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1.
AIDS Res Ther ; 17(1): 59, 2020 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-33012282

RESUMO

INTRODUCTION: During the COVID-19 pandemic, hospitals faced increasing pressure, where people living with HIV risked to either acquire SARS-CoV-2 and to interrupt the HIV continuum of care. METHODS: This is a retrospective, observational study. We compared the numbers of medical visits performed, antiretroviral drugs dispensed and the number of new HIV diagnosis and of hospitalizations in a cohort of people living with HIV (PLWH) followed by the Spedali Civili of Brescia between the bimester of the COVID-19 pandemic peak and the bimester of October-November 2019. Data were retrieved from administrative files and from paper and electronic clinical charts. Categorical variables were described using frequencies and percentages, while continuous variables were described using mean, median, and interquartile range (IQR) values. Means for continuous variables were compared using Student's t-tests and the Mann-Whitney test. Proportions for categorical variables were compared using the χ2 test. RESULTS: As of December 31st, 2019, a total of 3875 PLWH were followed in our clinic. Mean age was 51.4 ± 13 years old, where 28% were females and 18.8% non-Italian. Overall, 98.9% were on ART (n = 3834), 93% were viro-suppressed. A total of 1217 and 1162 patients had their visit scheduled at our out-patient HIV clinic during the two bimesters of 2019 and 2020, respectively. Comparing the two periods, we observed a raise of missed visits from 5 to 8% (p < 0.01), a reduction in the number of new HIV diagnosis from 6.4 in 2019 to 2.5 per month in 2020 (p = 0.01), a drop in ART dispensation and an increase of hospitalized HIV patients due to COVID-19. ART regimens including protease inhibitors (PIs) had a smaller average drop than ART not including PIs (16.6 vs 21.6%, p < 0.05). Whether this may be due to the perception of a possible efficacy of PIs on COVID19 is not known. CONCLUSIONS: Our experience highlights the importance of a resilient healthcare system and the need to implement new strategies in order to guarantee the continuum of HIV care even in the context of emergency.


Assuntos
Infecções por Coronavirus/virologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Pneumonia Viral/virologia , Adulto , Fármacos Anti-HIV/administração & dosagem , Antirretrovirais/administração & dosagem , Betacoronavirus/isolamento & purificação , Estudos de Coortes , Continuidade da Assistência ao Paciente , Infecções por Coronavirus/epidemiologia , Feminino , Infecções por HIV/epidemiologia , Hospitalização , Humanos , Itália/epidemiologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/epidemiologia , Saúde Pública , Estudos Retrospectivos , Estatísticas não Paramétricas
2.
Nat Commun ; 11(1): 5412, 2020 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-33110078

RESUMO

Viral rebound following antiretroviral therapy (ART) discontinuation in HIV-1-infected individuals is believed to originate from a small pool of CD4+ T cells harboring replication-competent provirus. However, the origin and nature of the rebound virus has remained unclear. Recent studies have suggested that rebound virus does not originate directly from individual latent proviruses but rather from recombination events involving multiple proviruses. Here we evaluate the origin of rebound virus in 16 ART-suppressed, chronically SIV-infected rhesus monkeys following ART discontinuation. We sequence viral RNA and viral DNA in these animals prior to ART initiation, during ART suppression, and following viral rebound, and we compare rebound viral RNA after ART discontinuation with near full-length viral DNA from peripheral blood and lymph node mononuclear cells (PBMC and LNMC) during ART suppression. Sequences of initial rebound viruses closely match viral DNA sequences in PBMC and LNMC during ART suppression. Recombinant viruses are rare in the initial rebound virus populations but arise quickly within 2-4 weeks after viral rebound. These data suggest that intact proviral DNA in PBMC and LNMC during ART suppression is likely the direct origin of viral rebound in chronically SIV-infected rhesus monkeys following ART discontinuation.


Assuntos
Antirretrovirais/administração & dosagem , Síndrome de Imunodeficiência Adquirida dos Símios/tratamento farmacológico , Vírus da Imunodeficiência Símia/fisiologia , Animais , Linfócitos T CD4-Positivos/virologia , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , HIV-1/genética , HIV-1/fisiologia , Humanos , Macaca mulatta , Masculino , Pacientes Desistentes do Tratamento , Síndrome de Imunodeficiência Adquirida dos Símios/virologia , Vírus da Imunodeficiência Símia/efeitos dos fármacos , Vírus da Imunodeficiência Símia/genética , Carga Viral/efeitos dos fármacos , Latência Viral/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos
3.
PLoS One ; 15(9): e0236320, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32941433

RESUMO

HIV-infected older individuals may have a diminished immune response because of exhaustion/immune aging of T-cells. Therefore, we have investigated HIV-specific CD4 and CD8 T-cell responses in 100 HIV-infected patients (HIV+) who have aged on long-term antiretroviral therapy (ART) and achieved controlled viremia (mostly undetectable viral load; 92 patients with <20 to <40 HIV RNA copies/mL and 8 <60 to <100) and improved CD4 T-cell counts. We show that the median frequencies of HIV-specific CD4+ and CD8+ IFN-γ T-cells were higher in HIV+ than uninfected individuals (HIV-), including increasing levels of IFN-γproduced by CD4+ T-cells and decreasing levels by CD8+ T-cells with increasing CD4 T-cell counts in HIV+. No correlation was found between T-cell responses and varying levels of undetectable viremia. HIV-specific TNF-α made by CD8+ T-cells was higher in HIV+ than HIV-, including decreasing levels with increasing CD4 T-cell counts in HIV+. Furthermore, the CD8+ T-cell mediators, CD107a and Granzyme-B, were higher in HIV+ than HIV-, and decreased with increasing CD4 T-cell counts in HIV+. Remarkably, HIV-specific CD8 T-cells produced decreasing levels of IFN-γwith increasing age of HIV+, including decreased levels of CD107a and Granzyme-B in older HIV+. However, HIV-specific CD8+ T-cells produced increasing levels of TNF-α with increasing age of the HIV+, suggesting continued inflammation. In conclusion, HIV+ with controlled viremia on long-term ART and with higher CD4 T-cell counts showed reduced HIV-specific CD8 T-cell responses as compared to those with lower CD4 T-cell counts, and older HIV+ exhibited decreasing levels of CD8 T-cell responses with increasing age.


Assuntos
Antirretrovirais/uso terapêutico , Infecções por HIV/sangue , Linfócitos T/imunologia , Viremia/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Antirretrovirais/administração & dosagem , Relação CD4-CD8 , Feminino , Granzimas/genética , Granzimas/metabolismo , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Humanos , Interferon gama/genética , Interferon gama/metabolismo , Proteína 1 de Membrana Associada ao Lisossomo/genética , Proteína 1 de Membrana Associada ao Lisossomo/metabolismo , Masculino , Pessoa de Meia-Idade , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Viremia/tratamento farmacológico
4.
J Pharmacol Sci ; 144(3): 95-101, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32921396

RESUMO

Patients living with HIV in malarial endemic regions may experience clinically significant drug interaction between antiretroviral and antimalarial drugs. Effects of nevirapine (NVP), efavirenz (EFV) and lopinavir/ritonavir (LPVr) on lumefantrine (LM) therapeutic concentrations and toxicity were evaluated. In a four-arm parallel study design, the blood samples of 40 participants, treated with artemether/lumefantrine (AL), were analysed. Lumefantrine Cmax was increased by 32% (p = 0.012) and 325% (p < 0.0001) in the NVP and LPVr arms respectively but decreased by 62% (p < 0.0001) in the EFV-arm. AUC of LM was, respectively, increased by 50% (p = 0.27) and 328% (p < 0.0001) in the NVP and LPVr arms but decreased in the EFV-arm by 30% (p = 0.019). Median day 7 LM concentration was less than 280 ng/mL in EFV-arm (239 ng/mL) but higher in control (290 ng/mL), NVP (369 ng/mL, p = 0.004) and LPVr (1331 ng/mL, p < 0.0001) arms. There were no clinically relevant toxicities nor adverse events in both control and test arms. Artemether/lumefantrine is safe and effective for treatment of malaria in PLWHA taking NVP and LPVr based ART regimen but not EFV-based regimen.


Assuntos
Antirretrovirais/efeitos adversos , Antimaláricos/efeitos adversos , Combinação Arteméter e Lumefantrina/efeitos adversos , Benzoxazinas/efeitos adversos , Interações Medicamentosas , Infecções por HIV/tratamento farmacológico , Malária/tratamento farmacológico , Nevirapina/efeitos adversos , Adulto , Antirretrovirais/administração & dosagem , Antirretrovirais/sangue , Antimaláricos/administração & dosagem , Antimaláricos/sangue , Combinação Arteméter e Lumefantrina/administração & dosagem , Combinação Arteméter e Lumefantrina/sangue , Benzoxazinas/administração & dosagem , Benzoxazinas/sangue , Combinação de Medicamentos , Quimioterapia Combinada , Feminino , Infecções por HIV/complicações , Humanos , Lopinavir , Malária/complicações , Masculino , Pessoa de Meia-Idade , Nevirapina/administração & dosagem , Nevirapina/sangue , Nigéria , Ritonavir , Resultado do Tratamento , Adulto Jovem
5.
PLoS One ; 15(8): e0237739, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32817629

RESUMO

OBJECTIVE: To assess the effect of HIV infection and combined antiretroviral therapy (c-ART) on various proatherogenic biomarkers and lipids and to investigate their relationship with subclinical atherosclerosis in a cohort of treatment-naive HIV-infected patients. METHODS: We performed a prospective, comparative, multicenter study of 2 groups of treatment-naive HIV-infected patients (group A, CD4>500 cells/µL, not starting c-ART; and group B, CD4<500 cells/µL, starting c-ART at baseline) and a healthy control group. Laboratory analyses and carotid ultrasound were performed at baseline and at months 12 and 24. The parameters measured were low-density lipoprotein (LDL) particle phenotype, lipoprotein-associated phospholipase A2 (Lp-PLA2), interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), sCD14, sCD163, monocyte chemoattractant protein-1(MCP-1), and asymmetric dimethylarginine (ADMA). A linear mixed model based on patient clusters was used to assess differences in biomarkers between the study groups and over time. RESULTS: The study population comprised 62 HIV-infected patients (group A, n = 31; group B, n = 31) and 22 controls. Age was 37 (30-43) years, and 81% were men. At baseline, the HIV-infected patients had a worse LDL particle phenotype and higher plasma concentration of sCD14, sCD163, hs-CRP, and LDL-Lp-PLA2 than the controls. At month 12, there was an increase in total cholesterol (p = 0.002), HDL-c (p = 0.003), and Apo A-I (p = 0.049) and a decrease in sCD14 (p = <0.001) and sCD163 (p<0.001), although only in group B. LDL particle size increased in group B at month 24 (p = 0.038). No changes were observed in group A or in the healthy controls. Common carotid intima-media thickness increased in HIV-infected patients at month 24 (Group A p = 0.053; group B p = 0.048). Plasma levels of sCD14, sCD163, and hs-CRP correlated with lipid values. CONCLUSIONS: In treatment-naive HIV-infected patients, initiation of c-ART was associated with an improvement in LDL particle phenotype and inflammatory/immune biomarkers, reaching values similar to those of the controls. HIV infection was associated with progression of carotid intima-media thickness.


Assuntos
Aterosclerose/sangue , Biomarcadores/sangue , Infecções por HIV/sangue , Lipídeos/sangue , Adulto , Antirretrovirais/administração & dosagem , Antirretrovirais/sangue , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Aterosclerose/tratamento farmacológico , Aterosclerose/virologia , Proteína C-Reativa/metabolismo , Espessura Intima-Media Carotídea , Colesterol/sangue , Grupos Controle , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Humanos , Inflamação/sangue , Inflamação/tratamento farmacológico , Inflamação/virologia , Lipoproteínas LDL/sangue , Masculino , Estudos Prospectivos
6.
PLoS One ; 15(8): e0236642, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32756581

RESUMO

INTRODUCTION: The long-term prognosis of HIV-2-infected patients receiving antiretroviral therapy (ART) is still challenging, due to the intrinsic resistance to non-nucleoside reverse transcriptase inhibitors (NNRTI) and the suboptimal response to some protease inhibitors (PI). The objective was to describe the 5-years outcomes among HIV-2 patients harboring drug-resistant viruses. METHODS: A clinic-based cohort of HIV-2-patients experiencing virologic failure, with at least one drug resistance mutation was followed from January 2012 to August 2017 in Côte d'Ivoire. Follow-up data included death, lost to follow-up (LTFU), immuno-virological responses. The Kaplan-Meier curve was used to estimate survival rates. RESULTS: A total of 31 HIV-2 patients with virologic failure and with at least one drug resistance mutation were included. Two-third of them were men, 28(90.3%) were on PI-based ART-regimen at enrolment and the median age was 50 years (IQR = 46-54). The median baseline CD4 count and viral load were 456 cells/mm3 and 3.7 log10 c/mL respectively, and the participants have been followed-up in median 57 months (IQR = 24-60). During this period, 21 (67.7%) patients switched at least one antiretroviral drug, including two (6.5%) and three (9.7%) who switched to a PI-based and an integrase inhibitor-based regimen respectively. A total of 10(32.3%) patients died and 4(12.9%) were LTFU. The 36 and 60-months survival rates were 68.5% and 64.9%, respectively. Among the 17 patients remaining in care, six(35.3%) had an undetectable viral load (<50 c/mL) and for the 11 others, the viral load ranged from 2.8 to 5.6 log10 c/mL. Twelve patients were receiving lopinavir at the time of first genotype, five(42%) had a genotypic susceptibility score (GSS) ≤1 and 4(33%) a GSS >2. CONCLUSIONS: The 36-months survival rate among ART-experienced HIV-2 patients with drug-resistant viruses is below 70%,lower than in HIV-1. There is urgent need to improve access to second-line ART for patients living with HIV-2 in West Africa.


Assuntos
Terapia Antirretroviral de Alta Atividade/efeitos adversos , Farmacorresistência Viral/efeitos dos fármacos , Infecções por HIV/tratamento farmacológico , HIV-2/genética , Adulto , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/efeitos adversos , Antirretrovirais/administração & dosagem , Antirretrovirais/efeitos adversos , Costa do Marfim/epidemiologia , Farmacorresistência Viral/genética , Feminino , Genótipo , Infecções por HIV/epidemiologia , Infecções por HIV/genética , Infecções por HIV/virologia , Inibidores de Integrase de HIV/administração & dosagem , Inibidores de Integrase de HIV/efeitos adversos , HIV-2/efeitos dos fármacos , HIV-2/patogenicidade , Humanos , Lopinavir/administração & dosagem , Pessoa de Meia-Idade , Mutação , Ritonavir/administração & dosagem , Ritonavir/efeitos adversos , Carga Viral/efeitos dos fármacos , Carga Viral/genética
8.
Int J STD AIDS ; 31(7): 665-670, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32538328

RESUMO

Pre-exposure prophylaxis (PrEP) is the provision of antiretroviral drugs before HIV exposure to prevent infection for those in whom it is indicated. We conducted an online survey about PrEP in a national sample of infectious diseases physicians in Turkey. They were surveyed from March to April 2019 and they were asked about their attitudes, knowledge and clinical practise about PrEP. Overall, 209 of 2100 (10%) completed the survey, of whom 66.3% were female, 69.5% were specialist and 41.1% were working at education and research hospitals. Most of the participants reported their PrEP knowledge as 'low'. Men who have sex with men was the most suitable group for PrEP according to participants. 27.9% of them were requested to prescribe PrEP which was to be paid by individuals themselves and 24.2% of the participants had recommended PrEP in their clinical practice. The primary concerns among those who would not recommend PrEP were the possible increase in sexually transmitted infections, the potential low cost-effectiveness of PrEP, the ineffectiveness of PrEP in HIV transmission and the time lost to following-up the individuals taking PrEP. Developing a national guideline would support clinicians in order to change their attitudes and to find answers to their concerns.


Assuntos
Fármacos Anti-HIV/administração & dosagem , Antirretrovirais/administração & dosagem , Atitude do Pessoal de Saúde , Infecções por HIV/prevenção & controle , Conhecimentos, Atitudes e Prática em Saúde , Médicos/psicologia , Padrões de Prática Médica/estatística & dados numéricos , Profilaxia Pré-Exposição , Adulto , Feminino , Infecções por HIV/epidemiologia , Humanos , Infectologia , Internet , Masculino , Inquéritos e Questionários , Turquia/epidemiologia
9.
PLoS One ; 15(5): e0233693, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32469985

RESUMO

Efavirenz-based first-line regimens have been widely used for children ≥3 years of age starting antiretroviral therapy, despite possible resistance with prior exposure to non-nucleoside reverse transcriptase inhibitors for prevention of mother-to-child transmission (PMTCT). We used logistic regression to examine the association between PMTCT exposure and viral failure (VF) defined as two consecutive viral loads (VL)>1000 copies/ml between 6-18 months on ART. Children with previous nevirapine exposure for PMTCT were not at higher risk of VF compared to unexposed children (adjusted Odds Ratio (aOR): 0.79; 95% CI:0.56, 1.11).


Assuntos
Antirretrovirais/administração & dosagem , Benzoxazinas/administração & dosagem , Infecções por HIV , HIV-1 , Transmissão Vertical de Doença Infecciosa/prevenção & controle , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/transmissão , Humanos , Masculino , Fatores de Risco
11.
J Virol ; 94(15)2020 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-32434884

RESUMO

If strategies currently in development succeed in eradicating HIV reservoirs in peripheral blood and lymphoid tissues, residual sources of virus may remain in anatomic compartments. Paired blood and semen samples were collected from 12 individuals enrolled in a randomized, double-blind, placebo-controlled therapeutic vaccine clinical trial in people with HIV (PWH) who began antiretroviral therapy (ART) during acute or early infection (ClinicalTrials registration no. NCT01859325). After the week 56 visit (postintervention), all participants interrupted ART. At the first available time points after viral rebound, we sequenced HIV-1 env (C2-V3), gag (p24), and pol (reverse transcriptase) regions amplified from cell-free HIV RNA in blood and seminal plasma using the MiSeq Illumina platform. Comprehensive sequence and phylogenetic analyses were performed to evaluate viral population structure, compartmentalization, and viral diversity in blood and seminal plasma. Compared to that in blood, HIV RNA rebound in semen occurred significantly later (median of 66 versus 42 days post-ART interruption, P < 0.01) and reached lower levels (median 164 versus 16,090 copies/ml, P < 0.01). Three of five participants with available sequencing data presented compartmentalized viral rebound between blood and semen in one HIV coding region. Despite early ART initiation, HIV RNA molecular diversity was higher in semen than in blood in all three coding regions for most participants. Higher HIV RNA molecular diversity in the genital tract (compared to that in blood plasma) and evidence of compartmentalization illustrate the distinct evolutionary dynamics between these two compartments after ART interruption. Future research should evaluate whether the genital compartment might contribute to viral rebound in some PWH interrupting ART.IMPORTANCE To cure HIV, we likely need to target the reservoirs in all anatomic compartments. Here, we used sophisticated statistical and phylogenetic methods to analyze blood and semen samples collected from 12 persons with HIV who began antiretroviral therapy (ART) during very early HIV infection and who interrupted their ART as part of a clinical trial. First, we found that HIV RNA rebound in semen occurred significantly later and reached lower levels than in blood. Second, we found that the virus in semen was genetically different in some participants compared to that in blood. Finally, we found increased HIV RNA molecular diversity in semen compared to that in blood in almost all study participants. These data suggest that the HIV RNA populations emerging from the genital compartment after ART interruption might not be the same as those emerging from blood plasma. Future research should evaluate whether the genital compartment might contribute to viral rebound in some people with HIV (PWH) interrupting ART.


Assuntos
Antirretrovirais/administração & dosagem , Infecções por HIV , HIV-1/metabolismo , RNA Viral/metabolismo , Sêmen/metabolismo , Adulto , Método Duplo-Cego , Infecções por HIV/tratamento farmacológico , Infecções por HIV/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Sêmen/virologia
12.
Brasilia; s.n; 22 abr. , 2020. 24 p.
Não convencional em Português | LILACS, BRISA/RedTESA, PIE | ID: biblio-1095198

RESUMO

O objetivo da revisão sistemática foi investigar a eficácia e a segurança de tratamentos com antivirais para COVID-19, SARS e MERS. Ao todo, 22 estudos foram incluídos: 1 ensaio clínico, 16 séries de casos e 5 relatos de caso. Os antivirais mais utilizados foram lopinavir / ritonavir, oseltamivir, ribavirina e arbidol. Todos os estudos usaram outras terapias, como antibióticos, imunoglobulina, interferon, glicocorticoides, metilprednisolona e medicamentos antiparasitários e antifúngicos, além da terapia antiviral para pacientes com COVID-19. No único ECR incluído, os pacientes que receberam lopinavir / ritonavir tiveram um processo de recuperação semelhante aos pacientes que receberam tratamento padrão. Os desfechos de mortalidade em 28 dias e carga viral de RNA não foram significativamente diferentes entre os dois grupos. Dentre os achados dos demais estudos, vale destacar que estudos de séries e relatos de casos não avaliam a eficácia de medicamentos, e que em geral as amostras foram pequenas. O estudo de Guan, com 1099 pacientes, chegou a conclusão que oseltamivir foi ineficaz na diminuição da taxa de admissão na UTI, na necessidade de ventilação e na taxa de mortalidade entre os pacientes. O estudo de Shang, com 416 pacientes, indicou que medicamentos antivirais não têm efeito na taxa de mortalidade de pacientes com COVID-19. O estudo de Li, com cinco crianças com COVID-19, indicou que os agentes antivirais não alteraram o resultado ou a duração da internação. A revisão cita outros estudos que foram publicados com os pacientes ainda sob tratamento, sem o desfecho final dessas populações. Quanto a busca por ensaios clínicos para SARS e MERS, foram encontrados protocolos, mas nenhum resultado publicado.


Assuntos
Humanos , Pneumonia Viral/tratamento farmacológico , Ribavirina/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Progressão da Doença , Ritonavir/uso terapêutico , Antirretrovirais/administração & dosagem , Oseltamivir/uso terapêutico , Lopinavir/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Antifúngicos/administração & dosagem , Antiparasitários/administração & dosagem , Avaliação da Tecnologia Biomédica , Terapias em Estudo/instrumentação
13.
AIDS Behav ; 24(10): 2956-2965, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32232703

RESUMO

Antiretroviral therapy (ART) for HIV requires strict regimen adherence. Motivational interviewing (MI) can improve ART adherence. MI process studies have rarely focussed on ART adherence. Such studies may facilitate MI modifications to improve outcomes. This study employed a single group pre and post-test design with 62 adults with HIV (16 female; mean age 40 years). Therapist use of MI-consistent (MICO) methods, MI spirit, and client change and sustain talk were coded from an MI session. Relationships were assessed with ART schedule adherence. MICO methods positively correlated with change and sustain talk and were negatively associated with proportion of change talk. No variables were associated with ART adherence change. Mediation analysis did not support the MI model of change. This may be due to the fact that ART adherence is determined by both motivational and non-motivational factors. It may also be that bidirectional relationships exist between therapist and client speech.


Assuntos
Terapia Antirretroviral de Alta Atividade/psicologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/psicologia , Adesão à Medicação/psicologia , Entrevista Motivacional/métodos , Adulto , Antirretrovirais/administração & dosagem , Feminino , Infecções por HIV/epidemiologia , Humanos , Masculino , Adesão à Medicação/estatística & dados numéricos , Pessoa de Meia-Idade , Motivação
14.
AIDS Behav ; 24(9): 2650-2655, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32140876

RESUMO

Diversion of antiretroviral therapy (ART) for recreational use is concerning for countries with high HIV prevalence. This paper presents reports of recreational use of ART among adolescents from two HIV prevention studies in South Africa: (1) a cross-sectional survey of N = 200 adolescents and (2) a qualitative study of pre-exposure prophylaxis with N = 57 adolescents and N = 25 clinicians. Among adolescents, 3% used and 14% knew someone who used non-prescribed ART for recreational purposes. Administration included smoking (71%), snorting (15%), injecting (15%), ingesting (15%), and inserting (3%). Participants predicted increased crime as recreational use of ART increased. Future studies should investigate prevalence, composition, and diversion of ART from HIV prevention and treatment.


Assuntos
Fármacos Anti-HIV/administração & dosagem , Antirretrovirais/administração & dosagem , Infecções por HIV/prevenção & controle , Drogas Ilícitas/efeitos adversos , Profilaxia Pré-Exposição , Adolescente , Adulto , Fármacos Anti-HIV/efeitos adversos , Antirretrovirais/uso terapêutico , Comportamento Aditivo , Estudos Transversais , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , Prevalência , Pesquisa Qualitativa , Assunção de Riscos , África do Sul/epidemiologia , Inquéritos e Questionários
15.
PLoS Pathog ; 16(3): e1008339, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32163523

RESUMO

Despite the success of antiretroviral therapy (ART) to halt viral replication and slow disease progression, this treatment is not curative and there remains an urgent need to develop approaches to clear the latent HIV reservoir. The human IL-15 superagonist N-803 (formerly ALT-803) is a promising anti-cancer biologic with potent immunostimulatory properties that has been extended into the field of HIV as a potential "shock and kill" therapeutic for HIV cure. However, the ability of N-803 to reactivate latent virus and modulate anti-viral immunity in vivo under the cover of ART remains undefined. Here, we show that in ART-suppressed, simian-human immunodeficiency virus (SHIV)SF162P3-infected rhesus macaques, subcutaneous administration of N-803 activates and mobilizes both NK cells and SHIV-specific CD8+ T cells from the peripheral blood to lymph node B cell follicles, a sanctuary site for latent virus that normally excludes such effector cells. We observed minimal activation of memory CD4+ T cells and no increase in viral RNA content in lymph node resident CD4+ T cells post N-803 administration. Accordingly, we found no difference in the number or magnitude of plasma viremia timepoints between treated and untreated animals during the N-803 administration period, and no difference in the size of the viral DNA cell-associated reservoir post N-803 treatment. These results substantiate N-803 as a potent immunotherapeutic candidate capable of activating and directing effector CD8+ T and NK cells to the B cell follicle during full ART suppression, and suggest N-803 must be paired with a bona fide latency reversing agent in vivo to facilitate immune-mediated modulation of the latent viral reservoir.


Assuntos
Antirretrovirais/administração & dosagem , Linfócitos B/efeitos dos fármacos , Linfócitos T CD8-Positivos/efeitos dos fármacos , Infecções por HIV/tratamento farmacológico , Interleucina-15/antagonistas & inibidores , Células Matadoras Naturais/efeitos dos fármacos , Proteínas/administração & dosagem , Animais , Linfócitos B/citologia , Linfócitos B/imunologia , Linfócitos T CD8-Positivos/citologia , Linfócitos T CD8-Positivos/imunologia , Movimento Celular/efeitos dos fármacos , Modelos Animais de Doenças , Infecções por HIV/genética , Infecções por HIV/imunologia , Infecções por HIV/fisiopatologia , HIV-1/efeitos dos fármacos , HIV-1/fisiologia , Humanos , Interleucina-15/genética , Interleucina-15/imunologia , Células Matadoras Naturais/citologia , Células Matadoras Naturais/imunologia , Linfonodos/efeitos dos fármacos , Linfonodos/imunologia , Macaca mulatta , Síndrome de Imunodeficiência Adquirida dos Símios/tratamento farmacológico , Síndrome de Imunodeficiência Adquirida dos Símios/imunologia , Síndrome de Imunodeficiência Adquirida dos Símios/fisiopatologia , Síndrome de Imunodeficiência Adquirida dos Símios/virologia , Vírus da Imunodeficiência Símia/efeitos dos fármacos , Vírus da Imunodeficiência Símia/fisiologia , Latência Viral/efeitos dos fármacos
16.
Am J Epidemiol ; 189(8): 811-819, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32219384

RESUMO

Little is known about the functional relationship of delaying second-line treatment initiation for human immunodeficiency virus-positive patients and mortality, given a patient's immune status. We included 7,255 patients starting antiretroviral therapy during 2004-2017, from 9 South African cohorts, with virological failure and complete baseline data. We estimated the impact of switch time on the hazard of death using inverse probability of treatment weighting of marginal structural models. The nonlinear relationship between month of switch and the 5-year survival probability, stratified by CD4 count at failure, was estimated with targeted maximum likelihood estimation. We adjusted for measured time-varying confounding by CD4 count, viral load, and visit frequency. Five-year mortality was estimated to be 10.5% (95% CI: 2.2, 18.8) for immediate switch and to be 26.6% (95% CI: 20.9, 32.3) for no switch (51.1% if CD4 count was <100 cells/mm3). The hazard of death was estimated to be 0.37 (95% CI: 0.30, 0.46) times lower if everyone had been switched immediately compared with never. The shorter the delay in switching, the lower the hazard of death-delaying 30-59 days reduced the hazard by 0.53 (95% CI: 0.43, 0.65) times and 60-119 days by 0.58 (95% CI: 0.49, 0.69) times, compared with no switch. Early treatment switch is particularly important for patients with low CD4 counts at failure.


Assuntos
Antirretrovirais/administração & dosagem , Infecções por HIV/tratamento farmacológico , Adulto , Contagem de Linfócito CD4 , Feminino , Seguimentos , Infecções por HIV/imunologia , Infecções por HIV/mortalidade , Humanos , Masculino , África do Sul/epidemiologia
17.
AAPS PharmSciTech ; 21(3): 91, 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32060665

RESUMO

Doravirine is a non-nucleoside reverse transcriptase inhibitor indicated for the treatment of human immunodeficiency virus-1 infection, available as a single tablet in combination with other antiretroviral agents or as a fixed-dose regimen with lamivudine and tenofovir disoproxil fumarate (TDF). Alternative formulations of these drugs are being developed for individuals who have difficulty swallowing tablets. Two phase 1 trials were conducted, both in 24 healthy adults, to assess the pharmacokinetics of uncoated and coated oral granule formulations of doravirine, lamivudine, and TDF administered alone and with vanilla pudding or apple sauce. The pharmacokinetics for all uncoated granules, and of coated lamivudine and TDF granules, were similar to those of currently marketed tablets (geometric mean ratios [GMRs] 0.92-1.04). Coated doravirine granules had decreased AUC0-∞ (11%) and Cmax (23%) values versus the tablet. The pharmacokinetics were similar for uncoated and coated doravirine granules administered with or without pudding (GMRs 0.96-1.10); administration with apple sauce increased doravirine AUC0-∞ (26-29%), Cmax (56-59%), and C24 (20-21%) versus administration of granules alone. Lamivudine granules administered with pudding or apple sauce decreased AUC0-∞ and Cmax (14-25%) versus granules alone. Tenofovir AUC0-∞, Cmax, and C24 increased for TDF granules administered with pudding or apple sauce versus alone (11-23%). Pharmacokinetic differences when administering doravirine, lamivudine, or TDF as uncoated or coated granules versus tablets, or when granules were administered with (versus without) pudding or apple sauce, are not considered clinically meaningful, supporting further development of these granule formulations.


Assuntos
Fármacos Anti-HIV/farmacocinética , Antirretrovirais/farmacocinética , Lamivudina/farmacocinética , Piridonas/farmacocinética , Inibidores da Transcriptase Reversa/farmacocinética , Tenofovir/farmacocinética , Triazóis/farmacocinética , Adulto , Fármacos Anti-HIV/administração & dosagem , Antirretrovirais/administração & dosagem , Disponibilidade Biológica , Estudos Cross-Over , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/metabolismo , Humanos , Lamivudina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Piridonas/administração & dosagem , Inibidores da Transcriptase Reversa/administração & dosagem , Comprimidos , Tenofovir/administração & dosagem , Triazóis/administração & dosagem , Adulto Jovem
18.
PLoS One ; 15(2): e0229291, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32069309

RESUMO

Changes in the United States federal-level political landscape have been felt within immigrant communities, and the public health clinics that serve them. We sought to document how HIV prevention and care clinics are reaching and retaining their immigrant community patients during a period of retrenchment of accessible public resources and immigrant rights. From May 2018 through January 2019, we conducted 20 in-depth interviews with clinicians, case workers, advocates, legal experts, and peer navigators in Northern and Central California. Interviews were recorded and transcribed. Several themes emerged which can be grouped into three primary areas: changes post-election, challenges meeting the needs of patients, and best practices for maintaining access to prevention and care services. Post-election, providers reported some of their patients skipping clinic appointments due to fear of Immigration and Customs Enforcement (ICE) raids and deportation while other patients had moved to locations that they felt were less policed. Challenges emerged around linguistic competency, meeting basic needs such as housing stability and employment, and treating mental health sequelae resulting from trauma experienced in home countries or during migration itself. Best practices included hiring bi-lingual and bi-cultural staff, linking to legal services to assist with immigration status, holding trainings around immigrant rights and responses to ICE raids, and building trust with immigrant patients by assuring them that their status would not be collected or reported. In light of adverse policy changes affecting immigrants, agencies have begun to institute best practices to mitigate the negative impact of those policies on their clients and patients.


Assuntos
Assistência à Saúde/normas , Emigração e Imigração/legislação & jurisprudência , Infecções por HIV/prevenção & controle , Acesso aos Serviços de Saúde/normas , Determinação de Necessidades de Cuidados de Saúde/normas , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Guias de Prática Clínica como Assunto/normas , Antirretrovirais/administração & dosagem , Assistência à Saúde/legislação & jurisprudência , HIV/isolamento & purificação , Infecções por HIV/psicologia , Planejamento em Saúde , Acesso aos Serviços de Saúde/legislação & jurisprudência , Humanos , Política Pública , Inquéritos e Questionários
19.
Mem Inst Oswaldo Cruz ; 114: e190350, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32022169

RESUMO

BACKGROUND: Iron homeostasis contribute for the human immunodeficiency virus (HIV) pathogenesis. OBJECTIVES: We assessed the iron intake pattern in antiretroviral naïve Brazilian men living with HIV correlating with clinical and nutritional parameters. METHODS: The iron consumption mean was estimated according to a food frequency questionnaire (FFQ), and a 3-day food record (3dFR) submitted to the patients. HIV viral load, CD4+ T cell counts, serum iron, haematological and anthropometrics parameters were recorded. FINDINGS: Fifty-one HIV-infected adult men naïve for antiretroviral therapy (ART) were enrolled. The mean age of participants was 35 (SEM ± 1.28) years old, with mean time of HIV-1 infection of 1.78 (0-16.36, min-max) years. Majority (41.18%) had complete secondary, and 21.57% had tertiary educational level. The income was around 1x (54.90%) to 2x (41.18%) minimum wage. Fifty-four percent showed normal weight, while 40% were overweight. The patients showed normal mean values of haematological parameters, and mean serum iron was 14.40 µM (SEM ± 0.83). The FFQ showed moderate correlation with the 3dFR (ρ = 0.5436, p = 0.0009), and the mean values of iron intake were 10.55(± 0.92) mg/day, recorded by FFQ, and 15.75(± 1.51) mg/day, recorded by 3dFR. The iron intake, recorded by FFQ, negatively correlated with serum iron (ρ = -0.3448, p = 0.0132), and did not have influence in the CD4+ T cell counts [e.B 0.99 (0.97-1.01, 95% confidence interval (CI), p = 0.2]. However, the iron intake showed a positive effect in HIV viral load [e.B 1.12 (1.02-1.25, 95%CI), p < 0.01]. MAIN CONCLUSIONS: This study draws attention for the importance of iron intake nutritional counseling in people living with HIV. However, more studies are required to clarify the association between high iron intake and HIV infection and outcome.


Assuntos
Antirretrovirais/administração & dosagem , Infecções por HIV/virologia , Ferro na Dieta/efeitos adversos , Carga Viral/efeitos dos fármacos , Adulto , Contagem de Linfócito CD4 , Estudos Transversais , Feminino , Infecções por HIV/sangue , Infecções por HIV/tratamento farmacológico , Homeostase , Humanos , Ferro na Dieta/análise , Masculino , Estado Nutricional , Fatores Socioeconômicos , Inquéritos e Questionários
20.
Einstein (Sao Paulo) ; 18: eAO4995, 2020.
Artigo em Inglês, Português | MEDLINE | ID: mdl-32074221

RESUMO

OBJECTIVE: To describe antiretroviral treatment regimens prescribed and their compliance with the Clinical Protocol and Therapy Guidelines of the Ministry of Health for the management of HIV infection. METHODS: Observational and descriptive study. Secondary data of the state of Paraná (Brazil) on drugs, treatment regimens, lines of treatment and number of individuals on treatment, from January to June 2018, were accessed at the Antiretroviral Agents Logistic Control System. Combinations of antiretroviral drugs (treatment regimens) were compared according to the current Clinical Protocol and Therapy Guidelines and non-compliances were classified and quantified. RESULTS: In Paraná, 35,127 individuals with HIV were treated with 253 different treatment regimens. Of the prescribed regimens, 19.1% were first-line, 27.4% second-line and 48.5% third-line. Among non-compliances, the most prevalent were absence of association of protease inhibitors and ritonavir (42.8%), low efficacy triple therapy (36.9%), double therapy (26.1%), monotherapy (20.3%), and triple therapy of nucleoside analog reverse transcriptase inhibitors (17.1%). CONCLUSION: Most individuals receiving HIV treatment in the state of Paraná are on treatment regimens established in the current Clinical Protocol and Therapy Guidelines, which contributes to successful therapy. However, associations not provided by the current Clinical Protocol and Therapy Guidelines were identified in the initial treatment lines, which could lead to ineffectiveness, virologic failure and viral resistance.


Assuntos
Antirretrovirais/administração & dosagem , Protocolos Clínicos/normas , Fidelidade a Diretrizes/normas , Adesão à Medicação , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/uso terapêutico , Antirretrovirais/uso terapêutico , Brasil , Quimioterapia Combinada/normas , Quimioterapia Combinada/estatística & dados numéricos , Fidelidade a Diretrizes/estatística & dados numéricos , Infecções por HIV/tratamento farmacológico , Humanos , Adesão à Medicação/estatística & dados numéricos
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