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1.
Arch Virol ; 164(12): 3019-3026, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31598843

RESUMO

Polyethyleneimine (PEI) is a chemical compound that used is as a carrier in gene therapy/delivery. Some studies have investigated the microbicidal potential and antiviral activity (prophylactic or therapeutic) of PEI and its derivatives. The aim of this study was to investigate the effect of branched polyethyleneimine (bPEI) on human immunodeficiency virus (HIV) replication. Infected cells were treated with bPEI for 36 hours, and the concentration of the viral protein P24 (as a virus replication marker) was determined in cell culture supernatants. This study indicated that bPEI increased HIV replication and decreased the viability of infected cells through cytotoxicity. The toxicity of bPEI its association with and cell death (apoptosis, autophagy and necrosis) have been reported in several studies. To investigate bPEI-induced cytotoxicity, we examined apoptosis and autophagy in cells treated with bPEI, and a significant increase in HIV viral load, the P24 antigen level, autophagy, and necrosis observed. Thus, treatment with bPEI leads to cytotoxicity and higher HIV virus yield.


Assuntos
Infecções por HIV/virologia , HIV/efeitos dos fármacos , Polietilenoimina/farmacologia , Replicação Viral/efeitos dos fármacos , Autofagia/efeitos dos fármacos , HIV/genética , HIV/fisiologia , Proteína do Núcleo p24 do HIV/genética , Proteína do Núcleo p24 do HIV/metabolismo , Infecções por HIV/fisiopatologia , Humanos , Polietilenoimina/química , Carga Viral/efeitos dos fármacos
3.
Medicine (Baltimore) ; 98(32): e16683, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31393369

RESUMO

Interferon-alpha (IFN-α) is currently the preferred antiviral treatment for children with chronic hepatitis B (CHB) aged >1-year-old. However, the evidence regarding the exact efficacy and safety in the real world is not sufficient. This study aimed to investigate the efficacy of IFN-α therapy in children with CHB and to provide a theoretical basis for practically identifying ideal antiviral therapies for CHB children.Clinical manifestations, baseline characteristics, related laboratory tests, and adverse events were retrospectively analyzed in children with CHB who visited the Children's Hospital of Fudan University, were treated with IFN-α and were followed up from January 2003 to October 2018.A total of 18 immune-active patients without advanced fibrosis were enrolled, and their average age at the start of treatment was 4.45 ±â€Š2.75 years old. IFN α-2b was administered subcutaneously by body surface area (BSA) category, based on 3 MU/m, for a median 48 weeks. Before treatment, the alanine aminotransferase (ALT) range was 81 to 409 U/L (median 158 U/L). The median hepatitis B virus (HBV)-DNA load was 9.89 × 10 IU/mL, and the HBV-DNA load varied from 3.10 × 10 to 4.56 × 10 IU/mL. The ALT levels of 17 children became normal at an average of 12 weeks during treatment, and those of 1 child became normal at 6 weeks after IFN-α withdrawal. Sixteen (88.9%, 16/18) children became HBV-DNA negative (<10 IU/mL) at an average of 24 weeks during treatment, while 1 became negative at 96 weeks after IFN-α withdrawal and 1 remained HBV-DNA positive. HBV e antigen (HBeAg) seroconversion occurred in 13 of 14 (92.9%, 13/14) HBeAg-positive patients at an average of 12 weeks during treatment. HBV s antigen (HBsAg) loss or seroconversion occurred in 4 (22.2%, 4/18) patients at an average of 21 weeks during treatment. Only mild flu-like symptoms and transient neutropenia appeared in some children at the early treatment stage. No severe abnormal results were observed in other laboratory parameters.The antiviral monotherapy of 48 weeks of IFN-α was well tolerated and good responded, which was associated with higher rates of HBeAg seroconversion and HBsAg clearance in the children in this study than in previously reported adults and pediatric patients.


Assuntos
Antivirais/administração & dosagem , Hepatite B Crônica/tratamento farmacológico , Interferon-alfa/administração & dosagem , Adolescente , Antivirais/farmacologia , Criança , Pré-Escolar , China , Estudos de Coortes , Feminino , Seguimentos , Humanos , Injeções Subcutâneas , Interferon-alfa/farmacologia , Masculino , Soroconversão/efeitos dos fármacos , Carga Viral/efeitos dos fármacos
4.
Medicine (Baltimore) ; 98(32): e16721, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31393378

RESUMO

The aim of this retrospective cohort study was to compare safety, efficacy and rates and reasons of discontinuation of the 3 currently approved integrase strand transfer inhibitors (INSTIs) elvitegravir (EVG), dolutegravir (DTG), and raltegravir (RAL) in HIV-infected treatment-naïve and -experienced patients in a real-world cohort. One hundred four treatment-naïve patients were prescribed an INSTI-based combined antiretroviral therapy (cART)-regimen (first-line group) and 219 patients were switched to an INSTI-based cART-regimen from another treatment regimen (switch group) at our institution between May 2007 and December 2014. Twelve months after initiation of treatment, 92% of patients in the first-line group (EVG: 96%, n = 22/23; DTG: 92%, n = 34/37; RAL: 90%, n = 28/31) and 88% of patients in the switch group (EVG: 94%, n = 32/34; DTG: 90%, n = 69/77; RAL: 85%, n = 67/79) showed full virological suppression (viral load <50 copies/mL). Side effects of any kind occurred in 12% (n = 12/104) of patients in the first-line group, and 10% (n = 21/219) of patients in the switch group. In the switch group neuropsychiatric side effects (depression, vertigo, and sleep disturbances) occurred more frequently in patients treated with DTG (11%, n = 10) compared to the 2 other INSTI-based cART-regimen (EVG: 2%, n = 1; RAL: 1%, n = 1). Side effects only rarely led to discontinuation of treatment (first-line-group: 2%, n = 2/104; switch-group: 1%, n = 3/219). In this real-world setting, INSTI-based ART-regimens were highly efficacious with no significant differences between any of the 3 INSTIs. Overall, side effects were only rarely observed and generally mild in all subgroups. In light of a slightly higher incidence of vertigo and sleep disturbances in patients switched to DTG, awareness of the potential onset of psychiatric symptoms is warranted during follow-up in those patients.


Assuntos
Infecções por HIV/tratamento farmacológico , Inibidores de Integrase de HIV/administração & dosagem , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Quinolonas/administração & dosagem , Raltegravir Potássico/administração & dosagem , Adulto , Idoso , Antirretrovirais , Terapia Antirretroviral de Alta Atividade/métodos , Feminino , Inibidores de Integrase de HIV/efeitos adversos , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Quinolonas/efeitos adversos , Quinolonas/uso terapêutico , Raltegravir Potássico/efeitos adversos , Estudos Retrospectivos , Carga Viral/efeitos dos fármacos , Adulto Jovem
5.
N Engl J Med ; 381(9): 816-826, 2019 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-31339676

RESUMO

BACKGROUND: An efavirenz-based regimen (with a 600-mg dose of efavirenz, known as EFV600) was the World Health Organization preferred first-line treatment for human immunodeficiency virus type 1 (HIV-1) infection until June 2018. Given concerns about side effects, dolutegravir-based and low-dose efavirenz-based combinations have been considered as first-line treatments for HIV-1 in resource-limited settings. METHODS: We conducted an open-label, multicenter, randomized, phase 3 noninferiority trial in Cameroon. Adults with HIV-1 infection who had not received antiretroviral therapy and had an HIV-1 RNA level (viral load) of at least 1000 copies per milliliter were randomly assigned to receive either dolutegravir or the reference treatment of low-dose efavirenz (a 400-mg dose, known as EFV400), combined with tenofovir and lamivudine. The primary end point was the proportion of participants with a viral load of less than 50 copies per milliliter at week 48, on the basis of the Food and Drug Administration snapshot algorithm. The difference between treatment groups was calculated, and noninferiority was tested with a margin of 10 percentage points. RESULTS: A total of 613 participants received at least one dose of the assigned regimen. At week 48, a viral load of less than 50 copies per milliliter was observed in 231 of 310 participants (74.5%) in the dolutegravir group and in 209 of 303 participants (69.0%) in the EFV400 group, with a difference of 5.5 percentage points (95% confidence interval [CI], -1.6 to 12.7; P<0.001 for noninferiority). Among those with a baseline viral load of at least 100,000 copies per milliliter, a viral load of less than 50 copies per milliliter was observed in 137 of 207 participants (66.2%) in the dolutegravir group and in 123 of 200 participants (61.5%) in the EFV400 group, with a difference of 4.7 percentage points (95% CI, -4.6 to 14.0). Virologic failure (a viral load of >1000 copies per milliliter) was observed in 3 participants in the dolutegravir group (with none acquiring drug-resistance mutations) and in 16 participants in the EFV400 group. More weight gain was observed in the dolutegravir group than in the EFV400 group (median weight gain, 5.0 kg vs. 3.0 kg; incidence of obesity, 12.3% vs. 5.4%). CONCLUSIONS: In HIV-1-infected adults in Cameroon, a dolutegravir-based regimen was noninferior to an EFV400-based reference regimen with regard to viral suppression at week 48. Among participants who had a viral load of at least 100,000 copies per milliliter when antiretroviral therapy was initiated, fewer participants than expected had viral suppression. (Funded by Unitaid and the French National Agency for AIDS Research; NAMSAL ANRS 12313 ClinicalTrials.gov number, NCT02777229.).


Assuntos
Benzoxazinas/administração & dosagem , Infecções por HIV/tratamento farmacológico , Inibidores de Integrase de HIV/efeitos adversos , HIV-1 , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Adulto , Benzoxazinas/efeitos adversos , Quimioterapia Combinada , Feminino , Inibidores de Integrase de HIV/uso terapêutico , HIV-1/genética , HIV-1/isolamento & purificação , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Humanos , Lamivudina/administração & dosagem , Masculino , Obesidade/induzido quimicamente , Gravidez , RNA Viral/sangue , Tenofovir/administração & dosagem , Carga Viral/efeitos dos fármacos , Ganho de Peso/efeitos dos fármacos
6.
AIDS Behav ; 23(9): 2337-2346, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31297681

RESUMO

The HIV/AIDS epidemic can be eliminated if 73% of people living with HIV take antiretroviral medications and achieve undetectable viral loads. This study assessed the effects of financial incentives in suppressing viral load. People living with HIV with detectable viral loads (N = 102) were randomly assigned to Usual Care or Incentive groups. Incentive participants earned up to $10 per day for 2 years for providing blood samples that showed either reduced or undetectable viral loads. This report presents data on the 1st year after random assignment. Incentive participants provided more (adjusted OR = 15.6, CI 4.2-58.8, p < 0.001) blood samples at 3-month assessments with undetectable viral load (72.1%) than usual care control participants (39.0%). We collected most blood samples. The study showed that incentives can substantially increase undetectable viral loads in people living with HIV. Financial incentives for suppressed viral loads could contribute to the eradication of the HIV/AIDS epidemic.


Assuntos
Antirretrovirais/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Motivação , Carga Viral/efeitos dos fármacos , Adulto , Epidemias , Feminino , Infecções por HIV/epidemiologia , Humanos , Masculino , Adesão à Medicação , Avaliação de Resultados (Cuidados de Saúde)
7.
AIDS Behav ; 23(9): 2326-2336, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31324996

RESUMO

While poverty is an established barrier to achieving success at each step of the HIV care continuum, less is known about specific aspects of poverty and how they overlap with behavior in exceptionally low-income individuals who live in well-resourced areas. We considered unsuppressed viral load over 3 years among women living with HIV in San Francisco who used homeless shelters, low-income hotels and free meal programs. One-hundred twenty study participants were followed; 60% had > 1 unsuppressed viral load and 19% were unsuppressed at every visit. Across six-month intervals, the odds of unsuppressed viral load were 11% higher for every 10 nights spent sleeping on the street [Adjusted Odds Ratio (AOR) 1.11, 95% CI 1.02-1.20]; 16% higher for every 10 nights spent sleeping in a shelter (AOR/10 nights 1.16, 95% CI 1.06-1.27); 4% higher for every 10 nights spent sleeping in a single-room occupancy hotel (AOR/10 nights 1.04, 95% CI 1.02-1.07); and over threefold higher among women who experienced any recent incarceration (AOR 3.56, 95% CI 1.84-6.86). Violence and recent use of outpatient health care did not significantly predict viral suppression in adjusted analysis. While strategies to promote retention in care are important for vulnerable persons living with HIV, they are insufficient to ensure sustained viral suppression in low-income women experiencing homelessness and incarceration. Results presented here in combination with prior research linking incarceration to homelessness among women indicate that tailored interventions, which not only consider but prioritize affordable housing, are critical to achieving sustained viral suppression in low-income women living with HIV.


Assuntos
Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Pessoas em Situação de Rua/estatística & dados numéricos , Habitação Popular/estatística & dados numéricos , Carga Viral/efeitos dos fármacos , Adolescente , Adulto , Feminino , Infecções por HIV/epidemiologia , Pessoas em Situação de Rua/psicologia , Humanos , Estudos Longitudinais , Pessoa de Meia-Idade , Razão de Chances , Avaliação de Resultados (Cuidados de Saúde) , Pobreza , São Francisco/epidemiologia , Testes Sorológicos , Adulto Jovem
8.
Nat Immunol ; 20(8): 1059-1070, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31308541

RESUMO

Dysfunction of virus-specific CD4+ T cells in chronic human infections is poorly understood. We performed genome-wide transcriptional analyses and functional assays of CD4+ T cells specific for human immunodeficiency virus (HIV) from HIV-infected people before and after initiation of antiretroviral therapy (ART). A follicular helper T cell (TFH cell)-like profile characterized HIV-specific CD4+ T cells in viremic infection. HIV-specific CD4+ T cells from people spontaneously controlling the virus (elite controllers) robustly expressed genes associated with the TH1, TH17 and TH22 subsets of helper T cells. Viral suppression by ART resulted in a distinct transcriptional landscape, with a reduction in the expression of genes associated with TFH cells, but persistently low expression of genes associated with TH1, TH17 and TH22 cells compared to the elite controller profile. Thus, altered differentiation is central to the impairment of HIV-specific CD4+ T cells and involves both gain of function and loss of function.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Expressão Gênica/efeitos dos fármacos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Células Th1/patologia , Células Th17/patologia , Perfilação da Expressão Gênica , Infecções por HIV/virologia , Humanos , Receptores CXCR5/metabolismo , Células Th1/citologia , Células Th1/imunologia , Células Th17/citologia , Células Th17/imunologia , Carga Viral/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos
9.
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
10.
AIDS Behav ; 23(9): 2443-2452, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31098747

RESUMO

We examine the effect of the Undetectables Intervention (UI) on viral loads among socially vulnerable HIV-positive clients. The UI utilized a toolkit that included financial incentives, graphic novels, and community-based case management services. A pre-post repeated measures analysis (n = 502) through 4 years examined longitudinal effects of the intervention. Logistic models regressed social determinants on viral loads. Finally, in-depth qualitative interviews (n = 30) examined how UI shaped adherence. The proportion of virally suppressed time-points increased 15% (from 67 to 82% pre to post-enrollment, p < 0.0001). The proportion of the sample virally suppressed at all time-points increased by 23% (from 39 to 62% pre to post-enrollment, p < 0.0001). African Americans and the homeless were the most likely to be unsuppressed at baseline, but, along with substance users, benefitted the most from UI. The intervention shaped adherence through two pathways, by: (1) establishing worth around adherence, and (2) increasing motivation to become suppressed, and maintain adherence.


Assuntos
Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Pessoas em Situação de Rua/estatística & dados numéricos , Adesão à Medicação , Aceitação pelo Paciente de Cuidados de Saúde , Reembolso de Incentivo/organização & administração , Determinantes Sociais da Saúde , Carga Viral/efeitos dos fármacos , Populações Vulneráveis , Adulto , Afro-Americanos , Administração de Caso , Grupos de Populações Continentais , Feminino , Infecções por HIV/psicologia , Humanos , Entrevistas como Assunto , Pessoa de Meia-Idade , Motivação , Pesquisa Qualitativa
11.
BMC Infect Dis ; 19(1): 388, 2019 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-31068147

RESUMO

BACKGROUND: The compound letermovir (LMV) has recently been approved for the prophylaxis of cytomegalovirus (CMV) infection and disease in adult CMV seropositive recipients of an allogeneic hematopoietic stem cell transplant. LMV inhibits CMV replication by binding to the viral terminase complex. However, first cases of clinical LMV resistance have been occurred. Here we report a fast breakthrough of resistant cytomegalovirus during secondary LMV prophylaxis in a hematopoietic-cell transplant recipient. CASE PRESENTATION: A 44-year-old male patient with acute myeloid leukemia (AML) experienced a CMV-reactivation within the first 4 weeks of allogeneic hematopoietic-cell transplantation. Administration of LMV was initiated at day + 34. Due to increasing viral loads, LMV treatment was discontinued after 8 days. The patient was then administered with valganciclovir (valGCV) until viral DNA was undetectable. Due to neutropenia, valGCV treatment was switched to LMV secondary prophylaxis. For 4 weeks, the patient maintain virologic suppression. Then, CMV viral loads increased with a fast kinetic. Genotypic testing of the viral polymerase UL54, the kinase UL97 as well as the viral terminase UL56 and UL89 revealed the mutation C325Y in UL56, which is associated with the high level LMV resistance. CONCLUSION: It is known that Letermovir is approved for prophylactic purposes. However, it may be used for some patients with CMV infection who either have failed prior therapies or are unable to tolerate other anti-CMV compounds. Particularly, the administration of LMV should be avoided in patients with detectable viral loads. When this is not possible, viral load must be routinely monitored along with UL56 genotyping. Furthermore, LMV administration at high virus loads may foster the rapid selection of resistant CMV mutants.


Assuntos
Acetatos/uso terapêutico , Antivirais/uso terapêutico , Infecções por Citomegalovirus/prevenção & controle , Citomegalovirus/efeitos dos fármacos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Quinazolinas/uso terapêutico , Adulto , Citomegalovirus/genética , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/virologia , DNA Polimerase Dirigida por DNA/genética , Farmacorresistência Viral/efeitos dos fármacos , Humanos , Masculino , Mutação , Prevenção Secundária , Valganciclovir/uso terapêutico , Carga Viral/efeitos dos fármacos , Proteínas Virais/genética , Proteínas Estruturais Virais/genética
12.
Int J STD AIDS ; 30(6): 530-535, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31074360

RESUMO

With the increasing incidence of chronic kidney disease in patients with human immunodeficiency virus (HIV), the number of HIV-infected patients requiring hemodialysis has also increased. Dolutegravir is an integrase inhibitor that is a common component of HIV treatment regimens. Currently, there is no guidance regarding the use of dolutegravir in patients requiring hemodialysis. Therefore, we sought to evaluate the clinical correlates of safe and effective use of dolutegravir in hemodialysis. This was a retrospective cohort analysis of patients receiving dolutegravir and hemodialysis for at least six months at a single academic HIV medical clinic. The primary safety outcome was discontinuation of dolutegravir due to an adverse effect. The primary efficacy outcome was viral suppression six months after being on dolutegravir and hemodialysis simultaneously. Ten patients received dolutegravir while receiving hemodialysis for six months. No patients discontinued the medication during the six months. Eighty percent of the patients were virally suppressed at six months with 62.5% of those suppressed maintaining suppression and 37.5% achieving suppression over the course of the six months. In a retrospective review of ten patients receiving dolutegravir while on hemodialysis for at least six months, dolutegravir was generally safe and effective for use at standard dosages.


Assuntos
Infecções por HIV/tratamento farmacológico , Inibidores de Integrase de HIV/uso terapêutico , HIV-1/efeitos dos fármacos , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Falência Renal Crônica/terapia , Diálise Renal/métodos , Carga Viral/efeitos dos fármacos , Adulto , Feminino , Infecções por HIV/complicações , Infecções por HIV/virologia , HIV-1/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
13.
Int J STD AIDS ; 30(7): 680-688, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31042101

RESUMO

Information on the virologic durability of modern antiretroviral regimens is important to clinicians. We aimed to describe virologic durability of first-line integrase strand transfer inhibitor (INSTI)-, nonnucleoside reverse transcriptase inhibitor (NNRTI)-, or protease inhibitor (PI)-based antiretroviral regimens. This was a retrospective study of antiretroviral-naïve patients that initiated first-line antiretroviral regimens with two nucleoside reverse transcriptase inhibitors and an INSTI, NNRTI, or PI between January 2006 and June 2016. The outcome was time to virologic failure, which was assessed by Kaplan-Meier survival analysis and Cox regression models. There were 780 patients (median age = 37 years [interquartile range (IQR) = 30-45], 93.3% male, 56.2% Caucasian, median HIV duration = 1.8 years [IQR = 0.4-5.4], baseline log10 viral load [VL]=4.6 [IQR = 4.1-5.1], and baseline CD4+ cell count = 320 cells/µl [IQR = 217-440]). In total, 189/780 were on a third agent INSTI, 339/780 on a third agent NNRTI, and 252/780 on a third agent PI. Kaplan-Meier survival probability revealed longer time to virologic failure for INSTI, followed by NNRTI then PI (p < 0.001). Multivariable Cox regression revealed that being on an INSTI regimen (aHR = 0.27; 95%CI = 0.18-0.41) or NNRTI regimen (aHR = 0.64; 95%CI = 0.47-0.87) versus PI regimen, frequent VL testing (per year), (aHR = 0.64; 95%CI = 0.47-0.87), and duration of ART (aHR = 0.22; 95%CI = 0.17-0.30) (years) were inversely associated with time to virologic failure, and log10 of baseline VL (aHR = 1.94; 95%CI = 1.58-2.39 per log10) increased risk. Virologic failure was delayed and virologic durability prolonged for INSTI- compared to NNRTI- and PI-based regimens, supporting current antiretroviral therapy guidelines.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Infecções por HIV/tratamento farmacológico , Inibidores da Transcriptase Reversa/uso terapêutico , Carga Viral/efeitos dos fármacos , Adulto , Feminino , Infecções por HIV/virologia , Inibidores de Integrase de HIV/uso terapêutico , Inibidores da Protease de HIV/uso terapêutico , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos
14.
AIDS Behav ; 23(9): 2558-2575, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31049812

RESUMO

Using a case-control study of patients receiving antiretroviral treatment (ART) in 2010-2012 at McCord Hospital in Durban, South Africa, we sought to understand how residential locations impact patients' risk of virologic failure (VF). Using generalized estimating equations to fit logistic regression models, we estimated the associations of VF with socioeconomic status (SES) and geographic access to care. We then determined whether neighborhood-level poverty modifies the association between individual-level SES and VF. Automobile ownership for men and having non-spouse family members pay medical care for women remained independently associated with increased odds of VF for patients dwelling in moderately and severely poor neighborhoods. Closer geographic proximity to medical care was positively associated with VF among men, while higher neighborhood-level poverty was positively associated with VF among women. The programmatic implications of our findings include developing ART adherence interventions that address the role of gender in both the socioeconomic and geographical contexts.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Infecções por HIV/tratamento farmacológico , Características de Residência , Determinantes Sociais da Saúde , Carga Viral/efeitos dos fármacos , Adulto , Antirretrovirais/uso terapêutico , Automóveis , Estudos de Casos e Controles , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , Acesso aos Serviços de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Propriedade , Classe Social , África do Sul/epidemiologia
15.
Vet Microbiol ; 231: 63-70, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30955825

RESUMO

Porcine reproductive and respiratory syndrome (PRRS) is a severe respiratory disease that leads to huge economic losses in the pig industry throughout the world. Although there are several vaccines available, the protective efficacy is limited. Therefore, new control strategies to prevent PRRS virus (PRRSV) infection are urgently required. We have previously reported that CH25H and 25HC can significantly inhibit the replication of PRRSV by preventing viral entry. In the present study, we found that 25HC with a low IC50 value significantly decreased the replication of different PRRSV strains, and increased the production of IL-1ß and IL-8 in porcine primary alveolar macrophages and the lung tissue. In pigs challenged with highly pathogenic PRRSV, treatment with 25HC was associated with an obvious reduction in the level of viremia and viral load in lung samples and nasal swabs, as well as decreased lung injury and an increased survival rate. These findings suggest that 25HC could be a promising antiviral drug against PRRSV in the future.


Assuntos
Antivirais/farmacologia , Hidroxicolesteróis/farmacologia , Síndrome Respiratória e Reprodutiva Suína/tratamento farmacológico , Vírus da Síndrome Respiratória e Reprodutiva Suína/efeitos dos fármacos , Internalização do Vírus/efeitos dos fármacos , Animais , Linhagem Celular , Concentração Inibidora 50 , Interleucina-1beta/imunologia , Interleucina-8/imunologia , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pulmão/virologia , Macrófagos Alveolares/efeitos dos fármacos , Macrófagos Alveolares/virologia , Vírus da Síndrome Respiratória e Reprodutiva Suína/fisiologia , Suínos , Carga Viral/efeitos dos fármacos , Viremia/tratamento farmacológico , Replicação Viral/efeitos dos fármacos
16.
Arch Virol ; 164(6): 1597-1607, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30949813

RESUMO

Hazara virus (HAZV) is closely related to Crimean-Congo hemorrhagic fever virus (CCHFV), but differs in that it is non-pathogenic to humans. Since HAZV was isolated for the first time in 1954, the biological characteristics of this virus, particularly its behavior within culture cells, have not been well-studied, despite its importance as a surrogate model for CCHFV. Nucleoprotein (N) is the main component of viral nucleocapsid and is the most abundant virion protein, it is believed to play a pivotal role in the viral lifecycle. Generation of a series of anti-HAZV N monoclonal antibodies has enabled us to directly examine the involvement of this protein on viral growth. Observation of HAZV-infected cells revealed that this infection caused apoptosis, which was further characterized by DNA ladder and elevated caspase-3/7 activity. HAZV titers initially increased in cell culture, but after reaching the peak titer began to rapidly decline. HAZV particles were found to be very unstable in culture medium at 37 °C, and virus particles tend to lose infectivity at that point. HAZV N appears to inhibit apoptosis, thus can potentially support efficient viral propagation.


Assuntos
Anticorpos Monoclonais/farmacologia , Infecções por Bunyaviridae/virologia , Nairovirus/crescimento & desenvolvimento , Nucleoproteínas/antagonistas & inibidores , Carga Viral/efeitos dos fármacos , Células A549 , Animais , Anticorpos Antivirais/farmacologia , Apoptose/efeitos dos fármacos , Infecções por Bunyaviridae/metabolismo , Células COS , Caspase 3/metabolismo , Caspase 7/metabolismo , Linhagem Celular , Cercopithecus aethiops , Cães , Humanos , Células Madin Darby de Rim Canino , Nairovirus/efeitos dos fármacos , Proteínas Virais/antagonistas & inibidores
17.
Int J STD AIDS ; 30(5): 453-459, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30999831

RESUMO

Patient's gender may impact pharmacokinetics and play a role in viral suppression. Existing literature has focused on treatment-naïve patients and produced inconclusive results, often implicating differences in adherence as the driver of gender-based outcome differences. The present analysis assessed whether viral suppression on third-line HIV treatment among a closely followed population differs by gender. A retrospective cohort study of patients on third-line HIV treatment was initiated at the HIV Advanced Treatment Centre in Lusaka, Zambia between January 2012 and December 2015. The association between gender and viral suppression was assessed using log binomial regression adjusted for core drug, number of drug mutations, and baseline viral load. Of the 80 included patients (56% female; median age: 40 years), 50 (62%) were virally suppressed at six months. After adjustment, females were less likely to be virologically suppressed at six months on third-line treatment compared to male HIV patients (relative risk 0.82, 95% confidence interval: 0.56, 1.20). Our data suggest that women were less likely to be suppressed following six months of third-line therapy compared to men; however, the difference was not statistically significant. Larger studies are needed to determine whether women are at increased risk of viral failure on third-line therapy compared to men.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade/métodos , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , Carga Viral/efeitos dos fármacos , Adulto , Contagem de Linfócito CD4 , Farmacorresistência Viral/genética , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , HIV-1/genética , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores Sexuais , Resultado do Tratamento , Zâmbia/epidemiologia
18.
Int J Mol Sci ; 20(9)2019 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-31032814

RESUMO

In humans, Zika virus and viral RNA have been detected in semen up to 2.2 months and 6 months post infection (pi), respectively. Although the contribution of sexual transmission to the spread of ZIKV is too low to sustain an outbreak, it can increase the risk of infection and the epidemic size as well as prolong the duration of an outbreak. In this study, we explored the potential of antivirals to serve as an effective strategy to prevent sexual transmission. Male AG129 mice infected with a ZIKV isolate from Suriname were treated with the nucleoside analog, 7-deaza-2'-C-methyladenosine (7DMA), that was previously shown to be efficacious in reducing ZIKV viremia and delaying ZIKV-induced disease in mice. Following treatment, viral RNA and infectious virus titers were consistently reduced in the male reproductive organs compared to vehicle-treated mice. This reduction of ZIKV loads in the testis was confirmed by the detection of lower levels of ZIKV antigens. Our data illustrate the value of this mouse model to validate the efficacy of new potential ZIKV drugs at the level of the male reproductive system.


Assuntos
Antivirais/farmacologia , Inibidores Enzimáticos/farmacologia , Replicação Viral/efeitos dos fármacos , Infecção por Zika virus/virologia , Zika virus/efeitos dos fármacos , Zika virus/enzimologia , Animais , Linhagem Celular , Modelos Animais de Doenças , Humanos , Masculino , Camundongos , Carga Viral/efeitos dos fármacos , Infecção por Zika virus/tratamento farmacológico , Infecção por Zika virus/patologia
19.
Ann Hematol ; 98(8): 1953-1959, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31025161

RESUMO

The change in the incidence of lymphomas in function of the presence or absence of sustained virological response after anti-hepatitis C therapy in a cohort of human immunodeficiency (HIV)-hepatitis C (HCV) viruses coinfected patients was analyzed. A prospective cohort of 755 HIV-HCV coinfected patients who received their first anti-HCV therapy, based on interferon + ribavirin schemas, was evaluated. Incidence and histologic types of lymphomas were analyzed in two periods: (1) before administration of anti-HCV therapy and (2) after anti-HCV therapy. The association between lymphoma incidence and demographic, HIV- (minimum CD4+ cell count and CD4+ cell count at diagnosis of lymphoma, antiretroviral therapy, maximal HIV load and HIV load at diagnosis of lymphoma) and HCV-related variables (HCV load, genotype, sustained viral response to anti-HCV therapy) were analyzed. A total of 13 lymphomas [incidence rate (95% confidence interval), 0.72 (0.33-1.11) × 1000 person-years, time from HIV diagnosis to lymphoma diagnosis (median, interquartile range), 15 (11-19) years] were diagnosed. Nine of them were non-Hodgkin and four Hodgkin lymphomas. The median CD4+ T cell count at diagnosis of lymphoma was 457/mm3, with only two cases with values lower than 200/mm3. The incidence rate of non-Hodgkin lymphomas was similar pre- and post-anti HCV therapy [0.33 (0.00-0.65) vs 0.68 (0.08-1.26) × 1000 person-years, respectively, p > 0.05]. Patients with sustained virologic HCV response showed similar incidence rate of lymphomas than that of those without anti-HCV response. In conclusion, anti-HCV therapy does not modify the incidence rate of lymphomas in HIV-HCV coinfected patients.


Assuntos
Antivirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , Hepatite C Crônica/tratamento farmacológico , Doença de Hodgkin/tratamento farmacológico , Interferon alfa-2/uso terapêutico , Linfoma não Hodgkin/tratamento farmacológico , Ribavirina/uso terapêutico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Antirretroviral de Alta Atividade/métodos , Contagem de Linfócito CD4 , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/patologia , Linfócitos T CD4-Positivos/virologia , Coinfecção , Combinação de Medicamentos , HIV/efeitos dos fármacos , HIV/crescimento & desenvolvimento , Infecções por HIV/complicações , Infecções por HIV/patologia , Infecções por HIV/virologia , Hepacivirus/efeitos dos fármacos , Hepacivirus/crescimento & desenvolvimento , Hepatite C Crônica/complicações , Hepatite C Crônica/patologia , Hepatite C Crônica/virologia , Doença de Hodgkin/complicações , Doença de Hodgkin/patologia , Doença de Hodgkin/virologia , Humanos , Linfoma não Hodgkin/complicações , Linfoma não Hodgkin/patologia , Linfoma não Hodgkin/virologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Carga Viral/efeitos dos fármacos
20.
Clin Drug Investig ; 39(6): 585-590, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30976998

RESUMO

BACKGROUND AND OBJECTIVE: Integrase strand transfer inhibitors (INSTIs) have become the preferred first-line antiretroviral therapy in adults. There is paucity of published data on their use in children outside of clinical trials, particularly long-term safety and tolerability. This study aimed to describe INSTI use including the number of, and reasons for INSTI discontinuation. METHODS: We conducted a retrospective cohort analysis by database and electronic record review of children aged under 18 years with perinatally acquired human immunodeficiency virus who started INSTI-based antiretroviral therapy between May 2009 and March 2018, in a single tertiary centre. RESULTS: Fifty-six INSTI-based regimens were prescribed in 54 children, 64.9% from 2015 onwards. Twenty-one of 56 (37.5%) regimens commenced with raltegravir, 29 (51.8%) with dolutegravir and six (10.7%) with elvitegravir. The median age at the start of treatment was 15 years (interquartile range 13.5-16.4) with a median duration of INSTI-antiretroviral therapy of 1.65 years (range 0.01-8.8). Twenty-four children had a detectable viral load at the start INSTI therapy; 20 (83%) achieving viral suppression in a median of 26 days (interquartile range 19.5-34.5). There were 26 discontinuations of INSTI-based antiretroviral therapy after a median of 183 days; 9/26 because of adverse events. Four of nine adverse events were attributed to INSTI use, all in patients taking dolutegravir and the adverse events were neuropsychiatric and gastrointestinal in nature. CONCLUSIONS: INSTI-based regimens were generally efficacious and well tolerated in this paediatric cohort, with 4/26 discontinuations due to INSTI-attributed adverse events. Further post-marketing surveillance of INSTI use in children is warranted.


Assuntos
Infecções por HIV/tratamento farmacológico , Inibidores de Integrase de HIV/administração & dosagem , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Quinolonas/administração & dosagem , Raltegravir Potássico/administração & dosagem , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Masculino , Raltegravir Potássico/uso terapêutico , Estudos Retrospectivos , Carga Viral/efeitos dos fármacos
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