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1.
AIDS Rev ; 21(3): 135-142, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31532396

RESUMO

Since HIV has evolved from being a fatal illness to a chronic condition, this brings new challenges relating to long-term health, as increasing numbers of people living with HIV (PLHIV) navigate their lives beyond viral suppression. This review presents the challenges facing patients and health-care providers managing HIV in Europe today. We highlight the challenges that the evolving landscape in HIV brings, including managing an aging and more diverse population of PLHIV; this requires a shift from managing disease to managing health and may best be achieved by multidisciplinary teams in the long term. We introduce the concept of "health goals for me:" an individualized approach to the management of HIV, and use this as the basis for a proposed framework for assessing health-related quality of life for PLHIV. Our framework comprises a continuous cycle of "ask and measure," "feedback and discussion," and "intervention," based on collaboration between the health-care professional and patient. For improved long-term management of PLHIV, we consider that this framework should become an intrinsic part of HIV care in the future and that the "health goals for me" concept be used as a tool to facilitate healthy living for PLHIV beyond viral suppression.

2.
PLoS Pathog ; 15(8): e1007991, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31425551

RESUMO

Latency reversal agents (LRAs) have proven to induce HIV-1 transcription in vivo but are ineffective at decreasing the size of the latent reservoir in antiretroviral treated patients. The capacity of the LRAs to perturb the viral reservoir present in distinct subpopulations of cells is currently unknown. Here, using a new RNA FISH/flow ex vivo viral reactivation assay, we performed a comprehensive assessment of the viral reactivation capacity of different families of LRAs, and their combinations, in different CD4+ T cell subsets. We observed that a median of 16.28% of the whole HIV-reservoir induced HIV-1 transcripts after viral reactivation, but only 10.10% of these HIV-1 RNA+ cells produced the viral protein p24. Moreover, none of the LRAs were powerful enough to reactivate HIV-1 transcription in all CD4+ T cell subpopulations. For instance, the combination of Romidepsin and Ingenol was identified as the best combination of drugs at increasing the proportion of HIV-1 RNA+ cells, in most, but not all, CD4+ T cell subsets. Importantly, memory stem cells were identified as highly resistant to HIV-1 reactivation, and only the combination of Panobinostat and Bryostatin-1 significantly increased the number of cells transcribing HIV within this subset. Overall, our results validate the use of the RNA FISH/flow technique to assess the potency of LRAs among different CD4+ T cell subsets, manifest the intrinsic differences between cells that encompass the latent HIV reservoir, and highlight the difficulty to significantly impact the latent infection with the currently available drugs. Thus, our results have important implications for the rational design of therapies aimed at reversing HIV latency from diverse cellular reservoirs.

3.
J Antimicrob Chemother ; 74(6): 1693-1700, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30838386

RESUMO

BACKGROUND: Integrase strand-transfer inhibitors (INSTIs) constitute at present one of the pillars of first-line ART. OBJECTIVES: To study the prevalence of and the trend in transmitted drug resistance (TDR) to INSTIs in ART-naive patients in Spain. METHODS: During the period 2012-17, 1109 patients from CoRIS were analysed. The Stanford algorithm v8.7 was used to evaluate TDR and transmission of clinically relevant resistance. To describe individual mutations/polymorphisms, the most recent IAS list (for INSTIs) and the 2009 WHO list update (for the backbone NRTIs used in combination with INSTIs in first-line treatment) were used. RESULTS: Clinically relevant resistance to the INSTI class was 0.2%: T66I, 0.1%, resistance to elvitegravir and intermediate resistance to raltegravir; and G163K, 0.1%, intermediate resistance to raltegravir and elvitegravir. No clinical resistance to dolutegravir or bictegravir was observed. The prevalence of INSTI TDR following the IAS-USA INSTI mutation list was 2.6%, with no trend towards changes in the prevalence throughout the study period. The overall prevalence of NRTI WHO mutations was 4.3%, whereas clinically relevant resistance to tenofovir, abacavir and emtricitabine/lamivudine was 1.7%, 1.9% and 0.7%, respectively. CONCLUSIONS: Given the low prevalence of clinically relevant resistance to INSTIs and first-line NRTIs in Spain, it is very unlikely that a newly diagnosed patient will present with clinical resistance to a first-line INSTI-based regimen. These patients may not benefit from INSTI and NRTI baseline resistance testing.

4.
AIDS Res Hum Retroviruses ; 35(6): 513-518, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30909716

RESUMO

Our aim was to evaluate the effectiveness and safety of darunavir/cobicistat (DRV/c) monotherapy as an antiretroviral treatment simplification strategy in HIV-infected patients already on suppressive darunavir/ritonavir (DRV/r) monotherapy in routine clinical practice. We conducted a retrospective multicenter study including all adult patients switched from DRV/r monotherapy to DRV/c monotherapy while HIV-1 RNA was <50 copies/mL and who had at least one follow-up visit. The primary endpoint was the percentage of patients remaining free of treatment failure (TF), defined as discontinuation of monotherapy for any reason, including loss of follow-up. Virological failure (VF) was defined as a confirmed HIV-1 RNA ≥50 copies/mL or any change in the regimen after a single determination with HIV-1 RNA ≥50 copies/mL. Changes in renal function parameters and lipid profile were also evaluated. Factors associated with VF were analyzed using Cox regression. In this study, 173 subjects were included. The median (interquartile range) time of follow-up was 58 (50-67) weeks. Overall, 90% of patients remained free of TF during follow-up. Ten (6%) patients discontinued DRV/c monotherapy for nonvirological reasons and eight (5%) developed VF. No DRV-related mutations were identified in patients with VF. A decrease in triglyceride levels (p = .006) and estimated glomerular filtration rate (p = .005) were observed during follow-up. The presence of blips and CD4+ nadir <100 cells/mm3 were predictors of VF. In conclusion, switching to DRV/c monotherapy seems to be safe and effective in routine clinical practice in HIV-infected patients undergoing suppressive DRV/r monotherapy.

5.
Euro Surveill ; 24(7)2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30782268

RESUMO

INTRODUCTION: Although human papillomavirus (HPV) routine vaccination programmes have been implemented around the world and recommendations have been expanded to include other high-risk individuals, current recommendations often differ between countries in Europe, as well as worldwide. AIM: To find and summarise the best available evidence of HPV vaccination in high-risk patients aiding clinicians and public health workers in the day-to-day vaccine decisions relating to HPV in Spain. METHODS: We conducted a systematic review of the immunogenicity, safety and efficacy/effectiveness of HPV vaccination in high-risk populations between January 2006 and June 2016. HPV vaccination recommendations were established with levels of evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. RESULTS: A strong recommendation about HPV vaccination was made in the following groups: HIV infected patients aged 9-26 years; men who have sex with men aged 9-26 years; women with precancerous cervical lesions; patients with congenital bone marrow failure syndrome; women who have received a solid organ transplant or hematopoietic stem cell transplantation aged 9-26 years; and patients diagnosed with recurrent respiratory papillomatosis. CONCLUSIONS: Data concerning non-routine HPV vaccination in populations with a high risk of HPV infection and associated lesions were scarce. We have developed a document to evaluate and establish evidence-based guidelines on HPV vaccination in high-risk populations in Spain, based on best available scientific evidence.

6.
Pharmacotherapy ; 39(4): 501-507, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30723941

RESUMO

STUDY OBJECTIVE: Dual therapy with once/day dolutegravir (DTG) plus boosted darunavir (DRV/b) may be a suitable and effective strategy with a high genetic barrier to resistance in patients infected with human immunodeficiency virus (HIV). Our aim was to evaluate the effectiveness of DTG plus DRV/b (DTG+DRV/b) as a switch strategy in HIV-infected patients, irrespective of their history of virologic failure (VF). DESIGN: Multicenter retrospective cohort study. SETTING: Human immunodeficiency outpatient treatment clinics at three university hospitals in Spain. PATIENTS: Fifty HIV-infected adults who had a stable antiretroviral treatment (ART) regimen and an undetectable viral load for at least 6 months, and whose ART was switched to once/day DTG+DRV/b between January 2015 and January 2018 were included in the analysis. Historical genotype at the time of VF was available in 44 patients. MEASUREMENTS AND MAIN RESULTS: Patients were followed until VF or treatment discontinuation for any reason. The primary outcome was the percentage of patients with a viral load of 50 copies/mL or lower at the last follow-up visit. Secondary outcomes included changes in CD4+ cell count, lipid profile, and renal function. Of the 50 patients included, median time of viral suppression was 52 months (interquartile range [IQR] 18-103 mo) and nadir CD4+ 89 cells/mm3 (IQR 37-241 cells/mm3 ). Patients had a history of a median of 8 ART combinations (IQR 4-11 combinations) and 3 VFs (IQR 2-8 VFs). The historical genotypes from 44 patients showed 41 patients (93.2%) with nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) resistance-associated mutations (RAMs), 32 (72.7%) with nonnucleoside reverse transcriptase inhibitor (NNRTI) RAMs, and 12 (27.3%) with primary protease inhibitor (PI) RAMs; 7 (15.9%) had darunavir RAMs, and no patients had baseline integrase strand transfer inhibitor RAMs. Thirty-seven patients (84.1%) had resistance to at least two antiretroviral classes. After a median of 25 months (IQR 17-28 mo) of follow-up, 49 patients (98%) maintained a viral load of 50 copies/mL or lower, and 1 patient (2%) had VF. No new RAMs emerged at VF. At week 4, serum creatinine concentration increased a median of 0.12 mg/dl (0.03-0.23 mg/dl). At last visit, total cholesterol and low-density lipoprotein cholesterol levels increased by a median of 9 mg/dl (IQR -18 to 40 mg/dl) and 16 mg/dl (IQR -9 to 40 mg/dl), respectively, whereas CD4+ cell count remained stable (median +13 cell/mm3 ). CONCLUSION: In this cohort of heavily treated HIV-infected patients with virologic suppression, switching to the combination of DTG+DRV/b was a convenient regimen that was highly effective and had good tolerability.

7.
Enferm Infecc Microbiol Clin ; 36 Suppl 2: 10-16, 2018 12.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-30545466

RESUMO

Symtuza® is the first and only treatment for HIV-1 that combines 2 nucleos(t)ide analogues (emtricitabine and tenofovir alafenamide) together with a boosted protease inhibitor (darunavir/cobicistat) in a once-daily single tablet regimen (STR). This combination is active against a wide variety of HIV strains and, in turn, avoids bone and renal toxicity associated with the use of tenofovir disoproxil fumarate, combining efficacy, convenience, tolerability and high genetic barrier. Pharmacokinetic studies of its components show a favourable profile, allowing its use in a wide variety of patients and clinical situations. Although, as in any boosted combination, possible interactions with concomitant medication should be borne in mind, cobici-stat inhibits cytochrome P-450 more selectively and has no inducing effect, so it has a more predictable interaction profile than ritonavir. Supplement information: This article is part of a supplement entitled "Co-formulated cobicistat-boosted darunavir, emtricitabine, and tenofovir alafenamide for the treatment of HIV infection", which is sponsored by Janssen.


Assuntos
Fármacos Anti-HIV/farmacologia , Darunavir/farmacologia , Tenofovir/farmacologia , Fármacos Anti-HIV/farmacocinética , Darunavir/farmacocinética , Combinação de Medicamentos , Interações de Medicamentos , Humanos , Tenofovir/farmacocinética
8.
Enferm. infecc. microbiol. clín. (Ed. impr.) ; 36(supl.2): 10-16, dic. 2018. tab, ilus
Artigo em Espanhol | IBECS | ID: ibc-177042

RESUMO

Symtuza(R) es el primer y único tratamiento del VIH-1 que combina 2 análogos de nucleós(t)idos (emtricita-bina y tenofovir alafenamida) junto con un inhibidor de la proteasa potenciado (darunavir/cobicistat) en un solo comprimido una vez al día. Esta combinación es activa frente a una gran variedad de cepas del VIH y, a su vez, evita la toxicidad renal y ósea asociada con el uso de tenofovir disoproxil fumarato, y aúna eficacia, conveniencia, tolerabilidad y elevada barrera genética. Los estudios farmacocinéticos de sus componentes demuestran un perfil favorable que permite su uso en una gran variedad de pacientes y situaciones clínicas. Aunque, como en toda combinación potenciada, es necesario considerar posibles interacciones con medicación concomitante, el potenciador cobicistat inhibe más selectivamente el citocromo P-450 y no posee ningún efecto inductor, por lo que su perfil de interacciones es más predecible que el de ritonavir. Información sobre el suplemento: este artículo forma parte del suplemento titulado "Darunavir, cobicistat, emtricitabina y tenofovir alafenamida coformulados en el tratamiento de la infección por el VIH", que ha sido patrocinado por Janssen


Symtuza(R) is the first and only treatment for HIV-1 that combines 2 nucleos(t)ide analogues (emtricitabine and tenofovir alafenamide) together with a boosted protease inhibitor (darunavir/cobicistat) in a once-daily single tablet regimen (STR). This combination is active against a wide variety of HIV strains and, in turn, avoids bone and renal toxicity associated with the use of tenofovir disoproxil fumarate, combining efficacy, convenience, tolerability and high genetic barrier. Pharmacokinetic studies of its components show a favourable profile, allowing its use in a wide variety of patients and clinical situations. Although, as in any boosted combination, possible interactions with concomitant medication should be borne in mind, cobici-stat inhibits cytochrome P-450 more selectively and has no inducing effect, so it has a more predictable interaction profile than ritonavir. Supplement information: This article is part of a supplement entitled "Co-formulated cobicistat-boosted darunavir, emtricitabine, and tenofovir alafenamide for the treatment of HIV infection", which is sponsored by Janssen


Assuntos
Humanos , Darunavir/administração & dosagem , Cobicistat/administração & dosagem , Emtricitabina/administração & dosagem , Tenofovir/administração & dosagem , Quimioterapia Combinada , Infecções por HIV/tratamento farmacológico
9.
J Virus Erad ; 4(3): 196-207, 2018 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-30050686

RESUMO

The 20th International Symposium on HIV and Emerging Infectious Diseases took place in Marseille, France. It had a refreshing European look with reinforced partnerships with the European AIDS Clinical Society and the British HIV Association and with international speakers and participants. Topics included HIV and global health, HIV and hepatitis cure, the microbiome and immunotherapies, clinical research and methodology, as well as chemsex, pre-exposure prophylaxis, sexually transmitted infections and emerging infectious diseases. Novel areas of research were also described, such as electronic technology in order to improve HIV management, and the expert patient.

10.
Int J Rheum Dis ; 21(2): 487-496, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29314762

RESUMO

AIM: To describe the prevalence, clinical characteristics and risk factors of opportunistic infection (OI) in a cohort of patients with inflammatory myopathies, and compare mortality rates between those with and without OIs. METHODS: In total, 204 patients from our myositis cohort were reviewed to identify patients who had experienced an OI during the period 1986-2014. The patients' clinical characteristics, treatments received, and outcomes were systematically recorded. Disease activity at the OI diagnosis and the cumulative doses of immunosuppressive drugs were analyzed, as well as the specific pathogens involved and affected organs. RESULTS: The prevalence of OI in the total cohort was 6.4%: viruses, 44.4% (varicella-zoster virus, cytomegalovirus); bacteria, 22.2% (Salmonella sp., Mycobacterium tuberculosis, M. chelonae); fungi, 16.7% (Candida albicans, Pneumocystis jirovecii); and parasites, 16.7% (Toxoplasmosis gondii, Leishmania spp.). Lung and skin/soft tissues were the organs most commonly affected (27.8%). Overall, 55.6% of OIs developed during the first year after the myositis diagnosis and OI was significantly associated with administration of high-dose glucocorticoids (P = 0.0148). Fever at onset of myositis (P = 0.0317), biological therapy (P < 0.001) and sequential administration of four or more immunosuppressive agents during myositis evolution (P = 0.0032) were significantly associated with OI. All-cause mortality in the OI group was 3.69 deaths per 100 patients/year versus 3.40 in the remainder of the cohort (P = 0.996). CONCLUSIONS: The prevalence of OI was 6.4% in our myositis cohort, higher than the rest of the inpatients of our hospital (1.7%; P < 0.01). High-dose glucocorticoids at disease onset and severe immunosuppression are the main factors implicated.


Assuntos
Infecções Bacterianas/induzido quimicamente , Produtos Biológicos/efeitos adversos , Glucocorticoides/efeitos adversos , Imunossupressores/efeitos adversos , Miosite/tratamento farmacológico , Infecções Oportunistas/induzido quimicamente , Viroses/induzido quimicamente , Adulto , Infecções Bacterianas/diagnóstico , Infecções Bacterianas/imunologia , Infecções Bacterianas/mortalidade , Produtos Biológicos/administração & dosagem , Feminino , Glucocorticoides/administração & dosagem , Humanos , Hospedeiro Imunocomprometido , Imunossupressores/administração & dosagem , Incidência , Masculino , Pessoa de Meia-Idade , Miosite/diagnóstico , Miosite/mortalidade , Infecções Oportunistas/diagnóstico , Infecções Oportunistas/imunologia , Infecções Oportunistas/mortalidade , Prevalência , Estudos Retrospectivos , Fatores de Risco , Espanha/epidemiologia , Fatores de Tempo , Viroses/diagnóstico , Viroses/imunologia , Viroses/mortalidade
11.
J Antimicrob Chemother ; 73(3): 732-737, 2018 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-29237008

RESUMO

Objectives: To determine the effect of etravirine on the pharmacokinetics of darunavir/cobicistat and vice versa. Safety and tolerability of this combination were also evaluated. Methods: Open-label, fixed-sequence trial in two cohorts of HIV-infected patients on therapy with darunavir/cobicistat 800/150 mg once daily (DRV cohort; n = 15) or etravirine 400 mg once daily (ETR cohort; n = 15). Etravirine or darunavir/cobicistat were added on days 1-14 and 1-7 in participants in the DRV or ETR cohort, respectively. Full pharmacokinetic profiles were obtained on days 0 and 14 in the DRV cohort, and on days 0 and 7 in the ETR cohort. Darunavir, cobicistat and etravirine pharmacokinetic parameters [AUC0-24, Cmax and trough concentrations in plasma (C24)] were calculated for each individual by non-compartmental analysis and were compared using linear mixed-effects models. Adverse events and HIV-1 RNA in plasma were monitored. Results: Etravirine co-administration decreased cobicistat AUC0-24, Cmax and C24 by 30%, 14% and 66%, respectively. Although darunavir AUC0-24 and Cmax were unchanged by etravirine, darunavir C24 was 56% lower for darunavir/cobicistat co-administered with etravirine relative to darunavir/cobicistat alone. Etravirine pharmacokinetics were unchanged by darunavir/cobicistat. Treatments were well tolerated, and HIV-1 RNA remained undetectable in all participants. Conclusions: Although etravirine pharmacokinetics was unchanged by darunavir/cobicistat, there was a significant decrease in cobicistat exposure and in darunavir C24 when darunavir/cobicistat was co-administered with etravirine. Boosting darunavir with ritonavir instead of with cobicistat may be preferred if darunavir is to be combined with etravirine in clinical practice.


Assuntos
Fármacos Anti-HIV/farmacocinética , Cobicistat/farmacocinética , Darunavir/farmacocinética , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/farmacocinética , Piridazinas/farmacocinética , Adulto , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/sangue , Cobicistat/administração & dosagem , Cobicistat/sangue , Estudos de Coortes , Darunavir/administração & dosagem , Darunavir/sangue , Quimioterapia Combinada , Feminino , HIV/efeitos dos fármacos , Inibidores da Protease de HIV/administração & dosagem , Inibidores da Protease de HIV/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Piridazinas/administração & dosagem , Piridazinas/sangue , RNA Viral/sangue , Adulto Jovem
12.
Clin Infect Dis ; 65(12): 2112-2118, 2017 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-29020293

RESUMO

Background: Our objective was to assess the therapeutic noninferiority of dual therapy with darunavir/ritonavir and lamivudine compared to triple therapy with darunavir/ritonavir plus 2 nucleos(t)ides for maintenance of human immunodeficiency virus type 1 (HIV-1) suppression. Methods: This was a multicenter, open-label, noninferiority trial (margin 12%). Patients with HIV-1 RNA <50 copies/mL for 6 months or longer on triple therapy with darunavir/ritonavir and 2 nucleos(t)ides (tenofovir disoproxil fumarate and emtricitabine or abacavir and lamivudine) and with no resistance were randomized to continue therapy (n = 128) or switch to darunavir/ritonavir and lamivudine (n = 129). The primary endpoint was the proportion of participants with HIV-RNA <50 copies/mL after 48 weeks of follow-up according to the snapshot algorithm. Results: A total of 249 participants received study drugs (intention-to-treat exposed). The proportion of participants with HIV-RNA <50 copies/mL in the dual- and triple-therapy arms was 88.9% (112/126) and 92.7% (114/123; difference, -3.8%; 95% confidence interval, -11.0 to 3.4), respectively. Four participants in the dual-therapy arm and 2 in the triple-therapy arm developed protocol-defined virological failure. Switching to dual therapy was associated with a significant increase in total, low-density lipoprotein, and high-density lipoprotein (HDL) cholesterol, but not in the total-to-HDL cholesterol ratio. Serious adverse events and study drug discontinuations due to adverse events occurred in 4.8% vs 4.9%P = .97) and in 0.8% (1/126) vs 1.6% P = .55) in dual therapy vs triple therapy, respectively. Conclusions: Dual therapy with darunavir/ritonavir and lamivudine demonstrated noninferior therapeutic efficacy and similar tolerability compared to triple therapy. Clinical Trials Registration: NCT02159599.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/uso terapêutico , HIV-1/efeitos dos fármacos , Carga Viral/efeitos dos fármacos , Adulto , Fármacos Anti-HIV/administração & dosagem , Contagem de Linfócito CD4 , Darunavir/administração & dosagem , Darunavir/uso terapêutico , Didesoxinucleosídeos/administração & dosagem , Didesoxinucleosídeos/uso terapêutico , Emtricitabina/administração & dosagem , Emtricitabina/uso terapêutico , Feminino , Infecções por HIV/virologia , Inibidores da Protease de HIV/administração & dosagem , Humanos , Lamivudina/administração & dosagem , Lamivudina/uso terapêutico , Masculino , Conduta do Tratamento Medicamentoso , Pessoa de Meia-Idade , RNA Viral/sangue , Ritonavir/administração & dosagem , Ritonavir/uso terapêutico , Tenofovir/administração & dosagem , Tenofovir/uso terapêutico
13.
Antivir Ther ; 22(1): 89-90, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-27546463

RESUMO

An HIV-infected patient treated with tenofovir disoproxil fumarate/emtricitabine/elvitegravir/cobicistat developed severe acute ischaemia of both legs during a migraine episode. After being interrogated he admitted taking an ergotamine-containing preparation. Ergotism due to interaction between ergotics and cobicistat was diagnosed. We describe the first reported case of this interaction.


Assuntos
Fármacos Anti-HIV/efeitos adversos , Cobicistat/efeitos adversos , Ergotamina/efeitos adversos , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Isquemia/etiologia , Doença Aguda , Adulto , Fármacos Anti-HIV/administração & dosagem , Cobicistat/administração & dosagem , Interações de Medicamentos , Quimioterapia Combinada , Ergotamina/administração & dosagem , Humanos , Perna (Membro) , Masculino , Transtornos de Enxaqueca/complicações , Transtornos de Enxaqueca/tratamento farmacológico
14.
HIV AIDS (Auckl) ; 8: 175-182, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27843352

RESUMO

Efficacy is the main objective of antiretroviral treatment and adherence is one of the cornerstones to achieve it. For this reason, treatment simplification is of key importance with regard to antiretroviral regimens. Rezolsta® (darunavir/cobicistat) is the first fixed-dose combination containing a protease inhibitor approved for HIV treatment. This coformulation includes darunavir, a protease inhibitor that has shown its efficacy and safety in naïve and treatment-experienced patients, and cobicistat, the new pharmacokinetic enhancer that is expected to replace ritonavir. Bioequivalence between ritonavir and cobicistat as darunavir boosters has been shown in studies involving healthy volunteers. Furthermore, efficacy and safety of darunavir/cobicistat observed in phase III studies, including naïve and pretreated patients without darunavir-associated resistance mutations, are comparable to historical data of darunavir/ritonavir 800/100 mg once-daily formulation. Adverse events with darunavir/cobicistat are scarce and mild, and basically include skin reactions and gastrointestinal disturbances. Although small increases in plasma creatinine are expected in patients receiving cobicistat due to the inhibition of creatinine transporters in kidney tubules, actual glomerular filtrate rate remains unaltered. Cobicistat does not have an inducer effect on metabolic pathways and shows much more selective inhibition than ritonavir. Therefore, isoenzyms different from CYP3A4 are supposed to be less affected by cobicistat, and thus fewer drug-drug interactions are expected.

15.
J Antimicrob Chemother ; 71(12): 3510-3514, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27591292

RESUMO

OBJECTIVES: To describe the effectiveness and safety of an abacavir/lamivudine + rilpivirine regimen in naive HIV-1-infected patients, as there is a lack of data with this combination. METHODS: This was an observational, retrospective, multicentre study in eight Spanish hospitals. All antiretroviral-naive patients ≥18 years old and starting abacavir/lamivudine + rilpivirine were included. Effectiveness (ITT and on-treatment) and safety (adverse events and laboratory parameters) were assessed during follow-up. Values are expressed as n (%) or median (IQR). The Wilcoxon signed-rank test was used to compare baseline and 6 and 12 month values. RESULTS: Eighty-four patients were included [93% males, age = 36 (30-45) years]. Time since HIV diagnosis was 12 (4-35) months. Fifty-one per cent of patients had comorbidities. Baseline CD4+ was 425 (340-519) cells/mm3 and baseline HIV-RNA was 19 000 (9500-42 000) copies/mL. Median follow-up was 18 (9-22) months; 100% and 68% patients with at least 6 and 12 months, respectively. At 6 and 12 months effectiveness was 94% and 86% by ITT analysis and 96% and 97% by on-treatment analysis. At 12 months, there were significant increases in CD4+ (+262 cell/mm3) and HDL cholesterol (+4 mg/dL) and a significant decrease in the total cholesterol/HDL cholesterol ratio (-0.2). There were two (2.4%) virological failures (HIV-RNA 50-100 copies/mL); one patient later achieving virological suppression without changing the treatment. Six patients (7.1%) changed treatment due to reasons other than virological failure or side effects. One patient discontinued treatment due to gastrointestinal complaints attributed to abacavir/lamivudine. CONCLUSIONS: Abacavir/lamivudine + rilpivirine was an effective and safe option in a selected group of HIV-1-infected treatment-naive patients.


Assuntos
Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/efeitos adversos , Didesoxinucleosídeos/administração & dosagem , Didesoxinucleosídeos/efeitos adversos , Infecções por HIV/tratamento farmacológico , Lamivudina/administração & dosagem , Lamivudina/efeitos adversos , Rilpivirina/administração & dosagem , Rilpivirina/efeitos adversos , Adulto , Combinação de Medicamentos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Feminino , HIV-1/efeitos dos fármacos , Hospitais , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Espanha , Resultado do Tratamento
18.
Antivir Ther ; 21(4): 345-52, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26756461

RESUMO

BACKGROUND: Low-level viraemia (LLV) occurs in 20-40% of patients achieving viral suppression with antiretroviral therapy (ART). The risk of virological failure (VF: confirmed HIV RNA >200 copies/ml) in these patients is still a matter of debate. METHODS: This is a prospective cohort study in HIV-infected adults attending the HIV clinic of a tertiary care hospital in Spain. Patients with HIV RNA <25 copies/ml and stable ART for at least 6 months presenting LLV (defined as HIV RNA between 25-1,000 copies/ml) from January 2011 to January 2013 were included and followed until VF or end of follow-up in June 2014. RESULTS: A total of 300 out of 1,733 (17.3%) patients with undetectable viraemia for 4.2 years showed LLV: 25-50 copies/ml in 167 (55.7%) patients, 51-200 copies/ml in 111 (37%) and 201-1,000 copies/ml in 22 (7.3%) cases. After a median follow-up of 2.6 years, 23 (7.7%) patients presented VF. No patient with a single or multiple unconfirmed LLV went on to develop VF. HIV RNA >200 copies/ml (HR 59.6; 95% CI 15.7, 227), ritonavir-boosted protease inhibtor (PI/r)-based dual therapy (HR 10.2; 95% CI 2.1, 49.8) and PI/r monotherapy (HR 7.9; 95% CI 1.4, 43.3) were associated with VF. Persistent LLV, defined as HIV RNA <200 copies/ml in at least three consecutive samples, for at least 12 weeks, was detected in 27 (1.6%) patients and 14 (51.9%) of those evolved to VF. CONCLUSIONS: Nearly one-fifth of patients on suppressive ART showed LLV and 8% of them developed VF. HIV RNA >200 copies/ml was the strongest predictor of VF. Over half of patients with persistent viraemia <200 copies/ml showed VF.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , HIV-1 , Viremia , Adulto , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , RNA Viral/sangue , Falha de Tratamento
19.
Antimicrob Agents Chemother ; 59(11): 6782-90, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26282411

RESUMO

Our objective was to describe the pharmacokinetic (PK) parameters of total and unbound darunavir and ritonavir concentrations in HIV-hepatitis C virus (HCV)-coinfected patients with cirrhosis, as ritonavir-boosted darunavir is mainly metabolized in the liver, and hepatic cirrhosis might modify darunavir-ritonavir concentrations. This was a prospective, case-control, and unicenter study. HIV-HCV-coinfected patients with compensated cirrhosis (cases) and HIV-monoinfected patients with normal liver function (controls) were included. Darunavir-ritonavir was given at 800/100 mg once daily. Patients were followed for 24 weeks to assess safety and efficacy. A steady-state 12-h PK study was performed. Total and unbound concentrations were determined by liquid chromatography-tandem mass spectrometry. The unbound fraction was obtained by ultrafiltration. The plasma area under the concentration-time curve (AUC) and oral clearance (CL/F) were assessed by noncompartmental models. Thirty patients (20 cases and 10 controls) were included. Among cirrhotic patients, the Child-Pugh score was C in 4 cases, B in 1 case, and A in 15 cases; the median (interquartile range) transient elastography values were 20 kPa (14 to 26 kPa), and 5 patients had prior clinical decompensations. There were no significant differences in the darunavir PK parameters between cases and controls except for longer time to maximum plasma concentrations (Tmax) and half-lives in the cirrhotic patients. There were no significant differences in ritonavir total concentrations, but the unbound concentrations were higher in cirrhotic patients. There were significant correlations between the darunavir total and unbound concentrations in both cirrhotic patients and controls. There were no differences in PK parameters based on Child-Pugh score, liver elasticity, gender, or use of concomitant medications. In conclusion, in HIV-HCV-coinfected patients with clinically compensated cirrhosis receiving darunavir-ritonavir at 800/100 mg once daily, the darunavir total and unbound concentrations are similar to those observed in noncirrhotic patients, and dose adjustments are not necessary.


Assuntos
Darunavir/sangue , Infecções por HIV/sangue , Hepatite C/sangue , Ritonavir/sangue , Adulto , Estudos de Casos e Controles , Coinfecção/sangue , Darunavir/uso terapêutico , Feminino , Infecções por HIV/tratamento farmacológico , Hepatite C/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Ritonavir/uso terapêutico
20.
AIDS Rev ; 17(2): 114-20, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26035169

RESUMO

Rezolsta® (darunavir/cobicistat) is the first boosted protease inhibitor in a fixed-dose combination to be approved for the treatment of HIV infection. It contains darunavir, a protease inhibitor with a well-known safety and efficacy profile, and the new pharmacokinetic enhancer cobicistat. The convenience of this combination makes boosted darunavir easier to take, thus improving adherence. Exposure to darunavir is equivalent when it is administered with cobicistat or with ritonavir. Darunavir/cobicistat-based antiretroviral therapy has shown considerable efficacy and good tolerability in several clinical trials. Data from the single-arm, open-label, phase III GS-US-216-130 trial showed virological efficacy rates comparable to those from ARTEMIS and ODIN. Darunavir/cobicistat was well tolerated; most adverse events were mild and consisted of gastrointestinal disturbances. Cobicistat inhibits transporters of creatinine in kidney tubules, thus causing a minimal and reversible reduction in estimated glomerular filtration rate. Like ritonavir, cobicistat is a strong CYP3A4 inhibitor and, as such, shares most of its drug interactions. However, inhibition by cobicistat seems to be more specific than with ritonavir, and cobicistat has no inducer effect; therefore, differences in its drug interaction profile may be observed.


Assuntos
Cobicistat/uso terapêutico , Darunavir/uso terapêutico , Inibidores da Protease de HIV/uso terapêutico , Ensaios Clínicos como Assunto , Cobicistat/efeitos adversos , Cobicistat/farmacocinética , Darunavir/efeitos adversos , Darunavir/farmacocinética , Combinação de Medicamentos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/efeitos adversos , Inibidores da Protease de HIV/farmacocinética , Humanos , Adesão à Medicação , Resultado do Tratamento
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