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1.
HIV Res Clin Pract ; : 1-7, 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31478478

RESUMO

Objective: To assess the effect of omega-3 polyunsaturated fatty acids (n-3 PUFA) supplementation on bone metabolism in HIV-infected patients presenting with hypertriglyceridemia. Methods: Patients were randomized 1:1 to receive 2 g of n-3 PUFA or fenofibrate (FF). The primary endpoint was % change in bone mineral density (BMD) from baseline to month 24 in lumbar spine (LS) and femoral neck (FN). Secondary endpoints were changes in Z-score, calcitriol, calcitonin, parathyroid hormone, osteocalcin, and C-terminal telopeptide of type I collagen (CTX-I) at 12 and 24 months. Differences in continuous variables were evaluated using the t test or Mann-Whitney U-test for independent samples and differences in means of intra- and inter-subject continuous variables using a general linear model. Categorical variables were compared by the chi-squared or Fisher's exact test. Results: 30 patients were included in each arm; 23 in the n-3 PUFA arm and 22 in the FF arm completed follow-up. No significant differences between arms were observed after 24 months in either region (FN: -12.51% ± 7.89 in the n-3 PUFA arm and -8.18% ± 7.72 in the FF arm, p = .07; LS: 2.94% ± 6.63 in the n-3 PUFA arm, -3.07% ± 16.85 in the FF arm, p = .07), although the BMD reduction in the FN region after 24 months was noticeable in both arms (n-3 PUFA: -12.51% ± 7.89%, p =< .001; FF: -8.183% ± 7.72%, p =< .001). There was a significant difference in calcitriol changes between arms after 96 weeks. No differences in Z-score or bone turnover markers were observed between the two arms. Conclusions: Omega-3 fatty acid supplementation resulted in no beneficial changes in BMD or bone turnover markers. n-3 PUFA supplementation achieved similar reductions in triglyceride levels as FF.

2.
Clin Infect Dis ; 2018 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-30561517

RESUMO

Objective: This study assessed the penetration and efficacy of tenofovir alafenamide (TAF) in the male genital tract (MGT) and semen quality in HIV-1 infected individuals treated with a TAF-containing regimen. Methods: Prospective, open-label, single-arm study including 14 virologically suppressed HIV-1-infected men on stable antiretroviral therapy with elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (E/C/F/TDF) switched to E/C/F/TAF). At baseline (pre-switch) and 12 weeks post-switch, we measured HIV-1 RNA in seminal plasma (SP) and blood plasma (BP), tenofovir (TFV) in SP and BP, and TFV-diphosphate (dp) in peripheral blood mononuclear cells (PBMCs) and seminal mononuclear cells (SMCs) at the end of the dosing interval (C24h). Semen quality was assessed before switching and after 12 weeks on TAF. Results: With TAF, TFV C24 was 11.9-fold higher in SP than in BP. This concentration was significantly lower than TFV C24 in SP with TDF but 9.6-fold higher than the IC50 (11.5 ng/mL). By contrast, the median TFV-dp concentration achieved with TAF in SMCs was 6% that of TFV-dp in PBMCs. The TFV-dp SMC:PBMC ratio was also significantly lower with TAF. Nonetheless, TFV-dp C24 in SMC was comparable with TAF and TDF. All the patients had HIV-1 RNA <40 copies/mL in BP and SP at baseline and 12 weeks post-switch. No significant differences were observed in semen quality between TAF and TDF. Conclusions: Extracellular and intracellular seminal TFV distribution differs between TAF and TDF. Nevertheless, both formulations combined with elvitegravir/cobicistat/emtricitabine maintained HIV-1 RNA suppression in semen. Differences in MGT distribution were not associated with differences in semen quality.

3.
Artigo em Inglês | MEDLINE | ID: mdl-30371793

RESUMO

Objectives: To describe the changes in body fat distribution(BFD) occurring over 60 months in a group of ART-naïve individuals starting different antiretroviral regimens. Methods: Prospective ongoing fat change assessment including clinical evaluation and DXA scan is being conducted in all consecutive patients initiating ART from January 2008. Arm, leg, trunk and total fat as well as fat mass ratio were determined. Results: 146 patients were included (80% male, 40% MSM). The mean age was 44 years, HIV-1 RNA 4.98 log10 copies/mL, and CD4 254 cells/µL. The most common initial antiretroviral combination included non nucleoside reverse transcriptase inhibitor (NNRTI) drugs followed by protease inhibitor (PI) and integrase strand transfer inhibitor (INSTI) based regimens. At month 36, an increase was seen in the body mass index (BMI), total fat, trunk fat, and limb fat. The FMR also showed a significant increase in both men and women (p=0.001). In patients receiving NNRTI- or INSTI-based regimens (but not PIs), there was a marginal but statistically significant increase in the FMR (0.10 and 0.07, respectively; p=0.01). Sixty-two subjects completed 60 months of follow up. FMR showed a significant increase even in the PI group at this time point (p<0.03). Conclusions: We observed a significant increase in the fat and lean body mass in all compartments and treatment groups over 36 and 60 months. Clinically irrelevant differences were found in fat distribution, regardless of the treatment group and baseline characteristics. This data suggest that current antiretroviral regimens have low impact on BFD during the first years of treatment.

4.
J Neurovirol ; 24(4): 391-397, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29542028

RESUMO

This study aimed to assess cerebrospinal fluid (CSF) drug concentrations and viral suppression in HIV-1-infected patients on ritonavir-boosted atazanavir (ATV/r) plus lamivudine (3TC) dual therapy. HIV-1-infected adults with suppressed plasma HIV-1 RNA who switched to ATV/r plus 3TC were studied. Total ATV and 3TC concentrations at the end of the dosing interval (C24h), using a validated LC-MS/MS method, and HIV-1 RNA were measured in paired CSF and plasma samples 12 weeks after switching. Ten individuals were included. Median (range) age was 42.5 (33-70) years, time on ART was 39.5 (11-197) months, and time with plasma HIV-1 RNA < 40 copies/mL was 15.5 (6-46) months. At baseline, CSF HIV-1 RNA was < 40 copies/mL in all patients. Twelve weeks after switching to ATV/r plus 3TC, HIV-1 RNA remained at < 40 copies/mL in both plasma and CSF in 9/10 patients. One patient with suboptimal adherence to ART had HIV-1 RNA rebound in both plasma and CSF. The median CSF-to-plasma concentration ratios of ATV and 3TC were 0.013 and 0.417, respectively. Median ATV C24h in CSF was 10.4 (3.7-33.4) ng/mL (in vitro ATV IC50 range, 1-11 ng/mL). Median 3TC C24h in CSF was 43.4 (16.2-99.3) ng/mL (in vitro 3TC IC50 range, 0.68-20.6 ng/mL). Most patients maintained HIV-1 RNA in CSF < 40 copies/mL despite CSF ATV C24h close to or within the IC50 range in the majority. ATV PK data in CSF should be considered and rigorous patient selection is advisable to assure effective CSF viral suppression with this two-drug simplification regimen.

5.
AIDS ; 32(8): 1007-1015, 2018 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-29438199

RESUMO

BACKGROUND: Maraviroc-intensified antiretroviral therapy (ART) may be associated with cognitive benefits. METHODS: Therapy-naive, cognitively asymptomatic, HIV-positive individuals were randomly allocated on a 1 : 1 basis to standard ART (Arm1: tenofovir-emtricitabine and atazanavir/ritonavir) or maraviroc intensified ART (Arm2: abacavir-lamivudine and darunavir/ritonavir/maraviroc). Over 48 weeks, detailed assessments of cognitive function tests were undertaken and cerebral metabolites measured using proton magnetic resonance spectroscopy. Our primary endpoint was mean change in cognitive function across treatment arms with factors associated with cognitive function changes also assessed. RESULTS: Of 60 individuals randomized (30 Arm1 and 30 Arm2), 58 were men and 44 of white ethnicity. Treatment groups had similar disease characteristics including overall mean (SD) baseline CD4 cell count 428 (209) and 414 (229) cells/µl, Arms1 and 2, respectively. At week 48, plasma HIV RNA was less than 50 copies/ml in 55 of 56 of those completing study procedures. Cognitive function improved over 48 weeks [mean change z-score (SD) 0.16 (0.09) Arm1 and 0.25 (0.08) Arm2, P = 0.96 for differences between study arms]. A greater increase in frontal grey matter N-acetyl aspartate/creatine ratio was observed in Arm1 [ratio change of 0.071 (SD 0.16)] versus Arm2 [change -0.097 (SD 0.18), P = 0.009], although this was not associated with changes in cognitive function (P = 0.17). CONCLUSION: Maraviroc-intensified ART had no demonstrable benefit on cognitive function in individuals initiating ART. Greater improvement in neuronal metabolites (N-acetyl aspartate/creatine) was observed with standard ART. Future work should focus on maraviroc-intensified ART in individuals with cognitive impairment.

6.
HIV Clin Trials ; 18(2): 49-53, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28081673

RESUMO

BACKGROUND: The objective of this study was to determine the impact of tenofovir or abacavir discontinuation on low-density lipoprotein (LDL) phenotype and lipoprotein-associated phospholipase A2 (Lp-PLA2) activity in HIV-infected patients treated with lopinavir/ritonavir plus 2 nucleos(t)ide reverse transcriptase inhibitors (NRTI). METHODS: Multicenter, open-label study. Patients were randomized to continue with lopinavir/ritonavir plus 2 NRTI (triple therapy) or to switch to lopinavir/ritonavir plus lamivudine (dual therapy). LDL phenotype (by gradient gel electrophoresis) and Lp-PLA2 (by 2-thio-PAF) were determined at baseline and week 48. RESULTS: Forty-four patients included (triple therapy n = 19, dual therapy n = 25): men 63.6%, age 41.5 years (25-61), Framingham score 4.9% (0.2-22). Tenofovir was part of the regimen in 28 (63.6%) patients. Dual therapy patients were younger (p = 0.013) and had lower baseline apolipoprotein A1 (p = 0.029). At week 48, there were no changes in standard lipid measurements, except ApoA1/Apo B, which increased in dual therapy (p = 0.038) with no differences between arms. At week 48, no change in LDL phenotype was found in either arm. No changes in total Lp-PLA2 activity or the relative distribution of LDL and HDL particles were found at week 48 in either arm. CONCLUSIONS: Discontinuing the third nucleos(t)ide, mainly tenofovir and abacavir, in a lopinavir/ritonavir-containing regimen was not associated with a deleterious effect on LDL phenotype nor in Lp-PLA2 activity.


Assuntos
Didesoxinucleosídeos/efeitos adversos , Infecções por HIV/metabolismo , Lamivudina/efeitos adversos , Lipoproteínas LDL/metabolismo , Lopinavir/efeitos adversos , 1-Alquil-2-acetilglicerofosfocolina Esterase/sangue , 1-Alquil-2-acetilglicerofosfocolina Esterase/metabolismo , Fármacos Anti-HIV , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Biomarcadores , Contagem de Linfócito CD4 , Didesoxinucleosídeos/administração & dosagem , Combinação de Medicamentos , Substituição de Medicamentos , Feminino , Infecções por HIV/sangue , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Humanos , Lamivudina/administração & dosagem , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipídeos/sangue , Lipoproteínas LDL/sangue , Lopinavir/administração & dosagem , Masculino , Carga Viral
7.
AIDS Res Hum Retroviruses ; 33(2): 143-146, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27917639

RESUMO

We show that intensification of treatment with maraviroc in patients chronically infected with HIV-1 receiving successful long-term antiretroviral therapy was not associated with improvements in HIV-related morbidity, HIV reservoir, microbial translocation, immune activation, or immune exhaustion in either gut or peripheral blood. The measurement of reservoir in both gut and blood longitudinally contributes to a paucity of data in the area.


Assuntos
Sangue/virologia , Antagonistas dos Receptores CCR5/administração & dosagem , Cicloexanos/administração & dosagem , Trato Gastrointestinal/virologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Triazóis/administração & dosagem , Humanos , Masculino , Maraviroc , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Resultado do Tratamento
8.
J Acquir Immune Defic Syndr ; 73(3): 252-257, 2016 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-27727157

RESUMO

To investigate the pharmacokinetics/pharmacodynamics of single-dose maraviroc 300 mg in HIV-1 exposure compartments. Maraviroc concentrations in blood, secretions (vaginal, urethral, oral, and rectal), and tissue (vaginal and rectal) were measured, and ex vivo challenge was performed in 54 healthy volunteers to study protection from HIV infection. Maraviroc Cmax occurred within 4 hours in most compartments. Concentrations from 4 to 72 hours were above intracellular (IC) IC90 in all compartments, range 15-8095 ng/mL. Mean AUC0-72 compartment-to-plasma ratios were highest in the rectum (45-819) and urethra (144) compared with the female genital tract (1.6-4.8) and saliva (0.2). No sex differences in AUC0-72 or Cmax were observed. No ex vivo protection from HIV-1BaL occurred in rectal or vaginal tissue. Despite high and sustained concentrations, single-dose maraviroc was not protective against ex vivo challenge of vaginal/rectal tissue.


Assuntos
Antagonistas dos Receptores CCR5/farmacocinética , Cicloexanos/farmacocinética , Inibidores da Fusão de HIV/farmacocinética , Infecções por HIV/prevenção & controle , Infecções por HIV/virologia , Profilaxia Pré-Exposição , Triazóis/farmacocinética , Administração Oral , Adulto , Antagonistas dos Receptores CCR5/administração & dosagem , Antagonistas dos Receptores CCR5/farmacologia , Cicloexanos/administração & dosagem , Cicloexanos/farmacologia , Feminino , Inibidores da Fusão de HIV/administração & dosagem , Inibidores da Fusão de HIV/farmacologia , HIV-1/efeitos dos fármacos , Voluntários Saudáveis , Humanos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/virologia , Masculino , Maraviroc , Modelos Biológicos , Ensaios Clínicos Controlados Aleatórios como Assunto , Reto/efeitos dos fármacos , Reto/virologia , Saliva/efeitos dos fármacos , Saliva/virologia , Resultado do Tratamento , Triazóis/administração & dosagem , Triazóis/farmacologia , Uretra/efeitos dos fármacos , Uretra/virologia , Vagina/efeitos dos fármacos , Vagina/virologia
9.
AIDS Res Hum Retroviruses ; 32(12): 1198-1201, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27216134

RESUMO

We investigated whether a treatment switch from Atripla® (tenofovir, emtricitabine, and efavirenz) to DRV/r monotherapy may improve neuropsychological performance, health-related quality of life, and sleep function. Virologically suppressed subjects and asymptomatic on Atripla for ≥6 months were randomized 1:1 to continue Atripla or switch to boosted darunavir (DRV/r) 800/100 mg once daily for 48 weeks. Neurocognitive tests, the International HIV Dementia Scale (IHDS), Medical Outcomes Study HIV Health Survey (MOS-HIV), EQ-5D-3L, and the Hospital Anxiety and Depression Scale (HADS) were completed at baseline and at week 48. Sleep function was evaluated at week 48. Twenty-six patients on DRV/r and 31 on Atripla completed the 48-week study. No significant difference in the change in scores from week 0 to week 48 between the two arms was observed in neurocognitive outcomes, IHDS, health outcomes (EQ-5D-3L and QOL), and HADS score. By contrast, the HADS score and sleep quality were both significantly better in the DRV/r arm. In conclusion, switching to DRV/r monotherapy did not affect neurocognitive function or quality of life but improved anxiety, and sleep quality was significantly better than in continued Atripla.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Cognição/efeitos dos fármacos , Darunavir/uso terapêutico , Substituição de Medicamentos , Combinação Efavirenz, Emtricitabina, Fumarato de Tenofovir Desoproxila/uso terapêutico , Infecções por HIV/tratamento farmacológico , Ritonavir/uso terapêutico , Sono/efeitos dos fármacos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida
10.
Antivir Ther ; 21(5): 461-4, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26732023

RESUMO

Although currently available data suffice to support the use of protease inhibitor monotherapy in selected patients, there is concern about the antiviral activity of this regimen in the long term and in viral sanctuaries, such as the central nervous system. We report a case of encephalitis related to viral escape while receiving darunavir/ritonavir monotherapy in a carefully selected patient for participation in a clinical trial.


Assuntos
Encefalite Viral/etiologia , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/efeitos adversos , Adulto , Encéfalo/diagnóstico por imagem , Darunavir/efeitos adversos , Encefalite Viral/líquido cefalorraquidiano , Encefalite Viral/diagnóstico por imagem , Infecções por HIV/líquido cefalorraquidiano , HIV-1 , Humanos , Imagem por Ressonância Magnética , Masculino , Ritonavir/efeitos adversos , Falha de Tratamento , Carga Viral
11.
Antivir Ther ; 21(4): 359-63, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26656921

RESUMO

BACKGROUND: Lopinavir/ritonavir (LPV/r) monotherapy is used in selected virologically suppressed HIV-infected patients. Some would prefer a once-daily (OD) dose instead of the usual twice-daily dose to favour adherence. However, trough concentrations of the drug in blood and particularly in cerebrospinal fluid (CSF) may not be adequate to maintain viral suppression. METHODS: Prospective, open-label pilot study to evaluate the efficacy and safety of LPV/r monotherapy OD. HIV-1-infected patients, virologically suppressed for at least 6 months were enrolled. HIV viral load (VL) was determined at baseline and at weeks 4, 8, 12, 16, 24, 36 and 48. Lumbar puncture was performed in a subgroup of patients to evaluate CSF VL and CSF LPV concentrations. RESULTS: A total of 21 patients were included. At week 48, 85.7% (n=18) showed viral suppression (VL<40 copies/ml). Two patients had viral failure (9.5%) and a third was withdrawn from the study because of gastrointestinal symptoms. Nine patients were enrolled in the substudy. CSF VL was <40 copies/ml in all cases. Median (range) LPV concentration was 9.78 ng/ml (1.93-78.3) in CSF and 1,970 (154-16,700) ng/ml in plasma; the CSF/plasma ratio was 0.004 (0.001-0.186). CONCLUSIONS: In this small pilot study, LPV/r monotherapy OD maintained plasma HIV RNA suppression at 48 weeks in most patients, with no cases of CSF viral escape. However, CSF LPV concentrations were close to the 50% inhibitory concentration threshold in several patients; hence, this intervention should be avoided in patients with advanced immune suppression and/or those individuals presenting with significant comorbidities such as hepatitis C coinfection.


Assuntos
Fármacos Anti-HIV/sangue , Fármacos Anti-HIV/líquido cefalorraquidiano , Infecções por HIV/tratamento farmacológico , Lopinavir/sangue , Lopinavir/líquido cefalorraquidiano , Ritonavir/uso terapêutico , Adulto , Fármacos Anti-HIV/uso terapêutico , Esquema de Medicação , Combinação de Medicamentos , Feminino , Infecções por HIV/sangue , Humanos , Lopinavir/uso terapêutico , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Falha de Tratamento
12.
Antivir Ther ; 21(4): 287-96, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26460504

RESUMO

BACKGROUND: Efavirenz (EFV) has been associated with reductions in vitamin D (25[OH]D) and tenofovir (TDF) with increased bone turnover, reductions in bone mineral density (BMD) and renal tubular dysfunction. We hypothesized that switching from fixed-dose TDF/emtricitabine (FTC)/EFV to darunavir/ritonavir monotherapy (DRV/r) might increase 25(OH)D and BMD, and improve renal tubular function. METHODS: Subjects with HIV RNA <50 copies/ml on TDF/FTC/EFV for ≥6 months were randomized 1:1 to ongoing TDF/FTC/EFV or DRV/r (800/100 mg once daily) for 48 weeks. The primary end point was change from baseline in 25(OH)D at week 48. Secondary end points included changes in BMD, bone turnover markers and renal tubular function. RESULTS: A total of 64 subjects (86% male, 66% white, mean [sd] CD4(+) T-cell count 537.3 [191.5]/mm(3)) were analysed. After adjustment for baseline 25(OH)D and demographics, at week 48 DRV/r monotherapy was associated with a +3.6 (95% CI 0.6, 6.6) ng/ml increase in 25(OH)D compared to TDF/FTC/EFV (P=0.02). DRV/r monotherapy was associated with an increase in BMD (+2.9% versus -0.003% at the neck of femur and +2.6% versus +0.008% at the lumbar spine for DRV/r versus TDF/FTC/EFV; P<0.05 for all) and reductions in bone biomarkers compared with those remaining on TDF/FTC/EFV. No significant difference in renal tubular function was observed. Reasons for discontinuation in the DRV/r arm included side effects (n=4) and viral load rebound (n=3), all of which resolved with DRV/r discontinuation or regimen intensification. CONCLUSIONS: Switching from TDF/FTC/EFV to DRV/r in patients with suppressed HIV RNA resulted in significant improvements in 25(OH)D and bone biomarkers, and a 2-3% increase in BMD.


Assuntos
Fármacos Anti-HIV/farmacologia , Osso e Ossos/efeitos dos fármacos , Infecções por HIV/tratamento farmacológico , Rim/efeitos dos fármacos , Vitamina D/sangue , Adulto , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/uso terapêutico , Densidade Óssea/efeitos dos fármacos , Calcifediol/sangue , Darunavir/efeitos adversos , Darunavir/uso terapêutico , Combinação Efavirenz, Emtricitabina, Fumarato de Tenofovir Desoproxila/efeitos adversos , Combinação Efavirenz, Emtricitabina, Fumarato de Tenofovir Desoproxila/farmacologia , Combinação Efavirenz, Emtricitabina, Fumarato de Tenofovir Desoproxila/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ritonavir/efeitos adversos , Ritonavir/uso terapêutico
13.
J Antimicrob Chemother ; 70(5): 1513-6, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25608583

RESUMO

OBJECTIVES: The objective of this study was to assess whether a lower dose than the currently used one of darunavir/ritonavir might achieve good CSF concentrations and contribute to inhibition of CNS viral replication. PATIENTS AND METHODS: This was a substudy of a randomized, open, multicentre study (eudraCT 2011-006272-39), comparing the efficacy and safety of 800/100 mg of darunavir/ritonavir (darunavir 800) versus 600/100 mg of darunavir/ritonavir (darunavir 600) once daily plus tenofovir/emtricitabine or abacavir/lamivudine in 100 virologically suppressed patients. Paired blood and CSF samples were obtained. Total plasma darunavir concentrations were determined by HPLC, and CSF concentrations by liquid chromatography-tandem MS. Viral load (VL) was determined in plasma and CSF (limit of detection = 40 copies/mL) by PCR. RESULTS: Sixteen patients were enrolled. The median (range) of darunavir CSF concentrations in darunavir 600 (n = 8) and darunavir 800 (n = 8) patients was 17.08 (5.79-30.19) and 13.23 (3.47-32.98) ng/mL, respectively (P = 0.916). The median (range) darunavir CSF:plasma ratio was 0.010 (0.005-0.022) in darunavir 600 patients and 0.008 (0.004-0.017) in the darunavir 800 arm (P = 0.370). All 16 patients had a VL < 40 copies/mL in plasma and 14 had a VL < 40 copies/mL in CSF. Of the two patients with detectable CSF VL (280 copies/mL and 159 copies/mL), one was receiving darunavir 600 and the other darunavir 800 plus tenofovir/emtricitabine. Of note, these patients had the lowest CSF darunavir concentrations in their respective groups: 5.79 ng/mL (802 ng/mL in plasma) and 3.47 ng/mL (958 ng/mL in plasma). CONCLUSIONS: Darunavir CSF and plasma concentrations were comparable between the two arms. However, one patient from each group (with the lowest CSF darunavir concentrations in their respective groups) had detectable CSF VL despite undetectable plasma VL.


Assuntos
Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/farmacocinética , Líquido Cefalorraquidiano/química , Darunavir/administração & dosagem , Darunavir/farmacocinética , Ritonavir/administração & dosagem , Ritonavir/farmacocinética , Adolescente , Adulto , Idoso , Fármacos Anti-HIV/farmacologia , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Darunavir/farmacologia , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , HIV-1/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Plasma/química , Ritonavir/farmacologia , Espectrometria de Massas em Tandem , Carga Viral , Viremia/tratamento farmacológico , Viremia/virologia , Adulto Jovem
14.
J Int AIDS Soc ; 17(4 Suppl 3): 19553, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25394060

RESUMO

INTRODUCTION: Lipodystrophy is still a matter of concern in HIV+ patients receiving ART. However, long-term fat change in patients taking non-thymidine regimens is not well known. MATERIALS AND METHODS: A prospective ongoing fat change assessment including clinical evaluation and dexa scans (Hologic QDR 4500) is being conducted in all consecutive patients initiating ART from January 2008. Arm, leg, trunk and total fat as well as fat mass ratio (FMR=% trunk fat/% leg fat) were determined. Patients with data at baseline (BL), 12 and 36 m are included in this analysis. ITT and OT were performed. Multivariate general linear models were used to assess changes in fat measures. RESULTS: One hundred patients were included. 81% men, 42.9 years, 18% AIDS, CD4 218.5 (6-756), viral load 5 log (2.9-6.8), leg fat 4644g, trunk fat 6693g, FMR 0.94. Around 40 patients (40%) initiated a PIr (17 LPVr, 11 ATVr, 9 DRVr, 3 FPVr), 34 (34%) NVP and 21 (21%) EFV. About 83% received TDF/FTC and 10% ABC/3TC. Groups were comparable at BL except for a lower viral load in NVP patients (p=0.047) and lower c-LDL in PI patients (p=0.043). After 36 m, no patient presented a clinically evident lipodystrophy. At 12 m, an overall significant increase was found from baseline in trunk, leg and FMR (median 759 g, 479.4 g and 0.03, respectively, p<0.05) and at 36 m in trunk and leg fat (median 989.9 g, 566 g, respectively, p<0.05). According to ART, at 12 m a significant increase in trunk and leg fat was observed in EFV and PIr. At 36 m, in NVP patients trunk and leg fat as well as FMR increased, whereas in PIr patients only leg fat increased (see figure). In ITT analysis, adjusted by age, sex, risk practice and BL CD4, EFV was associated with a greater increase in FMR (p=0.036) at 36 m vs PIr. In OT analysis, at 12 m, NVP was associated with a smaller percentage increase in trunk fat (vs PIr and EFV, p=0.006) and in leg fat (vs PIr, p=0.046). These differences did not persist at 36 m. CONCLUSIONS: In this cohort of patients taking non-thymidine-based regimens, after 36 m without a clinically evident lipodystrophy, no significant changes in FMR were observed. However, some differences in fat redistribution according to ART were present: PIr was associated with an initial and continuous increase in trunk and leg fat, NVP with a slower and progressive increase in both fat compartments, while in EFV patients, the initial fat increase was followed by a decrease in peripheral fat at 36 m. Longer follow up will help to confirm these trends.

15.
J Int AIDS Soc ; 17(4 Suppl 3): 19587, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25394093

RESUMO

INTRODUCTION: Plasma trough concentrations of lopinavir (LPV) given as LPV/r 800/200 mg once daily (OD) are reduced in comparison with 400/100 mg twice daily (BID). While OD dosage of LPV/r is sufficient to achieve viral suppression in plasma, data about drug penetration and viral suppression in central nervous system (CNS) is needed, mainly if LPVr is used as maintenance monotherapy strategy in selected patients. The objective of this study was to evaluate CSF HIV-1 RNA and CSF LPV concentrations in patients receiving LPV/r monotherapy OD (LPVrMOD). MATERIAL AND METHODS: This is a cross-sectional sub-study within a prospective, open-label pilot simplification study to evaluate the efficacy and safety of LPV/rMOD in virologically suppressed patients previously receiving a BID LPV/r monotherapy regimen (LPV/rMBID), the "Kmon study" (NCT01581853). To assess LPV concentrations and HIV-1 RNA in CSF, a lumbar puncture (LP) was performed in a subgroup of patients after at least one month of LPVrMOD treatment. Plasma-paired samples of all patients were also obtained. HIV-1 RNA was determined by real-time PCR (limit of detection 40 copies/mL). Liquid chromatography-tandem mass spectrometry (Tandem labs, NJ) was used to determine CSF and blood plasma LPV concentrations. RESULTS: Nine patients were included. Median (range) age was 48 (34-56) years, median CD4 cell count 672 (252-1,408) cells/mL, median nadir CD4 count 125 (35-537) cells/mL and 40% of subjects were HCV-positive. Before starting LPV/rMOD median time on a LPV/r-containing regimen and on LPV/rMBID were 9 (4-11) years and 15 (7-24) months respectively, median time with undetectable HIV viral load was 5 (3-12) years and 2 patients had a previous documented blip. LP was performed a median of 24 (8-36) weeks after starting LPV/rMOD and 24 (11-28) hours after the last LPV/rMOD dose CSF and plasma HIV RNA was 40 copies/mL in all patients. Median LPV CSF concentration was 9.78 (1.93-78.3) ng/mL, median LPV plasma concentration 1,103 (377-16,700) ng/mL and median LPV CSF/plasma ratio 0.3% (0.1-1.2). CONCLUSIONS: No CSF viral escape was detected and LPV concentrations were above the IC50 for wtHIV-1 (1.9 ng/mL). However, as concentrations were close to IC50 in some patients, a careful clinical follow up of patients receiving this regimen would be advisable. Larger longitudinal studies will be helpful for a better understanding of the CNS antiviral activity of LPVr monotherapy.

16.
J Int AIDS Soc ; 17(4 Suppl 3): 19821, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25397565

RESUMO

INTRODUCTION: Darunavir/r (DRV/r) is currently used at a dose of 800/100 mg once daily (OD) in a high proportion of patients. Pharmacokinetic data suggest that 600/100 OD may be effective, reducing toxicity and cost. However, drug concentrations in reservoirs such as cerebrospinal fluid (CSF) might not be adequate to inhibit viral replication. We aimed to evaluate concentrations of DRV and HIV-1 viral load (VL) in CSF patients receiving DRV 600/100 mg OD. METHODS: DRV600 is an ongoing randomized open study comparing DRV/r 800/100 mg (DRV800) vs 600/100 mg (DRV600) OD plus TDF/FTC or ABC/3TC in 100 virologically suppressed patients (eudraCT 2011-006272-39). Here we present the results of a CSF sub-study. A lumbar puncture (LP) was performed in participating patients after at least six months of inclusion in the study, 20-28 hours after a dose of DRV/r. VL (PCR, LOD 40 copies/mL) was determined in CSF and in plasma. DRV concentrations were quantified in CSF by liquid chromatography mass spectrometry (LC/MS/MS) and in plasma using high-performance liquid chromatography (HPLC). RESULTS: Sixteen patients were included (eight in each arm). All DRV600 patients and four out of eight DRV800 patients received TDF/FTC, and the other four ABC/3TC. 75% were males, median (range) age was 48 (17-71) years, CD4 cell count 532 cells/mL (190-1,394). Median total time on DRV/r was 30 (11-57) months, and since the beginning of the study 8 (6-12) months in DRV800 and 10 (7-12) months in DRV600 patients. LP was performed a median of 26 (24-28) hours after the last DRV/r+TVD or KVX dose. In DRV600 patients the median DRV plasma levels were 1,674 (326-3,742) ng/mL, CSF levels 17.08 (5.79-30.19) ng/mL and DRV CSF:plasma ratio 0.0084 (0.0028-0.0388), while in the DRV800 arm, median DRV plasma levels were 1,707 (958-3,910) ng/mL, CSF levels 13.23 (3.47-32.98) ng/mL and DRV CSF:plasma ratio 0.0104 (0.0018-0.0262). All patients had VL<40 copies/mL in plasma and 14 patients VL<40 copies/mL in CSF. Two patients (1 in each arm, and taking TDF/FTC) had detectable VL in CSF (280 and 159 c/mL). These patients had the lowest CSF DRV concentrations (5.47 and 3.47 ng/mL), with plasma DRV concentrations of 802 and 958 ng/mL respectively. CONCLUSIONS: CSF DRV concentrations and CSF VL were similar between patients receiving DRV/r 800/100 mg or 600/100 mg OD. Low CSF DRV concentrations might be associated with viral escape in CNS. This may be taken into account in patients receiving OD DRV/r. Larger studies should confirm these findings.

17.
AIDS Res Hum Retroviruses ; 30(10): 984-7, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25096495

RESUMO

Monotherapy with boosted protease inhibitors has emerged as an antiretroviral therapy simplification alternative for selected patients, endorsed by the results of some randomized clinical trials. However, there are some concerns about the efficacy of such a strategy in achieving successful viral suppression in those anatomic compartments or reservoirs in which antiretroviral drug penetration is lower, such as the central nervous system (CNS). Several studies have demonstrated better neurocognitive performance in patients receiving antiretroviral drugs with better cerebrospinal fluid (CSF) penetration. Nevertheless, cases of CSF viral escape accompanied by moderate or severe neurological symptoms have been reported with both standard triple therapy and boosted protease inhibitor (PI) monotherapy, and it is not well established whether ritonavir-boosted protease inhibitor (PI/r) monotherapy is associated with a higher risk of symptomatic CSF viral escape or not. Herein, we present a case of viral rebound and resistance emergence exclusively in CSF associated with an unusual clinical manifestation of focal encephalitis in a patient with plasma HIV-1 RNA suppression while receiving lopinavir/ritonavir monotherapy. Clinical resolution and CSF viral suppression were observed after switching to a genotype-guided combined antiretroviral regimen with good CSF penetration.


Assuntos
Encefalite Viral/complicações , Infecções por HIV/virologia , Inibidores da Protease de HIV/uso terapêutico , Lopinavir/uso terapêutico , Ritonavir/uso terapêutico , Adulto , Encefalite Viral/líquido cefalorraquidiano , Feminino , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos
18.
Antivir Ther ; 19(6): 569-77, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24458091

RESUMO

BACKGROUND: There are no clinical trials in which the main objective is to compare the efficacy of efavirenz versus ritonavir-boosted protease inhibitor (PI/r)-based initial antiretroviral therapy (ART) in patients with high plasma HIV-1 RNA levels. This study aims to compare these regimens in this patient population in the setting of routine clinical practice. METHODS: This was a multicentre, observational cohort study, including 596 consecutive treatment-naive patients with plasma HIV-1 RNA>100,000 copies/ml initiating efavirenz or PI/r-based ART between 2000 and 2010. The primary effectiveness end point was the percentage of patients with HIV-1 RNA<50 copies/ml at week 48 by intent-to-treat analysis. RESULTS: Among a total of 596 patients, 57% initiated efavirenz and 43% PI/r-regimens (73% lopinavir and fosamprenavir [62% lopinavir, 11% fosamprenavir]). HIV-1 RNA suppression to <50 copies/ml at week 48 was higher in the efavirenz group (84% versus 74% [difference 10%, 95% CI 3.4%, 16.7%; P=0.002]). The percentage of virological failures was similar (efavirenz 4% versus PI/r 4%; P=0.686), but voluntary discontinuations and toxicity-related treatment changes were higher with PI/r (4% versus 1%; P=0.006 and 11% versus 6%; P=0.069, respectively). However, resistance selection at failure was higher in patients receiving efavirenz (89% versus 50%; P=0.203). Efavirenz was significantly more effective than lopinavir/r or fosamprenavir/r, whereas no significant differences were observed between efavirenz and darunavir/r or atazanavir/r. The high viral suppression in the efavirenz group was also evident in patients with very high viral loads (>500,000 copies/ml) and in those with low CD4(+) T-cell counts. CONCLUSIONS: In routine clinical practice, the effectiveness of initial efavirenz-based regimens was at least similar to or even higher than various PI/r-based regimens in HIV-1-infected patients with plasma HIV-1 RNA>100,000 copies/ml.


Assuntos
Benzoxazinas/uso terapêutico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Inibidores da Protease de HIV/uso terapêutico , HIV-1/genética , Inibidores da Transcriptase Reversa/uso terapêutico , Ritonavir/uso terapêutico , Carga Viral , Adulto , Terapia Antirretroviral de Alta Atividade , Benzoxazinas/farmacologia , Contagem de Linfócito CD4 , Coinfecção , Feminino , Infecções por HIV/diagnóstico , Inibidores da Protease de HIV/farmacologia , HIV-1/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Inibidores da Transcriptase Reversa/farmacologia , Fatores de Risco , Ritonavir/farmacologia , Fatores de Tempo , Falha de Tratamento , Resultado do Tratamento
19.
Enferm Infecc Microbiol Clin ; 32(1): 37-47, 2014 Jan.
Artigo em Espanhol | MEDLINE | ID: mdl-23642283

RESUMO

OBJECTIVE: To develop a consensus document containing clinical recommendations for the management of human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND). METHODS: We assembled a panel of experts appointed by GeSIDA and the Secretariat of the National AIDS Plan (PNS), including internal medicine physicians with expertise in the field of HIV, neuropsychologists, neurologists and neuroradiologists. Scientific information was reviewed to October 2012 in publications and conference papers. In support of the recommendations using two levels of evidence: the strength of the recommendation in the opinion of the experts (A, B, C) and the level of empirical evidence (I, II, III), two levels based on the criteria of the Infectious Disease Society of America, already used in previous documents GeSIDA/SPNS. RESULTS: Multiple recommendations for the clinical management of these disorders are provided, including two graphics algorithms, considering both the diagnostic and possible therapeutic strategies. CONCLUSIONS: Neurocognitive disorders associated with HIV infection is currently highly prevalent, are associated with a decreased quality of life and daily activities, and given the possibility of occurrence of an increase in the coming years, there is a need to adequately manage these disorders, from a diagnostic as well as therapeutic point of view, and always from a multidisciplinary perspective.


Assuntos
Complexo AIDS Demência/diagnóstico , Complexo AIDS Demência/terapia , Algoritmos , Humanos
20.
AIDS Rev ; 12(3): 153-63, 2010 Jul-Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20842204

RESUMO

Until recently, methicillin-resistant Staphylococcus aureus was considered an uncommon community pathogen, almost exclusively associated with healthcare exposure. Over the last decade, however, methicillin-resistant S. aureus infection, particularly skin and soft tissue infection, has emerged in healthy individuals with no traditional risk factors for its acquisition. Several risk factors, including certain lifestyle behaviors, have been associated with community-acquired methicillin-resistant S. aureus colonization and infection. Regardless of other concurrent risk factors, HIV-infected patients have an increased risk for acquiring this pathogen. This article summarizes the current knowledge regarding associated risk factors, clinical manifestations, and management of community-acquired methicillin-resistant Staphylococcus aureus infections in HIV-infected patients.


Assuntos
Infecções Comunitárias Adquiridas/epidemiologia , Infecções por HIV/microbiologia , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , HIV , Humanos , Resistência a Meticilina , Fatores de Risco , Infecções dos Tecidos Moles/tratamento farmacológico , Infecções dos Tecidos Moles/microbiologia , Infecções Cutâneas Estafilocócicas/tratamento farmacológico , Infecções Cutâneas Estafilocócicas/epidemiologia
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