18 results on '"Lascoux-Combe, Caroline"'
Search Results
2. Effect of Viral Replication and Liver Fibrosis on All-Cause Mortality in Human Immunodeficiency Virus–Hepatitis B Virus–Coinfected Individuals: A Retrospective Analysis of a 15-Year Longitudinal Cohort.
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Dezanet, Lorenza N C, Kassime, Raisha, Miailhes, Patrick, Lascoux-Combe, Caroline, Chas, Julie, Maylin, Sarah, Gabassi, Audrey, Rougier, Hayette, Delaugerre, Constance, Lacombe, Karine, and Boyd, Anders
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HEPATITIS B ,CONFIDENCE intervals ,TENOFOVIR ,CIRRHOSIS of the liver ,RETROSPECTIVE studies ,ANTIRETROVIRAL agents ,HIV ,LONGITUDINAL method - Abstract
Background In individuals living with human immunodeficiency virus (HIV) and hepatitis B virus (HBV), widespread tenofovir (TDF)–containing antiretroviral therapy (ART) has led to substantial decreases in HBV-DNA and HIV-RNA detection. However, the links between viral replication, liver fibrosis, and mortality remain unclear. Methods A total of 300 individuals living with HIV-HBV and undergoing ART were prospectively followed. Virological and clinical data were obtained at baseline and every 6–12 months. We quantified the associations between HBV-DNA, HIV-RNA, and liver fibrosis with risk of all-cause mortality using a joint longitudinal survival model. Viral detection, viral loads, and time-averaged cumulative viral loads of HIV and HBV were modeled as 3 separate exposures. Results During a median of 10.5 years (interquartile range, 4.0–14.6), the proportion undergoing TDF-containing ART (baseline = 18.7%, end of follow-up = 79.1%) and with undetectable HBV-DNA (baseline = 36.7%, end of follow-up = 94.8%) substantially increased. 42 participants died (incidence rate = 1.30/100 person-years, 95% confidence interval [CI] =.96–1.76). The leading causes of death were non-AIDS/non–liver-related malignancies (28.6%), followed by liver-related (16.7%), AIDS-related (16.7%), and other (16.7%). All-cause mortality was associated with HBV-DNA viral load (adjusted hazards ratio [aHR] per log
10 IU/mL = 1.41, 95% CI = 1.04–1.93, P = .03) or time-averaged cumulative HBV-DNA (aHR per log10 copy-years = 1.37, 95% CI = 1.03–1.83, P = .03), but not undetectable HBV-DNA. Advanced liver fibrosis at baseline was also associated with increased mortality rates (aHR = 2.35, 95% CI = 1.16–4.76, P = .02). No significant association between HIV-RNA replication and mortality was observed. Conclusions Concurrent and historical HBV replication and liver fibrosis are important drivers of all-cause mortality in largely TDF-treated individuals living with HIV-HBV, despite one-fifth of deaths being liver-related. HBV-DNA and liver fibrosis remain important prognostic indicators for this patient population. [ABSTRACT FROM AUTHOR]- Published
- 2022
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3. HIV-1 RNA Kinetics in Blood Plasma and in Seminal Plasma of Men Starting a Dolutegravir-Based Triple-Combination Regimen at the Time of Primary HIV-1 Infection.
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Ghosn, Jade, Assoumou, Lambert, Lascoux-Combe, Caroline, Peytavin, Gilles, Amat, Karine, Gabassi, Audrey, Le, Minh P, Nzalakanda, Robert, Valin, Nadia, Landman, Roland, Chaix, Marie-Laure, and Delaugerre, Constance
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BLOOD plasma ,INFECTION ,HIV ,HIV infections ,RNA ,PYRIDINE ,ANTI-HIV agents ,RESEARCH ,SEMEN ,HETEROCYCLIC compounds ,VIRAL load ,RESEARCH methodology ,EVALUATION research ,DYNAMICS ,COMPARATIVE studies - Abstract
We compared the proportion of participants achieving first undetectable HIV-1 RNA (VL) in seminal plasma (SP) and blood plasma (BP) in 19 men starting dolutegravir-based regimen at primary HIV infection. At baseline, median VL was 6.5 (interquartile range [IQR], 5.6-7.9) and 4.5 (IQR, 3.5-5.0) log10 copies/mL in BP and SP, respectively. Between baseline and week 48, significantly higher proportion of participants achieved first VL below limit of quantification in SP (93.0%) than in BP (84.2%; P = .008). Time to first undetectable VL was 8 weeks in SP (95% confidence interval [CI], 5.6-10.4) and 24 weeks in BP (95% CI, 14.1-33.9). [ABSTRACT FROM AUTHOR]
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- 2022
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4. Atherosclerotic Cardiovascular Events in Patients Infected With Human Immunodeficiency Virus and Hepatitis C Virus.
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Tan, Boun Kim, Chalouni, Mathieu, Ceron, Dominique Salmon, Cinaud, Alexandre, Esterle, Laure, Loko, Marc Arthur, Katlama, Christine, Poizot-Martin, Isabelle, Neau, Didier, Chas, Julie, Morlat, Philippe, Rosenthal, Eric, Lacombe, Karine, Naqvi, Alissa, Barange, Karl, Bouchaud, Olivier, Gervais, Anne, Lascoux-Combe, Caroline, Garipuy, Daniel, and Alric, Laurent
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ATHEROSCLEROSIS risk factors ,HIV infection complications ,STATINS (Cardiovascular agents) ,CARDIOVASCULAR diseases risk factors ,CONFIDENCE intervals ,VIRAL load ,HEPATITIS C ,DISEASE incidence ,ATHEROSCLEROSIS ,RISK assessment ,MIXED infections ,ALCOHOL drinking ,DESCRIPTIVE statistics ,HIGH density lipoproteins ,LONGITUDINAL method ,PROPORTIONAL hazards models ,CHOLESTEROL ,DISEASE complications - Abstract
Background An increased risk of cardiovascular disease (CVD) was reported in patients coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV), without identifying factors associated with atherosclerotic CVD (ASCVD) events. Methods HIV-HCV coinfected patients were enrolled in the Agence Nationale de Recherches sur le Sida et les hépatites virales (ANRS) CO13 HEPAVIH nationwide cohort. Primary outcome was total ASCVD events. Secondary outcomes were coronary and/or cerebral ASCVD events, and peripheral artery disease (PAD) ASCVD events. Incidences were estimated using the Aalen-Johansen method. Factors associated with ASCVD were identified using cause-specific Cox proportional hazards models. Results At baseline, median age of the study population (N = 1213) was 45.4 (interquartile range [IQR] 42.1−49.0) years and 70.3% were men. After a median follow-up of 5.1 (IQR 3.9−7.0) years, the incidence was 6.98 (95% confidence interval [CI], 5.19−9.38) per 1000 person-years for total ASCVD events, 4.01 (2.78−6.00) for coronary and/or cerebral events, and 3.17 (2.05−4.92) for PAD ASCVD events. Aging (hazard ratio [HR] 1.06; 95% CI, 1.01−1.12), prior CVD (HR 8.48; 95% CI, 3.14−22.91), high total cholesterol (HR 1.43; 95% CI, 1.11−1.83), high-density lipoprotein cholesterol (HR 0.22; 95% CI, 0.08−0.63), statin use (HR 3.31; 95% CI, 1.31−8.38), and high alcohol intake (HR 3.18; 95% CI, 1.35−7.52) were independently associated with total ASCVD events, whereas undetectable baseline viral load (HR 0.41, 95% CI, 0.18−0.96) was associated with coronary and/or cerebral events. Conclusions HIV-HCV coinfected patients experienced a high incidence of ASCVD events. Some traditional cardiovascular risk factors were the main determinants of ASCVD. Controlling cholesterol abnormalities and maintaining undetectable HIV RNA are essential to control cardiovascular risk. [ABSTRACT FROM AUTHOR]
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- 2021
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5. Transmission of S230R integrase drug resistance mutation affecting second-generation integrase inhibitors in a French primary HIV-1 infected man.
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Salmona, Maud, Lascoux-Combe, Caroline, Nere, Marie Laure, Rubenstein, Emma, Molina, Jean Michel, Delaugerre, Constance, and Chaix, Marie Laure
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INTEGRASE inhibitors , *DRUG resistance , *REVERSE transcriptase , *HIV , *GENETIC mutation - Abstract
This suggests that this patient acquired this virus from an HIV-1-infected partner experiencing virological failure with INSTI and with a transmission of a majority S230R variants and a minority Q148R variants. In France, regular surveillance studies in individuals at the time of HIV-1 primary infection allow monitoring of emergence of transmitted drug-resistance-associated mutations (TDRAMs), HIV genetic diversity shifts and global transmission patterns.[1],[2] Since 1999, the emergence of TDRAMs has remained stable, at between 10% and 12% of new infections.[2] In Europe, Miranda I et al i .[3] reported a TDRAM prevalence of around 10% between 2011 and 2019, with a majority of NRTI and NNRTI mutations. [Extracted from the article]
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- 2023
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6. Kinetics of Hepatitis B Core–Related Antigen and Anti–Hepatitis B Core Antibody and Their Association With Serological Response in Human Immunodeficiency Virus–Hepatitis B Coinfection.
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Dezanet, Lorenza N. C., Maylin, Sarah, Gabassi, Audrey, Rougier, Hayette, Miailhes, Patrick, Lascoux-Combe, Caroline, Chas, Julie, Girard, Pierre-Marie, Delaugerre, Constance, Lacombe, Karine, and Boyd, Anders
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BackgroundThe aim of the current study was to describe the kinetics of quantified hepatitis B core–related antigen (qHBcrAg) and quantified anti–hepatitis B core antibody (qAnti-HBc) during tenofovir (TDF) treatment and assess their ability to predict hepatitis B e antigen (HBeAg) seroclearance in patients coinfected with human immunodeficiency virus (HIV) and hepatitis B virus.MethodsSerum qHBcrAg, qAnti-HBc, and hepatitis B virus DNA were obtained at TDF initiation and every 6–12 months. The on-treatment kinetics of qHBcrAg (ΔqHBcrAg) and qAnti-HBc (ΔqAnti-HBc) were estimated using mixed-effect linear regression. Hazard ratios (HRs) assessing the association between markers and HBeAg seroclearance were calculated using proportional hazards regression, and the sensitivity (Se) and specificity (Sp) of marker levels in predicting HBeAg seroclearance were assessed using time-dependent receiving operating characteristic curves.ResultsDuring a median of 4.6 years, the cumulative incidences of hepatitis B surface antigen and HBeAg seroclearance were 3.2% (n = 5 of 158) and 27.4% (n = 26 of 95), respectively. ΔqHBcrAg was biphasic in HBeAg-positive patients (−0.051 and −0.011 log
10 U/mL/mo during ≤18 and >18 months, respectively) and monophasic in HBeAg-negative patients. ΔqAnti-HBc was monophasic regardless of HBeAg status. In HBeAg-positive patients, baseline qHBcrAg and qAnti-HBc levels were associated with HBeAg seroclearance (adjusted HR, 0.48/log10 U/mL [95% confidence interval, .33–.70] and unadjusted HR, 1.49/log10 Paul Ehrlich Institute units/mL [1.08–2.07], respectively). Cutoffs with the highest accuracy in predicting HBeAg seroclearance at 36 months were qHBcrAg <6.5 log10 U/mL at month 24 (Se, 1; Sp, 0.58) and baseline qAnti-HBc ≥4.1 log10 Paul Ehrlich Institute units/mL (Se, 0.42; Sp, 0.81).ConclusionsIn coinfected patients undergoing TDF, qHBcrAg/qAnti-HBc could be of use in monitoring HBeAg seroclearance. [ABSTRACT FROM AUTHOR]- Published
- 2020
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7. Increased liver stiffness is associated with mortality in HIV/HCV coinfected subjects: The French nationwide ANRS CO13 HEPAVIH cohort study.
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Shili-Masmoudi, Sarah, Sogni, Philippe, de Ledinghen, Victor, Esterle, Laure, Valantin, Marc-Antoine, Poizot-Martin, Isabelle, Simon, Anne, Rosenthal, Eric, Lacombe, Karine, Pialoux, Gilles, Bouchaud, Olivier, Gervais-Hasenknoff, Anne, Goujard, Cécile, Piroth, Lionel, Zucman, David, Dominguez, Stéphanie, Raffi, François, Alric, Laurent, Bani-Sadr, Firouzé, and Lascoux-Combe, Caroline
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HIV infections ,HEPATITIS C virus ,LIVER ,MIXED infections ,MORTALITY - Abstract
Background: The association between liver stiffness measurements (LSM) and mortality has not been fully described. In particular the effect of LSM on all-cause mortality taking sustained virological response (SVR) into account needs further study. Methods: HIV/HCV participants in the French nation-wide, prospective, multicenter ANRS CO13 HEPAVIH cohort, with ≥1 LSM by FibroScan (FS) and a detectable HCV RNA when the first valid FS was performed were included. Cox proportional hazards models with delayed entry were performed to determine factors associated with all-cause mortality. LSM and SVR were considered as time dependent covariates. Results: 1,062 patients were included from 2005 to 2015 (69.8% men, median age 45.7 years (IQR 42.4–49.1)). 21.7% had baseline LSM >12.5 kPa. Median follow-up was 4.9 years (IQR 3.2–6.1). 727 (68.5%) were ever treated for HCV: 189 of them (26.0%) achieved SVR. 76 deaths were observed (26 liver-related, 10 HIV-related, 29 non-liver-non-HIV-related, 11 of unknown cause). At the age of 50, the mortality rate was 4.5% for patients with LSM ≤12.5 kPa and 10.8% for patients with LSM >12.5 kPa. LSM >12.5 kPa (adjusted Hazard Ratio [aHR] = 3.35 [2.06; 5.45], p<0.0001), history of HCV treatment (aHR = 0.53 [0.32; 0.90], p = 0.01) and smoking (past (aHR = 5.69 [1.56; 20.78]) and current (3.22 [0.93; 11.09]) versus never, p = 0.01) were associated with all-cause mortality independently of SVR, age, sex, alcohol use and metabolic disorders. Conclusion: Any LSM >12.5 kPa was strongly associated with all-cause mortality independently of SVR and other important covariates. Our results suggest that close follow-up of these patients should remain a priority even after achieving SVR. [ABSTRACT FROM AUTHOR]
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- 2019
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8. All-oral Direct-acting Antiviral Regimens in HIV/Hepatitis C Virus-coinfected Patients With Cirrhosis Are Efficient and Safe: Real-life Results From the Prospective ANRS CO13-HEPAVIH Cohort.
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Sogni, Philippe, Gilbert, Camille, Lacombe, Karine, Piroth, Lionel, Rosenthal, Eric, Miailhes, Patrick, Gervais, Anne, Esterle, Laure, Chas, Julie, Poizot-Martin, Isabelle, Dominguez, Stéphanie, Simon, Anne, Morlat, Philippe, Neau, Didier, Zucman, David, Bouchaud, Olivier, Lascoux-Combe, Caroline, Bani-Sadr, Firouzé, Alric, Laurent, and Goujard, Cécile
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HIV ,HEPATITIS C virus ,CIRRHOSIS of the liver ,ANTIVIRAL agents ,LOGISTIC regression analysis ,PATIENTS - Abstract
Background. Human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients with cirrhosis have long been considered to be difficult to treat, and real-life efficacy and tolerance data with all-oral direct-acting antiviral (DAA) combinations in these patients are scarce. Methods. Cirrhotic HIV/HCV-coinfected patients enrolled in the French National Agency for Research on AIDS and Viral Hepatitis (ANRS) CO13 HEPAVIH cohort initiating an all-oral DAA regimen were consecutively included. A negative HCV RNA result at 12 weeks of follow-up or thereafter was assumed as a sustained virologic response (SVR12). Adjusted exact logistic regression was used to study factors associated with treatment outcome. Results. We included 189 patients who initiated an all-oral DAA regimen with the following characteristics: median age 53.2 years; 74.6% male; Centers for Disease Control and Prevention classification A/B/C: 37%/31%/32%; Child-Pugh class A/B/C: 91%/ 8%/1%; 87% with HIV RNA <50 copies/mL; 99% on antiretrovirals; median CD4 count: 489 cells/μL; HCV treatment naive 29%; HCV genotype 1/2/3/4: 58%/4%/17%/21%. Sofosbuvir (SOF) + daclatasvir ± ribavirin (RBV) was used in 123 patients, SOF + RBV in 30, SOF + simeprevir in 11, and SOF + ledipasvir in 23. An SVR12 was reported in 93.1% of the patients (95% confidence interval, 88.5%-96.3%). In adjusted analyses, no difference was found between 12 or 24 weeks of treatment, in patients receiving RBV or not, and in treatment-naive vs experienced patients. Premature stop of DAA was reported for 8 patients. One patient died during treatment (unknown cause), and 12 other patients developed liver-related events. Conclusions. In this prospective real-life cohort, all-oral DAA regimens were well tolerated and associated with a high virologic efficacy in cirrhotic HIV/HCV-coinfected patients. This should not alleviate the surveillance for liver-related events in these patients. [ABSTRACT FROM AUTHOR]
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- 2016
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9. Dendritic Cells from HIV Controllers Have Low Susceptibility to HIV-1 Infection In Vitro but High Capacity to Capture HIV-1 Particles.
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Hamimi, Chiraz, David, Annie, Versmisse, Pierre, Weiss, Laurence, Bruel, Timothée, Zucman, David, Appay, Victor, Moris, Arnaud, Ungeheuer, Marie-Noëlle, Lascoux-Combe, Caroline, Barré-Sinoussi, Françoise, Muller-Trutwin, Michaela, Boufassa, Faroudy, Lambotte, Olivier, Pancino, Gianfranco, Sáez-Cirión, Asier, and null, null
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HIV prevention ,DENDRITIC cells ,DISEASE susceptibility ,VIRUS-like particles ,VIRAL replication ,CYTOTOXIC T cells - Abstract
HIV controllers (HICs), rare HIV-1 infected individuals able to control viral replication without antiretroviral therapy, are characterized by an efficient polyfunctional and cytolytic HIV-specific CD8+ T cell response. The mechanisms underlying the induction and maintenance of such response in many HICs despite controlled viremia are not clear. Dendritic cells play a crucial role in the generation and reactivation of T cell responses but scarce information is available on those cells in HICs. We found that monocyte derived dendritic cells (MDDCs) from HICs are less permissive to HIV-1 infection than cells from healthy donors. In contrast MDDCs from HICs are particularly efficient at capturing HIV-1 particles when compared to cells from healthy donors or HIV-1 patients with suppressed viral load on antiretroviral treatment. MDDCs from HICs expressed on their surface high levels of syndecan-3, DC-SIGN and MMR, which could cooperate to facilitate HIV-1 capture. The combination of low susceptibility to HIV-1 infection but enhanced capacity to capture particles might allow MDDCs from HICs to preserve their function from the deleterious effect of infection while facilitating induction of HIV-specific CD8+ T cells by cross-presentation in a context of low viremia. [ABSTRACT FROM AUTHOR]
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- 2016
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10. Drug resistance and tropism as markers of the dynamics of HIV-1 DNA quasispecies in blood cells of heavily pretreated patients who achieved sustained virological suppression.
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Gantner, Pierre, Morand-Joubert, Laurence, Sueur, Charlotte, Raffi, François, Fagard, Catherine, Lascoux-Combe, Caroline, Salmon, Dominique, Amiel, Corinne, Lambert-Niclot, Sidonie, Fofana, Djeneba Bocar, Viard, Jean-Paul, Fafi-Kremer, Samira, Rouzioux, Christine, Avettand-Fenoel, Véronique, and Ghosn, Jade
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HIV infections ,DRUG resistance in microorganisms ,VIRAL tropism ,BLOOD cells ,MEDICAL virology ,ANTI-HIV agents ,DNA ,HIV ,LONGITUDINAL method ,GENETIC mutation ,PROTEINS ,PROTEOLYTIC enzymes ,VIRAL physiology ,SEQUENCE analysis ,GENOTYPES ,PHYSIOLOGY - Abstract
Objectives: The objective of this study was to address the dynamics of archived resistant quasispecies in cell-associated HIV-1 DNA over time in heavily ART-experienced patients with currently suppressed plasma HIV-1 RNA.Methods: Longitudinal ultra-deep sequencing (UDS) analysis of reverse transcriptase, protease and V3 Env regions was performed on blood-cell-associated HIV-1 DNA samples. Drug-resistance-associated mutations (DRAMs) and tropism were interpreted using the ANRS and Geno2Pheno algorithms. We analysed frozen blood cells from patients enrolled in the INNOVE and ANRS 123 ETOILE studies who achieved sustained viral suppression after salvage optimized ART (SOT).Results: Samples were available at baseline and 6 and ≥12 months after SOT initiation in 10 patients. V3 loop sequences displayed wide intra-individual dynamics over time. Viral variants harbouring DRAMs exhibited three non-exclusive scenarios. First, when SOT exerted the same selective pressure as previous failing regimens, some viral quasispecies still harboured the same DRAMs at the same level as at the time of virological failure. Thus, as DRAMs were mostly associated with the same viral variant, variants with a complete resistance pattern remained archived. Second, some viral variants harbouring DRAMs were no longer detected over time when SOT consisted of new antiretroviral classes or had resistance profiles distinct from those of previous failing regimens. Third, variants with new DRAMs associated with SOT emerged in blood cells during follow-up despite sustained virological control.Conclusions: Using longitudinal UDS analysis and focusing on DRAMs and tropism as markers, we demonstrated that, despite sustained virological control, archived HIV-1 DNA quasispecies continued to evolve. [ABSTRACT FROM AUTHOR]- Published
- 2016
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11. Cannabis Use and Reduced Risk of Insulin Resistance in HIV-HCV Infected Patients: A Longitudinal Analysis (ANRS CO13 HEPAVIH).
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Carrieri, Maria Patrizia, Serfaty, Lawrence, Vilotitch, Antoine, Winnock, Maria, Poizot-Martin, Isabelle, Loko, Marc-Arthur, Lions, Caroline, Lascoux-Combe, Caroline, Roux, Perrine, Salmon-Ceron, Dominique, Spire, Bruno, and Dabis, Francois
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HEPATITIS C virus ,HIV-positive persons ,MIXED infections ,DIABETES risk factors ,INSULIN resistance risk factors ,HIV infection complications ,MEDICAL marijuana ,PATIENTS - Abstract
Background. Diabetes and insulin resistance (IR) is common in human immunodeficiency virus-hepatitis C virus (HIV-HCV)-coinfected patients, a population also concerned with elevated cannabis use. Cannabis has been associated with reduced IR risk in some population-based surveys. We determined whether cannabis use was consistently associated with reduced IR risk in HEPAVIH, a French nationwide cohort of HIV-HCV-coinfected patients. Methods. HEPAVIH medical and sociobehavioral data were collected (using annual self-administered questionnaires). We used 60 months of follow-up data for patients with at least 1 medical visit where IR (using homeostatic model assessment of insulin resistance [HOMA-IR]) and cannabis use were assessed. A mixed logistic regressionmodel was used to evaluate the association between IR risk (HOMA-IR > 2.77) and cannabis use (occasional, regular, daily). Results. Among the 703 patients included in the study (1287 visits), 323 (46%) had HOMA-IR > 2.77 for at least 1 follow-up visit and 319 (45%) reported cannabis use in the 6 months before the first available visit. Cannabis users (irrespective of frequency) were less likely to have HOMA-IR > 2.77 (odds ratio [95% confidence interval], 0.4 [.2-.5]) after adjustment for known correlates/confounders. Two sensitivity analyses with HOMA-IR values as a continuous variable and a cutoff value of 3.8 confirmed the association between reduced IR risk and cannabis use. Conclusions. Cannabis use is associated with a lower IR risk in HIV-HCV-coinfected patients. The benefits of cannabis-based pharmacotherapies for patients concerned with increased risk of IR and diabetes need to be evaluated in clinical research and practice. [ABSTRACT FROM AUTHOR]
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- 2015
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12. Is Clinical Practice Concordant with the Changes in Guidelines for Antiretroviral Therapy Initiation during Primary and Chronic HIV-1 Infection? The ANRS PRIMO and COPANA Cohorts.
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Krastinova, Evguenia, Seng, Remonie, Yeni, Patrick, Viard, Jean-Paul, Vittecoq, Daniel, Lascoux-Combe, Caroline, Fourn, Erwan, Pahlavan, Golriz, Delfraissy, Jean François, and Meyer, Laurence
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ANTIRETROVIRAL agents ,MEDICAL practice ,THERAPEUTICS ,HIV infections ,COHORT analysis ,PHYSICIANS ,HEALTH policy ,DIAGNOSIS of HIV infections - Abstract
Objective: Guidelines for initiating HIV treatment are regularly revised. We explored how physicians in France have applied these evolving guidelines for ART initiation over the last decade in two different situations: chronic (CHI) and primary HIV-1 infection (PHI), since specific recommendations for PHI are also provided in France. Methods: Data came from the ANRS PRIMO (1267 patients enrolled during PHI in 1996–2010) and COPANA (800 subjects enrolled at HIV diagnosis in 2004–2008) cohorts. We defined as guidelines-inconsistent during PHI and CHI, patients meeting criteria for ART initiation and not treated in the following month and during the next 6 months, respectively. Results: ART initiation during PHI dramatically decreased from 91% of patients in 1996–99 to 22% in 2007 and increased to 60% in 2010, following changes in recommendations. In 2007, however, after the CD4 count threshold was raised to 350 cells/mm
3 in 2006, only 55% of the patients with CD4≤350 were treated and 66% in 2008. During CHI, ART was more frequently initiated in patients who met the criteria at entry (96%) than during follow-up: 83% when recommendation to treat was 200 and 73% when it was 350 cells/mm3 . Independent risk factors for not being treated during CHI despite meeting the criteria were lower viral load, lower educational level, and poorer living conditions. Conclusion: HIV ART initiation guidelines are largely followed by practitioners in France. What can still be improved, however, is time to treat when CD4 cell counts reach the threshold to treat. Risk factors for lack of timely treatment highlight the need to understand better how patients’ living conditions and physicians’ perceptions influence the decision to initiate treatment. [ABSTRACT FROM AUTHOR]- Published
- 2013
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13. A Single HIV-1 Cluster and a Skewed Immune Homeostasis Drive the Early Spread of HIV among Resting CD4+ Cell Subsets within One Month Post-Infection
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Bacchus, Charline, Cheret, Antoine, Avettand-Fenoël, Véronique, Nembot, Georges, Mélard, Adeline, Blanc, Catherine, Lascoux-Combe, Caroline, Slama, Laurence, Allegre, Thierry, Allavena, Clotilde, Yazdanpanah, Yazdan, Duvivier, Claudine, Katlama, Christine, Goujard, Cécile, Seksik, Bao Chau Phung, Leplatois, Anne, Molina, Jean-Michel, Meyer, Laurence, Autran, Brigitte, and Rouzioux, Christine
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HIV ,HIV infections ,THERAPEUTICS ,IMMUNOLOGY ,HOMEOSTASIS ,T helper cells ,MONOCYTES ,NUCLEIC acids ,PHYLOGENY - Abstract
Optimizing therapeutic strategies for an HIV cure requires better understanding the characteristics of early HIV-1 spread among resting CD4+ cells within the first month of primary HIV-1 infection (PHI). We studied the immune distribution, diversity, and inducibility of total HIV-DNA among the following cell subsets: monocytes, peripheral blood activated and resting CD4 T cells, long-lived (naive [TN] and central-memory [TCM]) and short-lived (transitional-memory [TTM] and effector-memory cells [TEM]) resting CD4+T cells from 12 acutely-infected individuals recruited at a median 36 days from infection. Cells were sorted for total HIV-DNA quantification, phylogenetic analysis and inducibility, all studied in relation to activation status and cell signaling. One month post-infection, a single CCR5-restricted viral cluster was massively distributed in all resting CD4+ subsets from 88% subjects, while one subject showed a slight diversity. High levels of total HIV-DNA were measured among TN (median 3.4 log copies/million cells), although 10-fold less (p = 0.0005) than in equally infected TCM (4.5), TTM (4.7) and TEM (4.6) cells. CD3−CD4+ monocytes harbored a low viral burden (median 2.3 log copies/million cells), unlike equally infected resting and activated CD4+ T cells (4.5 log copies/million cells). The skewed repartition of resting CD4 subsets influenced their contribution to the pool of resting infected CD4+T cells, two thirds of which consisted of short-lived TTM and TEM subsets, whereas long-lived TN and TCM subsets contributed the balance. Each resting CD4 subset produced HIV in vitro after stimulation with anti-CD3/anti-CD28+IL-2 with kinetics and magnitude varying according to subset differentiation, while IL-7 preferentially induced virus production from long-lived resting TN cells. In conclusion, within a month of infection, a clonal HIV-1 cluster is massively distributed among resting CD4 T-cell subsets with a flexible inducibility, suggesting that subset activation and skewed immune homeostasis determine the conditions of viral dissemination and early establishment of the HIV reservoir. [ABSTRACT FROM AUTHOR]
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- 2013
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14. Correlates of poor perceived health among individuals living with HIV and HBV chronic infections: a longitudinal assessment.
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Marcellin, Fabienne, Lacombe, Karine, Fugon, Lionel, Molina, Jean-Michel, Bonnard, Philippe, Miailhes, Patrick, Lascoux-Combe, Caroline, Roux, Perrine, Carrieri, MariaP., Girard, Pierre-Marie, and Spire, Bruno
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ANALYSIS of variance ,CHRONIC diseases ,CONFIDENCE intervals ,EPIDEMIOLOGY ,HEALTH status indicators ,HEPATITIS B ,HIV infections ,LONGITUDINAL method ,MULTIVARIATE analysis ,SENSORY perception ,PROBABILITY theory ,COMORBIDITY ,DATA analysis ,BODY mass index - Abstract
Chronic hepatitis B virus (HBV) infection affects up to 14% of people living with HIV and AIDS (PLWHA) and is associated with a higher risk of non-AIDS death. While great advances have been made in the therapeutic management of co-infection with HIV and HBV, nothing is known about perceived health in people living with HIV and HBV. This study aimed at characterizing individuals with poor perceived overall health among 308 HIV-HBV co-infected individuals enrolled between May 2002 and May 2003 in a three-year French cohort. A binary score for perceived overall health (good vs. poor) was calculated from individuals' responses to the COOP-WONCA charts at cohort enrolment and at quarterly visits throughout the follow-up. Mixed models were used to explore factors associated with this score. At enrolment, 190 individuals (62%) reported poor overall health. In the multivariate analysis, low CD4 percentage, co-infection with hepatitis C or D viruses, HIV diagnosis before 1996 and HBeAg positivity were independently associated with poor perceived overall health. Poor perceived health concerns a considerable portion of individuals living with HIV and HBV. Individuals with wild-type HBV and multiple hepatitis infection require better clinical management. Further research is needed for hepatitis D virus infection, for which treatment options are currently very limited. [ABSTRACT FROM AUTHOR]
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- 2011
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15. Decay of ccc-DNA marks persistence of intrahepatic viral DNA synthesis under tenofovir in HIV-HBV co-infected patients.
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Boyd, Anders, Lacombe, Karine, Lavocat, Fabien, Maylin, Sarah, Miailhes, Patrick, Lascoux-Combe, Caroline, Delaugerre, Constance, Girard, Pierre-Marie, and Zoulim, Fabien
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CIRCULAR DNA , *DNA synthesis , *TENOFOVIR , *HEPATITIS B virus , *HIV , *HEPATITIS associated antigen , *LIVER cancer , *HIGHLY active antiretroviral therapy - Abstract
Background & Aims In the presence of highly-potent antivirals, persistence of hepatitis B virus (HBV) is most well-characterized by covalently-closed circular DNA (cccDNA) and total intrahepatic DNA (IH-DNA). We sought to determine how antiviral therapy could affect their levels during human immunodeficiency virus (HIV)-HBV co-infection. Methods Sixty co-infected patients from a well-defined cohort with ⩾1 liver biopsy were studied. HBV cccDNA and total IH-DNA were extracted from biopsies and quantified by real-time PCR. Factors associated with intrahepatic viral load were determined using mixed-effect linear regression and half-life viral kinetics during reconstructed follow-up using non-linear exponential decay models. Results At biopsy, 35 (58.3%) patients were hepatitis B “e” antigen (HBeAg)-positive and 33 (55.0%) had detectable plasma HBV-DNA (median = 4.58 log 10 IU/ml, IQR = 2.95–7.43). Overall, median cccDNA was −0.95 log 10 copies/cell (IQR = −1.70, −0.17) and total IH-DNA was 0.27 log 10 copies/cell (IQR = −0.39, 2.00). In multivariable analysis, significantly lower levels of cccDNA and total IH-DNA were observed in patients with HBeAg-negative serology, nadir CD4 + cell counts >250/mm 3 , and longer cumulative TDF-duration, but not lamivudine- or adefovir-duration. In post-hoc analysis using reconstructed TDF-duration (median 29.6 months, IQR = 15.0–36.1, n = 31), average half-life of cccDNA was estimated at 9.2 months (HBeAg-positive = 8.6, HBeAg-negative = 26.2) and total IH DNA at 5.8 months (HBeAg-positive = 1.3, HBeAg-negative = 13.6). Intrahepatic viral loads remained detectable for all patients, even with prolonged TDF-exposure. Conclusions In co-infection, TDF-use is associated with lower levels of HBV replication intermediates and cccDNA. Slow decay of intrahepatic viral loads underscores that TDF is unable to completely block intracellular viral DNA synthesis, which possibly accounts for continuous replenishment of the cccDNA pool. Lay summary Chronic hepatitis B virus (HBV) is a persistent infection, while the only real way of knowing the extent of this persistence is through measuring levels of virus in the liver. In this study, we examine levels of HBV in the liver among patients with both HBV and human immunodeficiency virus, or HIV, infection. It would appear that the currently available medication, namely “tenofovir”, works well to decrease virus levels in the liver, but it remains at low levels despite long periods of treatment. [ABSTRACT FROM AUTHOR]
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- 2016
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16. Role of a 48-week pegylated interferon therapy in hepatitis B e antigen positive HIV-co-infected patients on cART including tenofovir: EMVIPEG study.
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Miailhes, Patrick, Maynard-Muet, Marianne, Lebossé, Fanny, Carrat, Fabrice, Bouix, Cécile, Lascoux-Combe, Caroline, Sogni, Philippe, Rey, David, Barthe, Yoann, Pol, Stanislas, Cacoub, Patrice, Zoulim, Fabien, and Piroth, Lionel
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THERAPEUTIC use of interferons , *HEPATITIS B treatment , *HIV , *VIRUS diseases , *ANTIRETROVIRAL agents , *TENOFOVIR , *SEROCONVERSION , *PATIENTS , *THERAPEUTICS - Abstract
Background & Aims In hepatitis B e antigen (HBeAg) positive-HIV co-infected patients treated with combined antiretroviral therapy (cART), including tenofovir disoproxil fumarate (TDF), the rate of HBe seroconversion remains low. Whether adding pegylated interferon alfa (PegIFN) could increase the likelihood of HBeAg loss and HBe seroconversion has not been assessed. Methods A 48-week PegIFN therapy was added to HBeAg positive-HIV co-infected patients on TDF and emtricitabine, or lamivudine for at least 6 months. The primary endpoint was HBV sustained response: HBe seroconversion with undetectable HBV DNA levels 24 weeks after completing PegIFN therapy (W72). Results Fifty-one patients (49 men, median age 46 years, range: 32–65), were included. Median duration of HIV, HBV infections and TDF therapy was 10.3 (0.6–22), 9.8 (0.5–16), and 3.3 (0.5–6.8) years, respectively. Median baseline CD4 count was 506 (175–1316)/mm 3 . HIV viral load was <50 copies/ml in 49 (96%) patients. Nine (18%) patients stopped PegIFN prematurely. Ten (20%) patients experienced HBeAg loss at W72 and four (8%) patients had a HBV sustained response. No HBs seroconversion was observed. Only patients with more than 350 CD4/mm 3 at baseline achieved HBe loss. HBeAg level >10 PEI U/ml at W12 or a quantitative HBsAg decline <0.5 log IU/ml at W24 had 100% and 84% negative predictive values for response, respectively. Conclusions 48-week PegIFN additional therapy to cART including TDF did not significantly increase the HBe seroconversion rate, despite an HBeAg loss in 20% of the patients. HBe and HBs kinetics may nevertheless be of help in tailoring and optimising this strategy. [ABSTRACT FROM AUTHOR]
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- 2014
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17. HIV-1 group N: travelling beyond Cameroon.
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Delaugerre, Constance, De Oliveira, Fobienne, Lascoux-Combe, Caroline, Plantier, Jean-Christophe, and Simon, François
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HIV-positive persons , *HIV , *HIV infections , *PHYLOGENY - Abstract
The article presents a case study of a 57-year-old resident of France who has experienced fever, lymphadenopathy and genital ulceration. He had been reported to have a sexual contact with a Togolese partner, in which he acquired HIV primary infection. Several procedures are conducted including resistance genotyping using French guidelines, phylogenetic analysis, and full length genome sequencing.
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- 2011
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18. Performance of 11 biomarkers for liver fibrosis assessment in HIV/HBV co-infected patients
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Bottero, Julie, Lacombe, Karine, Guéchot, Jérôme, Serfaty, Lawrence, Miailhes, Patrick, Bonnard, Philippe, Wendum, Dominique, Molina, Jean-Michel, Lascoux-Combe, Caroline, and Girard, Pierre-Marie
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BIOMARKERS , *CYSTIC fibrosis , *HIV-positive persons , *LIVER biopsy , *PREDICTION theory , *HEPATITIS B , *CHRONIC diseases - Abstract
Background/Aims: The aim of this study was to compare the performance of 11 biochemical scores to estimate liver fibrosis in HIV/HBV co-infection. Methods: Performance was evaluated using the Receiver Operating Characteristics (ROC) curve method. The Kappa index was used to study overall agreement with liver biopsy results. Interpretative algorithms were established by optimizing sensitivity and specificity and the percentage of correctly classified patients. Results: One hundred and eight patients (F0–F1, n =47; F2, n =28; F3, n =17; F4, n =16) were considered for the evaluation of serum biomarker performance. The AUROCs of the Fibrotest®, Hepascore®, Fibrometer®, and Zeng’s scores ranged from 0.74 to 0.77 for significant fibrosis (⩾ F2), from 0.79 to 0.84 for advanced fibrosis (⩾ F3) and from 0.87 to 0.92 for cirrhosis (F4). Thresholds defined for each stage of fibrosis were close to those previously published for the Fibrotest® and Hepascore®. Strict concordance with biopsies correctly classified 50% of the patients. Conclusions: Fibrotest®, Fibrometer®, Hepascore®, and Zeng’s score were the most accurate non-invasive biochemical scores for liver fibrosis assessment in HIV/HBV co-infection. Global performance of biomarkers was not significantly improved by a decision tree combining the results of two biochemical scores. [Copyright &y& Elsevier]
- Published
- 2009
- Full Text
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