Bonaventura Clotet

University of Vic, Vic, Catalonia, Spain

Are you Bonaventura Clotet?

Claim your profile

Publications (899)4718.45 Total impact

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The human intestinal microbiota is essential for human health and well-being and is driven by genetic, lifestyle and environmental factors. Here, we show in two independent cohorts of HIV-1-infected subjects and HIV-1-negative controls in Europe that gay men often have a distinct composition of the human fecal microbiota, with increased microbial richness and diversity and enrichment in the Prevotella enterotype. This is independent of HIV-1 status, and with only a limited contribution of diet effects. After accounting for sexual orientation, however, HIV-1 infection remains associated to reduced bacterial richness, more so in subjects with suboptimal CD4 + T-cell count recovery under antiretroviral therapy. Future studies should evaluate if interventions to increase gut bacterial richness could improve HIV-associated immune dysfunction.
    Full-text · Article · Jan 2016 · EBioMedicine
  • E. Negredo · A. Bonjoch · B. Clotet
    [Show abstract] [Hide abstract]
    ABSTRACT: Introduction: Loss of bone mineral density is an emerging problem in persons living with HIV infection. Earlier and more rapid bone demineralization has been attributed not only to the high prevalence of traditional risk factors, but also to specific HIV-related factors. The aim of this guidance is to stimulate an appropriate management of osteoporosis in this population, to identify patients at risk and to better manage them. Areas covered: Appropriate screening of HIV-infected subjects to identify those at risk for bone fractures is described, as well as the recommended interventions. American and European recommendations in HIV-infected and non-infected populations were considered. As the etiology of bone loss is multifactorial, many factors have to be addressed. Overall, recommendations on traditional risk factors are the same for HIV-infected and non-HIV-infected subjects. However, we should consider some specific factors in the HIV-infected population, including an appropriate antiretroviral therapy in patients with low bone mineral density, and probably novel strategies that could provide an additional benefit, such as anti-inflammatory drugs, although data supporting this approach are scant. Expert opinion: Some personal opinions are highlighted on the management of bone health in HIV-infected subjects, mainly on the use of FRAX(®) score and DXA scans. In addition, the need to implement new strategies to delay demineralization is remarked upon.
    No preview · Article · Jan 2016 · Expert Opinion on Pharmacotherapy
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: Extensively pretreated subjects with virological failure (VF) may receive salvage regimens containing NRTIs with only residual or no activity. Once virological suppression is achieved, their contribution remains elusive. Methods: This was a multicentre, randomized, prospective study. Subjects with at least one prior VF, HIV-1 RNA <50 copies/mL for ≥6 months and receiving a regimen with at least two active drugs (one of them a boosted PI) were randomized 1:1 to stop (experimental arm) or maintain (control arm) NRTIs. EudraCT: 2012-000198-21. Results: Ninety subjects were randomized (experimental, n = 45; and control, n = 45). The mean age was 50 years, 80% were male, the mean CD4+ cell count was 542 cells/mm(3) and the median number of prior VFs was 3. Seventy-four subjects (82%) harboured the mutation M184V/I and the median number of thymidine-associated mutations was 3 (IQR: 0-4). In the experimental arm, thirty-two (71%) subjects removed one NRTI and 13 (29%) subjects removed two. Twenty-two of 45 (49%) discontinued tenofovir disoproxil fumarate. Forty-one of 45 (91.1%, experimental arm) and 44 of 45 (97.8%, control arm) had HIV-1 RNA <50 copies/mL at 48 weeks (difference: -6.7%; 95% CI: -17.4, 4.1). In a post-hoc analysis allowing NRTI reintroduction, efficacy rates were 95.6% and 97.8%, respectively (difference: -2.2%; 95% CI: -7.2, 2.7). Rates of discontinuation at 48 weeks were 2% in both arms. One subject developed a late VF with resistance selection. Conclusions: In patients receiving a successful multidrug salvage regimen with at least two active drugs (one a boosted PI), the withdrawal of inactive NRTIs was safe, rates of VF were low and drug resistance was uncommon at 48 weeks in this small study. This strategy could potentially prevent long-term toxicities, reduce the number of drugs and reduce costs if non-inferiority was met in a fully powered trial.
    No preview · Article · Jan 2016 · Journal of Antimicrobial Chemotherapy
  • José Moltó · Teresa Moran · Guillem Sirera · Bonaventura Clotet
    [Show abstract] [Hide abstract]
    ABSTRACT: The advent of combination antiretroviral treatment (cART) has been followed by a decrease in HIV-associated morbidity and mortality, but also by an apparent increase in the incidence of non-AIDS-defining cancers (NADCs). The risk of lung cancer is substantially higher in HIV-infected patients than in the general population, in part due to aging and tobacco use, and it is the most frequent NADC. The management of lung cancer in HIV-infected patients has some peculiarities that need to be taken into account. This review focuses on the epidemiology, risk factors, and clinical management of lung cancer in HIV-infected patients. In addition, screening tools and future perspectives are also discussed.
    No preview · Article · Jan 2016
  • [Show abstract] [Hide abstract]
    ABSTRACT: Antiretroviral treatment-simplification strategies based on monotherapy with darunavir/ritonavir (DRV/r) or lopinavir/ritonavir (LPV/r) have not been directly compared in clinical trials. We evaluated the 48-week efficacy and safety of DRV/r vs. LPV/r monotherapy as a treatment simplification strategy in a multicenter, randomized, open-label study. Maintenance of viral suppression in cerebrospinal fluid and semen were also explored. An intention to treat efficacy analysis was performed considering missing equals to failure (ITT:M=F). Virological failure (VF) was defined as a confirmed increase in plasma HIV-1 RNA >50 copies/mL. A total of 75 patients were enrolled: 40 were allocated to DRVr and 33 to LPVr. In the ITT: M=F analysis, 77.5% of patients on DRV/r and 66.6% of patients on LPV/r maintained HIV-1 RNA <50 copies/mL at week 48 (p=0.302, treatment difference 10.8% [95%CI, –12.6 to 34.2]). In the DRV/r arm, no patients developed VF and 15.0% discontinued treatment due to adverse events. In the LPV/r arm, 2 (6.1%) patients developed VF, and 18.2% discontinued monotherapy due to adverse events. Gastrointestinal disturbances were experienced by 18.2% and 2.5% of patients in the LPV/r and DRV/r arms, respectively (p=0.019). Two patients had detectable HIV-1 RNA ≥50 copies/mL in CSF or semen. Monotherapy with LPV/r or DRV/r seems to be virologically effective in selected HIV-1-infected patients with sustained viral suppression. Differences between both regimens seem driven mainly by the better tolerability profile of DRV/r.
    No preview · Article · Jan 2016 · AIDS Research and Human Retroviruses
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: As a first step towards HIV cure, we assessed a strategy of antiretroviral therapy (ART) intensification followed by interleukin-7 (IL-7) used as an HIV-reactivating agent. Methods: A multicentre, randomized clinical trial included patients on suppressive ART with CD4 cell counts at least 350/ml and HIV-DNA between 10 and 1000 copies/106 peripheral blood mononuclear cells (PBMCs). After an 8-week raltegravir and maraviroc intensification, patients were randomized to intensification alone or with 3 weekly IL-7 injections at weeks 8, 9 and 10. The primary endpoint was at least 0.5 log10 decrease in HIV-DNA in PBMC at W56. Secondary endpoints included ultrasensitive plasma viremia, immunologic changes and safety. Results: Twenty-nine patients were enrolled with median baseline 558 CD4 cell counts/ml, 360 HIV-DNA copies/106 PBMCs and 12 years on ART. No patient in either arm achieved the primary endpoint. Addition of IL-7 induced a significant expansion of CD4+ T cells, primarily central-memory cells (+5%, P=0.001) at week 12, together with an increase in levels of HIV-DNA/106 PBMC (+0.28 log10 copies/P=0.001), and the proportion of patients with detectable ultrasensitive plasma HIV-RNA increased compared with week 8 (P=0.07). At weeks 56 and 80, total and memory CD4+ cell counts and total HIV-DNA/ml of blood remained elevated. In contrast, HIV-DNA/million PBMC and plasma viremia returned to baseline levels whereas activated HLADR+CD4+ T cells significantly decreased. Conclusion: IL-7 administration and dual ART intensification induced, despite a mild HIV reactivation, an amplification of the HIV reservoir, as a result of central-memory CD4+ T-cell expansion, thus limiting this IL-7 based strategy.
    No preview · Article · Jan 2016 · AIDS
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objectives: To describe the pattern of drug resistance at virological failure in the NEAT001/ANRS143 trial (first-line treatment with ritonavir-boosted darunavir plus either tenofovir/emtricitabine or raltegravir). Methods: Genotypic testing was performed at baseline for reverse transcriptase (RT) and protease genes and for RT, protease and integrase (IN) genes for patients with a confirmed viral load (VL) >50 copies/mL or any single VL >500 copies/mL during or after week 32. Results: A resistance test was obtained for 110/805 (13.7%) randomized participants qualifying for resistance analysis (61/401 of participants in the raltegravir arm and 49/404 of participants in the tenofovir/emtricitabine arm). No resistance-associated mutation (RAM) was observed in the tenofovir/emtricitabine plus darunavir/ritonavir arm, and all further analyses were limited to the raltegravir plus darunavir arm. In this group, 15/55 (27.3%) participants had viruses with IN RAMs (12 N155H alone, 1 N155H + Q148R, 1 F121Y and 1 Y143C), 2/53 (3.8%) with nucleotide analogue RT inhibitor RAMs (K65R, M41L) and 1/57 (1.8%) with primary protease RAM (L76V). The frequency of IN mutations at failure was significantly associated with baseline VL: 7.1% for a VL of <100 000 copies/mL, 25.0% for a VL of ≥100 000 copies/mL and <500 000 copies/mL and 53.8% for a VL of ≥500 000 copies/mL (PTREND = 0.007). Of note, 4/15 participants with IN RAM had a VL < 200 copies/mL at time of testing. Conclusions: In the NEAT001/ANRS143 trial, there was no RAM at virological failure in the standard tenofovir/emtricitabine plus darunavir/ritonavir regimen, contrasting with a rate of 29.5% (mostly IN mutations) in the raltegravir plus darunavir/ritonavir NRTI-sparing regimen. The cumulative risk of IN RAM after 96 weeks of follow-up in participants initiating ART with raltegravir plus darunavir/ritonavir was 3.9%.
    No preview · Article · Dec 2015 · Journal of Antimicrobial Chemotherapy
  • [Show abstract] [Hide abstract]
    ABSTRACT: The paradigm, derived from bicyclams and other cyclams, by which it is necessary to use the p-phenylene moiety as the central core in order to achieve high HIV-1 antiviral activities has been reexamined for the more flexible and less bulky structures , previously described by our group as potent HIV-1 inhibitors. The symmetrical compounds {x,x} and the non-symmetrical compounds {x,y} were designed, synthesized and biologically evaluated in order to explore the impact on the biological activity of the distance between the phenyl ring and the first nitrogen atom of the side chains. EC50 exactly followed the order {x,x} < {x,x} < {x,x} indicating that, for such flexible tetramines, the presence of two methylene units on each side of the central phenyl ring increases the biological activity contrary to AMD3100. A computational study of the interactions of {3,3}, {3,3} and {3,3} with CXCR4 revealed interactions in the same pocket region with similar binding modes for {3,3} and {3,3} but a different one for {3,3}.
    No preview · Article · Dec 2015 · Organic & Biomolecular Chemistry
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: None of the HIV T-cell vaccine candidates that have reached advanced clinical testing have been able to induce protective T cell immunity. A major reason for these failures may have been suboptimal T cell immunogen designs. To overcome this problem, we used a novel immunogen design approach that is based on functional T cell response data from more than 1,000 HIV-1 clade B and C infected individuals and which aims to direct the T cell response to the most vulnerable sites of HIV-1. Our approach identified 16 regions in Gag, Pol, Vif and Nef that were relatively conserved and predominantly targeted by individuals with reduced viral loads. These regions formed the basis of the HIVACAT T-cell Immunogen (HTI) sequence which is 529 amino acids in length, includes more than 50 optimally defined CD4(+) and CD8(+) T-cell epitopes restricted by a wide range of HLA class I and II molecules and covers viral sites where mutations led to a dramatic reduction in viral replicative fitness. In both, C57BL/6 mice and Indian rhesus macaques immunized with an HTI-expressing DNA plasmid (DNA.HTI) induced broad and balanced T-cell responses to several segments within Gag, Pol, and Vif. DNA.HTI induced robust CD4(+) and CD8(+) T cell responses that were increased by a booster vaccination using modified virus Ankara (MVA.HTI), expanding the DNA.HTI induced response to up to 3.2% IFN-γ T-cells in macaques. HTI-specific T cells showed a central and effector memory phenotype with a significant fraction of the IFN-γ(+) CD8(+) T cells being Granzyme B(+) and able to degranulate (CD107a(+)). These data demonstrate the immunogenicity of a novel HIV-1 T cell vaccine concept that induced broadly balanced responses to vulnerable sites of HIV-1 while avoiding the induction of responses to potential decoy targets that may divert effective T-cell responses towards variable and less protective viral determinants.
    Full-text · Article · Dec 2015 · Journal of Translational Medicine
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: High levels of ex vivo CD4 T-cell death and the accumulation of highly differentiated and/or immunosenescent T cells have been associated with poor CD4 T-cell recovery in treated HIV-infected individuals. However, the relationship between cell death and T-cell differentiation is still unclear. Methods: We have analyzed cell death, immunosenescence and differentiation parameters in HAART-treated subjects (VL <50 copies/mL for more than 2 years) with CD4 T-cell count <350 cells/μL (immunodiscordant, n = 23) or >400 cells/μL (immunoconcordant, n = 33). We included 11 healthy individuals as reference. Results: As expected, suboptimal CD4 T-cell recovery was associated with low frequencies of naïve cells, high frequencies of transitional and effector memory cells and a subsequent low ratio of central/transitional memory cells in the CD4 compartment. These alterations correlated with spontaneous CD4 T-cell death. A deeper analysis of cell death in CD4 T-cell subsets showed increased cell death in memory cells of immunodiscordant individuals, mainly affecting central memory cells. Immunosenescence was also higher in immunodiscordant individuals albeit unrelated to cell death. The CD8 compartment was similar in both HIV-infected groups, except for an underrepresentation of naïve cells in immunodiscordant individuals. Conclusion: Immunodiscordant individuals show alterations in memory CD4 T-cell differentiation associated with a short ex vivo lifespan of central memory cells and an in vivo low central/transitional memory cell ratio. These alterations may contribute to poor CD4 T-cell repopulation.
    Full-text · Article · Dec 2015 · Journal of Translational Medicine
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Resilience is a predictor of emotional well-being and psychological adjustment in people living with HIV infection. We report the results of a cross-sectional study in which we evaluated resilience and its association with perception of aging, coping strategies, quality of life, and emotional status in a group of long-term diagnosed HIV-infected patients. The analysis included 151 consecutive participants (57.6% men). Resilience was moderately high to high in 65 (43%) participants, moderately low to moderate in 57 (37.7%), and very low in 29 (19.2%). Univariate and multivariate analyses were performed. Two factors of perception of aging (good cognitive self-concept and good subjective perception of social relationships), the use of positive reframing as a coping strategy and better emotional status remained associated with high resilience. Our findings suggest that successful aging is possible in people living with HIV infection. Resilience seems to play a key role in the aging process.
    Full-text · Article · Nov 2015 · AIDS Care
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objectives: Sterile α motif and histidine-aspartate domain-containing protein 1 (SAMHD1) has been shown to restrict retroviruses and DNA viruses by decreasing the pool of intracellular deoxynucleotides. In turn, SAMHD1 is controlled by cyclin-dependent kinases (CDK) that regulate the cell cycle and cell proliferation. Here, we explore the effect of CDK6 inhibitors on the replication of herpes simplex virus type 1 (HSV-1) in primary monocyte-derived macrophages (MDM). Methods: MDM were treated with palbociclib, a selective CDK4/6 inhibitor, and then infected with a GFP-expressing HSV-1. Intracellular deoxynucleotide triphosphate (dNTP) content was determined using a polymerase-based method. Results: CDK6 inhibitor palbociclib blocked SAMHD1 phosphorylation, intracellular dNTP levels and HSV-1 replication in MDM at subtoxic concentrations. Treatment of MDM with palbociclib reduced CDK2 activation, measured as the phosphorylation of the T-loop at Thr160. The antiviral activity of palbociclib was lost when SAMHD1 was degraded by viral protein X. Similarly, palbociclib did not block HSV-1 replication in SAMHD1-negative Vero cells at subtoxic concentrations, providing further evidence for a role of SAMHD1 in mediating the antiviral effect. Conclusions: SAMHD1-mediated HSV-1 restriction is controlled by CDK and points to a preferential role for CDK6 and CDK2 as mediators of SAMHD1 activation. Similarly, the restricting activity of SAMHD1 against DNA viruses suggests that control of dNTP availability is the major determinant of its antiviral activity. This is the first study describing the anti-HSV-1 activity of palbociclib.
    No preview · Article · Nov 2015 · Journal of Antimicrobial Chemotherapy

  • No preview · Article · Nov 2015 · AIDS (London, England)
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Long-term treatment with interferon (IFN) alfa plus ribavirin decreases the proviral human immunodeficiency virus type 1 (HIV) DNA level. However, the short-term impact of IFN alfa on persistent HIV and its effects on immune activation after antiretroviral therapy remain unknown. Our study showed that the cell-associated HIV RNA level and CD4+ T-cell activation decreased in the IFN group (n = 10). No changes were detected in levels of residual plasma viremia, replication-competent reservoirs, proviral DNA, or 2–long-terminal repeat circles, although APOBEC3G, TRIM5α, BST2, and TRIM22 were upregulated in the IFN group. These data suggest that short-term treatment with IFN alfa combined with RBV decreases HIV expression, in part through inhibition of HIV transcription by TRIM22 and decrease in T-cell activation.
    Full-text · Article · Nov 2015 · The Journal of Infectious Diseases
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Objectives The objective of this study was to evaluate the incidence, prevalence and clinical consequences of virological failure (VF) to raltegravir-based regimens in Spain. Methods A multicentre, retrospective, observational study was performed in 10 tertiary hospitals (January 2006 to June 2013). The study included HIV-1-infected patients with loss of virological suppression (LVS; two consecutive HIV-1 RNA ≥50 copies/mL) while receiving raltegravir. VF and low-level viraemia (LLV) were defined as two consecutive HIV-1 RNA ≥200 copies/mL and 50 to
    Full-text · Article · Nov 2015 · Journal of Antimicrobial Chemotherapy
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: In previous studies in virologically suppressed patients, protease inhibitor monotherapy has shown trends for more low-level elevations in HIV-1 RNA compared with triple therapy, but no increase in the risk of drug resistance. Methods: A total of 273 patients with HIV-1 RNA less than 50 copies/ml on first-line antiretrovirals switched to darunavir/ritonavir (DRV/r) 800/100 mg once daily, either as monotherapy (n = 137) or as triple therapy with two nucleoside analogues (n = 136). Treatment failure was defined as HIV-1 RNA levels 50 copies/ml or above, or discontinuation of study treatment by week 48 (FDA Snapshot algorithm). Results: Patients were 83% male and 88% white, with mean age 42 years. In the primary efficacy analysis, HIV-1 RNA less than 50 copies/ml by week 48 [intention-to-treat (ITT)] was 118 of 137 (86%) in the DRV/r monotherapy arm versus 129 of 136 (95%) in the triple therapy arm (difference = -8.7%, 95% confidence interval -15.50, -1.80). In a post-hoc analysis, for patients with nadir CD4 cell count 200 cells/μl or above, rates of HIV-1 RNA suppression were 91 of 96 (95%) in the DRV/r monotherapy arm and 100 of 106 (94%) in the triple therapy arm. There was no difference in neurocognitive function or the risk of neuropsychiatric adverse events between DRV/r monotherapy and triple therapy. Two patients in the monotherapy arm with CD4 nadir less than 200 cells/μl developed viraemia in both cerebrospinal fluid (CSF) and plasma, with one symptomatic case. Conclusions: In this study for patients with HIV-1 RNA less than 50 copies/ml at baseline, switching to DRV/r monotherapy showed lower efficacy versus triple therapy at week 48 in the primary ITT switch equals failure analysis, with two cases of viraemia in the CSF in the protease inhibitor monotherapy arm.
    No preview · Article · Sep 2015 · AIDS (London, England)
  • Source

    Full-text · Dataset · Aug 2015
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: While the overall percentage of unused antiretroviral medicines returned to the hospital pharmacy is low, their cost is quite high. Adverse events, treatment failure, pharmacokinetic interactions, pregnancy, or treatment simplification are common reasons for unplanned treatment changes. Socially inefficient antiretroviral packages prevent the reuse of drugs returned to the hospital pharmacy. We defined antiretroviral package categories based on the excellence of drug packaging and analyzed the number of pills and costs of drugs returned during a period of 1 year in a hospital-based HIV unit attending to 2,413 treated individuals. A total of 6,090 pills (34% of all returned antiretrovirals) - with a cost of 47,139.91€ - would be totally lost, mainly due to being packed up in the lowest efficiency packages. Newer treatments are packaged in low-excellence categories of packages, thus favoring the maintenance of these hidden costs in the near future. Therefore, costs of this low-efficiency drug packaging, where medication packages are started but not completed, in high-cost medications are substantial and should be properly addressed. Any improvement in the packaging by the manufacturer, and favoring the choice of drugs supplied through efficient packages (when efficacy, toxicity, and convenience are similar), should minimize the treatment expenditures paid by national health budgets.
    Full-text · Article · Aug 2015 · Drug Design, Development and Therapy
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The objective of this study was to define the natural genotypic variation of the HIV-1 integrase gene across Europe for epidemiological surveillance of integrase strand-transfer inhibitor (InSTI) resistance. This was a multicentre, cross-sectional study within the European SPREAD HIV resistance surveillance programme. A representative set of 300 samples was selected from 1950 naive HIV-positive subjects newly diagnosed in 2006-07. The prevalence of InSTI resistance was evaluated using quality-controlled baseline population sequencing of integrase. Signature raltegravir, elvitegravir and dolutegravir resistance mutations were defined according to the IAS-USA 2014 list. In addition, all integrase substitutions relative to HXB2 were identified, including those with a Stanford HIVdb score ≥10 to at least one InSTI. To rule out circulation of minority InSTI-resistant HIV, 65 samples were selected for 454 integrase sequencing. For the population sequencing analysis, 278 samples were retrieved and successfully analysed. No signature resistance mutations to any of the InSTIs were detected. Eleven (4%) subjects had mutations at resistance-associated positions with an HIVdb score ≥10. Of the 56 samples successfully analysed with 454 sequencing, no InSTI signature mutations were detected, whereas integrase substitutions with an HIVdb score ≥10 were found in 8 (14.3%) individuals. No signature InSTI-resistant variants were circulating in Europe before the introduction of InSTIs. However, polymorphisms contributing to InSTI resistance were not rare. As InSTI use becomes more widespread, continuous surveillance of primary InSTI resistance is warranted. These data will be key to modelling the kinetics of InSTI resistance transmission in Europe in the coming years. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
    Full-text · Article · Jul 2015 · Journal of Antimicrobial Chemotherapy
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objectives Fat mass ratio (FMR) has been suggested as an objective indicator of abnormal body fat distribution in HIV infection. Although it could provide more comprehensive information on body fat changes than limb fat mass, FMR has scarcely been used in clinical trials examining body fat distribution in HIV-infected patients.MethodsA subanalysis of a controlled, randomized clinical trial in virologically suppressed HIV-1-infected men switching from zidovudine (ZDV)/lamivudine (3TC) to emtricitabine (FTC)/tenofovir (TDF) versus continuing on ZDV/3TC was carried out. FMR was assessed by dual X-ray absorptiometry (DEXA) for a period of 72 weeks. Lipoatrophy was defined as FMR ≥ 1.5. Multivariate linear regression models for the change in FMR from baseline were fitted.ResultsSixty-five men were randomized and treated (28 in the FTC/TDF arm and 37 in the ZDV/3TC arm), and 57 completed the study (25 and 32 in each arm, respectively). In the FTC/TDF arm, adjusted mean FMR decreased by 0.52 at week 72 (P = 0.014), and in the ZDV/3TC arm it increased by 0.13 (P = 0.491; P between arms = 0.023). Among subjects with lipoatrophy (baseline FMR ≥ 1.5), adjusted FMR decreased by 0.76 (P = 0.003) in the FTC/TDF arm and increased by 0.21 (P = 0.411; P between arms = 0.009) in the ZDV/3TC arm. Baseline FMR and treatment group were significant predictors (P < 0.05) of post-baseline changes in FMR.Conclusions Switching from ZDV/3TC to FTC/TDF led to an improvement in FMR, compared with progressive worsening of FMR in subjects receiving ZDV/3TC, showing that fat mass not only increased but was also distributed in a healthier way after the switch.
    No preview · Article · Jul 2015 · HIV Medicine

Publication Stats

25k Citations
4,718.45 Total Impact Points

Institutions

  • 2013-2015
    • University of Vic
      Vic, Catalonia, Spain
    • University of California, San Diego
      • Department of Pathology
      San Diego, California, United States
  • 2011-2015
    • IrsiCaixa Institute for AIDS Research
      Badalona, Catalonia, Spain
  • 2007-2015
    • Fundación Lucha contra el Sida
      Badalona, Catalonia, Spain
    • Hospital Universitario Miguel Servet
      Caesaraugusta, Aragon, Spain
  • 1989-2015
    • Autonomous University of Barcelona
      • Department of Medicine
      Cerdanyola del Vallès, Catalonia, Spain
  • 1985-2015
    • Hospital Universitari Germans Trias i Pujol
      • • Department of Clinical Pharmacology
      • • Department of Internal Medicine
      • • Department of Clinical Hematology
      Badalona, Catalonia, Spain
  • 2011-2013
    • TAISS - Técnicas Avanzadas de Investigación en Servicios de Salud
      Madrid, Madrid, Spain
  • 2007-2013
    • IGTP Health Sciences Research Institute of the Germans Trias i Pujol Foundation
      Badalona, Catalonia, Spain
  • 2012
    • University of California, Los Angeles
      Los Angeles, California, United States
    • Karolinska Institutet
      • Department of Microbiology, Tumor and Cell Biology (MTC)
      Сольна, Stockholm, Sweden
  • 1990-2012
    • Universidad Autónoma de Madrid
      Madrid, Madrid, Spain
  • 1986-2012
    • Institut Marqués, Spain, Barcelona
      Barcino, Catalonia, Spain
  • 2009-2011
    • "la Caixa" Foundation
      Barcino, Catalonia, Spain
    • University Hospital Donostia
      San Sebastián, Basque Country, Spain
    • Universita' degli Studi "Magna Græcia" di Catanzaro
      Catanzaro, Calabria, Italy
  • 2010
    • University of Liverpool
      Liverpool, England, United Kingdom
  • 2003-2009
    • University of Alabama at Birmingham
      Birmingham, Alabama, United States
  • 2008
    • IR-Sant Pau - Sant Pau Institute of Biomedical Research
      Barcino, Catalonia, Spain
    • University College London
      • Department of Primary Care and Population Health (PCPH)
      London, ENG, United Kingdom
  • 1990-2008
    • Hospital de la Santa Creu i Sant Pau
      • Santa Creu i Sant Pau Hospital Research Institute
      Barcino, Catalonia, Spain
  • 1984-2008
    • University of Barcelona
      • Department of Medicine
      Barcino, Catalonia, Spain
  • 2005
    • Copenhagen University Hospital Hvidovre
      Hvidovre, Capital Region, Denmark
    • Deutsche Gesellschaft für Sportmedizin und Prävention e.V.
      Germany
  • 2004
    • Universitat Rovira i Virgili
      Tarraco, Catalonia, Spain
  • 1998-2003
    • Fundació Institut Investigació Germans Trias i Pujol
      Badalona, Catalonia, Spain
    • Hospital General Universitario Morales Meseguer
      Murcia, Murcia, Spain
  • 2002
    • Vanderbilt University
      Nashville, Michigan, United States
    • The University of Edinburgh
      • Credit Research Centre
      Edinburgh, Scotland, United Kingdom
    • George Washington University
      Washington, Washington, D.C., United States
    • Lerner Research Institute
      Cleveland, Ohio, United States
  • 2001-2002
    • Instituto de Salud Carlos III
      • National Center of Microbiology (CNM)
      Madrid, Madrid, Spain
  • 1989-2001
    • Hospital Clínic de Barcelona
      • Servicio de Enfermedades Infecciosas
      Barcino, Catalonia, Spain
  • 2000
    • Istituto Superiore di Sanità
      Roma, Latium, Italy
  • 1999
    • Hospital Universitario Virgen del Rocío
      Hispalis, Andalusia, Spain
  • 1993
    • Hospital Universitari de Bellvitge
      • Department of Infectious Diseases
      l'Hospitalet de Llobregat, Catalonia, Spain