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1.
Clin Infect Dis ; 73(7): e2026-e2033, 2021 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-32930720

RESUMO

BACKGROUND: Little is known about the effects of eradication of hepatitis C virus (HCV) on bone mineral density (BMD) and biomarkers of bone remodeling in human immunodeficiency virus (HIV)/HCV-coinfected patients. METHODS: We prospectively assessed standardized BMD (sBMD) at the lumbar spine and femoral neck, World Health Organization BMD categories at both sites, and plasma concentrations of soluble receptor activator of NF-κß ligand (sRANKL), and osteoprotegerin (OPG) at baseline (the date of initiation of anti-HCV therapy) and at 96 weeks. RESULTS: A total of 238 patients were included. The median age was 49.5 years, 76.5% were males, 48.3% had cirrhosis, 98.3% were on antiretroviral therapy, median CD4+ cell count was 527 cells/µL, and 86.6% had HIV-1 RNA <50 copies/mL. The prevalence of osteoporosis at baseline at the lumbar spine (LS) and femoral neck (FN) was 17.6% and 7.2%, respectively. Anti-HCV therapy comprised pegylated interferon (peg-IFN) and ribavirin (RBV) plus 1 direct-acting antiviral in 53.4%, peg-IFN/RBV in 34.5%, and sofosbuvir/RBV in 12.2%. A total of 145 (60.9%) patients achieved sustained virologic response (SVR). No significant effect of SVR was observed on sBMD for the interaction between time and SVR either in the LS (P = .801) or the FN (P = .911). Likewise, no significant effect of SVR was observed in plasma levels of sRANKL (P = .205), OPG (P = .249), or sRANKL/OPG ratio (P = .123) for the interaction between time and SVR. No significant correlation was found between fibrosis by transient elastography, and LS and FN sBMD, at baseline and week 96. CONCLUSIONS: SVR was not associated with significant changes in BMD nor biomarkers of bone remodeling in HIV/HCV-coinfected persons.


Assuntos
Coinfecção , Infecções por HIV , Hepatite C Crônica , Hepatite C , Antivirais/uso terapêutico , Densidade Óssea , Coinfecção/tratamento farmacológico , HIV , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Hepacivirus , Hepatite C/complicações , Hepatite C/tratamento farmacológico , Hepatite C Crônica/tratamento farmacológico , Humanos , Interferon-alfa/uso terapêutico , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis/uso terapêutico , Proteínas Recombinantes/uso terapêutico , Ribavirina/uso terapêutico
2.
J Antimicrob Chemother ; 73(9): 2444-2451, 2018 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-29897573

RESUMO

Background: Concerns have been voiced over the capacity of deintensification strategies to preserve neurocognitive function and prevent neurocognitive impairment. Methods: We present the 96 week results of a neurocognitive substudy nested within the SALT clinical trial: a randomized, open-label, non-inferiority trial that compares whether atazanavir/ritonavir + lamivudine is non-inferior to atazanavir/ritonavir + two NRTIs in HIV-suppressed patients on stable triple therapy. A global deficit score (GDS) for five neurocognitive tasks was used to assess neurocognitive function. Changes in neurocognitive function (GDS value) were determined at weeks 48 and 96. The effect of atazanavir/ritonavir + lamivudine, adjusted for significant confounders, on the change in neurocognitive function was determined using analysis of covariance (ANCOVA) at week 96. Results: The per-protocol analysis included 92 participants (47 atazanavir/ritonavir + lamivudine and 45 atazanavir/ritonavir + two NRTIs). All baseline characteristics were comparable in both groups. At weeks 48 and 96, changes in GDS [week 48, atazanavir/ritonavir + lamivudine -0.3 (95% CI -0.5 to -0.1) versus atazanavir/ritonavir + two NRTIs -0.2 (95% CI -0.4 to 0.0), P = 0.39; week 96, atazanavir/ritonavir + lamivudine -0.3 (95% CI -0.5 to -0.1) versus atazanavir/ritonavir + two NRTIs -0.2 (95% CI -0.4 to -0.1); P = 0.471] were similar. This absence of differences was also observed in all cognitive tasks. Atazanavir/ritonavir + lamivudine did not impact the change in neurocognitive function at week 96; the adjusted effect of atazanavir/ritonavir + lamivudine on GDS change, considering atazanavir/ritonavir + two NRTIs as a reference, was 0.01 (95% CI -0.18 to 0.21) (P = 0.90). Conclusions: Neurocognitive function remained stable after 96 weeks, both in the atazanavir/ritonavir + lamivudine and in the atazanavir/ritonavir + two NRTIs arms, provided HIV remained suppressed.


Assuntos
Fármacos Anti-HIV/efeitos adversos , Sulfato de Atazanavir/efeitos adversos , Infecções por HIV/tratamento farmacológico , Lamivudina/efeitos adversos , Transtornos Neurocognitivos/epidemiologia , Ritonavir/efeitos adversos , Adulto , Fármacos Anti-HIV/administração & dosagem , Sulfato de Atazanavir/administração & dosagem , Feminino , Infecções por HIV/complicações , Humanos , Lamivudina/administração & dosagem , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Transtornos Neurocognitivos/induzido quimicamente , Ritonavir/administração & dosagem
3.
Hepatology ; 66(2): 344-356, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28109003

RESUMO

We assessed non-liver-related non-acquired immunodeficiency syndrome (AIDS)-related (NLR-NAR) events and mortality in a cohort of human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients treated with interferon (IFN) and ribavirin (RBV), between 2000 and 2008. The censoring date was May 31, 2014. Cox regression analysis was performed to assess the adjusted hazard rate (HR) of overall death in responders and nonresponders. Fine and Gray regression analysis was conducted to determine the adjusted subhazard rate (sHR) of NLR deaths and NLR-NAR events considering death as the competing risk. The NLR-NAR events analyzed included diabetes mellitus, chronic renal failure, cardiovascular events, NLR-NAR cancer, bone events, and non-AIDS-related infections. The variables for adjustment were age, sex, past AIDS, HIV transmission category, nadir CD4+ T-cell count, antiretroviral therapy, HIV RNA, liver fibrosis, HCV genotype, and exposure to specific anti-HIV drugs. Of the 1,625 patients included, 592 (36%) had a sustained viral response (SVR). After a median 5-year follow-up, SVR was found to be associated with a significant decrease in the hazard of diabetes mellitus (sHR, 0.57; 95% confidence interval [CI], 0.35-0.93; P = 0.024) and decline in the hazard of chronic renal failure close to the threshold of significance (sHR, 0.43; 95% CI, 0.17-1.09; P = 0.075). CONCLUSION: Our data suggest that eradication of HCV in coinfected patients is associated not only with a reduction in the frequency of death, HIV progression, and liver-related events, but also with a reduced hazard of diabetes mellitus and possibly of chronic renal failure. These findings argue for the prescription of HCV therapy in coinfected patients regardless of fibrosis stage. (Hepatology 2017;66:344-356).


Assuntos
Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Coinfecção/tratamento farmacológico , Hepatite C Crônica/epidemiologia , Interferon-alfa/uso terapêutico , Ribavirina/uso terapêutico , Síndrome da Imunodeficiência Adquirida/diagnóstico , Síndrome da Imunodeficiência Adquirida/epidemiologia , Adulto , Estudos de Coortes , Coinfecção/fisiopatologia , Comorbidade , Bases de Dados Factuais , Quimioterapia Combinada , Feminino , Seguimentos , HIV/efeitos dos fármacos , HIV/isolamento & purificação , Hepacivirus/efeitos dos fármacos , Hepacivirus/isolamento & purificação , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/tratamento farmacológico , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Estudos Retrospectivos , Medição de Risco , Espanha/epidemiologia , Análise de Sobrevida , Fatores de Tempo , Resultado do Tratamento
4.
Enferm Infecc Microbiol Clin ; 34(6): 346-52, 2016.
Artigo em Espanhol | MEDLINE | ID: mdl-26530224

RESUMO

INTRODUCTION: The objective of the study is to validate the relevant GESIDA quality indicators for HIV infection, assessing the reliability, feasibility and adherence to them. METHODS: The reliability was evaluated using the reproducibility of 6 indicators in peer review, with the second observer being an outsider. The feasibility and measurement of the level of adherence to the 22 indicators was conducted with annual fragmented retrospective collection of information from specific databases or the clinical charts of the nine participating hospitals. RESULTS: Reliability was very high, with interobserver agreement levels higher than 95% in 5 of the 6 indicators. The median time to achieve the indicators ranged between 5 and 600minutes, but could be achieved progressively from specific databases, enabling obtaining them automatically. As regards adherence to the indicators related with the initial evaluation of the patients, instructions and suitability of the guidelines for ART, adherence to ART, follow-up in clinics, and achieve an undetectable HIV by PCR at week 48 of the ART. Indicators of quality related to the prevention of opportunistic infections and control of comorbidities, the standards set were not achieved, and significant heterogeneity was observed between hospitals. CONCLUSION: The GESIDA quality indicators of HIV infection enabled the relevant indicators to be feasibly and reliably measured, and should be collected in all the units that care for patients with HIV infection.


Assuntos
Infecções por HIV/terapia , Indicadores de Qualidade em Assistência à Saúde/normas , Estudos de Viabilidade , Infecções por HIV/epidemiologia , Humanos , Reprodutibilidade dos Testes , Estudos Retrospectivos , Espanha/epidemiologia
5.
Clin Infect Dis ; 60(6): 950-8, 2015 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-25422386

RESUMO

BACKGROUND: We compared the prognostic value of liver biopsy (LB) and FIB-4 index in patients with human immunodeficiency virus (HIV)/hepatitis C virus (HCV) coinfection. METHODS: We studied patients from the Grupo de Estudio del SIDA 3603 study cohort, in whom fibrosis was evaluated at baseline using both LB (Metavir score) and FIB-4 index. We assessed overall death (OD) and liver-related events (LREs), defined as decompensation or hepatocellular carcinoma, whichever occurred first. We used receiver operating characteristic (ROC) curves to determine the ability of LB and FIB-4 to predict outcomes. We also assessed the association between advanced fibrosis-LB (F3 or greater) or FIB-4 (≥3.25)-and outcomes using multivariate Cox regression analysis. RESULTS: The study sample comprised 903 patients (328 with sustained virologic response [SVR]). Baseline fibrosis by LB was as follows: F0, n = 71; F1, n = 242; F2, n = 236; F3, n = 236; F4, n = 118. Fibrosis by FIB-4 was as follows: ≤1, n = 148; >1 to <3.25, n = 597; ≥3.25, n = 158. After a median follow-up of 62 months, there were 46 deaths and 71 LREs. The area under the ROC curves for OD/LREs was 0.648 and 0.742 for LB and FIB-4, respectively (P = .006). Similar results were found for patients without SVR and for OD and LREs separately. The adjusted hazard ratios of OD or LRE were 1.740 (95% confidence interval [CI], 1.119-2.7.06; P = .014) for advanced fibrosis assessed by LB and 3.896 (95% CI, 2.463-6.160; P < .001) assessed by FIB-4. CONCLUSIONS: FIB-4 outperformed LB as a predictor of OD and LRE. These findings are of relevance for clinical practice and research and call into question the role of LB as a gold standard for assessing prognosis in HIV/HCV coinfection.


Assuntos
Coinfecção , Infecções por HIV/complicações , Hepatite C Crônica/complicações , Cirrose Hepática/diagnóstico , Fígado/patologia , Adulto , Biópsia , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Estudos de Coortes , Feminino , Seguimentos , Infecções por HIV/diagnóstico , Infecções por HIV/terapia , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/terapia , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Prognóstico , Curva ROC
6.
Clin Infect Dis ; 55(5): 728-36, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22610932

RESUMO

BACKGROUND: Sustained virological response (SVR) after therapy with interferon plus ribavirin reduces liver-related complications and mortality in patients coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV). We assessed the effect of SVR on HIV progression and mortality not related to liver disease. METHODS: An observational cohort study including consecutive HIV/HCV-coinfected patients treated with interferon plus ribavirin between 2000 and 2008 in 19 centers in Spain. RESULTS: Of 1599 patients, 626 (39%) had an SVR. After a median follow-up of approximately 5 years, we confirmed that failure to achieve an SVR was associated with an increased risk of liver-related events and liver-related death. We also observed higher rates of the following events in nonresponders than in responders: AIDS-defining conditions (rate per 100 person years, 0.84 [95% confidence interval (CI), .59-1.10] vs 0.29 [.10-.48]; P= .003), non-liver-related deaths (0.65 [.42-.87] vs 0.16 [.02-.30]; P = .002), and non-liver-related, non-AIDS-related deaths (0.55 [.34-.75] vs 0.16 [.02-.30]; P = .002). Cox regression analysis showed that the adjusted hazard ratios of new AIDS-defining conditions, non-liver-related deaths, and non-liver-related, non-AIDS-related deaths for nonresponders compared with responders were 1.90 (95% CI, .89-4.10; P = .095), 3.19 (1.21-8.40; P = .019), and 2.85 (1.07-7.60; P = .036), respectively. CONCLUSIONS: Our findings suggest that eradication of HCV after therapy with interferon plus ribavirin in HIV/HCV-coinfected patients is associated not only with a reduction in liver-related events but also with a reduction in HIV progression and mortality not related to liver disease.


Assuntos
Antivirais/uso terapêutico , Coinfecção/tratamento farmacológico , Infecções por HIV/tratamento farmacológico , Hepatite C/tratamento farmacológico , Interferons/uso terapêutico , Ribavirina/uso terapêutico , Adulto , Estudos de Coortes , Coinfecção/epidemiologia , Coinfecção/virologia , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , Hepatite C/epidemiologia , Hepatite C/virologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Modelos de Riscos Proporcionais , Espanha/epidemiologia , Resultado do Tratamento , Carga Viral
7.
HIV Clin Trials ; 13(3): 131-41, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22592093

RESUMO

BACKGROUND: We analyzed differences in response to combined antiretroviral therapy (cART) according to sex and geographic origin in a retrospective comparative study of Spanish-born and immigrant patients initiating cART. METHODS: The primary endpoint was time to treatment failure (TTF), defined as virological failure, death, opportunistic infection, interruption of cART, or loss to follow-up. Late diagnosis was defined as a CD4+ cell count ≤ 200 cells/mm3 and/or AIDS at initiation of cART. Survival was analyzed using Kaplan-Meier analysis and Cox regression. RESULTS: We followed 1,090 patients, of whom 318 were women (45.6% immigrant women [IW]). At initiation of treatment, women had a higher CD4+ count than men (217 vs 190 cells/mm3), a lower viral load (4.7 vs 5 log), and fewer were late starters (49% vs 59%). The adjusted risk of TTF between women and men was not significantly different (hazard ratio [HR], 1.10; 95% CI, 0.79-1.53). TTF was shorter among IW than Spanish-born women (124 weeks [95% CI, 64-183] vs 151 [95% CI, 127-174]) and loss to follow-up was double that of Spanish-born women (25.5% vs 11.6%). CONCLUSIONS: Although response to cART was similar for both sexes, men started treatment later. IW were more frequently lost to follow-up and switched treatment. Measures to improve medical follow-up after initiation of cART should be promoted among this minority group.


Assuntos
Fármacos Anti-HIV/administração & dosagem , Infecções por HIV/tratamento farmacológico , Adulto , Contagem de Linfócito CD4 , Estudos de Coortes , Quimioterapia Combinada , Emigrantes e Imigrantes , Feminino , Infecções por HIV/imunologia , Infecções por HIV/mortalidade , Infecções por HIV/virologia , Humanos , Masculino , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Caracteres Sexuais , Espanha , Fatores de Tempo , Falha de Tratamento
8.
Open Forum Infect Dis ; 9(9): ofac345, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36147597

RESUMO

Background: Although switching antiretroviral therapy (ART) in people with human immunodeficiency virus experiencing insomnia due to dolutegravir-related neurotoxicity is well founded upon evidence, there is a lack of proof in regard to the outcome of stopping dolutegravir-based ART in people without insomnia but reporting poor sleep quality. Methods: This is a randomized, multicenter, open-label study to evaluate the reversibility of patient-reported sleep disturbances in patients on dolutegravir/lamivudine/abacavir without insomnia after switching to darunavir/cobicistat/emtricitabine/tenofovir alafenamide. The participants were randomized to switch ART at baseline or at week 4 and then completed 8 weeks of darunavir/cobicistat/emtricitabine/tenofovir alafenamide. Our primary objective was to compare changes in sleep quality between arms at week 4. Secondary objectives were to compare changes in mood and neuropsychiatric symptoms (NS) at week 4 and 4 and 8 weeks after switching to darunavir/cobicistat/emtricitabine/tenofovir alafenamide. The participants completed a survey, including the Pittsburgh Sleep Quality Index (PSQI), the Hospital Anxiety and Depression scale (HADS), and specific questions to explore NS, at each visit to assess those objectives. Results: We included 72 participants. The results show that study arms were similar at baseline; however, at week 4, PSQI scores remained unchanged with dolutegravir/lamivudine/abacavir, whereas patients improved significantly after switching to darunavir/cobicistat/emtricitabine/tenofovir alafenamide. Similar differences between arms were also observed in HADS and NS changes. At weeks 4 and 8 after all participants switched to darunavir/cobicistat/emtricitabine/tenofovir alafenamide, we have observed significant improvements in PSQI and HAD scores and in NS. Conclusions: In patients reporting subclinical sleep disturbances without insomnia, switching from dolutegravir/lamivudine/abacavir to darunavir/cobicistat/emtricitabine/tenofovir alafenamide was associated with better sleep quality and improvements in mood and NS.

9.
Open Forum Infect Dis ; 5(1): ofx258, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29354658

RESUMO

BACKGROUND: We assessed the prevalence of antibodies against hepatitis C virus (HCV-Abs) and active HCV infection in patients infected with human immunodeficiency virus (HIV) in Spain in 2016 and compared the results with those of similar studies performed in 2002, 2009, and 2015. METHODS: The study was performed in 43 centers during October-November 2016. The sample was estimated for an accuracy of 2% and selected by proportional allocation and simple random sampling. During 2016, criteria for therapy based on direct-acting antiviral agents (DAA) were at least significant liver fibrosis, severe extrahepatic manifestations of HCV, and high risk of HCV transmissibility. RESULTS: The reference population and the sample size were 38904 and 1588 patients, respectively. The prevalence of HCV-Abs in 2002, 2009, 2015, and 2016 was 60.8%, 50.2%, 37.7%, and 34.6%, respectively (P trend <.001, from 2002 to 2015). The prevalence of active HCV in 2002, 2009, 2015, and 2016 was 54.0%, 34.0%, 22.1%, and 11.7%, respectively (P trend <.001). The anti-HCV treatment uptake in 2002, 2009, 2015, and 2016 was 23.0%, 48.0%, 59.3%, and 74.7%, respectively (P trend <.001). In 2016, HCV-related cirrhosis was present in 7.6% of all HIV-infected individuals, 15.0% of patients with active HCV, and 31.5% of patients who cleared HCV after anti-HCV therapy. CONCLUSIONS: Our findings suggest that with universal access to DAA-based therapy and continued efforts in prevention and screening, it will be possible to eliminate active HCV among HIV-infected individuals in Spain in the short term. However, the burden of HCV-related cirrhosis will continue to be significant among HIV-infected individuals.

10.
Haematologica ; 92(2): 191-8, 2007 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17296568

RESUMO

BACKGROUND AND OBJECTIVES: Although doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) is considered the standard chemotherapy regimen for Hodgkin's lymphoma (HL), information on the results of this therapy in human immunodeficiency (HIV)-related HL is scarce. We analyzed the results of the ABVD regimen and highly active antiretroviral therapy (HAART) in patients with advanced stage, HIV-related HL. DESIGN AND METHODS: From January 1996 to December 2005, 62 HIV-infected patients with newly diagnosed HL were treated in 15 Spanish hospitals. Six to eight cycles of ABVD and HAART were planned. Response to chemotherapy, overall survival (OS) and event-free survival (EFS) were recorded. RESULTS: The median age of the patients was 37 years (range, 24-61) and 29 (47%) had a previously known diagnosis of acquired immunodeficiency syndrome. The median CD4 lymphocyte count at diagnosis was 129/muL (range 5-1,209). The histologic subtype of HL was nodular sclerosis in 17 patients (27%), mixed cellularity in 25 (41%), lymphocyte depletion in 10 (16%) and non-specified in the remaining 10 (16%). Twenty-one (34%) patients were in stage III and 41 (66%) in stage IV. The scheduled six to eight ABVD cycles were completed in 82% of cases. Six patients died during induction, 54 (87%) achieved a complete response (CR) and two were resistant. After a median follow-up of 39 and 47 months, 5-year EFS and OS probabilities were 71% (47-95) and 76% (65-87), respectively. An immunological response was observed in 24 out of 43 patients (56%) and a virological response in 27 out of 40 (68%). The immunological response to HAART had a positive impact on OS and EFS (p=0.002 and p=0.001, respectively). INTERPRETATION AND CONCLUSIONS: In patients with advanced stage, HIV-related HL, treatment with ABVD together with HAART is feasible and effective. This supports the concept that patients with HIV-related HL should be treated in the same way as immunocompetent patients if HAART, adequate supportive therapy and anti-infectious prophylaxis are given concomitantly. An immunological response to HAART has a positive impact on OS and EFS.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Infecções por HIV/tratamento farmacológico , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/virologia , Linfoma Relacionado a AIDS/tratamento farmacológico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Bleomicina/administração & dosagem , Linfócitos T CD4-Positivos/metabolismo , Dacarbazina/administração & dosagem , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Feminino , Humanos , Linfoma Relacionado a AIDS/virologia , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Resultado do Tratamento , Vimblastina/administração & dosagem
12.
PLoS One ; 11(10): e0164455, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27727331

RESUMO

OBJECTIVES: Based on data from clinical practice, we evaluated the effectiveness and safety of switching to abacavir/lamivudine plus rilpivirine (ABC/3TC+RPV) treatment in virologically suppressed HIV-1-infected patients. METHODS: We performed a multicenter, non-controlled, retrospective study of HIV-1-infected patients who switched treatment to ABC/3TC+RPV. Patients had an HIV-RNA <50 copies/mL for at least 24 weeks prior to changing treatments. The primary objective was HIV-1 RNA <50 copies/mL at week 48. Effectiveness was analyzed by intention-to-treat (ITT), missing = failure and on-treatment (OT) analyses. The secondary objectives analyzed were adverse effects changes in renal, hepatic or lipid profiles, changes in CD4+ cell count and treatment discontinuations. RESULTS: Of the 205 patients included, 75.6% were men and the median age was 49. At baseline, before switching to ABC/3TC+RPV, median time since HIV diagnosis was 13.1 years, median time with undetectable HIV-1 RNA was 6.2 years and median time of previous antiretroviral regimen was 3.1 years (48.3% patients were taking efavirenz and ABC/3TC was the most frequent backbone coformulation in 69.7% of patients). The main reasons for switching were drug toxicity/poor tolerability (60.5%) and simplification (20%). At week 48, the primary objective was achieved by 187 out of 205 (91.2%) patients by ITT analysis, and 187 out of 192 (97.4%) patients by OT analysis. The CD4+ lymphocyte count and CD4+ percentage increased significantly from baseline to week 48 by a median of 48 cells/µL (-50 to 189) and 1.2% (-1.3% to 4.1%), respectively, P<0.001. Thirty-eight adverse events (AE) were detected in 32 patients. Of these, 25 had no clear association with treatment. Three patients interrupted therapy due to AE. We observed a decrease in all lipid parameters, P<0.001, and a slight improvement in the glomerular filtration rate, P<0.01. Therapy was considered to have failed in 18 patients owing to virological failure (5 [2.4%]), toxicity/poor tolerability (4 [2%]), clinical decision (3 [1.5%]), loss to follow-up (3 [1.5%]), death (1 [0.5%]), and no clinical data (2 [1%]). CONCLUSIONS: The results of this study confirms that ABC/3TC+RPV is an effective, safe, and cost-effective option for the treatment of patients with virologically stable HIV-1 infection.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Didesoxinucleosídeos/uso terapêutico , Infecções por HIV/tratamento farmacológico , Lamivudina/uso terapêutico , Rilpivirina/uso terapêutico , Adulto , Fármacos Anti-HIV/efeitos adversos , Contagem de Linfócito CD4 , Depressão/etiologia , Didesoxinucleosídeos/efeitos adversos , Esquema de Medicação , Combinação de Medicamentos , Quimioterapia Combinada , Feminino , Taxa de Filtração Glomerular , Infecções por HIV/virologia , HIV-1/genética , HIV-1/isolamento & purificação , Humanos , Rim/metabolismo , Lamivudina/efeitos adversos , Lipídeos/sangue , Fígado/metabolismo , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue , Estudos Retrospectivos , Rilpivirina/efeitos adversos , Resultado do Tratamento
13.
Lancet Infect Dis ; 15(7): 775-84, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26062881

RESUMO

BACKGROUND: Problems associated with lifelong antiretroviral therapy, such as need for strict adherence, drug-related toxic effects, difficulties with treatment schedules, and cost, mean that simplification strategies should be sought. We aimed to explore the efficacy and safety of dual treatment with atazanavir-ritonavir plus lamivudine as an option to switch to from standard combination antiretroviral therapy in patients with an HIV-1 infection who are virologically suppressed. METHODS: In this randomised, open-label, non-inferiority trial, we recruited patients aged 18 years and older with chronic HIV-1 infection and no previous treatment failure or resistance, and with HIV-1 RNA of less than 50 copies per mL for at least 6 months, negative hepatitis B virus surface antigen, and good general health, from 30 hospitals in Spain. Exclusion criteria were switch in antiretroviral therapy during the previous 4 months, previous virological failure, pregnancy or breastfeeding, Gilbert's syndrome, use of contraindicated drugs, grade 4 laboratory abnormalities, and previous intolerance to any of the study drugs. We randomly assigned patients (1:1; stratified by active hepatitis C virus infection and previous treatment; computer-generated random number sequence) to dual treatment with oral atazanavir (300 mg once daily) and ritonavir (100 mg once daily) plus lamivudine (300 mg once daily) or triple treatment with oral atazanavir (300 mg once daily) and ritonavir (100 mg once daily) plus two nucleos(t)ide reverse transcriptase inhibitors at the discretion of the investigators. The primary endpoint was virological response, defined as HIV-1 RNA of less than 50 copies per mL at week 48, in the per-protocol population, with a non-inferiority margin of 12%. We included patients who received at least one dose of the study drug in the safety analysis. This study is registered at ClinicalTrials.gov, number NCT01307488. FINDINGS: Between Sept 29, 2011, and May 2, 2013, we randomly assigned 286 patients (143 [50%] to each group). At week 48 in the per-protocol population, 112 (84%) of 133 patients had virological response in the dual-treatment group versus 105 (78%) of 135 in the triple-treatment group (difference 6% [95% CI -5 to 16%), showing non-inferiority at the prespecified level. 14 (5%) patients developed severe adverse events (dual treatment six [4%]; triple treatment eight [6%]), none of which we deemed related to the study drug. Grade 3-4 adverse events were similar between groups (dual treatment 77 [55%] of 140; triple treatment 78 [55%] of 141). Treatment discontinuations were less frequent in the dual-treatment group (three [2%]) than in the triple-treatment group (ten [7%]; p=0·047). INTERPRETATION: In our trial, dual treatment was effective, safe, and non-inferior to triple treatment in patients with an HIV-1 infection who are virologically suppressed who switch antiretroviral therapy because of toxic effects, intolerance, or simplification. This combination has the potential to suppress some of the long-term toxic effects associated with nucleos(t)ide reverse transcriptase inhibitors, preserve future treatment options, and reduce the cost of antiretroviral therapy. FUNDING: Bristol Myers-Squibb and Fundación SEIMC-GESIDA.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/uso terapêutico , HIV-1 , RNA Viral/sangue , Inibidores da Transcriptase Reversa/uso terapêutico , Adenina/análogos & derivados , Adenina/uso terapêutico , Adulto , Fármacos Anti-HIV/efeitos adversos , Sulfato de Atazanavir , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Substituição de Medicamentos , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Emtricitabina , Feminino , Infecções por HIV/virologia , Inibidores da Protease de HIV/efeitos adversos , Humanos , Lamivudina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Oligopeptídeos/uso terapêutico , Organofosfonatos/uso terapêutico , Piridinas/uso terapêutico , Inibidores da Transcriptase Reversa/efeitos adversos , Ritonavir/uso terapêutico , Tenofovir , Carga Viral , Zidovudina/uso terapêutico
14.
J Int AIDS Soc ; 17(4 Suppl 3): 19656, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25394160

RESUMO

INTRODUCTION: Due to their low CNS penetrance, there are concerns about the capacity of non-conventional PI-based ART (monotherapy and dual therapies) to preserve neurocognitive performance (NP). METHODS: We evaluated the NP change of aviremic participants of the SALT clinical trial (1) switching therapy to dual therapy (DT: ATV/r+3TC) or triple therapy (TT: ATV/r+2NRTI) who agreed to perform an NP assessment (NPZ-5) at baseline and W48. Neurocognitive impairment and NP were assessed using AAN-2007 criteria (2) and global deficit scores (GDS) (3). Neurocognitive change (GDS change: W48 - baseline) and the effect of DT on NP evolution crude and adjusted by significant confounders were determined using ANCOVA. RESULTS: A total of 158 patients were included (Table 1). They had shorter times because HIV diagnosis, ART initiation and HIV-suppression and their virologic outcome at W48 by snapshot was higher (79.1% vs 72.7%; p=0.04) compared to the 128 patients not included in the sub-study. By AAN-2007 criteria, 51 patients in each ART group (68% vs 63%) were neurocognitively impaired at baseline (p=0.61). Forty-seven patients were not reassessed at W48: 30 lost of follow-up (16 DT-14 TT) and 17 had non-evaluable data (6 DT-11 TT). Patients retested were more likely to be men (78.9% vs 61.4%) and had neurological cofounders (9.6% vs 0%) than patients non-retested. At W48, 3 out of 16 (5.7%) patients on DT and 6 out of 21 (10.5%) on TT who were non-impaired at baseline became impaired (p=0.49) while 10 out of 37 (18.9%) on DT and 7 out of 36 (12.3%) on TT who were neurocognitively impaired at baseline became non-impaired (p=0.44). Mean GDS changes (95% CI) were: Overall -0.2 (-0.3 to -0.04): DT -0.26 (-0.4 to -0.07) and TT -0.08 (-0.2 to 0.07). NP was similar between DT and TT (0.15). This absence of differences was also observed in all cognitive tests. Effect of DT: -0.16 [-0.38 to 0.06]) (r(2)=0.16) on NP evolution was similar to TT (reference), even after adjusting (DT: -0.11 [-0.33 to 0.1], TT: reference) by significant confounders (geographical origin, previous ATV use and CD4 cell count) (r(2)=0.25). CONCLUSIONS: NP stability was observed after 48 weeks of follow up in the majority of patients whether DT or TT was used to maintain HIV-suppression. Incidence rates of NP impairment or NP impairment recovery were also similar between DT and TT.

15.
J Acquir Immune Defic Syndr ; 66(3): 280-7, 2014 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-25157646

RESUMO

OBJECTIVE: We assessed the effects of sustained viral response (SVR), after treating with interferon-ribavirin (IF-RB), on mortality, liver-related (LR) events (decompensation, hepatocellular carcinoma), HIV progression, and liver stiffness in HIV/hepatitis C virus (HCV)-coinfected patients with nonadvanced liver fibrosis. METHODS: From a cohort of HIV/HCV-coinfected patients treated with IF-RB, we selected those with baseline liver fibrosis stages F0, F1, or F2 according to METAVIR. The study started when IF-RB was stopped and ended at death or at the last follow-up visit. RESULTS: A total of 695 patients were included (HCV genotype 1 or 4, 431; F0, 77; F1, 290; and F2, 328), and 274 patients achieved SVR. After a median follow-up of 4.9 years, the adjusted hazard ratio (aHR) [95% confidence interval (CI)] of LR events or overall death, for patients with SVR taking the group of patients with no SVR as a reference was 0.217 (0.079 to 0.599) (P = 0.003) for the whole cohort with F0 to F2. For patients with F0, the aHR (95% CI) was 0.514 (0.040 to 6.593) (P = 0.609), for patients with F1, the aHR (95% CI) was 0.305 (0.053 to 1.762) (P = 0.185), and for patients with F2, it was 0.075 (0.009 to 0.662) (P = 0.020). We also found that, in comparison with no SVR, SVR was followed by less frequent HIV progression for the entire population (F0 to F2) and less frequent liver stiffness across all categories of fibrosis. CONCLUSIONS: SVR in HIV/HCV-coinfected patients with moderate stages of liver fibrosis is associated with a reduction of mortality and LR events, and with a reduction of progression of HIV and liver fibrosis.


Assuntos
Antivirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , Hepatite C Crônica/tratamento farmacológico , Interferons/uso terapêutico , Cirrose Hepática/tratamento farmacológico , Ribavirina/uso terapêutico , Adulto , Alanina Transaminase/sangue , Contagem de Linfócito CD4 , Estudos de Coortes , Progressão da Doença , Quimioterapia Combinada , Técnicas de Imagem por Elasticidade , Feminino , Seguimentos , Infecções por HIV/complicações , Infecções por HIV/mortalidade , Infecções por HIV/virologia , Hepatite C Crônica/complicações , Hepatite C Crônica/mortalidade , Hepatite C Crônica/virologia , Humanos , Cirrose Hepática/mortalidade , Cirrose Hepática/patologia , Modelos Logísticos , Masculino , Valor Preditivo dos Testes , RNA Viral/análise , Carga Viral
16.
Curr HIV Res ; 8(7): 521-30, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21073441

RESUMO

OBJECTIVE: currently, 12% of the Spanish population is foreign-born, and a third of newly diagnosed HIV-infected patients are immigrants. We determined whether being an immigrant was associated with a poorer response to antiretroviral treatment. METHODS: historical multicenter cohort study of naïve patients starting HAART. The primary endpoint was time to treatment failure (TTF) defined as virological failure (VF), death, opportunistic disease, treatment discontinuation (D/C), or missing patient. Secondary endpoints were TTF expressed as observed data (TFO; censoring missing patients) and time to virological failure (TVF; censoring missing patients and D/C not due to VF). A multivariate analysis was performed to control for confounders. RESULTS: a total of 1090 treatment-naïve HIV-infected patients (387 immigrants and 703 autochthonous) from 33 hospitals were included. Most immigrants were from Sub-Saharan Africa (28.3%) or South-Central America/Caribbean (31%). Immigrants were significantly younger (34 y vs. 39 y), more frequently female (37.5% vs. 24.6%), with less HCV coinfection than autochthonous patients (7% vs. 31.3%). There were no differences in baseline viral load (4.95 Log(10) vs. 4.98 Log(10)), CD4 lymphocyte count (193.5/µL vs. 201.5/µL), late initiation of HAART (56.4% vs. 56.0%), or antiretrovirals used. Cox-regression analysis (HR; 95%CI) did not show differences in TTF (0.89; 0.66-1.20), TFO (0.95; 0.66-1.36), or TVF (1.00; 0.57-1.78) between immigrants and autochthonous patients. Losses to follow-up were more frequent among immigrants (17.8% vs. 12.1; p=0.009). Sub-Saharan African patients and immigrant females had a significantly shorter TTF. CONCLUSIONS: the response to HAART among immigrant patients was similar to that of autochthonous patients, although they had a higher rate of losses to follow-up. Sub-Saharan Africans and immigrant females may need particular measures to avoid barriers hindering antiviral efficacy.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Emigrantes e Imigrantes , Infecções por HIV/tratamento farmacológico , Infecções por HIV/etnologia , Adulto , Contagem de Linfócito CD4 , Estudos de Coortes , Determinação de Ponto Final , Etnicidade , Feminino , Geografia , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Espanha/epidemiologia , Falha de Tratamento , Resultado do Tratamento , Carga Viral
17.
Enferm Infecc Microbiol Clin ; 23(6): 340-8, 2005.
Artigo em Espanhol | MEDLINE | ID: mdl-15970166

RESUMO

INTRODUCTION: The aims of this study were to estimate the prevalence of HIV and hepatitis virus coinfection in the Spanish population and to determine the percentage of patients who are candidates for chronic hepatitis C virus (HCV) treatment and liver transplantation within this population. METHODS: A cross-sectional study was performed in 2002 in two Spanish populations of HIV-infected patients: 1,260 patients from 39 centers throughout Spain (P1) and 1,560 patients from three tertiary teaching hospitals in Madrid (P2). RESULTS: The following hepatitis A virus (HAV), hepatitis B virus (HBV) and HCV serological prevalence were found in the P1 and P2 groups, respectively: HAV-IgG antibodies: 74% and 78%; HBsAg1: 4.9% and 4.8%; HBsAg-, anti-HBc1, anti-HBs1: 39% and 39%; HBsAg-, anti-HBc1, anti-HBs-: 25% and 31%; HBsAg-, anti-HBc-, anti-HBs1: 7% and 8%; HBsAg-, anti-HBc-, anti-HBs-: 22% and 16%. Anti-HCV1: 61% and 65%, respectively. Of the patients with positive HCV serology, 88.8% and 84.6% of each group were positive for HCV-RNA by polymerase chain reaction. Multiple coinfections with hepatitis viruses were found in 3.2% and 2.8%, respectively; of these, 70% and 78% had coinfection with HBV, HCV and HDV. Liver cirrhosis was found in 5.8% and 9.6% of the patients coinfected with HIV and HCV, respectively. Liver transplant was indicated in approximately one out of every six coinfected patients with liver cirrhosis. The 43 and 37% of the HCV coinfected patients were good candidates for anti-HCV treatment, but only 14% and 15% of patients had initiated it. CONCLUSIONS: A high percentage of HIV-infected patients in Spain were coinfected with hepatitis viruses, especially HCV. The number of possible candidates for liver transplantation is rising and could increase in the next few years. In the future, greater efforts to treat HIV-and hepatitis virus-coinfected patients will be required.


Assuntos
Infecções por HIV/complicações , Soroprevalência de HIV , Hepatite Viral Humana/epidemiologia , Transplante de Fígado , Seleção de Pacientes , Adulto , Antivirais/uso terapêutico , Comorbidade , Estudos Transversais , Feminino , Infecções por HIV/epidemiologia , Inquéritos Epidemiológicos , Anticorpos Anti-Hepatite/sangue , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/epidemiologia , Hepatite Viral Humana/complicações , Humanos , Cirrose Hepática/epidemiologia , Cirrose Hepática/cirurgia , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue , Espanha/epidemiologia
18.
Leuk Lymphoma ; 50(10): 1718-20, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19757300
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