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Background: Data on incidence of cytomegalovirus (CMV) seroconversion in HIV-infected (HIV(+)) subjects was sparse.Goal: To determine the incidence of CMV seroconversion in sexually active HIV(+) subjects and sexual factors associated with CMV seroconversion.Study Design: One hundred eighty four persons not infected by CMV at enrollment in a cohort of HIV(+) persons were studied. A case-control study within the cohort was conducted to determine the effect of sexual behavior in the 6 months prior to CMV seroconversion. Thirty seven cases of CMV seroconversion were compared with 136 controls.Results: The overall incidence of CMV seroconversion was 9.18 per 100 person-years (95% confidence interval (CI), 6.67-12.28) and was particularly high among homosexual men. After adjustment for age, socio-professional category, sexual orientation, and casual sex, the risk of CMV seroconversion was higher in subjects who never used condoms than in those who used them systematically (adjusted odds ratio (OR) 3.37;95% CI, 1.05-11.00).Conclusions: In addition to the need to protect their sexual partners from HIV infection, HIV(+) subjects free of CMV infection should use condoms to avoid CMV infection and its complications. [ABSTRACT FROM AUTHOR]

Background: Many people infected by human immunodeficiency virus (HIV) acquire severe cytomegalovirus (CMV) diseases. Factors associated with CMV seropositivity are poorly documented in sexually active HIV-infected men.Goal: To study CMV seroprevalence in HIV-infected men according to sexual behavior before the diagnosis of HIV seropositivity.Study Design: Cross-sectional study. CMV seroprevalence was studied at enrollment in a prospective cohort of homosexual and heterosexual men infected by HIV through sexual contact.Results: In the study population (n = 723), age, sexual preference, previous lifetime history of sexually transmitted diseases, and multiple sexual partners were independently related to CMV seropositivity. Furthermore, routine condom use during the 6 months before diagnosis of HIV seropositivity was significantly related to CMV seropositivity (adjusted odds ratio [OR]: 0.4, 95% confidence interval [CI]: 0.1-1.0), occasional condom use being of borderline significance [adjusted OR: 0.5, CI: 0.2-1.3].Conclusions: This study confirms the importance of sexual factors in the acquisition of CMV infection by HIV-infected men and suggests a protective effect of condom use. [ABSTRACT FROM AUTHOR]

Background: Real-world data studies usually consider biases related to measured confounders. We emulate a target trial implementing study design principles of randomized trials to observational studies; controlling biases related to selection, especially immortal time; and measured confounders., Methods: This comprehensive analysis emulating a randomized clinical trial compared overall survival in patients with HER2-negative metastatic breast cancer (MBC), receiving as first-line treatment, either paclitaxel alone or combined to bevacizumab. We used data from 5538 patients extracted from the Epidemiological Strategy and Medical Economics-MBC cohort to emulate a target trial using advanced statistical adjustment techniques including stabilized inverse-probability weighting and G-computation, dealing with missing data with multiple imputation, and performing a quantitative bias analysis for residual bias due to unmeasured confounders., Results: Emulation led to 3211 eligible patients, and overall survival estimates achieved with advanced statistical methods favored the combination therapy. Real-world effect sizes were close to that assessed in the existing E2100 randomized clinical trial (hazard ratio = 0.88, P = .16), but the increased sample size allowed to achieve a higher level of precision in real-world estimates (ie, reduced confidence intervals). Quantitative bias analysis confirmed the robustness of the results with respect to potential unmeasured confounding., Conclusion: Target trial emulation with advanced statistical adjustment techniques is a promising approach to investigate long-term impact of innovative therapies in the French Epidemiological Strategy and Medical Economics-MBC cohort while minimizing biases and provides opportunities for comparative efficacy through the synthetic control arms provided., Database Registration: clinicaltrials.gov Identifier NCT03275311., (© The Author(s) 2023. Published by Oxford University Press.)

Background: Overall survival (OS) is the gold standard endpoint to assess treatment efficacy in cancer clinical trials. In metastatic breast cancer (mBC), progression-free survival (PFS) is commonly used as an intermediate endpoint. Evidence remains scarce regarding the degree of association between PFS and OS. Our study aimed to describe the individual-level association between real-world PFS (rwPFS) and OS according to first-line treatment in female patients with mBC managed in real-world setting for each BC subtype (defined by status for both hormone-receptor [HR] expression and HER2 protein expression/gene amplification)., Methods: We extracted data from the ESME mBC database (NCT03275311) which gathers deidentified data from consecutive patients managed in 18 French Comprehensive Cancer Centers. Adult women diagnosed with mBC between 2008 and 2017 were included. Endpoints (PFS, OS) were described using the Kaplan-Meier method. Individual-level associations between rwPFS and OS were estimated using the Spearman's correlation coefficient. Analyses were conducted by tumor subtype., Results: 20,033 women were eligible. Median age was 60.0 years. Median follow-up duration was 62.3 months. Median rwPFS ranged from 6.0 months (95% CI 5.8-6.2) for HR-/HER2 - subtype to 13.3 months (36% CI 12.7-14.3) for HR + /HER2 + subtype. Correlation coefficients were highly variable across subtypes and first-line (L1) treatments. Among patients with HR - /HER2 - mBC, correlation coefficients ranged from 0.73 to 0.81, suggesting a strong rwPFS/OS association. For HR + /HER2 + mBC patients, the individual-level associations were weak to strong with coefficients ranging from 0.33 to 0.43 for monotherapy and from 0.67 to 0.78 for combined therapies., Conclusions: Our study provides comprehensive information on individual-level association between rwPFS and OS for L1 treatments in mBC women managed in real-life practice. Our results could be used as a basis for future research dedicated to surrogate endpoint candidates., (© 2023. The Author(s).)

Background: The efficacy and added benefit of platinum-based chemotherapy (PtCT) for metastatic breast cancer (MBC) remain unclear in patients with and without germline BRCA1 or BRCA2 mutations (gBRCA1/2m and gBRCA1/2wt, respectively)., Methods: We selected from the French national real-world multicentre ESME cohort (2008-2016) all patients with HER2-negative MBC with known gBRCA1/2 status at first-line chemotherapy initiation. Using multivariable Cox models, we compared the outcome (progression-free (PFS) and overall survival (OS)) of first-line PtCT and non-PtCT regimens based on the patients' gBRCA1/2 status and tumour subtype., Results: Patients who received PtCT had more aggressive tumour features. In the multivariable analysis, first-line PtCT was associated with better adjusted PFS and OS in gBRCA1/2m carriers (N = 300), compared with non-PtCT (HR 0.54, 95% CI 0.4-0.73, P < 0.001, and HR 0.70, 95% CI 0.49-0.99, P = 0.047, respectively). Conversely, outcomes were similar in gBRCA1/2wt patients (N = 922) treated with PtCT and non-PtCT, whatever the tumour subtype. Landmark analyses at months 3 and 6 post treatment initiation supported these results., Conclusions: In this pre-PARP inhibitor real-world cohort, PFS and OS were better after PtCT than non-PtCT in patients with gBRCA1/2m, but not in those with gBRCA1/2wt. These results emphasise the need of early gBRCA1/2 testing in patients with MBC., Clinical Trial Number: NCT03275311., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Purpose: Observational studies using routinely collected data are faced with a number of potential shortcomings that can bias their results. Many methods rely on controlling for measured and unmeasured confounders. In this work, we investigate the use of instrumental variables (IV) and quasi-trial analysis to control for unmeasured confounders in the context of a study based on the retrospective Epidemiological Strategy and Medical Economics (ESME) database, which compared overall survival (OS) with paclitaxel plus bevacizumab or paclitaxel alone as first-line treatment in patients with HER2-negative metastatic breast cancer (MBC)., Patients and Methods: Causal interpretations and estimates can be made from observation data using IV and quasi-trial analysis. Quasi-trial analysis has the same conceptual basis as IV, however, instead of using IV in the analysis, a "superficial" or "pseudo" randomized trial is used in a Cox model. For instance, in a multicenter trial, instead of using the treatment variable, quasi-trial analysis can consider the treatment preference in each center, which can be informative, and then comparisons of results between centers or clinicians can be informative., Results: In the original analysis, the OS adjusted for major factors was significantly longer with paclitaxel and bevacizumab than with paclitaxel alone. Using the center-treatment preference as an instrument yielded to concordant results. For the quasi-trial analysis, a Cox model was used, adjusted on all factors initially used. The results consolidate those obtained with a conventional multivariate Cox model., Conclusion: Unmeasured confounding is a major concern in observational studies, and IV or quasi-trial analysis can be helpful to complement analysis of studies of this nature., Competing Interests: DP received honoraria from Roche. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Purpose: Among metastatic breast cancer (MBC) patients, those with a triple-negative breast cancer phenotype (mTNBC) have the worst prognosis, but the benefit of chemotherapy beyond second line on outcome remains uncertain. The purpose of this study was to identify predictive factors of outcome after third- or fourth-line chemotherapy., Methods: The ESME-MBC database is a French prospective real-life cohort with homogeneous data collection, including patients who initiated first-line treatment for MBC (2008-2016) in 18 cancer centers. After selection of mTNBC cases, we searched for independent predictive factors (Cox proportional-hazards regression models) for overall survival (OS) on third- and fourth-line chemotherapy (OS3, OS4). We built prognostic nomograms based on the main prognostic factors identified., Results: Of the 22,266 MBC cases in the ESME cohort, 2903 were mTNBC, 1074 (37%) and 598 (20%) of which had received at least 3 or 4 lines of chemotherapy. PFS after first- and second-line chemotherapy (PFS1, PFS2) and number of metastatic sites ≥3 at baseline were identified by multivariate analysis as prognostic factors for both OS3 (HR = 0.76 95%CI[0.66-0.88], HR = 0.55 95%CI[0.46-0.65], HR = 1.36 95%CI[1.14-1.62], respectively), and OS4 (HR = 0.76 95%CI[0.63-0.91], HR = 0.56 95%CI[0.45-0.7], HR = 1.37 95%CI[1.07-1.74]), respectively. In addition, metastasis-free interval was identified as a prognostic factor for OS3 (p = 0.01), while PFS3 influenced OS4 (HR = 0.75 95%CI[0.57-0.98]). Nomograms predicting OS3 and OS4 achieved a C-index of 0.62 and 0.61, respectively., Conclusion: The duration of each previous PFS is a major prognostic factor for OS in mTNBC patients receiving third- or fourth-line chemotherapy. The clinical utility of nomograms including this information was not demonstrated., Competing Interests: Declaration of competing interest Dr. De La Motte Rouge reports personal fees and non-financial support from ASTRAZENECA, grants, personal fees and non-financial support from PFIZER, grants from NOVARTIS, personal fees and non-financial support from EISAI, personal fees and non-financial support from ROCHE, grants and non-financial support from MSD, outside the submitted work. Dr. Robain reports ESME Platform was supported by Roche, Astra Zeneca, BMS, Pfizer, Daiichi Sankyo, Eisai. Prof. Campone reports grants from Pfizer, grants from AstraZeneca, grants from Sanofi, grants from Pierre Fabre, grants from Takeda, personal fees from Novartis, personal fees from Lilly, outside the submitted work. Dr. MOURET-REYNIER reports grants from Novartis, Lilly, Pfizer, Roche, Pierre Fabre, MSD, outside the submitted work. All other authors declare no conflict of interest., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: High Body mass index (BMI) is a risk factor for breast cancer among postmenopausal women and an adverse prognostic factor in early-stage. Little is known about its impact on clinical outcomes in patients with metastatic breast cancer (MBC)., Methods: The National ESME-MBC observational cohort includes all consecutive patients newly diagnosed with MBC between Jan 2008 and Dec 2016 in the 18 French comprehensive cancer centers., Results: Of 22 463 patients in ESME-MBC, 12 999 women had BMI data available at MBC diagnosis. Median BMI was 24.9 kg/m 2 (range 12.1-66.5); 20% of women were obese and 5% underweight. Obesity was associated with more de novo MBC, while underweight patients had more aggressive cancer features. Median overall survival (OS) of the BMI cohort was 47.4 months (95% CI [46.2-48.5]) (median follow-up: 48.6 months). Underweight was independently associated with a worse OS (median OS 33 months; HR 1.14, 95%CI, 1.02-1.27) and first line progression-free survival (HR, 1.11; 95%CI, 1.01; 1.22), while overweight or obesity had no effect., Conclusion: Overweight and obesity are not associated with poorer outcomes in women with metastatic disease, while underweight appears as an independent adverse prognostic factor., Competing Interests: Declaration of Competing interest V.D reports advisory boards from Roche, Genentech, Lilly, Pfizer, Astra Zeneca, MSD, Daiichi Sankyo and Seattle Genetics. PE-H reports research funding from Pfizer, Novartis E.B receive honoraria or consultation fees: AstraZeneca, BMS, Celgene, Clinigen, G1 Therapeutics, Hospira, Janssen, Mylan, OBI Pharma, Pfizer, Puma, Roche, Samsung; Receipt of grants/research supports: Amgen, HalioDX (Qiagen/Ipsogen), TEVA (Cephalon); Travel support: AstraZeneca, Novartis, Pfizer, Pierre Fabre, Roche, Sandoz. A.G reports travel expenses, accommodation and registration meeting from Astra Zeneca, Roche, Pfizer, Novartis. P.C reports grants form Pfizer and Novartis, personal fees from Pfizer and Lilly, non-financial support from Pfizer. S.D. reports institutional fees and non-financial support from Roche/Genentech; grants, institutional fees and nonfinancial support from Pfizer; institutional fees and nonfinancial support from Puma; grants, institutional fees and non-financial support from AstraZeneca; grants, institutional fees and non-financial support from Novartis; institutional fees and non-financial support from Amgen. E.D reports travel expenses from Pfizer, Novartis and Amgen and boards from Novartis and Pfizer. The other authors declare that they have no conflict of interest to disclose., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Young age is a poor prognostic factor in early stage breast cancer (BC) but its value is less established in metastatic BC (MBC). We evaluated the impact of age at MBC diagnosis on overall survival (OS) across three age groups (<40, 40 to 60 and > 60 years(y))., Methods: ESME MBC database is a national cohort, collecting retrospective data from 18 participating French cancer centers between January 01, 2008 and December 31, 2014., Results: Among 14 403 women included, 1077 (7.5%), 6436 (44.7%) and 6890 (47.8%) pts were <40, 40-60 and > 60 y respectively. Pts <40 had significantly more aggressive presentations than other age groups: more frequent HER2+ (25.7 vs 15.3% in >60y) and triple negative subtypes (27.4 vs 14.6% in >60y), and more frequent visceral involvement (36.3 vs 29.8% in >60y). At a median follow-up of 48 months, median OS differed across age groups: 38.8, 38.4 and 35.6 months for pts <40, 40-60 and > 60y, respectively (p < 0.0001). Compared to pts <40y, older pts had a statistically significant higher risk of death (all causes of death included), although of limited clinical value (HR = 1.1, IC 95%:1.01-1.20). There was a significant trend for better OS in pts <40y with HER2+ and luminal diseases. A possible explanation is a greater use of anti-Her2 therapies as first-line treatments: 86.6, 81.9 and 74.9% for pts <40, 40-60 and > 60y, respectively (p < 0.0001)., Conclusion: Although young age seems associated with more aggressive presentations at diagnosis of MBC, it has no deleterious effect on OS in this large series., Competing Interests: Declaration of competing interest Co-authors having declared no conflict of interests: Sophie Frank, Matthieu Carton, Coraline Dubot, Barbara Pistilli (GR), Audrey Mailliez (COL), Christelle Levy (CFB), Véronique D’Hondt (ICM), Marc Debled (IB), Thomas Vermeulin (CHB), Bruno Coudert (CGFL), Christophe Perrin (CEM), Anthony Gonçalves (IPC), Lionel Uwer (ICL), Jean-Marc Ferrero (CAL), Jean-Christophe Eymard (IJG), Thierry Petit (CPS), Marie-Ange Mouret-Reynier (CJP), Anne Patsouris (ICO PP), Tahar Guesmia (R&D Unicancer), Thomas Bachelot (CLB), Mathieu Robain (R&D Unicancer), Paul Cottu. Mario campone: Advisory Board: Consulting fees to my Institut:Astra ZENECA, Novartis, Abbvie, Sanofi, Pfizer, Sandoz, ACCORD. Personal fees to Lilly, G1 Therapeutic Consultant: Fees to my Institute: Pierre Fabre Oncology; Sanofi; Novartis; Servier. Speaker bureau: Personnal fees Novartis, Lilly Travel: Pfizer, Novartis, Roche, Astra Zeneca. Barbara Pistilli:P ersonal fees from AstraZeneca, Pfizer, Myriad, Pierre Fabre and non-financial support from Pfizer, Puma and Merus, Novartis outside the submitted work Florence Dalenc: Advisory Board: Novartis, Pfizer, Lilly Travel: Pfizer, Novartis, Roche, Astra Zeneca Paul Cottu: Advisory Board: Novartis, Pfizer, Lilly, Roche Travel: Pfizer, Novartis, Roche, Astra Zeneca., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background/aim: Vinorelbine is indicated for use in the treatment of MBC as a single agent or in combination but there is little real world data on this molecule and even less on its oral form. We exploited the Unicancer Epidemiology Strategy Medical-Economics (ESME) metastatic breast cancer (MBC) database to investigate current patterns of use of oral vinorelbine (OV), as well as outcomes of patients receiving this drug., Patients and Methods: Data were collected retrospectively from women and men treated for MBC between 2008 and 2014 at one of 18 French Comprehensive Cancer Centres. The efficacy of OV was evaluated in terms of progression-free (PFS) and overall survival (OS) and treatment duration. The population and patterns of OV usage were also described., Results: A total of 1806 patients (11% of the ESME MBC database) were included in this analysis. OV was prescribed as monotherapy (46%) or in combination (29%), especially with capecitabine. mainly in later treatment lines. Median PFS was 3.3 months: 2.9 months for single agent, 3.6 months for combination therapy. Median OS was 40.9 months., Conclusion: Real-world data offer complementary results to the data from traditional clinical trials, but they concern a much larger population. In this ESME MBC cohort, OV was only prescribed to a small subset of MBC patients. OV was mainly given as single agent to patients with heavily pre-treated MBC; less commonly, it was co-administered with capecitabine or anti-HER2, in earlier lines of therapy. PFS was modest but in line with previous reports., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Metastatic breast cancer (MBC) behaviour differs depending on hormone receptors (HR) and human epidermal growth factor receptor (HER2) statuses., Methods: The kinetics of central nervous system (CNS) metastases (CNS metastasis-free survival, CNSM-FS) and subsequent patient's prognosis (overall survival, OS) according to the molecular subtype were retrospectively assessed in 16703 MBC patients of the ESME nationwide multicentre MBC database (Kaplan-Meier method)., Results: CNS metastases occurred in 4118 patients (24.6%) (7.2% at MBC diagnosis and 17.5% later during follow-up). Tumours were HER2-/HR+ (45.3%), HER2+/HR+ (14.5%), HER2+/HR- (14.9%) and triple negative (25.4%). Median age at CNS metastasis diagnosis was 58.1 years (range: 22.8-92.0). The median CNSM-FS was 10.8 months (95% CI: 16.5-17.9) among patients who developed CNS metastases. Molecular subtype was independently associated with CNSM-FS (HR = 3.45, 95% CI: 3.18-3.75, triple-negative and HER2-/HR+ tumours). After a 30-month follow-up, median OS after CNS metastasis diagnosis was 7.9 months (95% CI: 7.2-8.4). OS was independently associated with subtypes: median OS was 18.9 months (HR = 0.57, 95% CI: 0.50-0.64) for HER2+/HR+ , 13.1 months (HR = 0.72, 95% CI: 0.65-0.81) for HER2+/HR-, 4.4 months (HR = 1.55, 95% CI: 1.42-1.69) for triple-negative and 7.1 months for HER2-/HR+ patients (p <0.0001)., Conclusions: Tumour molecular subtypes strongly impact incidence, kinetics and prognosis of CNS metastases in MBC patients., Clinical Trial Registration: NCT03275311.

Purpose: The currently ongoing Epidemiological Strategy and Medical Economics (ESME) research programme aims at centralising real-life data on oncology care for epidemiological research purposes. We draw on results from the metastatic breast cancer (MBC) cohort to illustrate the methodology used for data collection in the ESME research programme., Participants: All consecutive ≥18 years patients with MBC treatment initiated between 2008 and 2014 in one of the 18 French Comprehensive Cancer Centres were selected. Diagnostic, therapeutic and follow-up data (demographics, primary tumour, metastatic disease, treatment patterns and vital status) were collected through the course of the disease. Data collection is updated annually., Finding to Date: With a recruitment target of 30 000 patients with MBC by 2019, we currently screened a total of 45 329 patients, and >16 700 patients with a metastatic disease treatment initiated after 2008 have been selected. 20.7% of patients had an hormone receptor (HR)-negative MBC, 73.7% had a HER2-negative MBC and 13.9% were classified as triple-negative BC (ie, HER2 and HR status both negative). Median follow-up duration from MBC diagnosis was 48.55 months for the whole cohort., Future Plans: These real-world data will help standardise the management of MBC and improve patient care. A dozen of ancillary research projects have been conducted and some of them are already accepted for publication or ready to be issued. The ESME research programme is expanding to ovarian cancer and advanced/metastatic lung cancer. Our ultimate goal is to achieve a continuous link to the data of the cohort to the French national Health Data System for centralising data on healthcare reimbursement (drugs, medical procedures), inpatient/outpatient stays and visits in primary/secondary care settings., Trial Registration Number: NCT03275311; Pre-results., Competing Interests: Competing interests: DP has received personal fees (honoraria and travel/accommodation expenses) from Laboratoire Roche, outside the submitted work. BA has received personal fees for board membership and for consultancy from Roche Pharma, outside the submitted work. SG has received personal fees for board membership from Celgene and for consultancy from Roche, outside the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aim: To assess outcomes in patients treated with first-line bevacizumab-containing therapy for human epidermal growth factor receptor (HER)2-negative metastatic breast cancer (mBC) at a single centre with a homogenous standard-of-care., Patients and Methods: Information on patient and disease characteristics, efficacy, and safety was extracted from computer-based records of all patients receiving first-line bevacizumab-paclitaxel at the Curie Institute, Paris, France, between 2008 and 2011., Results: Median progression-free survival in the 116 treated patients was 13.2 months; median overall survival was 38.4 months. Corresponding values were 9.0 and 18.8 months, respectively, in patients with triple-negative mBC, and 19.4 and 58.8 months, respectively, in patients receiving maintenance endocrine therapy. No new safety signals were seen., Conclusion: Outcomes in patients treated with bevacizumab-paclitaxel at our center were consistent with efficacy in prospective clinical trials, with notable activity in poor-prognosis disease. Maintenance endocrine or oral therapy with bevacizumab after paclitaxel discontinuation was associated with long-term disease control., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: The impact of adjuvant chemotherapy on breast cancer prognosis has been demonstrated in randomized trials, but its impact is unknown in real-world populations. The aim of this study was to evaluate the effect of adjuvant chemotherapy on the survival of breast cancer patients in an unselected population., Methods: This prospective cohort study included 32,502 women treated at the Institut Curie between 1981 and 2008 for a first invasive breast cancer without metastasis. The patients were matched based on their propensity score to receive adjuvant chemotherapy., Results: The matching generated a subsample of 9,180 patients with an overlapping propensity score. In the group without chemotherapy, the overall survival (OS) rates at 5 and 10 years of follow-up were 87.6% (95% CI [86.7-88.6]) and 75.0% (95% CI [73.6-76.5]), respectively, versus 92.1% (95% CI [91.3-92.9]) and 81.9% (95% CI [80.6-83.2]), respectively, in the chemotherapy group. Distant disease-free survival (DDFS) was significantly improved in the five first years (absolute benefit of 3.5%). In a multivariate analysis, adjuvant chemotherapy was associated with better OS (HR = 0.75, 95% CI [0.69-0.83], p<0.0001) and DDFS (HR = 0.82, 95% CI [0.75-0.90], p<0.0001)., Conclusion: Adjuvant chemotherapy significantly improves OS and DDFS rates in an unselected population, in accordance with previous results reported by randomized trials.

To study the effects of reduced CD4 T cell activity on hepatitis C virus (HCV) genetic heterogeneity, HCV quasi-species complexity and diversification over time were analyzed for 56 human immunodeficiency virus-coinfected patients. Patients were selected retrospectively from the French Seroconverter Cohort (SEROCO) and the French Hemophilia Cohort (HEMOCO) for having stable CD4 cell counts for 3 years. HCV complexity was assessed by single-strand conformation polymorphism analysis of the envelope-coding region (HVR) and the core region at 2 time points 3 years apart. Increased HVR complexity was associated with higher CD4 cell count and HCV genotype 1 infection. Qualitative variation of HVR and core region was not related to CD4 cell count and depended on the initial complexity. Complexity of both regions remained unchanged over 3 years. Among these HCV-HIV-coinfected patients with stable CD4 cell counts, viral genotype and CD4 cell count may have influenced HVR complexity before their inclusion in the study but were not involved in HVR diversification during the 3-year follow-up period.

Objective: To study the impact of cytomegalovirus (CMV) seroconversion on HIV-1 disease progression., Design: Follow-up of CMV-seronegative subjects enrolled in the French SEROCO/HEMOCO cohorts of HIV-infected subjects., Methods: A total of 290 subjects were CMV-seronegative at enrolment in the cohort. Serological testing for CMV infection was done at enrolment and then every 6 months in CMV-seronegative subjects. The person-years method was used to calculate the incidence of CMV seroconversion. After adjustment for age, the CD4+ cell count at enrolment and the HIV exposure group in a Cox model, we studied CMV seroconversion as a time-dependent variable in progression to a CD4+ cell count below 200 x 10(6) cells/l and to clinical AIDS., Results: Overall, 61 CMV seroconversions were observed. The overall incidence rate was 4.4 per 100 person-years [95% confidence interval (CI), 3.3-5.5]. The risk of progression to a CD4+ cell count below 200 x 10(6) cells/l was not increased in CMV seroconverters. However, the risk of progression to AIDS was increased two-fold in CMV seroconverters compared with subjects who remained CMV-seronegative [relative risk (RR) = 2.09; 95% CI, 1.16-3.74; P = 0.01]., Conclusion: This analysis of 61 CMV seroconversions, the largest study in the literature, confirms the impact of recent CMV infection on progression to AIDS.