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1.
HIV Med ; 22(7): 581-591, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33817938

RESUMO

OBJECTIVES: To compare the prevalence of carotid atherosclerosis in virologically suppressed HIV patients with that of a community sample, and to evaluate the capacity of various cardiovascular risk (CVR) equations for predicting carotid atherosclerosis. METHODS: This was a cross-sectional study with two randomly selected groups: HIV patients from an HIV unit and a control group drawn from the community. Participants were matched by age (30-80 years) and sex without history of cardiovascular disease. Carotid plaque, common carotid intima-media thickness (cc-IMT) and subclinical atherosclerosis (carotid plaque and/or cc-IMT > 75th percentile) were assessed by carotid ultrasound. The Systematic Coronary Risk Evaluation (SCORE), Framingham, REGICOR, reduced Data Collection on Adverse Effects of Anti-HIV Drugs (D:A:D), and COMVIH equations were applied, and their abilities to predict carotid plaque were compared using the area under the curve (AUC). RESULTS: Each group included 379 subjects (77.8% men, age 49.7 years). Duration of antiretroviral therapy was 15.5 years. There were no differences between the groups for carotid plaque (HIV, 33.2%; control, 31.3%), mean cc-IMT (HIV, 0.63 mm; control, 0.61 mm) or subclinical atherosclerosis (HIV, 42.9%; control, 47.9%). Thymidine analogues were independently associated with subclinical atherosclerosis in HIV-infected patients. CVR equations revealed AUCs between 0.715 and 0.807 for prediction of carotid plaque; prediction was better in the control group and did not improve when HIV-adapted scales were used. CONCLUSIONS: The features of carotid atherosclerosis did not differ between the HIV-infected and the control group, although CVR equations were more predictive for carotid plaque in controls than in HIV-infected patients. HIV-specific equations did not improve prediction.


Assuntos
Doenças Cardiovasculares , Doenças das Artérias Carótidas , Infecções por HIV , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/epidemiologia , Espessura Intima-Media Carotídea , Estudos Transversais , Feminino , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Fatores de Risco de Doenças Cardíacas , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
2.
HIV Med ; 21(9): 599-606, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32588958

RESUMO

OBJECTIVES: Although outcomes of antiretroviral therapy (ART) have been evaluated in randomized controlled trials, experiences from subpopulations defined by age, CD4 count or viral load (VL) in heterogeneous real-world settings are limited. METHODS: The study design was an international multicohort collaboration. Logistic regression was used to compare virological and immunological outcomes at 12 ± 3 months after starting ART with an integrase strand transfer inhibitor (INSTI), contemporary nonnucleoside reverse transcriptase inhibitor (NNRTI) or boosted protease inhibitor (PI/b) with two nucleos(t)ides after 1 January 2012. The composite treatment outcome (cTO) defined success as VL < 200 HIV-1 RNA copies/mL with no regimen change and no AIDS/death events. Immunological success was defined as a CD4 count > 750 cells/µL or a 33% increase where the baseline CD4 count was ≥ 500 cells/µL. Poisson regression compared clinical failures (AIDS/death ≥ 14 days after starting ART). Interactions between ART class and age, CD4 count, and VL were determined for each endpoint. RESULTS: Of 5198 ART-naïve persons in the International Cohort Consortium of Infectious Diseases (RESPOND), 45.4% started INSTIs, 26.0% PI/b and 28.7% NNRTIs; 880 (17.4%) were aged > 50 years, 2539 (49.4%) had CD4 counts < 350 cells/µL and 1891 (36.8%) had VL > 100 000 copies/mL. Differences in virological and immunological success and clinical failure among ART classes were similar across age groups (≤ 40, 40-50 and > 50 years), CD4 count categories (≤ 350 vs. > 350 cells/µL) and VL categories at ART initiation (≤ 100 000 vs. > 100 000 copies/mL), with all investigated interactions being nonsignificant (P > 0.05). CONCLUSIONS: Differences among ART classes in virological, immunological and clinical outcomes in ART-naïve participants were consistent irrespective of age, immune suppression or VL at ART initiation. While confounding by indication cannot be excluded, this provides reassuring evidence that such subpopulations will equally benefit from contemporary ART.


Assuntos
Infecções por HIV/tratamento farmacológico , Inibidores de Integrase de HIV/uso terapêutico , HIV-1/genética , Inibidores de Proteases/uso terapêutico , Inibidores da Transcriptase Reversa/uso terapêutico , Adulto , Contagem de Linfócito CD4 , Estudos de Coortes , Feminino , Infecções por HIV/imunologia , Infecções por HIV/virologia , Inibidores de Integrase de HIV/farmacologia , HIV-1/efeitos dos fármacos , Humanos , Cooperação Internacional , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Inibidores de Proteases/farmacologia , RNA Viral/efeitos dos fármacos , Inibidores da Transcriptase Reversa/farmacologia , Resultado do Tratamento , Carga Viral
3.
HIV Med ; 20(3): 237-247, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30688007

RESUMO

OBJECTIVES: The aim of the study was to assess the rates of discontinuation of integrase inhibitor regimens because of any neuropsychiatric adverse event (NPAE) and the factors associated with discontinuation. METHODS: A population-based, prospective, multicentre cohort study was carried out. Treatment-naïve subjects starting therapy with a regimen containing integrase inhibitors, or those switching to such a regimen, with plasma HIV-1 RNA < 50 HIV-1 RNA copies/mL in 14 hospitals in Catalonia or the Balearic Islands (Spain) were included in the study. Every discontinuation because of adverse events (AEs) was double-checked directly with treating physicians. Multivariable Cox models identified factors correlated with discontinuation. RESULTS: A total of 4165 subjects (37% treatment-naïve) started regimens containing dolutegravir (n = 1650; 91% with abacavir), raltegravir (n = 930) or elvitegravir/cobicistat (n = 1585). There were no significant differences among regimens in the rate of discontinuation because of any AE. Rates of discontinuation because of NPAEs were low but higher for dolutegravir/abacavir/lamivudine [2.1%; 2.9 (95% confidence interval (CI) 2.0, 4.2) discontinuations/100 patients/year] versus elvitegravir/cobicistat (0.5%; 0.8 (95% CI 0.3, 1.5) discontinuations/100 patients/year], with significant differences among centres for dolutegravir/abacavir/lamivudine and NPAEs (P = 0.003). We identified an association of female gender and lower CD4 count with increased risk of discontinuation because of any AE [Incidence ratio (IR) 2.3 (95% CI 1.4, 4.0) and 1.8 (95% CI 1.1, 2.8), respectively]. Female gender, age > 60 years and abacavir use were not associated with NPAE discontinuations. NPAEs were commonly grade 1-2, and had been present before and improved after drug withdrawal. CONCLUSIONS: In this large prospective cohort study, patients receiving dolutegravir, raltegravir or elvitegravir/cobicistat did not show significant differences in the rate of discontinuation because of any toxicity. The rate of discontinuations because of NPAEs was low, but was significantly higher for dolutegravir than for elvitegravir/cobicistat, with significant differences among centres, suggesting that greater predisposition to believe that a given adverse event is caused by a given drug of some treating physicians might play a role in the discordance seen between cohorts.


Assuntos
Cobicistat/efeitos adversos , Infecções por HIV/tratamento farmacológico , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Quinolonas/efeitos adversos , Raltegravir Potássico/efeitos adversos , Adulto , Contagem de Linfócito CD4 , Cobicistat/administração & dosagem , Feminino , Infecções por HIV/imunologia , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Oxazinas , Piperazinas , Modelos de Riscos Proporcionais , Estudos Prospectivos , Piridonas , Quinolonas/administração & dosagem , Raltegravir Potássico/administração & dosagem , Espanha
4.
HIV Med ; 18(10): 777-781, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28719012

RESUMO

OBJECTIVES: Antiretroviral therapy (ART) during acute HIV infection (AHI) restricts the HIV reservoir, but additional interventions are necessary to induce a cure. Intravenous immunoglobulin (IVIG) is not HIV-specific but is safe and temporarily reduces the HIV reservoir in chronic HIV infection. We present a randomized controlled trial to investigate whether IVIG plus ART in AHI reduces the HIV reservoir and immune activation compared with ART alone. METHODS: Ten men with AHI (Fiebig II-IV) initiated ART (tenofovir, entricitabine, ritonavir boosted darunavir and raltegravir) at HIV-1 diagnosis and were randomized to ART alone or ART plus 5 days of IVIG, once virally suppressed (week 19). Blood samples were evaluated for viral reservoir, immune activation, immune exhaustion and microbial translocation. Flexible sigmoidoscopy was performed at weeks 19, 24 and 48, and gut proviral DNA and cell numbers determined. RESULTS: IVIG was well tolerated and no viral blips (> 50 HIV-1 RNA copies/mL) occurred during IVIG therapy. From baseline to week 48, total HIV DNA in peripheral blood mononuclear cells (PBMCs) (cases: -3.7 log10 copies/106 CD4 cells; controls: -3.87 log10 copies/106 CD4 cells) declined with no differences observed between the groups (P = 0.49). Declines were observed in both groups from week 19 to week 48 in total HIV DNA in PBMCs (P = 0.38), serum low copy RNA (P = 0.57) and gut total HIV DNA (P = 0.55), but again there were no significant differences between arms. Biomarkers of immune activation, immune exhaustion and microbial translocation and the CD4:CD8 ratio were similar between arms for all comparisons. CONCLUSIONS: Although safe, IVIG in AHI did not impact total HIV DNA, immune function or microbial translocation in peripheral blood or gut tissue.


Assuntos
Infecções por HIV/tratamento farmacológico , HIV-1/isolamento & purificação , Imunoglobulinas Intravenosas/uso terapêutico , Adulto , Antirretrovirais/uso terapêutico , Translocação Bacteriana , DNA Viral/sangue , Quimioterapia Combinada/métodos , Humanos , Masculino , Estudos Prospectivos , Resultado do Tratamento , Carga Viral
5.
HIV Med ; 16(6): 388-92, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25721471

RESUMO

OBJECTIVES: The aim of the study was to evaluate HIV-1 viral load (VL) and inflammatory markers in cerebrospinal fluid (CSF) and neurocognitive performance in patients with neurocognitive impairment (NCI) while they were receiving tenofovir (TDF)/ emtricitabine (FTC)/efavirenz (EFV) and after switching to a regimen with enhanced central nervous system (CNS) penetrability. METHODS: This was a prospective, single-arm pilot study. HIV-1-infected patients with plasma viral suppression and HIV-associated NCI on a regimen including TDF/FTC/EFV were switched to abacavir (ABC)/lamivudine (3TC)/maraviroc (MVC). The Global Deficit Score (GDS) was used to score cognitive function at baseline and 48 weeks after treatment switch. Both CSF and blood samples were taken at baseline and between weeks 24 and 36 after switching. HIV-1 RNA in plasma and CSF was determined by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Inflammatory biomarkers in CSF were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: A total of 71 patients receiving TDF/FTC/EFV were screened. Twelve of them (17%) had documented NCI, lacked the human leucocyte antigen (HLA)-B*57:01 haplotype and harboured Chemokine Receptor Type-5 (CCR5)-tropic virus. Eight patients had detectable HIV-1 RNA (between 2.7 and 41.6 HIV-1 RNA copies/mL) in CSF at baseline. All participants had elevated levels of neopterin and Monocyte Chemoattractant Protein 1 (MCP-1) in CSF at baseline. Eight out of 12 patients completed their follow-up assessment after treatment switch. The GDS decreased from 0.55 to 0.4 (P = 0.085). Median HIV-1 RNA in CSF decreased from 3.49 to 2.20 (P = 0.23). Among the inflammation markers in CSF, tumour necrosis factor (TNF)-α decreased significantly from median 0.51 to 0.35 pg/mL (P = 0.027), showing a correlation with the changes in neopterin, interferon (IFN)-γ and interleukin (IL)-6. CONCLUSIONS: Most patients with NCI receiving TDF/FTC/EFV had low-level viraemia and/or increased inflammatory markers in CSF. Treatment switching to an MVC-containing regimen with better CNS penetration resulted in a trend towards improvement in neurocognitive status and reduced TNF-α concentrations in CSF.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Transtornos Cognitivos/líquido cefalorraquidiano , Substituição de Medicamentos , Infecções por HIV/líquido cefalorraquidiano , Infecções por HIV/tratamento farmacológico , Adulto , Alcinos , Benzoxazinas/uso terapêutico , Biomarcadores/líquido cefalorraquidiano , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/prevenção & controle , Ciclopropanos , Didesoxinucleosídeos/uso terapêutico , Combinação de Medicamentos , Emtricitabina/uso terapêutico , Ensaio de Imunoadsorção Enzimática , Feminino , Infecções por HIV/complicações , Infecções por HIV/virologia , HIV-1 , Humanos , Lamivudina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Tenofovir/uso terapêutico , Fator de Necrose Tumoral alfa/líquido cefalorraquidiano , Carga Viral
6.
J Antimicrob Chemother ; 68(1): 184-7, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22954493

RESUMO

OBJECTIVES: To determine etravirine concentrations and the HIV-1 viral load (VL) in blood plasma (BP) and seminal plasma (SP) of HIV-infected patients. METHODS: Ten adult antiretroviral-experienced HIV-1 patients receiving an etravirine-containing regimen for at least 1 month were enrolled. Semen and blood samples were collected ~12 or 24 h after the last etravirine dose, depending on twice-daily or once-daily dosing, respectively. Liquid chromatography tandem mass spectrometry was used to determine etravirine concentrations and HIV-1 VL was determined by real-time PCR (detection limit 40 copies/mL). Results are presented as the median (range) unless otherwise indicated. RESULTS: Ten blood and 20 semen samples were collected. The CD4 count was 502 (252-817) cells/mm(3) and the BP VL was <40 (<40-362) copies/mL. The time on etravirine was 52 (12-124) weeks. The BP etravirine concentration was 452.5 (258-751) ng/mL. The SP etravirine concentration was 62.9 (31.2-166.0) ng/mL and values were above the IC(50) range (0.39-2.4 ng/mL) in all cases. The median etravirine SP:BP ratio was 0.16 (0.07-0.26). The SP VL was <40 copies/mL in all patients, whereas the BP VL was detectable in one patient with poor adherence to treatment. CONCLUSIONS: Etravirine concentrations in male genital secretions are modest, reaching only 16% of the BP concentration. Nevertheless, they are more than 10 times greater than the wild-type IC(50) range (not adjusted for protein binding).


Assuntos
Infecções por HIV/metabolismo , HIV-1/efeitos dos fármacos , Piridazinas/metabolismo , Piridazinas/uso terapêutico , Sêmen/efeitos dos fármacos , Sêmen/metabolismo , Adulto , Fármacos Anti-HIV/sangue , Fármacos Anti-HIV/metabolismo , Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/sangue , Infecções por HIV/tratamento farmacológico , HIV-1/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Nitrilas , Piridazinas/sangue , Pirimidinas , Carga Viral/efeitos dos fármacos
7.
J Antimicrob Chemother ; 67(6): 1446-8, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22357802

RESUMO

OBJECTIVES: To determine etravirine concentrations in CSF in HIV-infected patients. METHODS: Twelve HIV-1 adult antiretroviral-experienced patients receiving an etravirine-containing regimen for at least 1 month were enrolled. Both CSF and blood samples were taken around 12 h after the last etravirine dose. Liquid chromatography-tandem mass spectrometry was used to determine etravirine concentrations, and HIV-1 viral load was determined by real-time PCR (limit of detection 40 copies/mL). RESULTS: Twelve blood and 12 CSF samples were collected. The median CD4 count was 333 (84-765) cells/mm(3) and the median plasma HIV-1 viral load was <40 (range <40-1777) copies/mL. The median time on etravirine was 34 (range 4-140) weeks. The median etravirine concentration in plasma was 611.5 (range 148-991) ng/mL. The median CSF etravirine concentration was 7.24 (range 3.59-17.9) ng/mL; in all cases, values were above the IC(50) range (0.39-2.4 ng/mL). The median etravirine CSF:plasma ratio was 0.01 (range 0.005-0.03). The CSF viral load was >40 copies/mL in one patient and plasma viral load was still detectable after 4 weeks of therapy. CONCLUSIONS: Etravirine achieves concentrations several times greater than the IC(50) range in CSF. All patients with undetectable plasma viral load were virologically suppressed in CSF while receiving an etravirine-containing regimen. Etravirine may help in controlling HIV-1 in CNS.


Assuntos
Fármacos Anti-HIV/farmacocinética , Líquido Cefalorraquidiano/química , Infecções por HIV/tratamento farmacológico , Piridazinas/farmacocinética , Adulto , Fármacos Anti-HIV/administração & dosagem , Sangue/virologia , Cromatografia Líquida , Feminino , Infecções por HIV/virologia , HIV-1/isolamento & purificação , Humanos , Concentração Inibidora 50 , Masculino , Pessoa de Meia-Idade , Nitrilas , Plasma/química , Piridazinas/administração & dosagem , Pirimidinas , Reação em Cadeia da Polimerase em Tempo Real , Espectrometria de Massas em Tandem , Carga Viral
8.
Open Forum Infect Dis ; 9(3): ofab595, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35237700

RESUMO

BACKGROUND: Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) is the reference for combination therapy based on protease inhibitors due to its efficacy, tolerability, and convenience. Head-to-head randomized comparisons between D/C/F/TAF and combination therapy based on integrase inhibitors in antiretroviral-naive patients are lacking. METHODS: Adult (>18 years old) human immunodeficiency virus-infected antiretroviral-naive patients (HLA-B∗5701 negative and hepatitis B virus negative), with viral load (VL) ≥500 c/mL, were centrally randomized to initiate D/C/F/TAF or dolutegravir/abacavir/lamivudine (DTG/3TC/ABC) after stratifying by VL and CD4 count. Clinical and analytical assessments were performed at weeks 0, 4, 12, 24, and 48. The primary endpoint was VL <50 c/mL at week 48 in the intention-to-treat (ITT)-exposed population (US Food and Drug Administration snapshot analysis, 10% noninferiority margin). RESULTS: Between September 2018 and 2019, 316 patients were randomized and 306 patients were included in the ITT-exposed analysis (151 D/C/F/TAF and 155 DTG/3TC/ABC). Almost all (94%) participants were male and their median age was 35 years. Forty percent had a baseline VL >100 000 copies/mL, and 13% had <200 CD4 cells/µL. Median weight was 73 kg and median body mass index was 24 kg/m2. At 48 weeks, 79% (D/C/F/TAF) versus 82% (DTG/3TC/ABC) had VL <50 c/mL (difference, -2.4%; 95% confidence interval [CI], -11.3 to 6.6). Eight percent versus four percent experienced virologic failure but no resistance-associated mutations emerged. Four percent versus six percent had drug discontinuation due to adverse events. In the per-protocol analysis, 94% versus 96% of patients had VL <50 c/mL (difference, -2%; 95% CI, -8.1 to 3.5). There were no differences in CD4 cell count or weight changes. CONCLUSIONS: We could not demonstrate the noninferiority of D/C/F/TAF relative to DTG/ABC/3TC as initial antiretroviral therapy, although both regimens were similarly well tolerated.

9.
Curr HIV Res ; 10(6): 513-20, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22716109

RESUMO

OBJECTIVE: To evaluate long-term outcomes in patients maintaining a nevirapine (NVP)-based regimen. METHODS: Retrospective, multicenter, cohort study including patients currently receiving an NVP regimen that had been started at least 5 years previously. Demographic, clinical, and analytical variables were recorded. RESULTS: Median follow-up was 8.9 (5.7-11.3) years. Baseline characteristics: 74% men, 47 years old, 36% drug users, 40% AIDS, 40% HCV+, 51.4% detectable HIV-1 viral load, CD4 count 395 (4-1,421)/µL, 19% CD4 < 200/µL, 27% ALT grade 1-2, 36% AST grade 1-2. Thirty percent ART-naive, 83%received NVP associated with 2 nucleoside analogues during the study period, and 17% a protease inhibitor. A significant improvement was observed in general health status markers, including hemoglobin, platelets, and albumin, regardless of HCV coinfection. CD4 cell gain was +218 and +322/µL after 6 and 9 years, respectively (+321 and +391 in naive patients). Triglycerides significantly decreased in pretreated patients, whereas the percentage of patients with HDLc < 1.03 mmol/L and LDL-c > 3.37 mmol/L significantly decreased in a subsample with available values. A significant decrease in transaminases, alkaline phosphatase, and Fib4 score was observed, mainly in HCV+ and ARV-naive patients. CONCLUSIONS: In patients who tolerate NVP therapy, (even those with HCV coinfection), long term benefits may be significant in terms of a progressive improvement in general health status markers and CD4 response, a favorable lipid profile, and good liver tolerability.


Assuntos
Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Fármacos Anti-HIV/administração & dosagem , Hepatite C/tratamento farmacológico , Fígado/efeitos dos fármacos , Nevirapina/administração & dosagem , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Síndrome da Imunodeficiência Adquirida/sangue , Síndrome da Imunodeficiência Adquirida/epidemiologia , Contagem de Linfócito CD4 , Colesterol/sangue , Estudos de Coortes , Coinfecção , Quimioterapia Combinada , Feminino , Seguimentos , Hepatite C/sangue , Hepatite C/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Espanha/epidemiologia , Fatores de Tempo , Resultado do Tratamento , Triglicerídeos/sangue , Carga Viral
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