Christine Rouzioux

Publications (199)1040.5 Total impact

• Article: Immunovirologic Control 24 Months After Interruption of Antiretroviral Therapy Initiated Close to HIV Seroconversion.

  Laurent Hocqueloux, Asier Saez-Cirion, Christine Rouzioux
  JAMA internal medicine. 03/2013; 173(6):475-7.
• Article: Post-Treatment HIV-1 Controllers with a Long-Term Virological Remission after the Interruption of Early Initiated Antiretroviral Therapy ANRS VISCONTI Study.

  Asier Sáez-Cirión, Charline Bacchus, Laurent Hocqueloux, Véronique Avettand-Fenoel, Isabelle Girault, Camille Lecuroux, Valerie Potard, Pierre Versmisse, Adeline Melard, Thierry Prazuck, [......], Jean-Paul Viard, Faroudy Boufassa, Olivier Lambotte, Cécile Goujard, Laurence Meyer, Dominique Costagliola, Alain Venet, Gianfranco Pancino, Brigitte Autran, Christine Rouzioux
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  ABSTRACT: Combination antiretroviral therapy (cART) reduces HIV-associated morbidities and mortalities but cannot cure the infection. Given the difficulty of eradicating HIV-1, a functional cure for HIV-infected patients appears to be a more reachable short-term goal. We identified 14 HIV patients (post-treatment controllers [PTCs]) whose viremia remained controlled for several years after the interruption of prolonged cART initiated during the primary infection. Most PTCs lacked the protective HLA B alleles that are overrepresented in spontaneous HIV controllers (HICs); instead, they carried risk-associated HLA alleles that were largely absent among the HICs. Accordingly, the PTCs had poorer CD8+ T cell responses and more severe primary infections than the HICs did. Moreover, the incidence of viral control after the interruption of early antiretroviral therapy was higher among the PTCs than has been reported for spontaneous control. Off therapy, the PTCs were able to maintain and, in some cases, further reduce an extremely low viral reservoir. We found that long-lived HIV-infected CD4+ T cells contributed poorly to the total resting HIV reservoir in the PTCs because of a low rate of infection of naïve T cells and a skewed distribution of resting memory CD4+ T cell subsets. Our results show that early and prolonged cART may allow some individuals with a rather unfavorable background to achieve long-term infection control and may have important implications in the search for a functional HIV cure.
  PLoS Pathogens 03/2013; 9(3):e1003211. · 9.13 Impact Factor
• Article: Nevirapine versus efavirenz for patients co-infected with HIV and tuberculosis: a randomised non-inferiority trial.

  Maryline Bonnet, Nilesh Bhatt, Elisabeth Baudin, Carlota Silva, Christophe Michon, Anne-Marie Taburet, Laura Ciaffi, Agnès Sobry, Rui Bastos, Elizabete Nunes, Christine Rouzioux, Ilesh Jani, Alexandra Calmy
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  ABSTRACT: BACKGROUND: In countries with a high incidence of HIV and tuberculosis co-infection, nevirapine and efavirenz are widely used as antiretroviral therapy but both interact with antituberculosis drugs. We aimed to compare efficacy and safety of a nevirapine-based antiretroviral therapy (started at full dose) with an efavirenz-based regimen in co-infected patients. METHODS: We did a multicentre, open-label, randomised, non-inferiority trial at three health centres in Maputo, Mozambique. We enrolled adults (≥18 years) with tuberculosis and previously untreated HIV infection (CD4 cell counts <250 cells per μL) and alanine aminotransferase and total bilirubin concentrations of less than five times the upper limit of normal. 4-6 weeks after the start of tuberculosis treatment, we randomly allocated patients (1:1) with central randomisation, block sizes of two to six, and stratified by site and CD4 cell count to nevirapine (200 mg twice daily) or efavirenz (600 mg once daily), plus lamivudine and stavudine. The primary endpoint was virological suppression at 48 weeks (HIV-1 RNA <50 copies per mL) in all patients who received at least one dose of study drug (intention-to-treat population); death and loss to follow-up were recorded as treatment failure. The non-inferiority margin for the difference of efficacy was 10%. We assessed efficacy in intention-to-treat and per-protocol populations and safety in all patients who received study drug. This study is registered with ClinicalTrials.gov, number NCT00495326. FINDINGS: Between October, 2007, and March, 2010, we enrolled 285 patients into each group. 242 (85%) patients in the nevirapine group and 233 (82%) patients in the efavirenz group completed follow-up. In the intention-to-treat population, 184 patients (64·6%, 95% CI 58·7-70·1) allocated nevirapine achieved virological suppression at week 48, as did 199 patients (69·8%, 64·1-75·1) allocated efavirenz (one-sided 95% CI of the difference of efficacy 11·7%). In the per-protocol population, 170 (70·0%, 63·8-75·7) of 243 patients allocated nevirapine achieved virological suppression at week 48, as did 194 (78·9%, 73·2-83·8) of 246 patients allocated efavirenz (one-sided 95% CI 15·4%). The median CD4 cell count at randomisation was 89 cells per μL. 15 patients substituted nevirapine with efavirenz and six patients substituted efavirenz with nevirapine. 20 patients allocated nevirapine (7%) had grade 3-4 increase of alanine aminotransferase compared with 17 patients allocated efavirenz (6%). Three patients had severe rash after receipt of nevirapine (1%) but no patients did after receipt of efavirenz. 18 patients in the nevirapine group died, as did 17 patients in the efavirenz group. INTERPRETATION: Although non-inferiority of the nevirapine-regimen was not shown, nevirapine at full dose could be a safe, acceptable alternative for patients unable to tolerate efavirenz. FUNDING: French Research Agency for HIV/AIDS and hepatitis (ANRS).
  The Lancet Infectious Diseases 02/2013; · 17.39 Impact Factor
• Article: Long-term antiretroviral therapy initiated during primary HIV-1 infection is key to achieving both low HIV reservoirs and normal T cell counts.

  Laurent Hocqueloux, Véronique Avettand-Fènoël, Sophie Jacquot, Thierry Prazuck, Eric Legac, Adeline Mélard, Mohamadou Niang, Catherine Mille, Gwenaël Le Moal, Jean-Paul Viard, Christine Rouzioux
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  ABSTRACT: OBJECTIVES: To characterize viro-immunological outcomes following long-term combined antiretroviral therapy (cART) initiated during primary HIV infection (PHI) or chronic HIV infection (CHI) and to identify factors predictive of optimal viro-immunological responder (OVIR) status. METHODS: This was a prospective, single-centre cohort study of HIV-1-infected patients on effective cART. Total cell-associated HIV DNA levels and T cell counts before and during treatment were used to identify factors predictive of OVIR status {i.e. low HIV DNA level [<2.3 log(10) copies/10(6) peripheral blood mononuclear cells (PBMCs)], together with normalization of the absolute/relative CD4+ T cell counts and CD4+/CD8+ ratio}. RESULTS: A total of 307 patients were enrolled, of whom 35 started cART during PHI (<4 months post-infection) and 272 during CHI. HIV DNA decay was modelled with a non-linear mixed-effects model that showed two phases of HIV DNA decay, both of which were significantly more pronounced in the PHI group. At the end of follow-up, after a median of 4 years of viral suppression (<50 copies/mL), HIV DNA levels were lower in the PHI group than in the CHI group (median = 2.15 versus 2.84 log(10) copies/10(6) PBMCs; P< 0.0001). Immune reconstitution was more rapid and sustained in the PHI group (median = 883 versus 619 CD4+ cells/mm(3); 41% versus 31% CD4+; CD4+/CD8+ 1.31 versus 0.77; all P< 0.0001). Finally, OVIR status was obtained in 19/35 (54%) and 7/272 (3%) patients in the PHI and CHI groups (P< 0.0001), respectively. In a logistic regression analysis, cART initiation during PHI (OR = 16, 95% CI = 3.5-72.3) and HIV DNA level <3.3 log(10) before treatment (OR = 4.8, 95% CI = 1.2-19.3) were independently predictive of OVIR status. CONCLUSIONS: Initiating cART during PHI represents a major opportunity to reduce HIV reservoirs and achieve optimal immune reconstitution.
  Journal of Antimicrobial Chemotherapy 01/2013; · 5.07 Impact Factor
• Article: CD8 T-Cells from Most HIV-Infected Patients Lack Ex Vivo HIV-Suppressive Capacity during Acute and Early Infection.

  Camille Lécuroux, Isabelle Girault, Antoine Chéret, Pierre Versmisse, Georges Nembot, Laurence Meyer, Christine Rouzioux, Gianfranco Pancino, Alain Venet, Asier Sáez-Cirión
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  ABSTRACT: The strong CD8+ T-cell-mediated HIV-1-suppressive capacity found in a minority of HIV-infected patients in chronic infection is associated with spontaneous control of viremia. However, it is still unclear whether such capacities were also present earlier in the CD8+ T cells from non controller patients and then lost as a consequence of uncontrolled viral replication. We studied 50 patients with primary HIV-1-infection to determine whether strong CD8+ T-cell-mediated HIV suppression is more often observed at that time. Despite high frequencies of polyfunctional HIV-specific CD8+ T-cells and a strong CD4+ T-helper response, CD8+ T-cells from 48 patients lacked strong HIV-suppressive capacities ex vivo. This indicates that the superior HIV-suppressive capacity of CD8+ T-cells from HIV controllers is not a general characteristic of the HIV-specific CD8+ T cell response in primary HIV infection.
  PLoS ONE 01/2013; 8(3):e59767. · 4.09 Impact Factor
• Article: Increasing HIV-1 Non-B Subtype Primary Infections in Patients in France and Effect of HIV Subtypes on Virological and Immunological Responses to cART.

  Marie-Laure Chaix, Remonie Seng, Pierre Frange, Laurent Tran, Véronique Avettand-Fenoël, Jade Ghosn, Jacques Reynes, Yazdan Yazdanpanah, François Raffi, Cécile Goujard, Christine Rouzioux, Laurence Meyer
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  ABSTRACT: Background. To analyze the time trends of the viral subtype distributions according to gender, risk group, and geographical origin of the patients in 1128 primary HIV-1 infection (PHI), diagnosed in France (1996-2010). To study whether the viral diversity had an impact on the virological and immunological responses in patients initiating combined antiretroviral therapy (cART) soon after infection.Methods. The study population comprised PHI patients enrolled in the ANRS-PRIMO-cohort. Subtypes were determined by phylogenetic analysis of reverse transcriptase gene. Viral suppression (<400 copies/ml and <50 copies/ml) and CD4-T-cell counts increase were assessed for those who initiated cART at PHI diagnosis.Results. Non-B subtypes (285/1128, 25.3%) were present in all regions of France and all risk groups, and increased in frequency over time. Non-B strains were highly diverse and included six subtypes, ten CRFs and several URFs. Virological response in patients infected with a non-B virus was similar to that of patients with a subtype-B virus over the first 2 years of cART. Patients infected with either a CRF02_AG strain or another non-B virus had better immunological responses than those infected with a subtype-B.Conclusions. Over the last 15 years in France, viral diversity has increased in all risk groups. This is the first large study comparing the responses of patients treated since PHI and showing a similar virological and immunological response to cART between the two groups of patients (B and non-B). Our results are encouraging for countries where non-B strains predominate in view of the increasing availability of cART.
  Clinical Infectious Diseases 12/2012; · 9.15 Impact Factor
• Article: Does Pregnancy Affect the Early Response to cART?

  Antoine Rachas, Josiane Warszawski, Jérôme le Chenadec, Camille Legeai, Jean-Paul Teglas, Cécile Goujard, Christine Rouzioux, Laurent Mandelbrot, Roland Tubiana, Laurence Meyer
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  ABSTRACT: OBJECTIVE:: A part of women starting antiretroviral therapy during pregnancy fail to attain undetectable viral load (VL) by delivery. Here we studied whether pregnancy affects the early immunovirological response to cART, taking into account treatment duration and baseline characteristics. DESIGN:: ART-naive women initiating cART since 2004 and followed in 3 French ANRS multicenter HIV cohorts (EPF, PRIMO and COPANA). METHODS:: The early virological response (at 1, 3 and 6 months) and immunological increase after cART initiation were compared between women starting cART during (n = 708) and outside (n = 110) pregnancy. Relative risks were estimated in multivariate models adjusted for treatment duration, baseline VL and CD4, sociodemographic factors and chronic hepatitis B. CD4 increases were compared by using mixed models. RESULTS:: Only 63.8% of treated pregnant women attained a VL <50 copies/mL by delivery. Similarly to nonpregnant women, nearly 90% of pregnant women reached a VL <400 copies/mL at M3 (adjusted RR: 1.0 [95% Confidence Interval 0.7-1.4]), and nearly 100% at M6 following cART initiation (0.9 [0.4-1.9]). VL <50 copies/mL was attained by 61.5% of pregnant versus 67.9% of nonpregnant women at M3 (P = .26), and by 82.1% versus 87.0% at M6 (P = .48). CD4 recovery (both number and percentage) was similar in pregnant and nonpregnant women. Results were similar for the subset of women starting a boosted protease inhibitor-containing cART. CONCLUSIONS:: Pregnancy does not affect the virological response to cART below 400 copies/mL, or CD4 increase. The main reason for pregnant women not achieving VL <50 copies/mL at delivery appears to be a short duration of treatment.
  AIDS (London, England) 10/2012; · 4.91 Impact Factor
• Article: Prevalence and clinical impact of norovirus fecal shedding in children with inherited immune deficiencies.

  Pierre Frange, Fabien Touzot, Marianne Debré, Sébastien Héritier, Marianne Leruez-Ville, Guilhem Cros, Christine Rouzioux, Stéphane Blanche, Alain Fischer, Véronique Avettand-Fenoël
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  ABSTRACT: We report the first prospective study describing the prevalence and clinical consequences of norovirus infection in hospitalized children with primary immunodeficiencies. Fecal samples from 62 children were systematically screened for virus. Norovirus was the most frequent pathogen (11 of 24 positive samples) found in both combined and humoral immunocompromised children. Norovirus shedding was associated with gastrointestinal symptoms and concomitant viremia in 54.5% and 25% of cases, respectively. Norovirus excretion was prolonged: 57.1% of fecal samples were still positive after a median of 9.5-months follow-up. Further large longitudinal studies are needed to evaluate the clinical consequences of norovirus shedding in patients with primary immunodeficiencies.
  The Journal of Infectious Diseases 08/2012; 206(8):1269-74. · 6.41 Impact Factor
• Article: HIV-1 control after transient antiretroviral treatment initiated in primary infection: role of patient characteristics and effect of therapy.

  Cécile Goujard, Isabelle Girault, Christine Rouzioux, Camille Lécuroux, Christiane Deveau, Marie-Laure Chaix, Christine Jacomet, Amel Talamali, Jean-François Delfraissy, Alain Venet, Laurence Meyer, Martine Sinet
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  ABSTRACT: The occurrence of viral control after interruption of an antiretroviral treatment (ART) initiated during primary HIV-1 infection (PHI) is rare and the frequency and predictive factors of such a control are unknown. Within the French ANRS PRIMO Cohort, 164 patients interrupted ART initiated during PHI. We compared patients whose viral load (VL) remained undetectable (<50 copies/ml) or low (50-500 copies/ml) 1 year after ART interruption to those who evidenced a rapid viral rebound. After ART interruption, VL remained undetectable for a median time of 4.5 years in 14 patients ('post-ART controllers') and low in another 14 patients for a median time of 1.5 years. Post-ART controllers also maintained higher CD4(+) T-cell counts compared to other patients. Female gender, a high CD4(+) T-cell count and low VL during PHI, and a high CD4(+) T-cell count and low HIV DNA levels at interruption, were associated with post-ART HIV control. Treatment characteristics did not differ between controllers and non-controllers. Post-ART controllers had lower specific CD8(+) T-cell frequencies and CD8(+) T-cell activation on ART and after ART interruption than non-controllers. Few patients maintain very low VL after interruption of treatment initiated during PHI. Early patient characteristics were the main factors of viral control, although early initiation of ART and the effect of ART on reservoir might contribute to control.
  Antiviral therapy 08/2012; 17(6):1001-9. · 3.16 Impact Factor
• Article: Continuous versus intermittent treatment strategies during primary HIV-1 infection: the randomized ANRS INTERPRIM Trial.

  Cécile Goujard, Dominique Emilie, Caroline Roussillon, Véronique Godot, Christine Rouzioux, Alain Venet, Céline Colin, Gilles Pialoux, Pierre-Marie Girard, Valérie Boilet, Marie-Laure Chaix, Pierre Galanaud, Geneviève Chene
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  ABSTRACT: OBJECTIVES:: The ANRS-112 INTERPRIM trial assessed whether fixed-cycles of antiretroviral treatment interruption (ART-STI) combined or not with pegylated interferon alpha-2b (peg-IFN) could lower viral load and achieve a healthier immune system in patients diagnosed during primary HIV-1-infection (PHI). DESIGN AND METHODS:: Patients were randomized to receive either continuous ART (cART) during 72 weeks, or cART during 36 weeks followed by three ART-STIs, or the same ART-STIs associated with peg-IFN during the first 14 weeks and each interruption (ART-STI-IFN). Treatment was stopped at week 72. Final evaluation was based on plasma HIV-RNA level 6 months after the last treatment interruption. RESULTS:: Eighty-seven percent of patients achieved undetectable HIV-RNA at week 32, with no deleterious impact of sequential treatment interruptions (STIs). Viral rebounds during interruptions were lower in the ART-STI-IFN than in the ART-STI group and during the second and third interruptions compared with the first one. However, HIV-RNA levels, CD4 T-cell counts and CD4 T/CD8 T ratios were similar between groups after the 6-month interruption, with a persistent effect on CD4 T cells and total cell-associated HIV-DNA levels. Predictive factors of virological outcome were HIV-RNA and HIV-DNA levels at PHI and HIV-DNA levels at treatment interruption. HIV-specific responses did not differ between strategies and were not associated with outcome. Forty-eight percent of patients experienced treatment resumption during long-term follow-up without difference between groups. CONCLUSION:: When initiated during PHI, STIs associated or not with IFN did not result in a different outcome as compared to cART. All regimens showed a high response rate and a sustained immunological benefit after cessation.
  AIDS (London, England) 07/2012; 26(15):1895-1905. · 4.91 Impact Factor
• Article: CCR5 antagonists: a therapeutic option in HIV-1 perinatally infected children experiencing virologic failure?

  Pierre Frange, Nelly Briand, Florence Veber, Despina Moshous, Véronique Avettand-Fenoel, Christine Rouzioux, Stéphane Blanche, Marie-Laure Chaix
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  ABSTRACT: The risk of virologic failure and selection of resistant strains remains a challenge in HIV-1 perinatally infected children. HIV-1 coreceptor usage was determined in HAART-failing children followed in Necker Hospital (Paris, France) in order to estimate the proportion of these patients who may benefit from CCR5-antagonists therapy. HIV-1 coreceptor usage was determined with the SVM(Geno2pheno10%) algorithm in 51 children with virologic failure after a median treatment exposure of 7.8 years. CXCR4-tropic strains were found in 31.4% of the patients. CXCR4 usage was associated with high HIV-1 DNA (P=0.01), old age (P=0.02), long ART cumulative exposure (P=0.006), and previous exposure to high number of different drugs (P=0.03) and ART combinations (P=0.03) in univariate analysis. Selection of resistant viruses and current exposure to a darunavir-based HAART tended to be more frequent in the CXCR4 group compared with the children infected with CCR5-tropic strains (P=0.06). In multivariate analysis, CXCR4 usage was exclusively correlated with HIV-1 DNA (P=0.03), which accurately reflects the cumulative exposure to viral replication over the whole duration of HIV infection. Two-thirds of HAART-failing children could benefit from CCR5 antagonists-based strategies, even in case of triple-class virologic failure. Such therapy should be discussed more appropriately at early stages of infection, when CCR5-tropic strains are most frequently isolated. However, before considering such strategies, further studies are needed to evaluate the efficacy and the tolerability of CCR5 antagonists in this pediatric population.
  AIDS (London, England) 05/2012; 26(13):1673-7. · 4.91 Impact Factor
• Article: Premature delivery in HIV-infected women starting protease inhibitor therapy during pregnancy: role of the ritonavir boost?

  Jeanne Sibiude, Josiane Warszawski, Roland Tubiana, Catherine Dollfus, Albert Faye, Christine Rouzioux, Jean-Paul Teglas, Dieudonné Ekoukou, Stéphane Blanche, Laurent Mandelbrot
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  ABSTRACT: The association between combination antiretroviral (cARV) therapy use by human immunodeficiency virus (HIV)-infected women during pregnancy and risk of prematurity is still controversial. We explored this question, focusing on the initiation of ritonavir-boosted protease inhibitors (PIs) during pregnancy, which is now standard care. Trends in prematurity (<37 gestational weeks) were studied among all singleton pregnancies in the Agence Nationale de Recherche sur le SIDA (ANRS) French Perinatal Cohort from 1990 through 2009 (n = 13 271). In-depth analysis was conducted in a more detailed substudy of the cohort, among women starting PI-based ARV therapy during pregnancy (n = 1253). Multivariable analysis adjusted for immunovirological status and known risk factors for prematurity. Prematurity increased from 9.2% during 1990-1993 (no therapy) and 9.6% during 1994-1996 (mostly zidovudine monotherapy) to 12.4% during 1997-1999 (dual-nucleoside analog therapy) and 14.3% during 2005-2009 (routine cARV therapy; P < .01). Prematurity was associated with cARV therapy, compared with zidovudine monotherapy, with an adjusted odds ratio of 1.69 (95% confidence interval [CI], 1.38-2.07; P < .01) when accounting for maternal age, intravenous drug use, geographic origin, and CD4 cell count. During 2005-2009, the prematurity rate was higher with boosted than with nonboosted PI therapy started during pregnancy (14.4% vs 9.1% [P = .05]; adjusted hazard ratio, 2.03 [95% CI, 1.06-3.89; P = .03] in multivariate analysis). The difference concerned mainly induced preterm delivery for maternal or fetal indications (5.6% vs 1.6%; P = .02), The prematurity rate among HIV-infected pregnant women was twice that in the general population in France; this was not entirely explained by sociodemographic characteristics. Prematurity was independently associated with cARV therapy and, particularly, with the initiation of ritonavir-boosted PI therapy during pregnancy.
  Clinical Infectious Diseases 05/2012; 54(9):1348-60. · 9.15 Impact Factor
• Source

  Available from: biomedcentral.com

  Article: Is access to care different for women from sub-Saharan Africa than for French women according to prevention of mother-to-child HIV transmission in France?

  Carine Jasseron, Josiane Warszawski, Stéphane Blanche, Christine Rouzioux, Jérôme Le Chenadec, Catherine Dollfus, Albert Faye, Karima Hamrene, Jean-Paul Teglas, Roland Tubiana, Laurent Mandelbrot, ANRS French Perinatal Cohort EPF
  Retrovirology 04/2012; 5:1-2. · 6.47 Impact Factor
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  Available from: preview.retrovirology.com

  Article: High prevalence of cytomegalovirus (CMV) infection in infants born to HIV infected mothers–ANRS French Perinatal Cohort (EPF)

  Gaelle Guibert, Marianne Leruez-Ville, Christine Rouzioux, Roland Tubiana, Laurent Mandelbrot, Stéphane Blanche, Jean-Paul Teglas, Yassine BenMebarek, Jérôme Le Chenadec, Josiane Warszawski, ANRS French Perinatal Cohort (EPF
  Retrovirology 04/2012; 5:1-2. · 6.47 Impact Factor
• Article: Immune responses driven by protective human leukocyte antigen alleles from long-term nonprogressors are associated with low HIV reservoir in central memory CD4 T cells.

  Benjamin Descours, Veronique Avettand-Fenoel, Catherine Blanc, Assia Samri, Adeline Mélard, Virginie Supervie, Ioannis Theodorou, Guislaine Carcelain, Christine Rouzioux, Brigitte Autran
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  ABSTRACT: The stable immune control of human immunodeficiency virus (HIV) in long-term nonprogressors (LTNPs) with protective human leukocyte antigen (HLA) alleles raises the question of whether and how these alleles influence the immune distribution of the HIV reservoirs. Cell-associated HIV-DNA levels were quantified in blood sorted resting CD4 T-cell subsets from 8 LTNPs with and 10 without HLA-B*27 or HLA-B*57 alleles (HLA-B27/B57). A remarkably lower infection level of central memory CD4 T cells (T(CM)) was an exclusive feature that distinguished the HLA-B27/B57 HIV reservoirs from the other ones. In LTNPs, T(CM) protection was correlated with preservation of T(CM) counts, which correlated positively with the magnitude of HIV Gag-specific CD8 T cells. In HLA-B27/B57 LTNPs, a lower activation level of their memory CD4 T cells was associated with lower amounts of cell HIV-DNA in each resting memory CD4 subset and were also associated with higher ratios of HIV Gag-specific CD8 T cells per infected resting CD4 T cell (effector/target [E/T]). As a result, HLA-B27/B57 E/T ratios were negatively correlated with the contribution of memory CD4 T-cell subsets to the total HIV reservoirs. The potent antiviral immunity governed by the protective HLA-B27/B57 alleles, by limiting T(CM) infection and pool exhaustion, are associated with a reduced T(CM) contribution to the HIV reservoir.
  Clinical Infectious Diseases 03/2012; 54(10):1495-503. · 9.15 Impact Factor
• Article: Relationships between HIV disease history and blood HIV-1 DNA load in perinatally infected adolescents and young adults: the ANRS-EP38-IMMIP study.

  Véronique Avettand-Fenoel, Stéphane Blanche, Jérôme Le Chenadec, Daniel Scott-Algara, Catherine Dollfus, Jean-Paul Viard, Naima Bouallag, Yassine Benmebarek, Yves Rivière, Josiane Warszawski, Christine Rouzioux, Florence Buseyne
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  ABSTRACT: Our aim was to study the impact of lifelong human immunodeficiency virus (HIV) disease history on the current immune and virological status of perinatally infected patients reaching adulthood. We evaluated blood cell-associated HIV DNA load as an indicator of cell-associated HIV reservoirs and an independent predictor of disease progression. The ANRS-EP38-IMMIP Study included 93 patients aged 15-24 years who were infected with HIV during the perinatal period. HIV DNA load was quantified by real-time polymerase chain reaction. Eighty-five percent of patients were receiving highly active antiretroviral therapy (HAART), and HIV RNA was undetectable in the plasma of 75% of these patients. The median HIV DNA load was 2.84 (interquartile range, 2.51-3.16) log(10) copies per 10(6) peripheral blood mononuclear cells. In patients with viral suppression, HIV DNA load was independently associated with cumulative HIV RNA viremia over the last 5 years. HIV DNA load was negatively correlated with CD4 cell count in patients with active replication but not in those with undetectable HIV RNA. In perinatally infected youths who are successfully treated, sustained viral suppression is associated with a low HIV DNA load. The absence of association between current HIV DNA load and CD4 cell counts suggests that the unique physiological characteristics of pediatric infection persist after adolescence. NCT01055873.
  The Journal of Infectious Diseases 03/2012; 205(10):1520-8. · 6.41 Impact Factor
• Article: Effect of intermittent interleukin-2 therapy on CD4+ T-cell counts following antiretroviral cessation in patients with HIV.

  Yves Lévy, Rodolphe Thiébaut, Marie-Lise Gougeon, Jean-Michel Molina, Laurence Weiss, Pierre-Marie Girard, Alain Venet, Philippe Morlat, Béatrice Poirier, Anne-Sophie Lascaux, Céline Boucherie, Daniel Sereni, Christine Rouzioux, Jean-Paul Viard, Cliff Lane, Jean-François Delfraissy, Irini Sereti, Geneviève Chêne
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  ABSTRACT: Interleukin (IL)-2 therapy impacts T-cell homeostasis. Whether IL-2 expanded CD4(+) T cells may persist following viral rebound has not been fully investigated. Patients with CD4(+) T cells 500/μl or more and HIV RNA less than 50 copies/ml were randomized to continue antiretroviral therapy (ART) either alone (n = 67) or combined with three IL-2 cycles (n = 81; 6 million units) twice daily for 5 days at weeks 0, 8, and 16 before stopping ART (week 24). Patients were followed up to 168 weeks. At week 24, median CD4(+) T-cell counts were 1198 and 703 cells/μl in the IL-2 and control groups, respectively (P < 0.001). At week 72, 27% (IL-2 group) and 45% (control group; P = 0.03) of patients were in failure (defined as no interruption of ART at week 24, CD4 drop below 350 cells/μl or ART resumption). After week 24, a biphasic decline (before and after week 32) of CD4 was noted -106 and -7 cells/μl per month in controls and -234 and -17 in IL-2 group (all P ≤ 0.0001). At week 96, IL-2-expanded CD4(+)CD25(+) T cells remained higher than in the control group (26 vs. 16%, P = 0.006). In IL-2-treated patients, CD4(+)CD25(+) T cells persisting despite viral replication allow a longer period of ART interruption.
  AIDS (London, England) 02/2012; 26(6):711-20. · 4.91 Impact Factor
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  Available from: dx.plos.org

  Article: Recent HIV-1 infection contributes to the viral diffusion over the French territory with a recent increasing frequency.

  Pierre Frange, Laurence Meyer, Christiane Deveau, Laurent Tran, Cecile Goujard, Jade Ghosn, Pierre-Marie Girard, Philippe Morlat, Christine Rouzioux, Marie-Laure Chaix
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  ABSTRACT: To analyse the contribution of primary human immunodeficiency virus type 1 (HIV-1) infection (PHI) to the French viral epidemic. HIV-1 pol sequences included 987 PHI from the French ANRS PRIMO cohort between 1999 and 2010 and were analysed using a population-based phylogenetic approach. Clinical features, risk factors, sexual behaviour and drug resistance for clustered and nonclustered transmission events were ascertained. Viruses from 125 (12.7%) of PHI cosegregated into 56 transmission chains, with increasing frequency during the last years (10.2% before 2006 versus 15.2% of clusters in 2006-2010, p = 0.02). The mean number of patients per cluster was 2.44. Compared to unique PHI, clusters involved more often men, infected through homosexual intercourse, of young age, with a high number of casual sexual partnerships and frequent previous HIV serological tests. Resistant strains were found in 16.0% and 11.1% of clusters and unique PHI, respectively (p = 0.11). Overall, 34% (n = 9) clusters included patients followed in French regions far apart, involving 13 clusters with at least one Parisian patient. PHIs are a significant source of onward transmission, especially in the MSM population. Recently infected people contribute to the spread of the viral epidemic throughout the French territory. Survey of transmitted drug resistance and behavioural characteristics of patients involved into clustered PHI may help to guide prevention and treatment interventions.
  PLoS ONE 01/2012; 7(2):e31695. · 4.09 Impact Factor
• Article: Seronegativation in early treated HIV-infected infants: frequency and potential implications on care and follow-up in a resource-limited country.

  Anfumbom K W Kfutwah, Mathurin Cyrille Tejiokem, Francis N Ateba, Jean Audrey Ndongo, Ida Calixte Penda, Paul Alain T Ngoupo, Patrice Tchendjou, Gisele Chewa, Pascal Boisier, Christine Rouzioux, Josiane Warszawski, Albert Faye
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  JAIDS Journal of Acquired Immune Deficiency Syndromes 10/2011; 58(2):e43-6. · 4.43 Impact Factor
• Article: Greater diversity of HIV DNA variants in the rectum compared to variants in the blood in patients without HAART.

  Véronique Avettand-Fenoel, Laurent Hocqueloux, Michaela Müller-Trutwin, Thierry Prazuck, Adeline Melard, Marie-Laure Chaix, Eric Agoute, Christophe Michau, Christine Rouzioux
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  ABSTRACT: The gut-associated lymphoid tissue represents the largest reservoir of HIV-1. Improving knowledge of this reservoir by studying the diversity of viral population is a key step towards understanding the pathogenesis and dynamics of HIV. Obtaining samples is difficult and little information is available on gut viral quasispecies during the course of infection in humans. The aim of this study was to characterize rectal viral strains and their diversity and to investigate the relationships between the rectal tissue reservoir and viral variants in the blood. Phylogenetic analyses were performed on the env sequences for rectal HIV DNA, blood HIV DNA, and HIV RNA clones, with maximum-likelihood and neighbor-joining methods on seven patients. Genetic diversity was assessed. Higher diversity of HIV DNA clones was noted in the rectum compared to blood in four out of five patients without HAART. Viral diversity was present in the rectum from time of the primary infection. Similar degrees of diversity were observed in the rectum and blood during HAART. Rectal and blood HIV variants were interspersed partially or totally in the seven patients. A certain number of rectal HIV DNA clones were clustered together in six patients. These results suggest that variants in the rectum were more heterogeneous than variants in the blood from patients without HAART, probably because the activated milieu of gut-associated lymphoid tissue may provide an improved environment for viral replication, and indicate exchange of viral populations between blood and rectal tissues, reflecting the dynamics of HIV during course of infection.
  Journal of Medical Virology 09/2011; 83(9):1499-507. · 2.82 Impact Factor