Lambert Assoumou

Publications of Lambert Assoumou

• Determinants of low-density lipoprotein particle diameter during antiretroviral therapy including protease inhibitors in HIV-1-infected patients.

  Authors: Randa Bittar, Philippe Giral, Elisabeth Aslangul, Lambert Assoumou, Marc-Antoine Valantin, Olga Kalmykova, Valérie Fesel-Fouquier, Dominique Costagliola, Dominique Bonnefont-Rousselot

  Antiviral therapy. 02/2012;

  BACKGROUND: Lipid disorders are frequent in HIV-1-infected patients taking combination antiretroviral therapy (cART) that includes protease inhibitors (PIs). The presence of small dense low-densityBACKGROUND: Lipid disorders are frequent in HIV-1-infected patients taking combination antiretroviral therapy (cART) that includes protease inhibitors (PIs). The presence of small dense low-density lipoprotein particles might be an important predictive marker of cardiovascular disease in this setting. This cross-sectional substudy of the ANRS 126 trial was designed to identify variables influencing LDL diameter. METHODS: We studied 81 stable HIV-1-infected patients with dyslipidaemia (LDL-cholesterol >4.1 mmol/l, triglycerides <8.8 mmol/l) receiving PI-including cART regimens and no lipid-lowering drugs. LDL diameter was assessed by gradient gel electrophoresis. Relationships between LDL diameter and demographic, metabolic and HIV-related variables were identified by using non-parametric univariate tests and multiple linear regression models. RESULTS: In univariate analysis, LDL diameter was related to demographic variables, triglyceride (TG) levels, high-density lipoprotein cholesterol (HDL-c) levels, and the numbers and duration of exposure to nucleoside reverse transcriptase inhibitors and PIs. In multivariable linear regression analysis, LDL diameter was negatively associated with the TG level (P<0.0001) and positively associated with the HDL-c level (P<0.0001). For each 1-mmol/l increase in TG, LDL diameter fell by 0.281 nm. Conversely, for each 1-mmol/l increase in HDL-c, LDL diameter rose by 1.175 nm. CONCLUSIONS: Higher TG and lower HDL-c levels are associated with smaller LDL particle diameter. Small-diameter LDL particles could contribute to early atherogenic processes in HIV-1-infected patients on cART.

• Investigation of Super Learner Methodology on HIV-1 Small Sample: Application on Jaguar Trial Data.

  Authors: Allal Houssaïni, Lambert Assoumou, Anne Geneviève Marcelin, Jean Michel Molina, Vincent Calvez, Philippe Flandre

  AIDS research and treatment. 01/2012; 2012:478467.

  Background. Many statistical models have been tested to predict phenotypic or virological response from genotypic data. A statistical framework called Super Learner has been introduced either toBackground. Many statistical models have been tested to predict phenotypic or virological response from genotypic data. A statistical framework called Super Learner has been introduced either to compare different methods/learners (discrete Super Learner) or to combine them in a Super Learner prediction method. Methods. The Jaguar trial is used to apply the Super Learner framework. The Jaguar study is an "add-on" trial comparing the efficacy of adding didanosine to an on-going failing regimen. Our aim was also to investigate the impact on the use of different cross-validation strategies and different loss functions. Four different repartitions between training set and validations set were tested through two loss functions. Six statistical methods were compared. We assess performance by evaluating R(2) values and accuracy by calculating the rates of patients being correctly classified. Results. Our results indicated that the more recent Super Learner methodology of building a new predictor based on a weighted combination of different methods/learners provided good performance. A simple linear model provided similar results to those of this new predictor. Slight discrepancy arises between the two loss functions investigated, and slight difference arises also between results based on cross-validated risks and results from full dataset. The Super Learner methodology and linear model provided around 80% of patients correctly classified. The difference between the lower and higher rates is around 10 percent. The number of mutations retained in different learners also varys from one to 41. Conclusions. The more recent Super Learner methodology combining the prediction of many learners provided good performance on our small dataset.

• High-sensitivity C-reactive protein levels fall during statin therapy in HIV-infected patients receiving ritonavir-boosted protease inhibitors.

  Authors: Elisabeth Aslangul, Soraya Fellahi, Lambert K Assoumou, Jean-Philippe Bastard, Jacqueline Capeau, Dominique Costagliola

  AIDS (London, England). 03/2011; 25(8):1128-31.

  HIV-infected patients are at an increased risk of developing cardiovascular disease. Elevated levels of C-reactive protein (CRP) are associated with an increased risk of cardiovascular disease in theHIV-infected patients are at an increased risk of developing cardiovascular disease. Elevated levels of C-reactive protein (CRP) are associated with an increased risk of cardiovascular disease in the general population and are reduced by statin therapy. We examined the effect of pravastatin and rosuvastatin on CRP levels in 58 dyslipidemic HIV-infected patients. A 45-day course of either statin reduced the median CRP level from 3.0 to 2.4 mg/l (P < 0.001) with no correlation with changes in lipid parameters.

• A therapeutic dendritic cell-based vaccine for HIV-1 infection.

  Authors: Felipe García, Núria Climent, Lambert Assoumou, Cristina Gil, Nuria González, José Alcamí, Agathe León, Joan Romeu, Judith Dalmau, Javier Martínez-Picado, Jeff Lifson, Brigitte Autran, Dominique Costagliola, Bonaventura Clotet, Josep M Gatell, Montserrat Plana, Teresa Gallart

  The Journal of infectious diseases. 02/2011; 203(4):473-8.

  A double-blinded, controlled study of vaccination of untreated patients with chronic human immunodeficiency virus type 1 (HIV-1) infection with 3 doses of autologous monocyte-derived dendritic cellsA double-blinded, controlled study of vaccination of untreated patients with chronic human immunodeficiency virus type 1 (HIV-1) infection with 3 doses of autologous monocyte-derived dendritic cells (MD-DCs) pulsed with heat inactivated autologous HIV-1 was performed. Therapeutic vaccinations were feasible, safe, and well tolerated. At week 24 after first vaccination (primary end point), a modest significant decrease in plasma viral load was observed in vaccine recipients, compared with control subjects (P = .03). In addition, the change in plasma viral load after vaccination tended to be inversely associated with the increase in HIV-specific T cell responses in vaccinated patients but tended to be directly correlated with HIV-specific T cell responses in control subjects.

• A high HIV DNA level in PBMCs at antiretroviral treatment interruption predicts a shorter time to treatment resumption, independently of the CD4 nadir.

  Authors: Christophe Piketty, Laurence Weiss, Lambert Assoumou, Marianne Burgard, Aurélie Mélard, Jean-Michel Ragnaud, Michele Bentata, Pierre-Marie Girard, Christine Rouzioux, Dominique Costagliola

  Journal of medical virology. 11/2010; 82(11):1819-28.

  This study aimed to evaluate the safety of antiretroviral treatment interruption (TI) in HIV-infected patients who started treatment based on earlier guidelines, and to identify baseline factorsThis study aimed to evaluate the safety of antiretroviral treatment interruption (TI) in HIV-infected patients who started treatment based on earlier guidelines, and to identify baseline factors predictive of the time to reach fixed criteria for treatment resumption. Prospective, open-label, multicenter trial. Patients were eligible if they had a CD4 cell count >350/mm(3) and plasma HIV RNA <50,000 copies/ml when they first started antiretroviral therapy (ART); and if they had a CD4 count >450/mm(3) and stable plasma HIV RNA <5,000 copies/ml for at least 6 months prior to enrollment. The criteria for ART resumption were a CD4 cell count <300/mm(3) and/or a CDC stage B or C event. 116 patients had received ART for a median of 5.3 years. The median CD4 cell count and plasma HIV RNA values at inclusion were 809/mm(3) and 2.6 log copies/ml, respectively. Median HIV DNA load at inclusion was 2.3 log copies/10(6) peripheral blood mononuclear cells (PBMCs). Thirty-six months after TI, 63.9% of the patients had not yet reached the criteria for ART resumption, and 55.9% of patients had not resumed ART. In Cox multivariable analysis, a high HIV DNA level at TI, a low CD4 nadir, and pre-existing AIDS status were the only significant risk factors for reaching the criteria for ART resumption (hazards ratio: 2.15 (1.02-4.53), 4.59 (1.22-17.24), and 5.74 (1.60-20.56), respectively). Patients who started ART with a CD4 cell count above 350/mm(3) were able to interrupt treatment for long periods without a high absolute risk of either AIDS or severe non-AIDS morbidity/mortality. A high PBMC HIV DNA level at TI was a strong predictor for more rapid treatment resumption.

• Maraviroc does not affect humoral response to the pandemic influenza A-H1N1v 2009 adjuvanted vaccine in HIV-1-infected patients.

  Authors: Ana Canestri, Anne Krivine, Lambert Assoumou, Monique Le Corre, Flore Rozenberg, Anne-Geneviève Marcelin, Luminita Schneider, Assia Samri, Guislaine Carcelain, Brigitte Autran, Christine Katlama, Amélie Guihot

  AIDS (London, England). 10/2010; 24(18):2887-9.

  Immune changes induced by the CCR5 antagonist maraviroc raise the question of an impairment of responses to vaccines. We evaluated the immunogenicity of the adjuvanted pandemic influenza A-H1N1v 2009Immune changes induced by the CCR5 antagonist maraviroc raise the question of an impairment of responses to vaccines. We evaluated the immunogenicity of the adjuvanted pandemic influenza A-H1N1v 2009 vaccine in HIV-1-infected patients with suppressed HIV viremia with or without a maraviroc-containing regimen. Seroprotection, seroconversion, and geometric mean titer ratio of specific antibody titers did not differ between groups. These results suggest that maraviroc does not significantly affect the immune response to this adjuvanted vaccine.

• Relative contributions of baseline patient characteristics and the choice of statistical methods to the variability of genotypic resistance scores: the example of didanosine.

  Authors: Lambert Assoumou, Allal Houssaïni, Dominique Costagliola, Philippe Flandre

  The Journal of antimicrobial chemotherapy. 02/2010; 65(4):752-60.

  Our aim was to investigate the respective role of statistical methodology and patients' baseline characteristics in the selection of mutations included in genotypic resistance scores. As an example,Our aim was to investigate the respective role of statistical methodology and patients' baseline characteristics in the selection of mutations included in genotypic resistance scores. As an example, the FORUM database on didanosine including 1453 patients was used. We split this population into four samples based on countries of enrolment (France n = 474, Italy n = 440, USA/Canada n = 219, others n = 320). We used both a continuous outcome measure (the viral load reduction at week 8) and a binary outcome measure (viral load decline at week 8 <0.6 log(10) or > or =0.6 log(10)) and both parametric and non-parametric methods for each outcome. Overall, 61 distinct mutations were selected by at least one method in at least one data set. The variability due to baseline characteristics varies from 79% to 88%, i.e. for a given method applied to the four data sets >80% of the mutations are selected only once. The variability induced by the methodology varies from 49% to 56%, i.e. for a given data set approximately 50% of the mutations are selected by at least two methods. Baseline patient characteristics contribute more than the choice of statistical method to the variability of the mutations to be included in the genotypic resistance scores.

• Relationship between regulatory T cells and immune activation in human immunodeficiency virus-infected patients interrupting antiretroviral therapy.

  Authors: Laurence Weiss, Christophe Piketty, Lambert Assoumou, Céline Didier, Laure Caccavelli, Vladimira Donkova-Petrini, Yves Levy, Pierre-Marie Girard, Marianne Burgard, Jean-Paul Viard, Christine Rouzioux, Dominique Costagliola

  PloS one. 01/2010; 5(7):e11659.

  Persistent immune activation plays a central role in driving Human Immunodeficiency Virus (HIV) disease progression. Whether CD4+CD25+ regulatory T cells (Tregs) are harmful by suppressingPersistent immune activation plays a central role in driving Human Immunodeficiency Virus (HIV) disease progression. Whether CD4+CD25+ regulatory T cells (Tregs) are harmful by suppressing HIV-specific immune responses and/or beneficial through a decrease in immune activation remains debatable. We analysed the relationship between proportion and number of regulatory T cells (Tregs) and immune activation in HIV-infected patients interrupting an effective antiretroviral therapy (ART). Twenty-five patients were included in a substudy of a prospective multicenter trial of treatment interruption (TI) (ANRS 116). Proportions and numbers of Tregs and the proportion of activated CD4 and CD8 T cells were assessed at baseline and month 12 (M12) of TI. Specific anti-HIV CD4 and CD8 responses were investigated at baseline and M12. Non parametric univariate analyses and multivariate linear regression models were conducted. At baseline, the proportion of Tregs negatively correlated with the proportion of HLA-DR+CD8+T cells (r=-0.519). Following TI, the proportion of Tregs increased from 6.3% to 7.2% (p=0.029); absolute numbers of Tregs decreased. The increase in the proportion of HLA-DR+CD38+CD8+T cells was significantly related to the increase in proportion of Tregs (p=0.031). At M12, the proportion of Tregs did not negatively correlate with CD8 T-cell activation. Nevertheless, Tregs retain a suppressive function since depletion of Treg-containing CD4+CD25+ cells led to an increase in lymphoproliferative responses in most patients studied. Our data suggest that Tregs are efficient in controlling residual immune activation in patients with ART-mediated viral suppression. However, the insufficient increase in the proportion and/or the decrease in the absolute number of Tregs result in a failure to control immune activation following TI. TRIAL REGISTRATION: ClinicalTrials.gov NCT00118677.

• Immune and virological benefits of 10 years of permanent viral control with antiretroviral therapy.

  Authors: Amélie Guihot, Roland Tubiana, Guillaume Breton, Anne-Geneviève Marcelin, Assia Samri, Lambert Assoumou, Emilia Goncalves, François Bricaire, Dominique Costagliola, Vincent Calvez, Christine Rouzioux, Brigitte Autran, Christine Katlama, Guislaine Carcelain

  AIDS (London, England). 11/2009;

  The effects of a 10-year control of HIV replication without viral blips with antiretroviral therapy were examined in progressors. CD4 cell counts did not plateau but showed a continuous increaseThe effects of a 10-year control of HIV replication without viral blips with antiretroviral therapy were examined in progressors. CD4 cell counts did not plateau but showed a continuous increase until the 10th year. Ultrasensitive techniques showed very low plasma HIV RNA and cell-associated DNA levels. Robust memory T cell responses to HIV-p24 were higher than in 3-year treated patients and comparable to those of Elite controllers, whereas interferon-gamma-producing HIV-specific T cells were infrequent. Long-term and efficient antiretroviral therapy provides continuous benefits both on the immune system and on the HIV reservoirs.

• Development of a didanosine genotypic resistance interpretation system based on large derivation and validation datasets.

  Authors: Lambert Assoumou, Alessandro Cozzi-Lepri, Françoise Brun-Vézinet, Victor DeGruttola, Daniel Kuritzkes, Andrew Phillips, Andrew Zolopa, Veronica Miller, Philippe Flandre, Dominique Costagliola

  AIDS (London, England). 10/2009;

  OBJECTIVE:: To assess the genotypic determinants of the virological response to didanosine (ddI) in HIV-infected patients. METHODS:: The Forum database on ddI was randomly divided into a derivationOBJECTIVE:: To assess the genotypic determinants of the virological response to didanosine (ddI) in HIV-infected patients. METHODS:: The Forum database on ddI was randomly divided into a derivation set (n = 1000) and a validation set (n = 453). Linear regression models and bootstrap sampling were used to select resistance mutations and to estimate their resistance scores. Linear regression models, accounted for the censoring of viral load measurements due to assay lower limits, of the week 8 reduction in viral load from baseline were adjusted for baseline viral load, the exact number of weeks between baseline and the week 8 viral load measurements, and the Stanford genotypic sensitivity score. RESULTS:: The ddI resistance mutations and their resistance scores based on the derivation set were as follows: M41L (score of 14), T69D (24), D123S (40), T139M (54), I180V (53), M184V (-12), V189I (55), Q207K (37), L210W (25), and T215Y (eight). The total score is obtained by adding the individual scores. Viruses with scores of 19 or less, 20-59, and 60 or more are considered sensitive, intermediate, and resistant, respectively. In the validation set, respectively, 58.7, 36.9, and 4.4% of viruses were predicted to be sensitive, intermediate, and resistant to ddI. The observed viral load reductions at week 8 were, respectively, 1.51 log10 copies/ml [interquartile range (IQR) 1.26-1.76] (P = 0.0001 versus resistant), 1.11 (0.94-1.30) (P = 0.0077 versus sensitive), and 0.46 (0.32-0.74) (P = 0.0079 versus intermediate). CONCLUSION:: We developed a genotypic resistance score for didanosine including four mutations never previously used.

• Rosuvastatin versus pravastatin in dyslipidemic HIV-1-infected patients receiving protease inhibitors: a randomized trial.

  Authors: Elisabeth Aslangul, Lambert Assoumou, Randa Bittar, Marc-Antoine Valantin, Olga Kalmykova, Gilles Peytavin, Marie-Hélène Fiévet, Franck Boccara, Dominique Bonnefont-Rousselot, Jean-Claude Melchior, Philippe Giral, Dominique Costagliola

  AIDS (London, England). 10/2009;

  BACKGROUND:: HIV infection and its treatment with protease inhibitors, especially when boosted with ritonavir, can cause lipid disorders. Statins, with the exception of fluvastatin, pravastatin andBACKGROUND:: HIV infection and its treatment with protease inhibitors, especially when boosted with ritonavir, can cause lipid disorders. Statins, with the exception of fluvastatin, pravastatin and rosuvastatin, interact with protease inhibitor metabolism via CYP450. Pravastatin is recommended for patients with protease inhibitor-associated dyslipidemia. Rosuvastatin is the statin most effective on low-density lipoprotein cholesterol (LDL-c) in non-HIV patients. METHODS:: HIV-1-infected patients treated with boosted protease inhibitor were randomized to receive either rosuvastatin 10 mg/day or pravastatin 40 mg/day for dyslipidemia (LDL-c >4.1 mmol/l and triglycerides <8.8 mmol/l). The percentage change in LDL-c, triglyceride and high-density lipoprotein-cholesterol levels, measured in a central laboratory, was determined after 45 days of statin treatment. RESULTS:: Eighty-eight patients were randomized and 83 took the study drugs, 41 rosuvastatin and 42 pravastatin. The median duration of prior antiretroviral treatment was 9 years. At baseline, the median LDL-c level was 4.93 mmol/l, the triglyceride level 2.29 mmol/l, and the high-density lipoprotein-cholesterol level 1.27 mmol/l. The median percentage changes in the rosuvastatin and pravastatin arms were -37 and -19% for LDL-c (P < 0.001), respectively, and -19 and -7% for triglycerides (P = 0.035), respectively. The change in the high-density lipoprotein-cholesterol level was not significantly different between the two arms. None of the four severe adverse events was attributed to the statins; in particular, there were no renal, hepatic or muscular events. CONCLUSION:: Rosuvastatin 10 mg/day was more effective than pravastatin 40 mg/day on LDL-c and triglyceride levels in HIV-1-infected patients receiving a boosted protease inhibitor.

• Nucleoside reverse transcriptase inhibitor-sparing regimen (nonnucleoside reverse transcriptase inhibitor + protease inhibitor) was more likely associated with resistance comparing to nonnucleoside reverse transcriptase inhibitor or protease inhibitor + nucleoside reverse transcriptase inhibitor in the randomized ANRS 121 trial.

  Authors: Cathia Soulié, Lambert Assoumou, Jade Ghosn, Claudine Duvivier, Gilles Peytavin, Zaina Ait-Arkoub, Jean-Michel Molina, Dominique Costagliola, Christine Katlama, Vincent Calvez, Anne-Geneviève Marcelin

  AIDS (London, England). 05/2009;

  The use of nonnucleoside reverse transcriptase inhibitor (NNRTI) + protease inhibitor regimen for the treatment of antiretroviral-naive patients was less successful than classical nucleoside reverseThe use of nonnucleoside reverse transcriptase inhibitor (NNRTI) + protease inhibitor regimen for the treatment of antiretroviral-naive patients was less successful than classical nucleoside reverse transcriptase inhibitor (NRTI) based regimen and associated with more resistance for protease inhibitors and NNRTIs. The selection for NNRTI resistance was particularly observed in patients with high viral load (>100 000 copies/ml) and low efavirenz trough levels (<1100 ng/ml). Contrary to the results observed in trials evaluating mono or dual protease inhibitors strategies, gag gene mutations were not involved in the low efficacy of this strategy. The NNRTI + protease inhibitor strategy should not be recommended as an antiretroviral first-line regimen, particularly in patients with high viral load at baseline.

• Greater decrease in bone mineral density with protease inhibitor regimens compared with nonnucleoside reverse transcriptase inhibitor regimens in HIV-1 infected naive patients.

  Authors: Claudine Duvivier, Sami Kolta, Lambert Assoumou, Jade Ghosn, Sylvie Rozenberg, Robert L Murphy, Christine Katlama, Dominique Costagliola

  AIDS (London, England). 04/2009; 27(7):817-24.

  OBJECTIVE: To evaluate the change in bone mineral density (BMD) at specific sites in patients initiating antiretroviral therapy in a substudy of the ANRS 121 trial. METHODS: Antiretroviral-naiveOBJECTIVE: To evaluate the change in bone mineral density (BMD) at specific sites in patients initiating antiretroviral therapy in a substudy of the ANRS 121 trial. METHODS: Antiretroviral-naive patients were randomized (2: 1: 1) into three treatment strategy arms: a nonnucleoside reverse transcriptase inhibitor (NNRTI) and a boosted protease inhibitor (PI/r), a PI/r and two nucleoside reverse transcriptase inhibitors (NRTIs) or an NNRTI and NRTIs. Hip and lumbar spine standardized BMD were evaluated at baseline and week 48 by dual X-ray absorptiometry by a central reading laboratory. RESULTS: Seventy-one patients were enrolled: 36 in the PI/r and NNRTI, 19 in the PI/r and NRTIs and 16 in the NNRTI and NRTIs arms. Baseline characteristics were [median (interquartile range)]: male (77%), age 40 years (33-49), 69% white, 58% smokers, BMI 23 kg/m2 (21-24), CD4 cell count 219 cells/microl (144-285). In the arms with NRTIs, 86% of patients received zidovudine/lamivudine. At baseline, 31% had osteopenia and 3% had osteoporosis. At week 48, there was a mean change in BMD of -4.1 +/- 3.9% at lumbar spine and -2.8 +/- 4.7% at hip (both P< or = 0.001). The decrease of BMD at lumbar spine was significantly worse in the PI/r and NNRTI arm (-4.4 +/- 3.4%) and in the PI/r and NRTIs arm (-5.8 +/- 4.5%) compared with the NNRTI and NRTIs arm (-1.5 +/- 2.9%), P = 0.007 and P = 0.001, respectively. CONCLUSION: BMD was impaired in 34% of patients, before starting any antiretrovirals. After 1 year, the decrease in lumbar spine BMD was more pronounced in patients receiving either PI/r-containing regimen compared with NNRTI and NRTIs. BMD at specific sites should be monitored during lifelong antiretroviral therapy.

• Initial therapy with nucleoside reverse transcriptase inhibitor-containing regimens is more effective than with regimens that spare them with no difference in short-term fat distribution: Hippocampe-ANRS 121 Trial.

  Authors: Claudine Duvivier, Jade Ghosn, Lambert Assoumou, Cathia Soulié, Gilles Peytavin, Vincent Calvez, Michèle Algarté Génin, Jean-Michel Molina, Olivier Bouchaud, Christine Katlama, Dominique Costagliola

  The Journal of antimicrobial chemotherapy. 10/2008; 62(4):797-808.

  The aim of this study was to evaluate the impact on body fat of nucleoside reverse transcriptase inhibitor (NRTI)-sparing regimens compared with NRTI-containing therapy in HIV-1-infectedThe aim of this study was to evaluate the impact on body fat of nucleoside reverse transcriptase inhibitor (NRTI)-sparing regimens compared with NRTI-containing therapy in HIV-1-infected antiretroviral (ARV)-naive patients. A randomized, multicentre, open-label trial in ARV-naive patients. Subjects were randomized (2:1:1) to receive: (i) an NRTI-sparing regimen consisting of a non-nucleoside reverse transcriptase inhibitor (NNRTI) plus a boosted protease inhibitor (PI/r); or (ii) an NRTI-containing regimen of (a) a PI/r plus two NRTIs or (b) an NNRTI plus two NRTIs. The primary endpoint was the change in subcutaneous limb fat measured by dual-energy X-ray absorptiometry at week (W) 96. Secondary endpoints included the proportion of patients with treatment failure, plasma HIV-RNA (pVL) <50 copies/mL and safety. One hundred and seventeen patients were enrolled between November 2003 and May 2004: 26% female; 42% from sub-Saharan Africa; median plasma HIV-RNA (pVL) 5.1 log(10) copies/mL; median CD4 count 207 cells/mm(3). A planned interim analysis demonstrated significantly lower treatment and virological responses with the NRTI-sparing strategy, resulting in premature study termination on 19 July 2005. The proportion of patients who remained on their assigned treatment strategy and had pVL <50 copies/mL on the NRTI-sparing regimen was 60.0%, compared with 82.5% on the NRTI-containing regimen at W24 (P = 0.009) and 66.7% and 82.5%, respectively, at W48 (P = 0.059). Treatment failure was associated with the NRTI-sparing strategy in patients with suboptimal adherence and with being from sub-Saharan Africa. No differences in fat distribution were noted. An initial NRTI-sparing regimen is less successful and virologically less potent than standard NRTI-containing regimen and should not therefore be used as the first line of treatment.

• Greater viral rebound and reduced time to resume antiretroviral therapy after therapeutic immunization with the ALVAC-HIV vaccine (vCP1452).

  Authors: Brigitte Autran, Robert L Murphy, Dominique Costagliola, Roland Tubiana, Bonaventura Clotet, Jose Gatell, Schlomo Staszewski, Norma Wincker, Lambert Assoumou, Raphaelle El Habib, Vincent Calvez, Bruce Walker, Christine Katlama

  AIDS (London, England). 08/2008; 22(11):1313-22.

  OBJECTIVE: Evaluate immunogenicity and clinical efficacy of two immunization strategies with the ALVAC-HIV-recombinant canarypox vaccine (vCP1452) in treated HIV-infected patients. DESIGN:OBJECTIVE: Evaluate immunogenicity and clinical efficacy of two immunization strategies with the ALVAC-HIV-recombinant canarypox vaccine (vCP1452) in treated HIV-infected patients. DESIGN: Randomized, double-blind, placebo-controlled, phase II study of vCP1452 immunization in chronically HIV-infected patients on therapy with CD4 T-cell count more than 350 cells/microl, CD4 nadir less than 400 cells/microl and pHIV-RNA less than 400 copies/ml. Patients were equally randomized to four injections at weeks 0, 4, 8, 20; three injections at weeks 4, 8, 20; and placebo. The primary endpoint was vaccine immunogenicity at week 24 measured by enzyme-linked immunospot-interferon-gamma against the HIV-gag-reverse transcriptase-nef vaccine sequences. Secondary endpoints included time to treatment resumption and viral quantitation following treatment interruption at week 24. Criteria to resume therapy included CD4 T-cell count decline less than 250 cells/microl or 50% decrease from baseline or pHIV-RNA more than 50,000 copies/ml. RESULTS: Sixty-five patients enrolled. Changes from baseline in HIV-specific T cells in the four injection arms (+480 spot-forming cells/M-peripheral blood mononuclear cell) were significant compared to placebo (+8; P = 0.014), but not in the three injection arms (+322). The week 36 pHIV-RNA (log10 copies/ml) after treatment interruption was higher in the four (4.71; P = 0.023) and three (4.82; P = 0.009) injection arms compared to placebo (4.40). Percentages of patients reaching treatment resumption criteria by week 48 were 74, 55 and 23% in the three respective arms (P = 0.013). Two independent factors influenced time to therapy resumption: immunization (hazards ratio = 2.7, P = 0.048 for three injections; hazards ratio = 4.1, P = 0.003 for four injections) and CD4 nadir (hazards ratio = 0.4, P = 0.002). CONCLUSIONS: Significant immunogenicity was induced by vCP1452; however, this strategy was independently associated with a shorter time to resume therapy and higher viral rebound.

• Initiatives for Developing and Comparing Genotype Interpretation Systems: External Validation of Existing Systems for Didanosine against Virological Response.

  Authors: Lambert Assoumou, Françoise Brun-Vézinet, Alessandro Cozzi-Lepri, Daniel Kuritzkes, Andrew Phillips, Andrew Zolopa, Victor DeGruttola, Veronica Miller, Dominique Costagliola

  The Journal of infectious diseases. 07/2008;

  Background. @nbsp; This study was performed to investigate the concordance between commonly used human immunodeficiency virus type 1 (HIV-1) drug resistance interpretation systems for didanosineBackground. @nbsp; This study was performed to investigate the concordance between commonly used human immunodeficiency virus type 1 (HIV-1) drug resistance interpretation systems for didanosine (ddI) and their ability to predict responses at weeks 8 and 24. Methods. @nbsp; The study included drug-experienced HIV-infected patients who had viral loads >500 copies/mL and who underwent a genotypic resistance test when beginning a ddI-containing therapy. The interpretations of the level of resistance to ddI were compared for the 6 interpretation systems. Linear and logistic regression were used to assess their ability to predict responses for weeks 8 and 24, respectively. Results. @nbsp; The 1453 patients had a median viral load of 4.3 log(10) copies/mL, and 31% were preexposed to ddI. Complete concordance was found for 19% of samples, partial discordance for 49%, and complete discordance for 32%. The median viral load reduction at week 8 was 1.36 log(10) copies/mL, and 56% of patients had viral loads >400 copies/mL at week 24. At week 8, all systems correctly predicted a greater viral load reduction in patients with susceptible viruses than in those with resistant viruses, but only the Stanford system was able to discriminate between patients with resistant, intermediately resistant, and susceptible viruses. No systems predicted virological response correctly at week 24. Conclusions. @nbsp; Our results show the need for standardized methods to establish genotypic interpretation systems.

• HIV-1-infected patients from the French National Observatory experiencing virological failure while receiving enfuvirtide.

  Authors: Diane Descamps, Lambert Assoumou, Bernard Masquelier, Anne-Geneviève Marcelin, Souhila Saidi, Catherine Tamalet, Jacqueline Cottalorda, Jean-Christophe Plantier, Brigitte Montes, Jacques Izopet [......] Véronique Schneider, Constance Delaugerre, Virginie Ferré, Annick Ruffault, Coralie Pallier, Laurence Morand-Joubert, Marie-Laure Chaix, Vincent Calvez, Françoise Brun-Vézinet, Dominique Costagliola

  The Journal of antimicrobial chemotherapy. 06/2008;

  Objectives We studied gp41 mutations associated with failing enfuvirtide salvage therapy. Methods This multicentre study involved patients with HIV-1 plasma viral load (pVL) > 5000 copies/mL after atObjectives We studied gp41 mutations associated with failing enfuvirtide salvage therapy. Methods This multicentre study involved patients with HIV-1 plasma viral load (pVL) > 5000 copies/mL after at least 3 months of uninterrupted enfuvirtide therapy and with plasma samples available at inclusion (T0), at initial enfuvirtide failure (T1) and at last follow-up visit during continued failing enfuvirtide therapy (T2). The HR-1 and HR-2 domains of the gp41 gene were sequenced at T0, T1 and T2. Results Ninety-nine patients were enrolled. At baseline, the median pVL and CD4 cell count were 5.1 log copies/mL and 72 cells/mm(3), respectively. Based on the ANRS Resistance Group algorithm, the proportion of patients harbouring viruses with enfuvirtide resistance mutations increased significantly between T0 and T1. In the HR-1 domain, the V38A/M, Q40H, N42T, N43D and L45M mutations wereselected (P < 0.02). In the HR-2 domain, no mutations were significantly selected during the follow-up. None of the mutations was associated with a CD4 cell count increment. Conclusions Mutations selected during failing enfuvirtide salvage therapy are mainly located in the HR-1 domain of the gp41 gene, between codons 38 and 45. No mutations were associated with an increase in the CD4 cell count.

• HIV-1 X4/R5 co-receptor in viral reservoir during suppressive HAART.

  Authors: Cathia Soulié, Anne-Geneviève Marcelin, Jade Ghosn, Bahia Amellal, Lambert Assoumou, Sidonie Lambert, Claudine Duvivier, Dominique Costagliola, Christine Katlama, Vincent Calvez

  AIDS (London, England). 11/2007; 21(16):2243-5.

  As immune recovery during HAART is mainly caused by the expansion of X4-naive cells, we studied the evolution of HIV tropism in the reservoir of 34 patients receiving 48 weeks of HAART. No change inAs immune recovery during HAART is mainly caused by the expansion of X4-naive cells, we studied the evolution of HIV tropism in the reservoir of 34 patients receiving 48 weeks of HAART. No change in virus tropism was observed over time, but patients with X4 viruses had higher HIV-1 proviral DNA levels than patients with R5 viruses. This suggests that CCR5 antagonist activity should not be compromised in patients harbouring R5 viruses before starting HAART.

• Experience of indinavir/ritonavir 400/100 mg twice-daily highly active antiretroviral therapy-containing regimen in HIV-1-infected patients in Bamako, Mali: the NOGOMA Study.

  Authors: Ana Canestri, Mamadou Cisse, Anne-Geneviève Marcelin, Gilles Peytavin, Emmanuel Traore, Lambert Assoumou, Ousmane Traore, Victoria Koita, Fodie Diallo, Awa Thiero Sangare, Mayrama Koita Sidibé, Vincent Calvez, Aliou Sylla, Christine Katlama, Roland Tubiana

  Journal of acquired immune deficiency syndromes (1999). 09/2007; 45(4):477-9.

• Prevalence of HIV-1 drug resistance in treated patients: a French nationwide study.

  Authors: Dominique Costagliola, Diane Descamps, Lambert Assoumou, Laurence Morand-Joubert, Anne-Geneviève Marcelin, Véronique Brodard, Constance Delaugerre, Vincent Mackiewicz, Annick Ruffault, Jacques Izopet, Jean-Christophe Plantier, Catherine Tamalet, Sabine Yerly, Souhaha Saidi, Françoise Brun-Vezinet, Bernard Masquelier

  Journal of acquired immune deficiency syndromes (1999). 09/2007; 46(1):12-8.

  BACKGROUND: Surveillance of HIV-1 drug resistance in antiretroviral-treated patients is important from the public health perspective of the spread of resistance and to evaluate the proportion ofBACKGROUND: Surveillance of HIV-1 drug resistance in antiretroviral-treated patients is important from the public health perspective of the spread of resistance and to evaluate the proportion of patients for whom new drugs are needed. METHODS: Patients were consecutively included in 28 centers in France and 1 center in Switzerland if they had a viral load measurement performed in June 2004, with a result >or=1,000 copies/mL. Reverse transcriptase, protease, and gp41 genes were sequenced, and resistance mutations were reported as listed on the Web site ( www.iasusa.org). The genotypic resistance results were interpreted by the Agence Nationale de Recherches sur le SIDA et les Hepatites Virales (ANRS) and Stanford algorithms. RESULTS: The 498 patients included had been exposed to 9 (interquartile ratio [IQR]: 6 to 12) antiretroviral drugs. Patients' viruses harbored 4 nucleoside reverse transcriptase inhibitor (IQR: 1 to 6) and 4 protease inhibitor (PI; IQR: 2 to 8) resistance mutations, whereas 44% had at least 1 nonnucleoside reverse transcriptase inhibitor resistance mutation. The frequency of resistance to at least 1 drug was 88% with the ANRS algorithm and 83% with the Stanford algorithm. The frequencies of complete resistance to 1, 2, and 3 classes of drugs were 37%, 15%, and 4%, respectively, with the ANRS algorithm and 27%, 23%, and 24%, respectively, with the Stanford algorithm. The most important differences between algorithms were for PIs. Using the ANRS algorithm and extrapolation on the whole French database, 19% of all treated patients could contribute to the spread of resistance and 4% had complete resistance to 2 classes of antiretroviral drugs. CONCLUSIONS: The observed patterns of resistance are linked to a long-lasting history of antiretroviral therapy. The frequency of multiresistance can vary according to the interpretation systems.