at the end of the study period). Results: Therapeutic success was observed in 67.8% of 7218 patients (95% CI 66.7, 68.8) in the final analysis set after approximately 6 weeks of treatment with tiotropium/olodaterol. Mean change in PF-10 score between Visit 1 and Visit 2 was 16.6 points (95% CI 16.2, 17.0). Therapeutic success was 64.3% (95% CI 63.0-65.6%) in patients with infrequent (≤1) and 76.1% (95% CI 74.3-77.9%) in patients with frequent (≥2) exacerbations (p<0.0001). Patient general condition improved as indicated by an improvement in Physician's Global Evaluation scores between visits. Most patients were very satisfied or satisfied with tiotropium/olodaterol treatment in general (81%), reported inhalation satisfaction (85%), and satisfactory handling of the device (84%). 1.3% of patients reported an investigator-defined drug-related adverse event. Conclusion: Treatment with tiotropium/olodaterol led to an improvement in self-reported physical functioning in patients with COPD.


Assuntos
Benzoxazinas/uso terapêutico , Exercício Físico/fisiologia , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Autorrelato , Brometo de Tiotrópio/uso terapêutico , Idoso , Combinação de Medicamentos , Europa (Continente) , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
17.
Braz J Infect Dis ; 23(5): 363-367, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31562853

RESUMO

Erythema multiforme (EM), Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis (TEN) have been reported as possible adverse effects of some classes of first-line antiretroviral drugs (ART) for HIV treatment. Herein we report an unusual presentation of TEN lesions associated with ART in an HIV-infected patient. The patient presented disseminated cutaneous eruption and oral lesions from the lips to the oropharynx region, causing odynophagia and dysphagia. In the tongue, circular, atypical erythematous lesions appeared, increasing in diameter over seven days and coalescing since then to complete remission. TEN treatment included efavirenz interruption, use of methylprednisolone, prophylactic antibiotic, and daily laser therapy with low-intensity red light. The circular oral lesions have not been described yet. Reporting our findings and clinical management may help diagnosing other similar cases and guide the clinical conduct. Analgesia and acceleration of oral ulcer repair with red laser therapy are recommended.


Assuntos
Terapia Antirretroviral de Alta Atividade/efeitos adversos , Benzoxazinas/efeitos adversos , Infecções por HIV/tratamento farmacológico , Síndrome de Stevens-Johnson/etiologia , Adulto , Benzoxazinas/uso terapêutico , Feminino , Humanos , Síndrome de Stevens-Johnson/diagnóstico
18.
Malar J ; 18(1): 277, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31429785

RESUMO

BACKGROUND: HIV-infected individuals on antiretroviral therapy (ART) require treatment with artemisinin-based combination therapy (ACT) when infected with malaria. Dihydroartemisinin-piperaquine (DPQ) is recommended for treatment of Plasmodium falciparum malaria, but its efficacy and safety has not been evaluated in HIV-infected individuals on ART, among whom drug-drug interactions are expected. Day-42 adequate clinical and parasitological response (ACPR) and incidence of adverse events were assessed in HIV-infected individuals on non-nucleoside reverse transcriptase inhibitor-based ART (efavirenz and nevirapine) with uncomplicated P. falciparum malaria treated with dihydroartemisinin-piperaquine. METHODS: An open label single arm clinical trial was conducted in Malawi (Blantyre and Chikhwawa districts) and Mozambique (Manhiça district) involving patients aged 15-65 years with uncomplicated P. falciparum malaria who were on efavirenz-based or nevirapine-based ART. They received a directly-observed 3-day standard treatment of DPQ and were followed up until day 63 for malaria infection and adverse events. Day-42 PCR-corrected-ACPRs (95% confidence interval [CI]) were calculated for the intention-to-treat (ITT) population. RESULTS: The study enrolled 160 and 61 patients on efavirenz and nevirapine-based ART, with a baseline geometric mean (95% CI) parasite density of 2681 (1964-3661) and 9819 (6606-14,593) parasites/µL, respectively. The day-42 PCR-corrected ACPR (95% CI) was 99.4% (95.6-99.9%) in the efavirenz group and 100% in the nevirapine group. Serious adverse events occurred in 5.0% (8/160) and 3.3% (2/61) of the participants in the efavirenz and nevirapine group, respectively, but none were definitively attributable to DPQ. Cases of prolonged QT interval (> 60 ms from baseline) occurred in 31.2% (48/154) and 13.3% (8/60) of the patients on the efavirenz and nevirapine ART groups, respectively. These were not clinically significant and resolved spontaneously over time. As this study was not designed to compare the efficacy and safety of DPQ in the two ART groups, no formal statistical comparisons were made between the two ART groups. CONCLUSIONS: DPQ was highly efficacious and safe for the treatment of malaria in HIV-infected patients concurrently taking efavirenz- or nevirapine-based ART, despite known pharmacokinetic interactions between dihydroartemisinin-piperaquine and efavirenz- or nevirapine-based ART regimens. Trial registration Pan African Clinical Trials Registry (PACTR): PACTR201311000659400. Registered on 4 October 2013, https://pactr.samrc.ac.za/Search.aspx.


Assuntos
Antirretrovirais/uso terapêutico , Antimaláricos/efeitos adversos , Artemisininas/efeitos adversos , Malária Falciparum/prevenção & controle , Quinolinas/efeitos adversos , Adolescente , Adulto , Benzoxazinas/uso terapêutico , Combinação de Medicamentos , Feminino , Humanos , Malaui , Masculino , Pessoa de Meia-Idade , Moçambique , Nevirapina/uso terapêutico , Plasmodium falciparum/fisiologia , Adulto Jovem
19.
BMC Infect Dis ; 19(1): 741, 2019 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-31443633

RESUMO

BACKGROUND: The use of fixed combination antiretroviral therapy with a low genetic barrier for the treatment of patients infected with human immunodeficiency virus (HIV) may affect the local HIV transmitted drug resistance (TDR) pattern. The present study aimed to investigate changes in the prevalence of HIV TDR following the implementation of a fixed regimen of HIV treatment in Taiwan in 2012. METHODS: TDR was measured in antiretroviral treatment-naïve HIV-1-infected individuals who participated in voluntary counseling and testing between 2007 and 2015 in southern Taiwan. Antiretroviral resistance mutations were interpreted using the HIVdb program from the Stanford University HIV Drug Resistance Database. RESULTS: Sequences were obtained from 377 consecutive individuals between 2007 and 2015. The overall prevalence rates of TDR HIV among the study population from 2007 to 2011 and 2012-2015 were 10.6 and 7.9%, respectively. Among the detected mutations, K103 N and V179D + K103R were more frequently observed after 2012. Four HIV-infected patients with K103 N variants were detected after 2012, and 4 of the 5 patients with V179D + K103R variants were found after 2012. No significant differences were observed in the TDRs among nucleoside reverse transcriptase inhibitors (NRTIs), non-NRTIs (NNRTIs), protease inhibitors, multiple drug resistance, and any drug resistance between period 1 (2007-2011) and period 2 (2012-2015). CONCLUSIONS: A fixed treatment regimen with zidovudine/lamivudine + efavirenz or nevirapine as first-line therapy for treatment-naïve patients infected with HIV did not significantly increase the TDR during the 4-year follow-up period. Due to the increase in NNRTI resistance associated with mutations after 2012, a longer follow-up period and larger sample size are needed in future studies.


Assuntos
Farmacorresistência Viral/genética , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , HIV-1/genética , Mutação , Adulto , Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Benzoxazinas/uso terapêutico , Combinação de Medicamentos , Farmacorresistência Viral/efeitos dos fármacos , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , Humanos , Lamivudina/uso terapêutico , Masculino , Nevirapina/uso terapêutico , Prevalência , Inibidores da Transcriptase Reversa/uso terapêutico , Taiwan/epidemiologia , Zidovudina/uso terapêutico
20.
Semin Neurol ; 39(3): 391-398, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31378874

RESUMO

Treatment of neurological, neurocognitive, and neuropsychiatric impairment in the setting of human immunodeficiency virus (HIV) infection remains a complex problem, given several possible mechanisms of pathogenesis. The etiology must be determined based on clinical judgment and objective evidence, including cerebrospinal fluid (CSF) data from lumbar puncture and neuroimaging information from magnetic resonance imaging, when available and indicated. Other neuroinfectious etiologies must be ruled out, including central nervous system (CNS) opportunistic infections. HIV replication in the CNS (including CSF escape) should be evaluated for and excluded. If CSF HIV is detected, we recommend a treatment switch to antiretrovirals (ARVs) targeted to address any CSF HIV resistance mutations identified, or empiric treatment intensification using ARVs with high CNS penetration. If CSF HIV is not detected, treatment intensification with CCR5 inhibitors may be considered as an adjunct to reduce neuroinflammation. Finally, the current ARV regimen must be examined for possible neurotoxicity. Efavirenz has been well-recognized for its neuropsychiatric adverse effects and potential for causing sleep disturbances. Similar concerns have recently been raised with integrase inhibitors, especially dolutegravir and raltegravir, although further studies are needed to determine the risks for clinically relevant neuropsychiatric side effects from these medications, given their overall high potency and proven success in treating systemic HIV.


Assuntos
Antirretrovirais/uso terapêutico , Infecções do Sistema Nervoso Central/tratamento farmacológico , Infecções por HIV/tratamento farmacológico , Benzoxazinas/uso terapêutico , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Humanos , Raltegravir Potássico/uso terapêutico
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