Assessment of the kinetics of SARS-CoV-2 antibodies is essential in predicting protection against reinfection and durability of vaccine protection. Here, we longitudinally measured Spike (S) and Nucleocapsid (N)-specific antibodies in 1,309 healthcare workers (HCWs), including 916 COVID-19 negative HCWs and 393 convalescent COVID-19 for up to 422 days post-symptom. From month (M)1 to M7-9 post-infection, SARS-CoV-2 antibodies decreased moderately in convalescent HCWs in a biphasic model, with men showing a slower decay of anti-N (p=0.02), and a faster decay of anti-S (p=0.0008) than women. At M11-13, anti-N dramatically decreased (half-life: 283 days) while anti-S stabilized (half-life: 725 days) at a median of 2.39 log Arbitrary Units (AU)/mL (Interquartile Range (IQR): 2.10 -2.75). Overall, 69 SARS-CoV-2 infections developed in the COVID-19 negative group (incidence of 12.22 per 100 person-years) versus one in the COVID-19 positive group (incidence of 0.40 per 100 person-years), indicating a relative reduction in the incidence of SARS-CoV-2 reinfection of 96.7% (p<0.0001). Correlation with live-virus neutralization assay revealed that variants D614G and B.1.1.7, but not B.1.351, were sensitive to anti-S antibodies at 2.3 log AU/mL, while IgG ≥ 3 log AU/mL neutralized all three variants. After SARS-CoV-2 vaccination, anti-S levels reached at least 3 logs regardless of pre-vaccination IgG levels, type of vaccine, and number of doses. Our study demonstrates a long-term persistence of anti-S IgG antibodies that may protect against reinfection. By significantly increasing cross-neutralizing antibody titers, a single-dose vaccination strengthens protection against escape mutants.

BackgroundAssessment of the kinetics of SARS-CoV-2 antibodies is essential in predicting risk of reinfection and durability of vaccine protection.MethodsThis is a prospective, monocentric, longitudinal, cohort clinical study. Healthcare workers (HCW) from Strasbourg University Hospital were enrolled between April 6th and May 7th, 2020 and followed up to 422 days. Serial serum samples were tested for antibodies against the Receptor Binding Domain (RBD) of the spike protein and nucleocapsid protein (N) to characterize the kinetics of SARS-CoV-2 antibodies and the incidence of reinfection. Live-neutralization assays were performed for a subset of samples before and after vaccination to analyze sensitivity to SARS-CoV-2 variants.FindingsA total of 4290 samples from 393 convalescent COVID-19 and 916 COVID-19 negative individuals were analyzed. In convalescent individuals, SARS-CoV-2 antibodies followed a triphasic kinetic model with half-lives at month (M) 11–13 of 283 days (95% CI 231–349) for anti-N and 725 days (95% CI 623–921) for anti-RBD IgG, which stabilized at a median of 1.54 log BAU/mL (95% CI 1.42–1.67). The incidence of SARS-CoV-2 infections was 12.22 and 0.40 per 100 person-years in COVID-19-negative and COVID-19-positive HCW, respectively, indicating a relative reduction in the incidence of SARS-CoV-2 reinfection of 96.7%. Live-virus neutralization assay revealed that after one year, variants D614G and B.1.1.7, but less so B.1.351, were sensitive to anti-RBD antibodies at 1.4 log BAU/mL, while IgG ≥ 2.0 log BAU/mL strongly neutralized all three variants. These latter anti-RBD IgG titers were reached by all vaccinated HCW regardless of pre-vaccination IgG levels and type of vaccine.InterpretationOur study demonstrates a long-term persistence of anti-RBD antibodies that may reduce risk of reinfection. By significantly increasing cross-neutralizing antibody titers, a single-dose vaccination strengthens protection against variants.Fun1dingNone.

Objectives: The value of Epstein-Barr virus (EBV) biomarkers on the prognosis of HIV-related non-Hodgkin's lymphoma (NHL) has been poorly explored in the combined antiretroviral therapy (cART) era. Design: We evaluated EBV DNA load and EBV antibodies in HIV-NHL patients enrolled in the French ANRS-CO16 Lymphovir Cohort between 2008 and 2015. Methods: Whole blood and plasma EBV DNA load and serological profiles were analyzed in 76 HIV-infected patients at diagnosis of NHL and 6 months after the initiation of chemotherapy. Results: Prechemotherapy whole blood (WB) and plasma EBV DNA loads were positive for 80 and 45% of HIV-NHL patients, respectively. Pretreatment WB EBV DNA positivity was associated with a positive plasma HIV-1 RNA load (relative risk (RR), 4.42 [1.33; 14.72]) and plasma EBV DNA positivity with EBV in situ detection (RR 10.62 [2.38; 47.49]). Following chemotherapy, the proportions of patients with positive WB or plasma EBV DNA declined from 81 to 23% (P < 0.0001) and from 43 to 8% (P < 0.0001), respectively. Estimated 2-year progression-free survival did not differ according to prechemotherapy WB positivity (82% versus 67%, P = 0.15) or plasma EBV DNA positivity (76% versus 81%, P = 0.52). Conclusions: The plasma EBV DNA load correlates with in situ EBV detection. The WB EBV DNA load correlates with HIV load. WB and plasma EBV DNA loads at NHL diagnosis do not constitute prognostic markers for HIV-NHL patients in the modern cART era.

AbstractBackgroundIn the background of the current COVID-19 pandemic, serological tests are being used to assess past infection and immunity against SARS-CoV-2. This knowledge is paramount to determine the transmission dynamics of SARS-CoV-2 through the post pandemic period. Several individuals belonging to households with an index COVID-19 patient, reported symptoms of COVID-19 but discrepant serology results.MethodsHere we investigated the humoral and cellular immune responses against SARS-CoV-2 in seven families, including nine index patients and eight contacts, who had evidence of serological discordances within the households. Ten unexposed healthy donors were enrolled as controls.ResultsAll index patients recovered from a mild COVID-19. They all developed anti-SARS-CoV-2 antibodies and a significant T cell response detectable up to 69 days after symptom onset. Six of the eight contacts reported COVID-19 symptoms within 1 to 7 days after the index patients but all were SARS-CoV-2 seronegative. Six out of eight contacts developed a SARS-CoV-2-specific T cell response against structural and/or accessory proteins that lasts up to 80 days post symptom onset suggesting a past SARS-CoV-2 infection.ConclusionExposure to SARS-CoV-2 can induce virus-specific T cell responses without seroconversion. T cell responses may be more sensitive indicators of SARS-Co-V-2 exposure than antibodies. Our results indicate that epidemiological data relying only on the detection of SARS-CoV-2 antibodies may lead to a substantial underestimation of prior exposure to the virus.

OBJECTIVE:Chronic hepatitis C virus (HCV) and hepatitis B virus (HBV) infections are associated with increased risks of lymphomas in the non-HIV setting. Their impacts on HIV-associated lymphomas deserved further studies in the modern combined antiretroviral therapy (cART) era. DESIGN:We evaluated the associations between HCV, HBV and HIV-related lymphomas in the Lymphovir-ANRS-CO16 cohort. METHODS:Prevalence of HCV seropositivity and chronic HBV infections were compared with those observed in the French Hospital Database on HIV (FHDH-ANRS-CO4). RESULTS:Between 2008 and 2015, 179 patients with HIV-related lymphomas from 32 French hospitals were enrolled, 69 had Hodgkin's lymphoma (39%), and 110 non-Hodgkin's lymphoma (NHL) (61%). The prevalence of HCV infection was higher in patients with NHL than in the FHDH-ANRS-CO4 [26 versus 14%, odd ratio (OR): 2.15; 95% confidence interval (1.35-3.32)] whereas there was no association between Hodgkin's lymphoma and chronic HCV infection. Chronic HBV infection was not associated with NHL in our cohort with a prevalence of 5 versus 7% in FHDH-ANRS-CO4 but tended to be associated with Hodgkin's lymphoma [prevalence of 14%, OR: 2.16 (0.98-4.27)]. Chronic HCV infection tended to pejoratively impact 2-year overall survival in patients with NHL: 72% [57%, 91%] versus 82% [74%, 91%], hazard ratio: 2.14 [0.95-4.84]. In contrast, chronic HBV infection did not correlate with outcome. CONCLUSION:In the modern cART era, chronic HCV infection is associated with an increased risk of NHL in PLWHIV and tends to pejoratively impact overall survival. HBV infection is not associated with the risk of NHL but with a borderline increase of Hodgkin's lymphoma risk.

Fcɣ receptors (FcɣRs) are key immune regulatory receptors that connect antibody-mediated immune responses to cellular effector functions. They are involved in the control of various immune functions including responses to infections. Genetic polymorphisms of FcɣRs coding genes (FCGR) have been associated with the regulation of HIV infection and progression. In this study, we analyzed the potential impact of five candidate FcɣR SNPs on viral control by genotyping 251 HIV controllers and 250 progressors. The rs10800309 AA genotype of the FcɣRIIa coding gene FCGR2A was found to be significantly associated with HIV control and this association was independent of HLA-B57 and HLA-B27 (OR, 2.84; 95% CI, 1.20–6.89; Pcor = 0.033). We further confirmed the functional role of this polymorphism by showing an association of this same AA genotype with an increased in vitro FcɣRII expression on myeloid cells including dendritic cells (P = 0.0032). Together, these results suggest that the AA genotype of rs10800309 confers an improved immune response through FcɣRII upregulation and that this polymorphism may serve as an additional predictive marker of HIV control.

We investigated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–specific antibodies and T-cell responses against SARS-CoV-2 and human coronavirus (HCoV) 229E and OC43 in 11 SARS-CoV-2 serodiscordant couples in Strasbourg, France, in which 1 partner had evidence of mild coronavirus disease (COVID-19) and in 10 unexposed healthy controls. Patients with confirmed COVID-19 were considered index patients and their partners close contacts. All index patients displayed positive SARS-CoV-2–specific antibody and T-cell responses that lasted up to 102 days after symptom onset. All contacts remained seronegative for SARS-CoV-2; however, 6 reported COVID-19 symptoms within a median of 7 days after their partners, and 4 of those showed a positive SARS-CoV-2–specific T-cell response against 3 or 4 SARS-CoV-2 antigens that lasted up to 93 days after symptom onset. The 11 couples and controls displayed positive T-cell responses against HCoV-229E or HCoV-OC43. These data suggest that exposure to SARS-CoV-2 can induce virus-specific T-cell responses without seroconversion.

BACKGROUNDThe Data Collection on Adverse Events of Anti-HIV Drugs (DAD) study has reported an increased risk of cardiovascular diseases in people with human immunodeficiency virus who were exposed to darunavir (DRV) but not to atazanavir (ATV). Our objective was to evaluate associations between ATV or DRV exposures and the risk of myocardial infarction (MI) in a nested case-control study within ANRS-CO4 French Hospital Database on HIV (FHDH).METHODSCases were individuals who had a first validated MI between 2006 and 2012. Up to 5 controls were selected at random with replacement among individuals with no history of MI, followed at the time of MI diagnosis, and matched for age and sex. Conditional logistic regression models were used to adjust for potential confounders (MI risk factors and HIV-related parameters) and for cumulative exposure to each antiretroviral drug (ARV).RESULTSOverall, 408 MI cases and 1250 controls were included: 109 (27%) cases and 288 (23%) controls had been exposed to ATV, and 41 (10%) cases and 107 (9%) controls had been exposed to DRV. There was no significant association between exposure to ATV (adjusted odds ratio [OR] = 1.54; 95% confidence interval [CI], .87-2.73) or DRV (adjusted OR = 0.51; 95% CI, .11-2.32) and the risk of MI.CONCLUSIONSIn FHDH, exposures to ATV or to DRV were not significantly associated with the risk of MI, adjusting for complete ARV history, contrary to the analysis in DAD.

Objectives: Epstein-Barr virus (EBV) has been implicated in lymphomagenesis of HIV-related classical Hodgkin lymphoma (HIV-cHL). The utility of EBV molecular and serological biomarkers has scarcely been examined in HIV-cHL in the recent combined antiretroviral therapy (cART) era. Design: We evaluated EBV DNA load and a panel of EBV antibodies in HIV-cHL patients prospectively enrolled in the French ANRS-CO16 Lymphovir cohort between 2008 and 2015. Methods: Pretreatment whole blood, plasma EBV DNA load and serological profiles were analysed in 63 HIV-infected patients diagnosed with cHL. For the 42 patients with available material, comparisons were performed between values at diagnosis and 6 months after the initiation of chemotherapy. Results: Pretreatment whole blood and plasma EBV DNA loads were positive in 84 and 59% of HIV-cHL patients, respectively. Two-year progression-free survival estimates did not differ between the patients with pretreatment whole blood (n = 53) or plasma (n = 37) EBV DNA(thorn) and the patients with pretreatment whole blood (n = 10) or plasma (n = 26) EBV DNA(-) (92 vs. 80% or 89 vs. 92%, P = 0.36 and 0.47, respectively). At diagnosis, 47% of patients harboured an EBV reactivation serological profile. Following chemotherapy, whole blood and plasma EBV DNA levels significantly declined from medians of 1570 [interquartile range, 230-3760) and 73 (0-320) copies/ml to 690 (0-1830) and 0 (0-0) copies/ml, respectively (P = 0.02 and P < 0.0001, respectively]. Anti-EBV IgG antibody level significantly dropped at 6-month follow-up (P = 0.004). Conclusion: Whole blood and plasma EBV DNA loads do not constitute prognostic markers in HIV-cHL patients in the modern cART era. Copyright (C) 2019 Wolters Kluwer Health, Inc. All rights reserved.

Background: "Treatment as Prevention" (TasP) aims to reduce new HIV infections through higher enrolment on suppressive antiretroviral therapy (ART). Objectives: We studied the current epidemic and possible impact of TasP in a French HIV cohort including MSM and migrant subjects. Study design: Socio-demographic, clinical and laboratory variables were collected during the follow-up of 6995 HIV-infected patients. The numbers of individuals living with HIV in each year were estimated from diagnoses up to that year minus recorded deaths. Patients were classified according to gender, transmission mode, country of birth and treatment status. Results: The cohort includes 6995 individuals diagnosed from 1985 to 2015, of whom 72% were men. Unprotected sexual intercourse was the main mode of transmission. Women were more likely to be migrants (45% versus 13%), whereas men were more likely to have been born in France (52% versus 27%). Diagnoses were more correlated with untreated than treated prevalence in each group. MSM diagnoses was strongly correlated to untreated prevalence whatever the country of birth (p < 0.0001). However, heterosexual diagnoses were better correlated with prevalence within individual country groups (b = 0.29 female diagnoses/year per untreated male born in France, compared to b = 0.73 for foreigners). Using these transmission rates, mathematical modelling estimated that enrolling 75% of untreated individuals per year would decrease diagnoses tenfold by 2021. Conclusions: Enrolling at least 75% of individuals on ART is necessary to substantially impact numbers of new HIV infections in this cohort. Treatment as prevention will actually be effective to reduce HIV prevalence.

We examined trends in the MI incidence and age at MI diagnosis among adults living with HIV-1 between 2000 and 2009, by comparison with the French MI registries, by gender. Age standardized incidence rates and standardized incidence-ratios (SIRs) were estimated for individuals included in the French hospital database on HIV (n = 71 204, MI = 663) during three periods: 2000-2002, 2003-2005 and 2006-2009. Median ages at MI diagnosis were compared using the Brown-Mood test. Over the study periods, the absolute rate difference and relative risks were higher in women than in men in 2000-2002 and 2006-2009, with respective SIRs 1.99 (1.39-2.75) and 1.12 (0.99-1.27) in 2006-2009. The trends were different for men and women with a decreasing trend in SIRs in men and no change in women. In both sexes, among individuals with CD4 ≥500/μL and controlled viral-load on cART, the risk was no longer elevated. Age at MI diagnosis was significantly younger than in the general population, especially among women (-6.2 years, p<0.001; men: -2.1 years, p = 0.02). In HIV-1-positive adults, absolute rate difference and relative risks and trends of MI were different between men and women and there was no additional risk among individuals on effective cART.

Objectives:Better understanding of the dynamics of HIV reservoirs under ART is a critical step to achieve a functional HIV cure. Our objective was to assess the genetic diversity of archived HIV-1 DNA over 48 weeks in blood cells of individuals starting treatment with a dolutegravir-based regimen.Methods:Eighty blood samples were prospectively and longitudinally collected from 20 individuals (NCT02557997) including: acutely (n = 5) and chronically (n = 5) infected treatment-naive individuals, as well as treatment-experienced individuals who switched to a dolutegravir-based regimen and were either virologically suppressed (n = 5) or had experienced treatment failure (n = 5). The integrase and V3 loop regions of HIV-1 DNA isolated from PBMCs were analysed by pyrosequencing at baseline and weeks 4, 24 and 48. HIV-1 genetic diversity was calculated using Shannon entropy.Results:All individuals achieved or maintained viral suppression throughout the study. A low and stable genetic diversity of archived HIV quasispecies was observed in individuals starting treatment during acute infection. A dramatic reduction of the genetic diversity was observed at week 4 of treatment in the other individuals. In these patients and despite virological suppression, a recovery of the genetic diversity of the reservoirs was observed up to 48 weeks. Viral variants bearing dolutegravir resistance-associated substitutions at integrase position 50, 124, 230 or 263 were detected in five individuals (n = 5/20, 25%) from all groups except those who were ART-failing at baseline. None of these substitutions led to virological failure.Conclusions:These data demonstrate that the genetic diversity of the HIV-1 reservoir is reshaped following the initiation of a dolutegravir-based regimen and strongly suggest that HIV-1 can continue to replicate despite successful treatment.

Objective: To determine whether changing antiretroviral therapy (ART) during pregnancy because of concern about fetal risks led to poorer virological outcomes. Methods: All pregnancies in women with HIV-1 infection enrolled in the national multicenter prospective French Perinatal cohort at 14 week gestation or more were included between January 2005 and December 2015, if the mother was on ART at conception with a plasma viral load,50 copies/mL. The reasons for a change in the ART were analyzed according to treatment guidelines at the time of the pregnancy and defined as for safety concerns in the absence of reported maternal intolerance. Virological and pregnancy outcomes were studied by survival analysis and logistic regression adjusted for a propensity score established for each patient according to baseline characteristics. Results: Of 7079 pregnancies in the overall cohort, 1797 had ART at conception with a viral load,50 copies/mL before 14 week gestation. Of these, 22 changed regimens in the first trimester for intolerance, and 411 of the remaining 1775 (23%) solely for safety concerns. The proportion of change was higher when the initial treatment was not recommended in the national guidelines (OR adjusted: 23.1 [14.0-38.2]), than when it was an alternative option (ORa: 2.2 [1.3-3.7]), as compared to recommended first-line regimens. Treatment changes for safety concerns did not lead to poorer virological control, compared with pregnancies without such changes (19.3% vs. 15.6%, HRa: 1.0 [0.7-1.4]). Conclusions: Changing ART early in pregnancy to regimens considered safer for pregnancy, and neonatal health did not have a destabilizing effect on viral suppression.

Objective: The aim of our study was to analyze the dynamics of HIV-DNA levels in CD4(+) T-cell subsets in individuals starting successful dolutegravir-based regimens. Design: Twenty-seven individuals with acute infection (AI, n = 8) or chronic infection (CI, n = 5) and patients in virological success (VS, n = 10) or virological failure (VF, n = 4) on antiretroviral therapy (ART) who initiated a dolutegravir-based regimen were enrolled (NCT02557997). Methods: CD4(+) T-cells from baseline and week 48 of successful treatment were sorted into effector memory (TEM), transitional memory (TTM), central memory (TCM) and naive (TN) cell groups for total HIV-DNA measurements by qPCR. Bayesian methods were used to estimate the posterior probability of a HIV-DNA decrease more than 0.25 log copies/10(6) cells at week 48. Results: All patients achieved HIV-RNA suppression at 48 weeks. At baseline and week 48, the highest contributions to the HIV-DNA-infected pool from CD4(+) T cells were observed in TTM cells in the AI group (62.4 and 60.2%, respectively), but in TCM cells for the CI, VS and VF groups (54.6 and 59.4%, 58.2 and 62.9%, 62.4 and 67.2%), respectively. HIV-DNA burden declined in all subsets after 48 weeks of treatment in the AI (probability (Pr) > 91%), CI (Pr > 52%) and VF (Pr > 52%) groups, but only in TEM cells in the VS group (Pr = 95%). Conclusion: Our study showed that dolutegravir-based treatment reduced the HIV-DNA cellular burden in individuals from the AI, CI and VF groups, though the reduction levels differed between the patient subgroups. Early treated patients had the highest probability of HIV-DNA reduction. Interestingly, in the aviremic VS group, HIV-DNA reduction was limited to TEM cells. Copyright (C) 2018 Wolters Kluwer Health, Inc. All rights reserved.

Objective: Non-Hodgkin's lymphoma (NHL) remains among the most frequent malignancies in persons living with HIV (PLWHIV). Survival among patients with HIV-associated diffuse large B-cell lymphoma (DLBCL), the most frequent NHL subtype, has improved markedly in recent years. We aimed to analyze characteristics and outcomes of DLBCL in HIV-infected patients in the era of modern combined antiretroviral therapy (cART). Design: PLWHIV with lymphoma were prospectively enrolled in the French ANRS-CO16 Lymphovir cohort between 2008 and 2015. We compared the patients treated with R-CHOP) (rituximab, cyclophosphamide, daunorubicin, vin-cristine, prednisolone) with HIV-negative DLBCL patients enrolled simultaneously in the R-CHOP arms of Lymphoma Study Association trials. Results: Among 110 PLWHIV with NHL, 52 (47%) had systemic DLBCL. These 52 cases had frequent extranodal disease (81%), poor performance status (35%) and advanced age-adjusted international prognostic index (aaIPI) (58%), and were mainly treated with R-CHOP (n = 44, 85%). Their median CD4(+) T-cell count was 233 cells/mu l, and 79% of patients were on cART. The 2-year overall and progression-free survival rates were both 75% (95% confidence interval: 64%, 88%). Factors associated with progression or death in univariate analysis were poor performance status [hazard ratio: 3.3 (1.2, 8.9)], more than one extranodal site [hazard ratio: 3.4 (1.1, 10.5)] and an advanced aaIPI [hazard ratio: 3.7 (1.0, 13.1)]. Progression-free survival after R-CHOP therapy did not differ from that of the HIV-negative counterparts (P = 0.11). Conclusion: In the recent cART era, despite frequent high-risk features, the 2-year overall survival of HIV-DLBCL patients reaches 75%. Outcomes after R-CHOP therapy are similar to those of HIV-negative patients with similar aaIPI. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

BACKGROUND Human immunodeficiency virus (HIV) infection has been linked to an increased risk of non-Hodgkin's lymphoma (NHL) and Hodgkin's lymphoma (HL). In the HIV-uninfected population, hepatitis C virus (HCV) and hepatitis B virus (HBV) infections are both associated with an increased risk of NHL. Scarce data suggest an increased risk of HL in patients chronically infected with HBV. HCV and HBV coinfections are frequent among persons living with HIV (PLWHIV). The impact of HCV and HBV infections on HIV-associated lymphoma in the era of combined antiretroviral therapy (cART) deserves evaluation. METHODS We compared the prevalence of HBV and HCV coinfections between PLWHIV with lymphoma who were enrolled in the Lymphovir French National Agency for Research on AIDS and Viral Hepatitis (ANRS)-CO16 cohort and PLWHIV enrolled in the French Hospital Database on HIV (FHDH-ANRS-CO4) with at least one follow-up visit in 2011 (n = 48 186). This cohort has been shown to be representative of PLWHIV under care in France. Lymphovir-ANRS-CO16 cohort enrolled consecutive HIV-infected individuals with lymphoma (NHL or HL) in 32 centers. The histological diagnosis was established using the 2008 WHO classification and was confirmed within the French hematopathology network (LYMPHOPATH). Finally, we analyzed the characteristics and outcomes of lymphomas in coinfected patients. RESULTS Between 2008 and 2015, 179 patients with HIV-related lymphomas were enrolled, of whom 110 had NHL (61%) and 69 had HL (39%), The HCV serology, available for all the patients, was positive in 38 cases (29 with NHL and 9 with HL). Among 26 HCV+ patients with available data, 15 had detectable HCV RNA load at lymphoma diagnosis, five had Child-Pugh A cirrhosis, two had liver fibrosis, and one had an extrahepatic manifestation (type III cryoglobulinemia). Overall, the HCV seroprevalence was 26% among patients with NHL, a proportion significantly higher than that in the FHDH-ANRS-CO4 cohort (14%) (odds ratio (OR): 2.15, 95% confidence interval [1.35-3.32])(Table). There was no association between HCV and HL (prevalence 13%, OR: 0.90 [0.39-1.82]). The distribution of NHL subtypes among the 29 patients with HCV infection was as follows: DLBCL (n=17), MZL (n=3), plasmablastic lymphomas (n=3), primary effusion lymphoma (PEL) (n=3), BL (n=2), and T-cell lymphoma (n=1). HCV was significantly associated with DLBCL (prevalence 33%, OR: 2.91 [1.53-5.34]). Among the patients with DLBCL, 13/17 HCV+ patients had at least one site of extranodal involvement, compared to 16/34 HCV- patients (p=0.05). Four DLBCL patients received anti-HCV therapy after treatment of their lymphoma, consisting of IFN/ribavirin, either alone (n=1) or direct antiviral agents (n=3). A sustained virological reponse and a durable remission of their lymphoma were obtained in each case. Remarkably, a man with splenic MZL received anti-HCV therapy with interferon and ribavirin with no other lymphoma treatment, leading to long-lasting both virological and hematological complete responses. During follow-up, 10 deaths occurred among HCV+ patients with NHL due to progression of lymphoma (n=8) or solid tumours (n=2). With a median follow-up of 43 months, the 2-year OS among NHL patients tended to be lower in HCV+ patients (Figure). HBV status was available for 177 of the 179 lymphoma patients, of whom 15 had chronic HBV infection based on HBs Ag positivity (n=13) or HBV DNA positivity (n=2). Five patients had NHL (DLBCL (n=2) and BL (n=3)) and 10 had HL. Overall, chronic HBV infection was present in 5% of patients with NHL, which did not differ from the value of the FHDH-ANRS-CO4 cohort (7%) (OR: 0.60 [0.19-1.45]). In contrast, the prevalence of chronic HBV infection was higher among patients with HL than in the FHDH-ANRS-CO4 (14%; OR: 2.16 [0.98-4.27]). CONCLUSION As compared with the general cohort of HIV-infected patients, HCV coinfection was associated with an increased risk of NHL, especially DLBCL, and tended to be associated with poorer outcome. While no increase in the risk of NHL was observed among HBV coinfected patients, chronic HBV infection was associated with an increased risk of HL. Our findings suggest that chronic antigenic stimulation induced by HCV or HBV contribute to lymphomagenesis in HIV-infected patients. It paves the way for evaluation of novel therapeutic strategies based on the newest direct antiviral agents for HCV coinfected patients. Download : Download high-res image (142KB) Download : Download full-size image Disclosures Coiffier: Celltrion, Inc: Consultancy, Honoraria. Coppo: Alexion: Consultancy, Research Funding; Ablynx: Consultancy, Research Funding; Octapharma: Consultancy.

Chez la femme vivant avec le VIH, la procreation naturelle trouve une place grandissante. En cas de desir d’enfant, la consultation preconceptionnelle revet une importance capitale pour guider au mieux les couples. La recommandation actuelle est de proposer systematiquement a toute personne infectee un traitement au long cours ayant pour objectif une charge virale indetectable. Dans ces conditions, le risque de transmission virale de la mere a l’enfant est nul. Plusieurs traitements sont utilisables en cours de grossesse, c’est la fin de la predominance de l’AZT. Cependant, la prudence est de mise avec les medicaments plus recents. La perfusion d’AZT et la cesarienne ne sont pratiquees que si la charge virale est superieure a 400 copies/mL. Pour la contraception, il est necessaire de maintenir le preservatif jusqu’a autorisation contraire de l’infectiologue. Le choix d’une contraception doit etre personnalise et decide en discussion pluridisciplinaire. Si on opte pour une contraception orale, on peut utiliser preferentiellement un progestatif derive de la 17-0H-progesterone associe a l’œstradiol naturel. L’utilisation du dispositif intra-uterin doit etre encouragee. Ainsi, bien qu’au prix d’une surveillance pluridisciplinaire rapprochee, la sante reproductive de la femme VIH+, de la contraception au desir de devenir parents, de la grossesse au suivi du bebe, se rapproche de plus en plus de celle de la femme non infectee.

BACKGROUND:Human immunodeficiency virus (HIV) infection is associated with a high risk of classical Hodgkin's lymphoma (cHL) in the combined antiretroviral therapy (cART) era.METHODS:We analyzed the characteristics and outcome of HIV-associated cHL diagnosed in the modern cART era. The French ANRS-CO16 Lymphovir cohort enrolled 159 HIV-positive patients with lymphoma, including 68 (43%) with cHL. HIV-HL patients were compared with a series of non-HV-infected patients consecutively diagnosed with HL.RESULTS:Most patients (76%) had Ann-Arbor stages III-IV and 96% of patients were treated with ABVD. At diagnosis, median CD4 T-cell count was 387/µL and 94% of patients were treated with cART. All patients received cART after diagnosis. Five patients died from early progression (n = 2), sepsis (1) or after relapse (2). Two additional patients relapsed during follow-up. Two-year overall and progression free survivals (PFS) were 94% [95% CI, 89%, 100%] and 89% [82%, 97%], respectively. The only factor associated with progression or death was age with a relative risk of 8.1 [1.0; 67.0] above 45 years. The PFS of Lymphovir patients appeared similar to PFS of HIV-negative patients, 86% [82%, 90%], but patients with HIV infection displayed higher risk features than HIV-negative patients.CONCLUSIONS:Although high-risk features still predominate in HIV-HL, the prognosis of these patients, treated with cART and mainly ABVD, has markedly improved in the modern cART era and is now similar to non-HIV-infected patients.

Avec la simplification des traitements antirétroviraux, faut-il penser que l’éducation thérapeutique du patient (ETP) chez les patients vivant avec le virus de l’immunodéficience humaine (VIH) n’est plus une nécessité ? L’ETP ne s’arrête pas à soutenir l’adhésion thérapeutique mais a pour objectif de renforcer la qualité de vie des personnes en répondant à leurs besoins. Décrire les besoins des personnes vivant avec le VIH dans une approche centrée sur la personne par une méthodologie mixte. Étude française monocentrique qualitative sous forme d’entretiens semi-directifs (n = 40) et quantitative par auto-questionnaires (n = 200) auprès de patients suivis en consultation en 2013. Dans l’étude quantitative, 80 % des participants étaient des hommes de 46 ans d’âge médian. Dans le contexte soignant, un patient sur deux souhaitait s’exprimer sur le vécu de sa maladie, sa vie affective, sa sexualité et ses projets de vie. Trois patients sur quatre avaient besoin d’informations sur les effets indésirables ou les complications liées au VIH, notamment « le risque cardiovasculaire ». Des sous-groupes de patients ont été identifiés : certains participants considéraient qu’on ne leur demandait jamais leur avis concernant les décisions médicales (n = 13), se sentaient isolés (n = 54) et d’autres n’avaient personne à qui parler en cas de problème (n = 43). Le « regard des autres » est une problématique du quotidien chez ces personnes qui souffrent principalement des stéréotypes persistants sur l’infection par le VIH dans la société française, notamment sur le mode de transmission. Les personnes vivant avec le VIH ont encore de nombreux besoins d’accompagnement qui doivent être au centre des interventions d’ETP. With the simplification of antiretroviral treatments, is it conceivable to consider that therapeutic patient education for patients living with the human immunodeficiency virus (HIV) is no longer necessary? TPE does not stop at supporting patients in changing their behaviour and ensuring their compliance but also aims to improve people's quality of life by meeting their needs. To describe the needs of people living with HIV in a person-centred approach and using mixed methods. French monocentric study, both qualitative in the form of semi-structured interviews (n = 40), and quantitative through self-administered questionnaires (n = 200), of patients monitored through consultations in 2013. In the quantitative study, 80% of participants were men with an average age of 46. In the context of caregiving, one out of two patients wanted to talk about their experience of the disease, their emotional life, their sex life and their life projects. Three out of four patients needed information regarding the adverse effects or complications linked to HIV, notably the “cardiovascular risk”. Sub-groups of patients were identified: some participants considered that they were never consulted about medical decisions (n = 13), felt isolated (n = 54) and others had no one to talk to when they had a problem (n = 43). “Other people's perceptions” is a daily problem for people who suffer mainly from persistent stereotypes regarding HIV infection in French society, notably in relation to the mode of transmission. People living with HIV still have great need for support, which must be at the centre of TPE.