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Biomedical subjects

Christine Rouzioux

Publications and source records attributed to Christine Rouzioux.

At least 19 recordsLinked to original sources
PubMed2006

Sustained control of viremia following therapeutic immunization in chronically HIV-1-infected individuals.

OBJECTIVE: Viral rebounds inevitably follow interruption of antiretroviral treatment in HIV-1-infected individuals. The randomized ANRS 093 aimed at investigating whether a therapeutic immunization was effective in containing the long-term viral replication following discontinuation of antiretroviral drugs in patients. METHODS: Seventy HIV-1-infected patients effectively treated with antiretroviral drugs were randomized to continue treatment alone or in combination with four boosts of ALVAC 1433 and HIV-LIPO-6T vaccines followed by three cycles of subcutaneous interleukin-2. The impact of vaccination on viral replication was assessed by interrupting antiretroviral drugs first at week 40 and thereafter during follow-up until week 100. Antiretroviral drugs were re-initiated according to predefined criteria. RESULTS: The median cumulative time (days) off treatment was greater in the vaccine group (177) than in the control group (89) (P = 0.01). The proportion of time (mean, SE) without antivirals per-patient was 42.8% (5.1) and 26.5% (4.2) in the vaccine and control groups, respectively (P = 0.005). Viremia (median log10 copies/ml), 4 weeks following the first, second and third treatment interruption was higher in control patients (4.81, 4.44, 4.53) in comparison with vaccinated patients (4.48, 4.00, 3.66) (P = 0.42, 0.015 and 0.024, respectively). HIV-specific CD4 and CD8 T-cell responses elicited by the therapeutic immunization strongly correlated with the reduction of the time of antiviral therapy (P = 0.0027 and 0.016, respectively). CONCLUSION: Our findings provide evidence that therapeutic immunization significantly impacts on HIV-1 replication. This translated into a decrease of up to 40% in the duration of exposure to antiretroviral drugs over 15 months of patients' follow-up.

AIDS Vaccines↗
PubMed2006

Low risk of nevirapine resistance mutations in the prevention of mother-to-child transmission of HIV-1: Agence Nationale de Recherches sur le SIDA Ditrame Plus, Abidjan, Cote d'Ivoire.

The frequency of resistance mutations was estimated in the cohort of Agence Nationale de Recherches sur le SIDA Ditrame Plus, a study that evaluated the combination of short-course zidovudine (ZDV) plus lamivudine (3TC) and single-dose nevirapine (SD-NVP) followed by 3 days of postpartum ZDV plus 3TC for the prevention of mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1). The frequency with which resistance mutations were detected in mothers at week 4 postpartum was 1.14% (95% confidence interval [CI], 0.03%-6.17%) for NVP and 8.33% (95% CI, 3.66%-15.76%) for 3TC. In multivariate analysis, 3TC resistance was associated with a longer duration of ZDV plus 3TC prepartum prophylaxis (P=.009). This regimen, which is feasible in resource-limited settings, prevents most peripartum HIV-1 transmission and minimizes the development of NVP resistance.

Cote d'Ivoire↗
PubMed2005

Quantitation of HIV-1 RNA in breast milk by real time PCR.

HIV-1 RNA in breast milk is a strong predictor of HIV-1 transmission through breastfeeding. In the present report, breast milk samples from HIV-1 uninfected donors were spiked with dilution of quantified culture supernatant from HIV-1(NDK) infected PBMC. Two RNA extraction techniques based on silica extraction, Nuclisens (BioMerieux) and Triazol (Qiagen), two techniques based on guanidine thiocynanate/chloroforme extraction, TRIzol (Life Technologie) and Amplicor HIV-1 Monitor (Roche Diagnostic Systems), and one technique based on electrostatic adsorption on iron oxide micro beads (Promega) were compared. HIV-1 RNA was quantitated by real time PCR (LTR gene) and Amplicor HIV-1 Monitor. Combining magnetic micro beads extraction and real time PCR quantitation allowed to correctly quantify breast milk HIV-1 RNA, with a difference between the expected and measured HIV-1 RNA levels always lower than 0.3 log copies/ml. The same combination was confirmed on 25 breast milk samples from HIV-1 infected women collected in Kwazulu-Natal, South Africa, by comparing measurements with those obtained by the Amplicor HIV-1 Monitor (r(2)=0.88). Nucleic acid extraction by magnetic micro beads followed by real time PCR is a reliable, sensitive, rapid and simple procedure to quantify HIV-1 RNA in breast milk and allows for PCR inhibitors found frequently in these samples.

Female↗
PubMed2005

A virologic survey of patients admitted to a critical care unit for acute cardiorespiratory failure.

OBJECTIVE: To document the prevalence of respiratory virus infections in patients with chronic cardiac or pulmonary disorders admitted to a critical care unit for acute cardiorespiratory failure. DESIGN, SETTING, PATIENTS: The study took place in a critical care unit during two consecutive winters. All patients admitted to the unit for acute respiratory or cardiac failure were enrolled. A nasal swab was taken for polymerase chain reaction (PCR) detection of influenza virus, respiratory syncytial virus (RSV), metapneumovirus, rhinovirus, and coronavirus. RESULTS: One hundred twenty-two patients were enrolled. Their mean age was 69 years; 42% of the patients were female; the new simplified acute physiology score (SAPS II) score on admission was 35.6; 94% of patients had acute respiratory failure, 14% reported "influenza-like" illness before admission, and 11% of patients died in the unit. Twenty-one patients (17%) tested positive for a respiratory virus. The per-1,000 positivity rates were influenza virus 66, RSV 49, rhinovirus 33, metapneumovirus 16, and coronavirus 8. No link was found between virologic results and clinical outcome. A strong link was found between the rate of influenza virus positivity and the incidence of flu-like illness in the community (p=0.017). CONCLUSION: These results show that respiratory virus infection-particularly influenza virus infection during epidemic periods-is common among patients hospitalized for acute cardiorespiratory failure.

Aged↗
PubMed2005

Hepatitis C virus in the semen of men coinfected with HIV-1: prevalence and origin.

OBJECTIVE: To compare the prevalence of hepatitis C (HCV) RNA in semen from men infected with HCV and those coinfected with HIV-1/HCV and to study the origin of HCV shed in semen. DESIGN: Two prospective studies (HC EP09 and BINECO) included 120 HCV-positive men, 82 coinfected with HIV-1; all had positive HCV RNA detection in blood. METHODS: Paired blood and semen samples were collected for HCV RNA detection and quantification in seminal plasma and in blood serum; repeated semen samples were obtained for 45 men. HCV RNA was sought in spermatozoa and non-sperm cells. Phylogenetic analysis of the HVR-1 region of HCV compared the quasispecies in blood serum and seminal plasma of two men. RESULTS: HCV RNA was more frequently found in the semen of men coinfected with HIV-1 (37.8%) than in those with only HCV infection (18.4%) (P = 0.033). HCV RNA detection in semen was intermittent and was positive in at least one semen sample of 42.8% of HIV-1/HCV-coinfected men who provided repeated samples. Men with HCV-positive semen had significantly higher HCV load in blood than men with HCV-negative semen (P = 0.038). Phylogenetic comparison of HCV quasispecies in blood and in semen showed no evidence of HCV replication in genital leukocytes; however, a phenetic structure was observed between compartments (P < 0.001). CONCLUSIONS: HCV particles in semen originate from passive passage from blood, with preferential transfer of some variants. Nearly half of HIV-1/HCV-coinfected men may intermittently harbour HCV in their semen. Recommendations of protected sex for HIV-infected individuals should be reinforced.

Adult↗
PubMed2005

Structured treatment interruptions in primary HIV-1 infection: the ANRS 100 PRIMSTOP trial.

BACKGROUND: Whether structured treatment interruptions (STIs) can induce anti-HIV immune response and control HIV replication following discontinuation of highly active antiretroviral therapy (HAART) in patients with primary HIV infection is controversial. METHODS: In this multicenter, prospective trial, patients with early symptomatic primary HIV infection were given HAART continuously for 34 weeks. Afterward, patients with plasma viral load (PVL) <50 copies/mL entered the STI phase, which consisted of 3 consecutive periods of 2, 4, and 8 weeks off HAART, each separated by 12 weeks on HAART. HAART was permanently stopped at week 84 and patients were followed up for 24 weeks. The primary endpoint for definition of virologic success was a PVL <50 copies/mL during the 6 months following HAART discontinuation. RESULTS: Of the 29 patients enrolled, 26 completed the trial. Six months after HAART discontinuation, only 1 patient (3.8%, 95% CI: 0.1% to 19.6%) had PVL <50 copies/mL, whereas 6 of 26 (23.1%, 95% CI: 9.0% to 43.7%) had PVL <1000 copies/mL. Female gender was the only parameter significantly associated with a PVL <1000 copies/mL. No other parameter, either at baseline or before HAART discontinuation, predicted virologic success at week 108. A major protease inhibitor resistance mutation (L90M) developed in 3 patients. CONCLUSIONS: This trial failed to confirm that a significant proportion of patients with primary HIV infection can maintain suppression of viremia after a sequence of HAART/STIs followed by HAART discontinuation.

Adult↗
PubMed2005

HIV controllers: a homogeneous group of HIV-1-infected patients with spontaneous control of viral replication.

We identified a total 15 patients who have maintained undetectable plasma HIV RNA loads without antiretroviral treatment for >10 years from cohorts of 1300 and 1551 patients infected with human immunodeficiency virus (HIV). These 15 patients, whom we have referred to as "HIV controllers," are characterized by a low HIV DNA load in peripheral blood mononuclear cells and by a strong HIV-specific immune response.

Adult↗
PubMed2005

Causal pathways of the effects of age and the CCR5-Delta32, CCR2-64I, and SDF-1 3'A alleles on AIDS development.

OBJECTIVE: To investigate the causal pathways by which age and the CCR5-Delta32, CCR2-64I, and SDF-1 3'A alleles influence progression to AIDS. DESIGN: Analysis of follow-up data from 2 cohort studies among homosexual men (n=400), having >10 years of follow-up. METHODS: The effects of the 4 cofactors on the CD4 and HIV-1 RNA trajectories after seroconversion were modeled in a random-effects model. A proportional hazards model was used to investigate their effect on the risk of AIDS after correction for CD4 cell count and RNA level. This approach allows investigation as to whether they influence AIDS progression by affecting CD4 count and RNA level or by other pathways. RESULTS: Persons of younger age or having the CCR2-64I or SDF-1 3'A mutation have significantly higher CD4 levels. Persons with the CCR5-Delta32 deletion or CCR2-64I mutation have significantly lower RNA levels. After correction for both CD4 count and RNA level, only the SDF-1 3'A mutation significantly increases the AIDS risk. CONCLUSIONS: Age and the CCR5-Delta32 deletion and CCR2-64I mutation influence AIDS progression by affecting CD4 and HIV-1 RNA. The SDF-1 3'A allele increases the AIDS risk, but this effect is countered by its effect on CD4 and HIV-1 RNA level.

Acquired Immunodeficiency Syndrome↗
PubMed2005

Early levels of HIV-1 DNA in peripheral blood mononuclear cells are predictive of disease progression independently of HIV-1 RNA levels and CD4+ T cell counts.

BACKGROUND: The objective of this work was to assess the role of human immunodeficiency virus (HIV) reservoirs in the risk of disease progression, by studying the relationship between HIV DNA level in peripheral blood mononuclear cells (PBMCs) and progression toward acquired immunodeficiency syndrome (AIDS). METHODS: HIV-1 DNA levels in PBMCs were determined by quantitative polymerase chain reaction for 383 patients enrolled in the SEROCO Cohort Study who had experienced seroconversion and had been followed up for >8 years. We compared the predictive values of HIV DNA level, HIV RNA level, and CD4+ cell count. RESULTS: Between 6 and 24 months after seroconversion, HIV DNA level was a major predictor of progression to AIDS independently of HIV RNA level and CD4+ T cell count (adjusted relative risk [RR] for a 1-log(10) increase, 3.20 [95% confidence interval {CI}, 1.70-6.00]). HIV DNA level was also a major predictor of disease progression during the first 6 months after seroconversion (adjusted RR, 4.16 [95% CI, 1.70-10.21]), when HIV RNA level and CD4+ T cell count were less predictive. Thus, a combination of these 3 markers provides the best estimate of the risk of disease progression for each patient. CONCLUSIONS: Our results suggest that HIV DNA level could be a useful additional marker in clinical practice and could aid in helping to define the best time to initiate treatment for each patient.

Adult↗
PubMed2005

Combination of HIV-1-specific CD4 Th1 cell responses and IgG2 antibodies is the best predictor for persistence of long-term nonprogression.

BACKGROUND: Strong T cell and antibody responses to human immunodeficiency virus (HIV), low virus production, and some genetic traits have been individually associated with nonprogression of HIV infection, but the best correlate with protection against disease progression remains unknown. METHODS: We prospectively followed 66 untreated long-term nonprogressors and analyzed relationships between HIV-1-specific CD4 T helper (Th) 1 and CD8 T cell responses and HIV-1-specific antibodies, HIV-1 RNA and proviral DNA loads, host genes, and CD4 Th1 cell counts at entry into the study and 4 years later. RESULTS: HIV-1 p24-specific CD4 Th1 cell proliferation, interferon (IFN)- gamma production, and IFN- gamma -producing cell frequencies at entry significantly and negatively correlated with HIV-1 RNA and proviral DNA loads and were independent of CD4 Th1 cell counts and host genes. HIV-1 Gag-specific IFN- gamma -producing CD8 T cell frequencies correlated with HIV-1 proviral DNA loads but not with RNA loads. Only high frequencies of HIV-1 p24-specific CD4 Th1 cells combined with HIV-1 gp41-specific IgG2 antibodies significantly predicted persistence of high CD4 Th1 cell counts. CONCLUSION: HIV-1-specific CD4 Th1 responses combined with IgG2 antibodies and IFN- gamma -producing CD4 Th1 cells are better predictors of long-term nonprogression than are virus parameters, host genes, or HIV-1-specific CD4 Th1 or CD8 T cell proliferation.

Adult↗
PubMed2005

French national sentinel survey of antiretroviral drug resistance in patients with HIV-1 primary infection and in antiretroviral-naive chronically infected patients in 2001-2002.

OBJECTIVE: To survey the frequency of genotypic antiretroviral resistance and the spread of non-B subtypes in patients with primary HIV-1 infection (2001-2002) and in treatment-naive chronically HIV-1-infected patients (2001). METHODS: Plasma samples from 303 patients with acute HIV-1 infection (Primo study) and 363 treatment-naive patients with chronic HIV-1 infection (Odyssee study) were tested for genotypic resistance. Resistance mutations were identified from the International AIDS Society Resistance Testing-USA panel and resistant viruses were defined according to the French Agence Nationale de Recherches sur le SIDA (ANRS) resistance algorithm. RESULTS: In the Primo study, 14% of the patients had viruses with resistance mutations and 12% of patients had viruses with mutations conferring resistance to least 1 antiretroviral drug. Thirty patients had viruses with mutations to at least 1 antiretroviral drug in a single pharmacologic class. Six patients were infected by viruses resistant to 2 or 3 classes of drugs. In the Odyssee study, the prevalence of reverse transcript (RT) associated and major protease inhibitor-associated mutations was 6.1% (95% CI: 3.6-8.6). Six patients had viruses resistant to at least 1 antiretroviral drug and 3 patients had viruses resistant to 2 classes of antiretroviral drugs. Twenty-four percent of acutely infected patients harbored non-B subtype strains (19% in 1999-2000) and 33.2% of chronically infected patients (10% in 1998; P < 0.0001). CONCLUSION: In France, the frequency of HIV-1 resistance in untreated patients was not significantly higher in 2001-2002 than in previous surveys while the prevalence of non-B subtypes is increasing.

Acquired Immunodeficiency Syndrome↗
PubMed2005

Undetectable viremia without antiretroviral therapy in patients with HIV seroconversion: an uncommon phenomenon?

BACKGROUND: The objective of this study was to identify the frequency and characteristics of patients with human immunodeficiency virus (HIV) infection who had spontaneously achieved viremia below the detection limit of either 400 or 500 copies/mL (depending on the test used) and to describe the duration of undetectable viremia without antiretroviral therapy (ART). METHODS: In the French Agence Nationale de Recherches sur le SIDA SEROCO cohort, 426 patients with HIV seroconversion (i.e., seroconverters) enrolled between 1988 and 1995 had serial measurement of HIV RNA levels during follow-up (with a cutoff date of 31 December 2002). Factors that distinguished those patients who had spontaneously achieved undetectable viremia (> or =2 consecutive viral loads <400 or <500 copies/mL while not receiving ART) were identified by logistic regression. A Cox model was used to estimate the predictive value of factors related to the duration of undetectable viremia. RESULTS: Undetectable viremia had been spontaneously achieved in 36 of 426 seroconverters. Women (adjusted odds ratio [aOR], 2.44; 95% confidence interval [CI], 1.03-5.80) and subjects with baseline HIV RNA level < or =3.76 log10 copies/mL (aOR, 0.31; 95% CI, 0.11-0.82), baseline HIV DNA level < or =2.61 log10 copies/mL (aOR, 0.14; 95% CI, 0.04-0.44), and high baseline CD4+ cell count (aOR, 1.18 for each 100 cells/mm3; 95% CI, 1.03-1.35]) were more likely to have achieved undetectable viremia. The sustainability of this phenomenon (median duration, 11.9 months; range, 4.6-62.8 months) was associated with low baseline HIV DNA and RNA levels. CONCLUSIONS: Achieving undetectable viremia without ART was not rare, because 6.7% of seroconverters still had a viral load of <400 or <500 copies/mL 5 years after seroconversion. These data should be considered when assessing virologic outcome for patients who interrupt highly active ART initiated during primary infection.

Adolescent↗
PubMed2005

Immunological and virological efficacy of a therapeutic immunization combined with interleukin-2 in chronically HIV-1 infected patients.

OBJECTIVE: Several lines of evidence suggest that the immune system may control HIV-1 replication, but that it could fail in the long term. Strategies aimed to elicit specific immune responses may enable patients to contain virus replication. METHODS: HIV-1-infected patients were randomized to continue either their antiviral therapy alone (controls; n = 37) or with four boosts of vaccination combining ALVAC-HIV (vCP1433) and Lipo-6T vaccines (weeks 0, 4, 8, 12) followed by three cycles of subcutaneous interleukin-2 (weeks 16, 24, 32) (Vac-IL-2 group; n = 34). RESULTS: Of the Vac-IL-2 group, 15/32 (47%) exhibited a stable HIV p24 antigen-proliferative response compared with 8/33 (24%) controls (P = 0.049). After vaccination, 19/33 (58%) of the Vac-IL-2 group exhibited a multiepitopic HIV-1-specific CD4 cell proliferative response compared with 9/36 (25%) of controls (P = 0.006). The breadth and the magnitude of HIV-specific interferon-gamma-producing CD8 T cells improved in the Vac-IL-2 group. After stopping antiviral drugs, 24% of the Vac-IL-2 group lowered their viral set point compared with 5% of controls (P = 0.027). Logistic-regression analysis demonstrated that vaccine-elicited immunological responses were predictive of virological control (P = 0.046 and 0.014 for stable and multiepitopic CD4 T cell responses, respectively). CONCLUSION: This study provides proof of the concept that therapeutic immunization before antiviral drug cessation may contribute to the containment of HIV replication.

AIDS Vaccines↗
PubMed2005

Not all tetramer binding CD8+ T cells can produce cytokines and chemokines involved in the effector functions of virus-specific CD8+ T lymphocytes in HIV-1 infected children.

In the pediatric human immunodeficiency virus type-1 (HIV-1) infection, the presence of cytotoxic T lymphocytes (CTL) is associated with a slow progression to AIDS. The secretion of cytokines by CTLs may be critical in the control of viral infection. We used the combination of cell surface and intracellular staining to study the functionality of tetramer binding CD8+ T cells recognizing two HIV-1 immunodominant epitopes, in peripheral blood mononuclear cells from HIV-1-infected children. A fraction of tetramer positive CD8+ T cells produce cytokines (IFN-gamma, TNF-alpha) or chemokines (CCL4, CCL5) after ex vivo stimulation with the cognate peptide. There was a negative correlation between the plasma viral load and the percentage of CD8+ Tetramer Gag+ T cells secreting IFN-gamma. This is the first report in the context of pediatric HIV-1 infection showing that only a fraction of HIV-1-specific CD8+ T cells have the capacity to produce cytokines and chemokines implicated in their antiviral functions.

Adolescent↗
PubMed2005

Selection of a rare resistance profile in an HIV-1-infected patient exhibiting a failure to an antiretroviral regimen including tenofovir DF.

The human immunodeficiency virus type 1 (HIV-1) resistance profile, K65R, K70E and M184V, on reverse transcriptase gene was associated with the virologic rebound consecutively to the switch of lopinavir/r to tenofovir DF in a stable regimen with nucleoside backbone of abacavir, lamivudine and didanosine. The high selective pressure on the same resistance pathway was probably associated with the loss of antiviral potency, even in well-controlled patient.

Adenine↗
PubMed2005

A vaccinia-based elispot assay for detection of CD8+ T cells from HIV-1 infected children.

HIV-specific CD8+ T lymphocytes participate in the control of viral replication in infected patients. These responses are of low intensity in young infants and are decreased by antiretroviral therapy. In the present study, we report on a recombinant Vaccinia virus (rVV)-based Elispot assay for the detection of HIV-specific CD8+ T cells immediately after isolation of peripheral blood mononuclear cells (PBMC). The rVV-based assay was highly sensitive; 48 out of 50 children had a positive response against the rVV encoding HIV Env-Gag-Pol antigen. Interferon-gamma was produced by CD8+ T cells, and CD14+/15+ cells were the main cell subset presenting antigens expressed by rVV. We observed that the cell input per well had a critical influence on the sensitivity of the assay. Results from the ex vivo Elispot assay correlated poorly with those of the 51Cr release assay performed after expansion of PBMC in vitro; thus, both assays gave information on different subsets and/or functions of the HIV-specific T cell response.

Animals↗