Anne-Geneviève Marcelin

Publications of Anne-Geneviève Marcelin

• Circulating interleukin-6 levels correlate with residual HIV viraemia and markers of immune dysfunction in treatment-controlled HIV-infected patients.

  Authors: Jean-Philippe Bastard, Cathia Soulié, Soraya Fellahi, Stephanie Haïm-Boukobza, Anne Simon, Christine Katlama, Vincent Calvez, Anne-Geneviève Marcelin, Jacqueline Capeau

  Antiviral therapy. 03/2012;

  BACKGROUND: Antiretroviral therapy (ART)-controlled HIV-infected patients have elevated levels of systemic inflammatory markers, C-reactive protein (CRP) and interleukin (IL)-6, which correlate withBACKGROUND: Antiretroviral therapy (ART)-controlled HIV-infected patients have elevated levels of systemic inflammatory markers, C-reactive protein (CRP) and interleukin (IL)-6, which correlate with increased cardiovascular risk and/or mortality. Persistent low-level viral replication could be involved in this inflammatory state. We evaluated whether residual viral load (VL) correlated with the level of systemic inflammatory/immune markers in ART-controlled HIV-infected patients. METHODS: We evaluated 122 antiretroviral-controlled patients with VL 1-500 copies/ml for circulating levels of high-sensitivity (hs)CRP, hsIL-6, IL-8, soluble (s)CD14 and soluble tumour necrosis factor (TNF) receptors, sTNFR1 and sTNFR2. RESULTS: The patients were 80.3% men, the median age was 47 years, the median CD4(+) T-cell count was 519 cells/mm(3), the median nadir CD4(+) T-cell count was 180 cells/mm(3), the median VL was 28 copies/ml and the median body mass index was 23.3 kg/m(2). The median (range) values for IL-6, CRP, IL-8, sCD14, sTNFR1 and sTNFR2 were 0.685 pg/ml (0.15-5.46), 1.8 mg/l (0.2-9.7), 10.0 pg/ml (1.6-71.1), 1,174 ng/ml (214-3,145), 1,112 pg/ml (583-5,834) and 2,412 pg/ml (1,142-7,688), respectively. IL-6 values correlated positively with HIV VL (rho=0.217, P=0.017). The VL threshold value for significantly increased IL-6 was 31 copies/ml (P=0.023). IL-6 values correlated with markers of immune dysfunction: the CD4/CD8 ratio (rho=-0.248, P=0.011), CD4 nadir level (rho=-0.186, P=0.04) and nadir CD4/CD8 ratio (rho=-0.257, P=0.008). They negatively correlated with markers of immune activation sCD14 (rho=-0.236, P=0.011) and IL-8 (rho=-0.290, P=0.002). We found no correlation between VL and CRP or other markers of inflammation/immune dysfunction including sTNFR1, sTNFR2, sCD14 and IL-8. CONCLUSIONS: We report here that low-range IL-6 levels correlated with low-range VL and inversely with sCD14 and IL-8. Our findings suggest that maintaining VL<30 copies/ml in HIV-infected patients might therefore reduce IL-6.

• Emergence of cytomegalovirus resistance to foscarnet in a patient receiving foscarnet salvage therapy for multidrug-resistant HIV infection.

  Authors: David Boutolleau, Ana Canestri, Sonia Burrel, Marc Wirden, Sophie Seang, Cyril Clavel-Osorio, Anne-Geneviève Marcelin, Christine Katlama, Henri Agut

  Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology. 03/2012;

  Foscarnet (FOS) is a pyrophosphate analogue that inhibits both cytomegalovirus (CMV) and human immunodeficiency virus (HIV) replication. We describe herein the emergence of CMV resistance to FOS in aFoscarnet (FOS) is a pyrophosphate analogue that inhibits both cytomegalovirus (CMV) and human immunodeficiency virus (HIV) replication. We describe herein the emergence of CMV resistance to FOS in a 54-year-old man receiving FOS salvage therapy because of multidrug-resistant HIV-1 infection. Oral valganciclovir (VGCV) treatment allowed subsequently the improvement of FOS-resistant CMV infection.

• Detection of HIV-1 RNA in seminal plasma samples from treated patients with undetectable HIV-1 RNA in blood plasma on a 2002-2011 survey.

  Authors: Sidonie Lambert-Niclot, Roland Tubiana, Céline Beaudoux, Gilles Lefebvre, Fabienne Caby, Manuela Bonmarchand, Michèle Naouri, Benoit Schubert, Marc Dommergues, Vincent Calvez, Philippe Flandre, Catherine Poirot, Anne-Geneviève Marcelin

  AIDS (London, England). 02/2012;

  OBJECTIVE:: The objective of this study was to estimate the frequency of detectable seminal HIV-1 viral load in men with repeatedly undetectable blood viral load, these last years and over an 10-yearOBJECTIVE:: The objective of this study was to estimate the frequency of detectable seminal HIV-1 viral load in men with repeatedly undetectable blood viral load, these last years and over an 10-year period (2002-2011) in a large cohort of HIV-1-infected men from couples requesting Assisted Reproduction Technologies (ART). We also searched for an association between HIV-1 RNA seminal viral load, HIV-1 RNA plasma viral load measured by ultrasensitive assay and blood HIV-1 DNA on a sub-group of 98 patients. METHODS:: Three hundred and four HIV-1 infected men have provided 628 paired blood and semen samples. In a subset of 98 patients for which a blood sample was available, residual viremia, HIV-1 RNA in semen and HIV-1 DNA were studied. RESULTS:: Twenty on 304 patients (6.6%) had detectable HIV-1 RNA in semen, ranging from 135 to 2365 copies/ml and corresponding to 23 samples, although they had concomitantly undetectable HIV-1 RNA in blood while they were under antiretroviral therapy. This prevalence was stable over time even in recent years. There was an association between HIV-1 RNA plasma viral load measured by ultrasensitive assay and HIV-1 DNA in blood but both were not associated with seminal HIV-1 RNA viral load. CONCLUSIONS:: It seems cautious individually to maintain the recommendations of safe sex and the recourse to ART, or at least to inform the couple of the residual potential risk, in serodiscordant couples desiring a child.

• Multicenter assessment of HIV-1 RNA quantitation in semen in the CREAThE network.

  Authors: Christophe Pasquier, Corinne Andreutti, Evelyne Bertrand, Alionka Bostan, Thomas Bourlet, Irene Molina, Zehava Grossman, Philippe Halfon, Marianne Leruez-Ville, Margrethe Lüneborg-Nielsen, Carmen Mar, Anne-Geneviève Marcelin, Catherine Roussel-Ronserail, Marie-Paule Schmitt, Sepehr Tabrizi, Maria Vourliotis, Louis Bujan

  Journal of medical virology. 02/2012; 84(2):183-7.

  Detection of HIV-1 RNA in semen is used commonly to determine the safety of semen processing procedures before assisted reproductive technology (ART). Using two panels of prepared semen samplesDetection of HIV-1 RNA in semen is used commonly to determine the safety of semen processing procedures before assisted reproductive technology (ART). Using two panels of prepared semen samples containing HIV-1 the performances of protocols from 14 centers have been compared. No false-positive results were detected but false-negative results were frequent when the concentration was below 500 HIV-1 RNA copies/ml of seminal plasma. Frequency of HIV-1 RNA detection was higher on seminal cells than on seminal plasma. Assays (or protocols) for quantifying HIV-1 RNA in semen performed less well than standardized blood plasma assays. The HIV load in seminal plasma could be a useful marker of the risk of sexual transmission of the virus. Its use as a marker of global HAART efficiency in the HIV reservoir needs further study. Standardized assays are required for detection and measurement of HIV-1 RNA in semen samples.

• 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.

• E17A mutation in HIV-1 Vpr confers resistance to didanosine in association with thymidine analog mutations.

  Authors: Slim Fourati, Isabelle Malet, Carolin A Guenzel, Cathia Soulie, Priscilla Maidou-Peindara, Laurence Morand-Joubert, Marc Wirden, Sophie Sayon, Gilles Peytavin, Anne Simon, Christine Katlama, Serge Benichou, Vincent Calvez, Anne-Geneviève Marcelin

  Antiviral research. 11/2011; 93(1):167-74.

  HIV-1 accessory Vpr protein is involved in the reverse transcription process and has been shown to modulate the virus mutation rate. This process may play a role in the kinetics of appearance of drugHIV-1 accessory Vpr protein is involved in the reverse transcription process and has been shown to modulate the virus mutation rate. This process may play a role in the kinetics of appearance of drug resistance mutations under antiretroviral treatment. Vpr sequences were analyzed from plasma viruses derived from 97 HIV-1-infected individuals failing antiretroviral treatment and 63 antiretroviral-naïve patients. Vpr genetic variability was analyzed for association with specific drug treatment and drug resistance mutations. Biological and virological experiments were employed to characterize a mutation in Vpr found to be associated with virological failure. E17A mutation located in the first α-helix of Vpr was more prevalent in HAART-treated individuals compared to untreated individuals. E17A was associated with thymidine analog mutations (TAMs) in reverse transcriptase M41L, L210W and T215Y and with the use of didanosine in the patients' treatment histories. E17A had no impact on the biochemical and functional properties of Vpr, and did not affect kinetics of replication of wild-type or TAMs-containing viruses. However, its association with TAMs and the use of didanosine was consistent with phenotypic susceptibility assays showing a significant 3-fold decrease in didanosine susceptibility of viruses harboring Vpr E17A combined with TAMs compared to viruses harboring TAMs alone. These findings highlight a novel role of Vpr in HIV-1 drug resistance. Vpr E17A confers resistance to didanosine when associated with TAMs. Whether Vpr E17A facilitates excision of didanosine is still to be determined.

• The HIV-1 integrase G118R mutation confers raltegravir resistance to the CRF02_AG HIV-1 subtype.

  Authors: Isabelle Malet, Slim Fourati, Charlotte Charpentier, Laurence Morand-Joubert, Daniele Armenia, Marc Wirden, Sophie Sayon, Margriet Van Houtte, Francesca Ceccherini-Silberstein, Françoise Brun-Vézinet, Carlo-Federico Perno, Diane Descamps, André Capt, Vincent Calvez, Anne-Geneviève Marcelin

  The Journal of antimicrobial chemotherapy. 09/2011; 66(12):2827-30.

  Most of the previous studies that explored the molecular basis of raltegravir resistance were conducted studying the HIV-1 B subtype. It has been shown that the CRF02_AG subtype in relation to itsMost of the previous studies that explored the molecular basis of raltegravir resistance were conducted studying the HIV-1 B subtype. It has been shown that the CRF02_AG subtype in relation to its natural integrase (IN) sequence could develop different genetic pathways associated with raltegravir resistance. The aim of this study was to explore resistance pathways preferably used by CRF02_AG viruses compared with subtype B. Twenty-five HIV-1 CRF02_AG-infected patients failing a raltegravir-containing regimen were studied. IN gene sequences were examined for the presence of previously described IN inhibitor (raltegravir, elvitegravir, dolutegravir and MK-2048) resistance mutations at 20 amino acid positions. Among the 25 studied patients, 7 showed viruses harbouring major raltegravir resistance mutations mainly associated with the 155 genetic pathways and 18 showed viruses harbouring none of them; however, for 1 patient, we found a 118R mutation, associated with MK-2048 in vitro resistance, in a 74M background. For this patient, the phenotypic analysis showed that addition of only the G118R mutation conferred a high level of resistance to raltegravir (fold change = 25.5) and elvitegravir (fold change = 9.2). This study confirmed that mutation pathways for raltegravir resistance could be different between the two subtypes CRF02_AG and B with a preferential use of the 155 mutation in non-B subtypes. A new genetic pathway associated with raltegravir resistance, including the 118R mutation, has also been identified. This new genetic pathway, never described in subtype B, should be further evaluated for phenotypic susceptibility to dolutegravir and MK-2048.

• Effect of antiretroviral drugs on the quality of semen.

  Authors: Sidonie Lambert-Niclot, Catherine Poirot, Roland Tubiana, Allal Houssaini, Cathia Soulié, Stéphanie Dominguez, Benoit Schubert, Marie Prades, Manuela Bonmarchand, Vincent Calvez, Philippe Flandre, Gilles Peytavin, Anne-Geneviève Marcelin

  Journal of medical virology. 08/2011; 83(8):1391-4.

  The aim of this cross-sectional study was to determine which antiretroviral drugs (ARVs) are associated with changes in the characteristics of semen and the impact of these ARVs according to theirThe aim of this cross-sectional study was to determine which antiretroviral drugs (ARVs) are associated with changes in the characteristics of semen and the impact of these ARVs according to their score penetration into the male genital compartment. Data from 144 men infected with HIV-1 enrolled in an Assisted Reproductive Technology program were analyzed retrospectively. A seminal penetration score of ARV was based on the available literature. The nonparametric Kruskal-Wallis test and chi-square test were used. There was no difference on sperm parameters between NRTI, NNRTI, or PI regimen. In patients receiving NRTIs or PIs no differences were observed between antiretrovirals of these classes. However, in patients receiving NNRTIs, nevirapine (n = 22) was associated with a higher percentage of progressively motile spermatozoa (P < 0.0001) versus efavirenz (n = 38) as well as vitality (P = 0.0004). No relationship was observed between semen quality and the penetration score. NRTIs and PIs were not associated with any semen changes. Nevirapine was associated with a better quality of semen versus efavirenz. It would be of interest to validate, improve and test our penetration score in a prospective study.

• Prevalence of resistance mutations related to integrase inhibitor S/GSK1349572 in HIV-1 subtype B raltegravir-naive and -treated patients.

  Authors: Isabelle Malet, Marc Wirden, Slim Fourati, Daniele Armenia, Bernard Masquelier, Lavinia Fabeni, Sophie Sayon, Christine Katlama, Carlo Federico Perno, Vincent Calvez, Anne-Geneviève Marcelin, Francesca Ceccherini-Silberstein

  The Journal of antimicrobial chemotherapy. 07/2011; 66(7):1481-3.

  To compare the frequency of previously in vitro-selected integrase mutations (T124A, T124A/S153F, S153Y, T124A/S153Y and L101I/T124A/S153Y) conferring resistance to S/GSK1349572 between HIV-1 subtypeTo compare the frequency of previously in vitro-selected integrase mutations (T124A, T124A/S153F, S153Y, T124A/S153Y and L101I/T124A/S153Y) conferring resistance to S/GSK1349572 between HIV-1 subtype B integrase inhibitor (INI)-naive and raltegravir-treated patients. Integrase sequences from 650 INI-naive patients and 84 raltegravir-treated patients were analysed. The T124A mutation alone and the combination T124A/L101I were more frequent in raltegravir-failing patients than in INI-naive patients (39.3% versus 24.5%, respectively, P = 0.005 for T124A and 20.2% versus 10.0%, respectively, P = 0.008 for T124A/L101I). The S153Y/F mutations were not detected in any integrase sequence (except for S153F alone, only detected in one INI-naive patient). T124A and T124A/L101I, more frequent in raltegravir-treated patients, could have some effect on raltegravir response and their presence could play a role in the selection of other mutations conferring S/GSK1349572 resistance. The impact of raltegravir-mediated changes such as these on the virological response to S/GSK1349572 should be studied further.

• Improved V3 genotyping with duplicate PCR amplification for determining HIV-1 tropism.

  Authors: Stéphanie Raymond, Patricia Recordon-Pinson, Adrien Saliou, Pierre Delobel, Florence Nicot, Diane Descamps, Anne-Geneviève Marcelin, Philippe Flandre, Vincent Calvez, Bernard Masquelier, Jacques Izopet

  The Journal of antimicrobial chemotherapy. 06/2011; 66(9):1972-5.

  To determine whether genotyping of HIV-1 by duplicate PCR amplification of the region encoding the V3 loop is more sensitive than single PCR for detecting CXCR4-using viruses. The V3 genotypes of theTo determine whether genotyping of HIV-1 by duplicate PCR amplification of the region encoding the V3 loop is more sensitive than single PCR for detecting CXCR4-using viruses. The V3 genotypes of the HIV-1 infecting 152 patients enrolled in the multicentre GenoTropism ANRS study were determined by all the participating laboratories using a single PCR and V3 bulk sequencing. In parallel, one laboratory determined the V3 genotype using duplicate PCR and bulk sequencing of pooled amplicons. HIV tropism was predicted with the geno2pheno10 algorithm. The phenotypes of all samples were determined with the Trofile assay and the Toulouse tropism test (TTT) recombinant virus assay. Geno2pheno10 was 56.8% sensitive and 75.9% specific when compared with the Trofile assay for detecting CXCR4-using viruses after a single PCR. Duplicate amplification and bulk sequencing of the pooled PCR amplicons increased the sensitivity to 68.2% and specificity to 79.6%. Geno2pheno10 was 64.1% sensitive and 77.0% specific when compared with the TTT assay for detecting CXCR4-using viruses after a single PCR. Duplicate amplification and sequencing of the pooled PCR amplicons increased sensitivity to 76.9% and specificity to 80.5%. The genotypic determination of HIV-1 tropism can be improved by duplicate amplifications and sequencing the pooled PCR products. This is a good compromise between improved sensitivity and reasonable cost for the genotype-based determination of tropism.

• Impact of adding enfuvirtide to the predictive value of the darunavir genotypic resistance score.

  Authors: Charlotte Charpentier, Sidonie Lambert-Niclot, Lucile Larrouy, Gilles Peytavin, Marc-Antoine Valantin, Roland Landman, Christine Katlama, Patrick Yeni, Mathieu Felices, Françoise Brun-Vézinet, Vincent Calvez, Anne-Geneviève Marcelin, Diane Descamps

  Journal of acquired immune deficiency syndromes (1999). 05/2011; 57(1):e15-7.

• Raltegravir concentrations in the genital tract of HIV-1-infected women treated with a raltegravir-containing regimen (DIVA 01 study).

  Authors: Cyril Clavel, Gilles Peytavin, Roland Tubiana, Cathia Soulié, Catherine Crenn-Hebert, Isabelle Heard, François Bissuel, Houria Ichou, Claudia Ferreira, Christine Katlama, Anne-Geneviève Marcelin, Laurent Mandelbrot

  Antimicrobial agents and chemotherapy. 03/2011; 55(6):3018-21.

  We studied the penetration of raltegravir and HIV shedding in the genital tract among 14 HIV-1-infected women receiving a raltegravir-containing regimen who had <40 copies/ml blood plasma (BP) HIVWe studied the penetration of raltegravir and HIV shedding in the genital tract among 14 HIV-1-infected women receiving a raltegravir-containing regimen who had <40 copies/ml blood plasma (BP) HIV RNA. None of the cervicovaginal fluid (CVF) samples showed detectable HIV RNA. Median raltegravir concentrations were 235 ng/ml in BP and 93 ng/ml in CVF, with a CVF/BP ratio of approximately 2.3. This good penetration of raltegravir may contribute to the control of viral replication in the female genital tract.

• Low frequency of HIV-1 tropism evolution in patients successfully treated for at least 2 years.

  Authors: Cathia Soulie, Sidonie Lambert-Niclot, Marc Wirden, Anne Simon, Marc-Antoine Valantin, Slim Fourati, Roland Tubiana, Christine Katlama, Vincent Calvez, Anne-Geneviève Marcelin

  AIDS (London, England). 02/2011; 25(4):537-9.

  The aim of this study was to analyse tropism evolution in HIV-1 patients with at least 2 years of viral load undetectability. For this purpose, HIV-1-infected antiretroviral-treated patients (n =The aim of this study was to analyse tropism evolution in HIV-1 patients with at least 2 years of viral load undetectability. For this purpose, HIV-1-infected antiretroviral-treated patients (n = 128) with a viral load less than 50 copies/ml for 4 years in median were studied. No change of virus tropism was observed in 92.9% of patients. Therefore, before the use of CCR5 antagonists, genotypic viral DNA tropism determination is an available tool.

• Higher efficacy of nevirapine than efavirenz to achieve HIV-1 plasma viral load below 1 copy/ml.

  Authors: Stéphanie Haïm-Boukobza, Laurence Morand-Joubert, Philippe Flandre, Nadia Valin, Slim Fourati, Sophie Sayon, Marc Lavignon, Anne Simon, Pierre-Marie Girard, Christine Katlama, Vincent Calvez, Anne-Geneviève Marcelin

  AIDS (London, England). 01/2011; 25(3):341-4.

  To compare the level of HIV-1 residual viremia, defined by a viral load below 50 copies/ml in patients receiving a tenofovir/emtricitabine and nevirapine (NVP) or efavirenz (EFV)-containingTo compare the level of HIV-1 residual viremia, defined by a viral load below 50 copies/ml in patients receiving a tenofovir/emtricitabine and nevirapine (NVP) or efavirenz (EFV)-containing regimen. One hundred and sixty-five HIV-1-infected patients were retrospectively included since they achieved virological suppression (viral load <50 copies/ml) for at least 6 months with a tenofovir/emtricitabine and non-nucleoside reverse transcriptase inhibitor-containing regimen (NVP, n = 75 and EFV, n = 90). Residual plasma viremia was measured using an ultrasensitive assay with a limit of quantification of 1 copy/ml. A Fisher's exact test was used to compare the percentage of patients with HIV-1 RNA below 1 copy/ml between the two treatment groups. Logistic regression was used to search for factors associated with a viral load below 1 copy/ml among the different patient characteristics. Patients in the NVP group had more frequently a viral load below 1 copy/ml than patients in the EFV group (81.3 vs. 55.6%, P < 0.001). In multivariate analysis, only NVP vs EFV (P = 0.005) and duration of viral suppression under antiretroviral treatment (P = 0.005) were independently associated with viral load below 1 copy/ml. It is well known that NVP has a good penetration in anatomic compartments that could explain a deep control of virus replication in some compartments and consequently decrease the residual level of viral load. The clinical relevance of having a viral load below 1 copy/ml has now to be studied for example on systemic inflammatory or immune activation markers.

• Positive impact of HIV-1 gag cleavage site mutations on the virological response to darunavir boosted with ritonavir.

  Authors: Lucile Larrouy, Sidonie Lambert-Niclot, Charlotte Charpentier, Slim Fourati, Benoit Visseaux, Cathia Soulié, Marc Wirden, Christine Katlama, Patrick Yeni, Françoise Brun-Vézinet, Vincent Calvez, Anne-Geneviève Marcelin, Diane Descamps

  Antimicrobial agents and chemotherapy. 01/2011; 55(4):1754-7.

  We assessed the roles of baseline gag and gag-pol cleavage site mutations (CSM) on the virological outcome of a darunavir-based regimen in highly antiretroviral-experienced patients. We showed theWe assessed the roles of baseline gag and gag-pol cleavage site mutations (CSM) on the virological outcome of a darunavir-based regimen in highly antiretroviral-experienced patients. We showed the association, in multivariate analysis, between the A431V gag CSM and the virological response, defined as a reduction in plasma HIV-1 RNA to <50 copies/ml at month 3 (P = 0.028). Our results suggest that a specific gag CSM might have a role on protease inhibitor susceptibility in an inhibitor-specific manner.

• High prevalence of antiretroviral drug resistance among HIV-1-untreated patients in Guinea-Conakry and in Niger.

  Authors: Charlotte Charpentier, Pantxika Bellecave, Mohamed Cisse, Saidou Mamadou, Mandiou Diakite, Gilles Peytavin, Stéphanie Tchiombiano, Pierre Teisseire, Louis Pizarro, Alexandre Storto, Françoise Brun-Vézinet, Christine Katlama, Vincent Calvez, Anne-Geneviève Marcelin, Bernard Masquelier, Diane Descamps

  Antiviral therapy. 01/2011; 16(3):429-33.

  The aim of the study was to assess the prevalence of antiretroviral drug resistance mutations in HIV-1 from recently diagnosed and untreated patients living in Conakry, Guinea-Conakry and in Niamey,The aim of the study was to assess the prevalence of antiretroviral drug resistance mutations in HIV-1 from recently diagnosed and untreated patients living in Conakry, Guinea-Conakry and in Niamey, Niger. The study was performed in two countries of Western Africa - Guinea-Conakry and Niger - using the same survey method in both sites. All newly HIV-1 diagnosed patients, naive of antiretroviral drugs, were consecutively included during September 2009 in each of the two sites. Protease and reverse transcriptase sequencing was performed using the ANRS procedures. Drug resistance mutations were identified according to the 2009 update surveillance drug resistance mutations. In Conakry, 99 patients were included, most of whom (89%) were infected with CRF02_AG recombinant virus. Resistance analysis among the 93 samples showed that ≥1 drug resistance mutation was observed in 8 samples, leading to a prevalence of primary resistance of 8.6% (95% CI 2.91-14.29%). In Niamey, 96 patients were included; a high diversity in HIV-1 subtypes was observed with 47 (51%) patients infected with CRF02_AG. Resistance analysis performed among the 92 samples with successful genotypic resistance test showed that ≥1 drug resistance mutation was observed in 6 samples, leading to a prevalence of primary resistance of 6.5% (95% CI 1.50-11.50%). We reported the first antiretroviral drug resistance survey studies in antiretroviral-naive patients living in Guinea-Conakry and in Niger. The prevalence of resistance was between 6% and 9% in both sites, which is higher than most of the other countries from Western Africa region.

• Low frequency of intermittent HIV-1 semen excretion in patients treated with darunavir-ritonavir at 600/100 milligrams twice a day plus two nucleoside reverse transcriptase inhibitors or monotherapy.

  Authors: Sidonie Lambert-Niclot, Gilles Peytavin, Claudine Duvivier, Catherine Poirot, Michèle Algarte-Genin, Sophie Pakianather, Jean-Luc Meynard, Marc-Antoine Valantin, Jean-Michel Molina, Philippe Flandre, Christine Katlama, Vincent Calvez, Anne-Geneviève Marcelin

  Antimicrobial agents and chemotherapy. 11/2010; 54(11):4910-3.

  HIV-1 RNA level and darunavir concentration in the genital tract were measured in 45 men receiving darunavir-ritonavir mono- or tritherapy. At week 48, a low frequency (3/45) of HIV-1 RNA sheddingHIV-1 RNA level and darunavir concentration in the genital tract were measured in 45 men receiving darunavir-ritonavir mono- or tritherapy. At week 48, a low frequency (3/45) of HIV-1 RNA shedding was observed in patients (1 on monotherapy and 2 on triple therapy), although they had undetectable HIV-1 RNA in plasma. The median darunavir seminal plasma concentration was close to the blood plasma free fraction, demonstrating a good penetration of darunavir into the male genital tract.

• 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.

• Increasing prevalence of transmitted drug resistance mutations and non-B subtype circulation in antiretroviral-naive chronically HIV-infected patients from 2001 to 2006/2007 in France.

  Authors: Diane Descamps, Marie-Laure Chaix, Brigitte Montes, Sophie Pakianather, Charlotte Charpentier, Alexandre Storto, Francis Barin, Georges Dos Santos, Anne Krivine, Constance Delaugerre [......] Laurence Morand-Joubert, Coralie Pallier, Jean-Christophe Plantier, Catherine Tamalet, Jacqueline Cottalorda, Delphine Desbois, Vincent Calvez, Françoise Brun-Vezinet, Bernard Masquelier, Dominique Costagliola

  The Journal of antimicrobial chemotherapy. 10/2010; 65(12):2620-7.

  To estimate the prevalence of transmitted drug resistance mutations and non-B subtype circulation in antiretroviral-naive chronically HIV-1-infected patients in France. Resistance mutations wereTo estimate the prevalence of transmitted drug resistance mutations and non-B subtype circulation in antiretroviral-naive chronically HIV-1-infected patients in France. Resistance mutations were sought in samples from 530 newly diagnosed HIV-1-infected patients from October 2006 to March 2007. Protease and reverse transcriptase mutations were identified from the 2007 Stanford Resistance Surveillance list. Reverse transcriptase and protease resistance mutations were determined in 466 patients with duration of seropositivity <5 years. 42% of patients were infected with non-B subtype strains (CRF02 18.3%). The overall prevalence of viruses with protease or reverse transcriptase mutations was 10.6% (95% confidence interval 6.7-16.3). The prevalence of protease inhibitor, nucleoside reverse transcriptase inhibitor and non-nucleoside reverse transcriptase inhibitor resistance-associated mutations was 4.7%, 5.8% and 2.8%, respectively. Frequency of resistance was not different in patients infected with B (9.5%) and non-B (CRF02 7.8% and other 11.2%) subtypes. Baseline characteristics such as gender, age, transmission group, country of transmission, disease stage, CD4 counts and viral load were not associated with the prevalence of transmitted drug resistance. In France in 2006/2007, the prevalence of transmitted drug-resistant variants was 10.6%. Prevalence of transmitted drug resistance was comparable in B and non-B subtypes. Prevalence of non-B subtypes is still rising.

• Partially active HIV-1 Vif alleles facilitate viral escape from specific antiretrovirals.

  Authors: Slim Fourati, Isabelle Malet, Mawuena Binka, Stephanie Boukobza, Marc Wirden, Sophie Sayon, Anne Simon, Christine Katlama, Viviana Simon, Vincent Calvez, Anne-Geneviève Marcelin

  AIDS (London, England). 09/2010; 24(15):2313-21.

  The HIV-1 Vif protein counteracts the antiviral activity of the cytidine deaminases APOBEC3G and APOBEC3F. Natural variation in Vif may result in reduced efficacy against APOBEC3 proteins and inThe HIV-1 Vif protein counteracts the antiviral activity of the cytidine deaminases APOBEC3G and APOBEC3F. Natural variation in Vif may result in reduced efficacy against APOBEC3 proteins and in increased HIV-1 diversity. We speculated that this mechanism could facilitate viral escape from certain antiretroviral drugs. We analyzed the protease, reverse transcriptase and Vif sequences of viruses from plasma obtained from 92 HIV-1-infected individuals failing antiretroviral treatment and 65 antiretroviral-naive patients. Mutation K22H in Vif was more frequent in patients failing to antiretroviral compared to antiretroviral-naive patients. In-vitro experiments showed that mutant K22H failed to completely neutralize APOBEC3G. Upon infection of MT-2 cells, most of the K22H proviral clones encoded increased numbers of G-to-A mutations. Among these mutations, the lamivudine drug-resistance-associated mutation M184I in reverse transcriptase was detected in 25% of clones in the absence of any lamivudine exposure. In our population, among pretreated patients, 72% of K22H viruses versus 42% in WT K22 viruses harbored at least two drug-resistance-associated mutations in a GA/GG dinucleotide context. More specifically, K22H viruses harbored significantly more G16E and M36I in protease than in those isolated from pretreated patients harboring WT K22 viruses. This study provides evidence that patients experiencing virological failure frequently harbor Vif point mutants (i.e. K22H). Such Vif alleles lose their ability to counteract APOBEC3 proteins, leading to an increase of G-to-A viral mutations that can facilitate the emergence of some antiretroviral resistance mutations.