Background: The ANRS COV1-COHVAC cohort was a long-term safety cohort of healthy volunteers who received preventive HIV-vaccine candidates in 17 phase I/II clinical trials. Methods: Data collected from the first vaccine candidate administration and annually after inclusion in the cohort included grade 3/4 adverse events and all grade adverse events suggestive of neurological, ophthalmological and immune disorders, self-administered questionnaires on behaviors and HIV ELISA results. Age-and-sex-standardized mortality ratios (SMRs) were calculated with respect to the French population. The cohort was early terminated in 2016 due to the absence of safety signal. Results: Of 496 volunteers, 488 were included: 355 in the 7-year prospective follow-up and 133 in the retrospective data collection only. The total follow-up after the first vaccination was 4934 person-years (median: 10 years) and 270 (76%) volunteers completed their follow-up. No relevant adverse event possibly related to the vaccine was reported. Breast cancer incidence and woman mortality did not differ from those of the French general population (standardized incidence ratio = 1.47, P = 0.45 and SMR = 0.65, P = 0.28, respectively) while man mortality was significantly lower (SMR = 0.26, P = 0.0003). At the last visit, 21/29 (72%) volunteers who received the recombinant HIV gp160 protein still showed vaccine-induced seropositivity after a median follow-up of 23 years. Only a few volunteers reported risky sexual practices (men: 20/192, women: 2/162). Conclusion: Volunteers showed a sustained high commitment. No long-term safety alert was identified during the postvaccine follow-up. Participating in vaccine trials did not increase risky behaviors for HIV infection. Vaccine-induced seropositivity may persist for more than 23 years after receiving rgp160.

AIDS Research and Human RetrovirusesVol. 30, No. S1 Vaccine Clinical TrialsUpdate of the Long-term Follow-up of Healthy Volunteers from Preventive HIV-1 Vaccine Trials: ANRS COV1-COHVAC CohortCorinne Desaint, Christine Durier, Jean-Daniel Lelièvre, Benjamin Silbermann, Gilles Pialoux, Lise Cuzin, Isabelle Poizot-Martin, Pascale Morineau, Amel Bouakane, Bruno Spire, Yves Lévy, Jean-Pierre Aboulker, Odile Launay, and ANRS COHVAC Study Group, Paris, France and Vaccine Research Institute (VRI), Créteil, FranceCorinne DesaintUniversité Paris-Descartes, Sorbonne Paris Cité, Faculté de Médecine, Paris, FranceInserm, CIC 1417, Paris, FranceAP-HP, Hôpital Cochin, CIC de Vaccinologie Cochin Pasteur, Paris, FranceSearch for more papers by this author, Christine DurierInserm, SC10-US019, Villejuif, FranceSearch for more papers by this author, Jean-Daniel LelièvreInserm, U955, Créteil, FranceUniversité Paris-Est Créteil Val de Marne (UPEC), Créteil, FranceAP-HP, Hôpital Henri Mondor, Service d'Immunologie Clinique, Créteil, FranceSearch for more papers by this author, Benjamin SilbermannAP-HP, Hôpital Cochin, Service de Médecine Interne, Paris, FranceSearch for more papers by this author, Gilles PialouxAP-HP, Hôpital Tenon, Service des Maladies Infectieuses et Tropicales, Paris, FranceSearch for more papers by this author, Lise CuzinCHU Toulouse, Service des Maladies Infectieuses, Toulouse, FranceSearch for more papers by this author, Isabelle Poizot-MartinUniversité Aix-Marseille, Marseille, FranceAPHM Hôpital Sainte Marguerite, Service d'Immuno-hématologie clinique, Marseille, FranceInserm, U912 (SESSTIM), Marseille, FranceSearch for more papers by this author, Pascale MorineauCHU Nantes, Service des Maladies Infectieuses, Nantes, FranceSearch for more papers by this author, Amel BouakaneANRS, Service de Recherche Vaccinale, Paris, FranceSearch for more papers by this author, Bruno SpireUniversité Aix-Marseille, Marseille, FranceInserm / IRD, UMR 912, Marseille, FranceSearch for more papers by this author, Yves LévyInserm, U955, Créteil, FranceUniversité Paris-Est Créteil Val de Marne (UPEC), Créteil, FranceAP-HP, Hôpital Henri Mondor, Service d'Immunologie Clinique, Créteil, FranceSearch for more papers by this author, Jean-Pierre AboulkerInserm, SC10-US019, Villejuif, FranceSearch for more papers by this author, Odile LaunayUniversité Paris-Descartes, Sorbonne Paris Cité, Faculté de Médecine, Paris, FranceInserm, CIC 1417, Paris, FranceAP-HP, Hôpital Cochin, CIC de Vaccinologie Cochin Pasteur, Paris, FranceSearch for more papers by this author, and ANRS COHVAC Study Group, Paris, France and Vaccine Research Institute (VRI), Créteil, FranceSearch for more papers by this authorPublished Online:30 Oct 2014https://doi.org/10.1089/aid.2014.5406.abstractAboutSectionsView articleView Full TextPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View article"Update of the Long-term Follow-up of Healthy Volunteers from Preventive HIV-1 Vaccine Trials: ANRS COV1-COHVAC Cohort." AIDS Research and Human Retroviruses, 30(S1), pp. A189–A190FiguresReferencesRelatedDetails Volume 30Issue S1Oct 2014 InformationCopyright 2014, Mary Ann Liebert, Inc.To cite this article:Corinne Desaint, Christine Durier, Jean-Daniel Lelièvre, Benjamin Silbermann, Gilles Pialoux, Lise Cuzin, Isabelle Poizot-Martin, Pascale Morineau, Amel Bouakane, Bruno Spire, Yves Lévy, Jean-Pierre Aboulker, Odile Launay, and ANRS COHVAC Study Group, Paris, France and Vaccine Research Institute (VRI), Créteil, France.Update of the Long-term Follow-up of Healthy Volunteers from Preventive HIV-1 Vaccine Trials: ANRS COV1-COHVAC Cohort.AIDS Research and Human Retroviruses.Oct 2014.A189-A190.http://doi.org/10.1089/aid.2014.5406.abstractPublished in Volume: 30 Issue S1: October 30, 2014PDF download

BackgroundIn low hepatitis B virus (HBV)-prevalent countries, most HBV-infected persons are unaware of their status. We aimed to evaluate whether (i) previous HBV-testing, (ii) physicians decision to screen, and (iii) CDC's recommendations identified infected individuals and which risk-factor groups needing testing.MethodsDuring a mass, multi-center HBV-screening study from September 2010-August 2011, 3929 participants were screened for hepatitis B surface antigen (HBsAg), anti-HBs and anti-Hepatitis B core antibodies (anti-HBcAb). Questions on HBV risk-factors and testing practices were asked to participants, while participants' eligibility for HBV-testing was asked to study medical professionals.Results85 (2.2%) participants were HBsAg-positive, while 659 (16.8%) had either resolved HBV infection or isolated anti-HBcAb. When comparing practices, HBV-testing was more likely to occur in HBV-infected participants if Centers for Disease Control and Prevention (CDC) recommendations were used (Sensitivity = 100%, 95%CI: 95.8-100) than physicians' discretion (Sensitivity = 87.1%, 95%CI: 78.0-93.4) or previous HBV-test (Sensitivity = 36.5%, 95%CI: 26.3-47.6) (p<0.0001). Nevertheless, many non-infected individuals would still have been screened using CDC-recommendations (Specificity = 31.1%, 95%CI: 29.6-32.6). Using multivariable logistic regression, HBsAg-positive status was significantly associated with the following: males, originating from high HBV-endemic region, contact with HBV-infected individual, without national healthcare, and intravenous-drug user (IDU). Of these risk-factors, physician's discretion for testing HBV was not significantly associated with participants' geographical origin or IDU.ConclusionsMissed opportunities of HBV-screening are largely due to underestimating country of origin as a risk-factor. Applying CDC-recommendations could improve HBV-screening, but with the disadvantage of many tests. Further development of HBV-testing strategies is necessary, especially before severe disease occurs.

Objectives: To assess the long-term serological impact of HIV preventive vaccine trial participation, vaccine- induced HIV seropositivity (VISP) was evaluated and related factors were investigated. The anti-HIV antibody reactivity ratio distribution was estimated. Methods: ANRS COHVAC is an open national prospective multicentre cohort study including healthy volunteers who received at least one dose of vaccine candidate of ANRS HIV preventive vaccine trials since 1992. VISP was studied in a cross-sectional study at the time of the cohort's initial visit, starting in 2008. Anti-HIV antibody detection was performed using the ABBOTT ARCHITECT® HIV Ag/Ac Combo Enzyme Immunoassay (EIA) in a centralized laboratory. A ratio greater than or equal to 1 was considered to define HIV seropositivity. Results: 293 participants were evaluated for a median period of 6 years (range: 2-18 years) after their inclusion in vaccine preventive trials. The frequency of VISP was estimated at 7.2% (21 out of 293) for all volunteers, and 69.0% (20 out of 29) for volunteers who received recombinant HIV-1 envelope protein, after a median period of 16.6 years after immunization (range: 16.3-18.4). The ARCHITECT test ratio among positive volunteers was low, with a median of 3.02 (range: 1.02 -14.04). Conclusion: Healthy volunteers should be informed of possible VISP persistence for nearly 17 years, following HIV envelope vaccination inducing antibody responses. A single, routine serology test is unable to differentiate between VISP and a recent HIV infection. The combination of different technologies, applicable to resource-limited settings, is needed to distinguish vaccine-induced seropositivity from an HIV infection.

Background & Aims: The systematic use of rapid tests performed at points-of-care may facilitate hepatitis B virus (HBV) screening and substantially increase HBV infection awareness. The aim of this study was to evaluate the effectiveness of such tests for HBsAg and anti-HBsAb detection among individuals visiting a variety of healthcare centers located in a low HBV-prevalent area.Methods: Three rapid tests for hepatitis B surface antigen (HBsAg) detection (VIKIA (R), Determine (TM) and Quick Profile (TM)) and one test for anti-hepatitis B surface antibody (anti-HBsAb) detection (Quick Profile (TM)) were evaluated in comparison to ELISA serology. Sensitivity (Se), specificity (Sp), positive and negative predictive values (PPV and NPV, respectively) and area under the ROC curve were used to estimate test performance. Non-inferiority criteria of the joint Se, Sp were set at 0.80, 0.95.Results: Among the 3956 subjects screened, 85 (2.1%) were HBsAg-positive and 2225 (56.5%) had a protective anti-HBsAb titer. Test Se and Sp (lower bound of 97.5% CI) were as follows: 96.5% (89.0%), 99.9% (99.8%) for Vikia (R); 93.6% (80.7%), 100.0% (99.8%) for Determine (TM); and 90.5% (80.8%), 99.7% (99.5%) for Quick Profile (TM); with all three tests achieving minimal non-inferiority criteria. False negatives were typically observed in inactive HBsAg carriers. The anti-HBsAb Quick Profile (TM) test had excellent specificity (97.8%) and PPV (97.8%) albeit low sensitivity (58.3%), thus failing to establish non-inferiority.Conclusions: All three HBsAg rapid tests could be considered ideal for HBV screening in low HBV-prevalent countries, given the ease of use, rapidity, and high classification probabilities. The anti-HBsAb Quick Profile (TM) could be considered reliable only for positive tests. (C) 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Long-term persistence of HIV vaccine-induced seropositivity in uninfected HIV vaccine recipients remains unknown. The duration of HIV humoral-induced responses was assessed in 72 volunteers who had received rgp160 and/or HIV recombinant canarypox virus constructs able to induce immune responses detectable using standard serological tests. Among the 43 rgp160 recipients, 94% and 83% remained HIV seropositive after 5 and 8 years of follow-up, respectively, while all the 29 volunteers who had received canarypox constructs alone were seronegative after 5 years. Because rgp160 induces long-term persistence (>8 years) of vaccine-induced HIV seropositivity, volunteers should be offered long-term follow-up to monitor their serological evolution.

Deux nouveaux vaccins ont obtenu recemment l’autorisation de mise sur le marche : un vaccin quadrivalent contre les infections a papillomavirus humains (HPV) 6, 11, 16 et 18, indique chez l’enfant a partir de 9 ans et le jeune adulte jusqu’a 26 ans, et un vaccin contre le zona pour l’adulte de 60 ans et plus. Un vaccin bivalent contre les infections a HPV 16 et 18 sera prochainement disponible. Les vaccins HPV representent une avancee majeure dans le domaine de la vaccinologie car ces vaccins sont susceptibles d’etre efficaces dans la prevention du cancer du col de l’uterus. Leur utilisation doit s’associer a la poursuite du depistage par frottis du cancer du col de l’uterus et aux mesures de prevention des autres infections sexuellement transmissibles. Le vaccin zona permet de reduire l’incidence du zona et des douleurs post-zosteriennes. Actuellement reserve aux sujets de plus de 60 ans, il est susceptible d’etre plus largement utilise et doit permettre de reduire significativement la morbidite liee a cette complication tardive de l’infection par le virus de la varicelle-zona.

Objective The objective was to compare the safety and cellular immunogenicity of intradermal versus intramuscular immunization with an HIV-lipopeptide candidate vaccine (LIPO-4) in healthy volunteers. Methodology A randomized, open-label trial with 24 weeks of follow-up was conducted in France at six HIV-vaccine trial sites. Sixty-eight healthy 21– to 55–year-old HIV-uninfected subjects were randomized to receive the LIPO-4 vaccine (four HIV lipopeptides linked to a T-helper–stimulating epitope of tetanus-toxin protein) at weeks 0, 4 and 12, either intradermally (0.1 ml, 100 µg of each peptide) or intramuscularly (0.5 ml, 500 µg of each peptide). Comparative safety of both routes was evaluated. CD8+ T-cell immune responses to HIV epitopes (ELISpot interferon-γ assay) and tetanus toxin-specific CD4+ T-cell responses (lymphoproliferation) were assessed at baseline, two weeks after each injection, and at week 24. Results and Conclusion No severe, serious or life-threatening adverse events were observed. Local pain was significantly more frequent after intramuscular injection, but local inflammatory reactions were more frequent after intradermal immunization. At weeks 2, 6, 14 and 24, the respective cumulative percentages of induced CD8+ T-cell responses to at least one HIV peptide were 9, 33, 39 and 52 (intradermal group) or 14, 20, 26 and 37 (intramuscular group), and induced tetanus toxin-specific CD4+ T-cell responses were 6, 27, 33 and 39 (intradermal), or 9, 46, 54 and 63 (intramuscular). In conclusion, intradermal LIPO-4 immunization was well tolerated, required one-fifth of the intramuscular dose, and induced similar HIV-specific CD8+ T-cell responses. Moreover, the immunization route influenced which antigen-specific T-cells (CD4+ or CD8+) were induced. Trial Registration ClinicalTrials.gov NCT00121121

Two new vaccines have been recently licensed : a quadrivalent vaccine against Human papillomavirus infections (HPV) 6, 11, 16 and 18, recommended to children from 9 years old and to young adults under the age of 26 years, and a vaccine against herpes zoster for adults from 60 years old onwards. A bivalent vaccine against HPV 16 and 18 will be shortly available. HPV vaccines are composed of the L1 structural proteins of 2 or 4 HPV genotypes, produced by genetic engineering and self-assembled. These inert vaccines are devoid of genetic materials and mimic the viral particle (virus-like particle, VLP). They allow, as suggested by the 4.5 to 5 years follow-up, to prevent HPV infections and the onset of pre-cancerous lesions associated with genotypes contained within the vaccine. They represent a major overhang in the vaccinology field, and, as anti-hepatitis B vaccine, will probably be effective in cancer prevention. Their use must be associated with the continued detection of cervix cancer by smears and also with the prevention of other sexually transmitted diseases. The herpes zoster vaccine is a living attenuated vaccine produced from the OKA/Merck strain already used in the vaccine against varicella. Its safety is good among persons 50 years old and over and its efficiency on lowering herpes zoster incidence, on the burden of illness and on post-herpetic neuralgia has been demonstrated in persons over 60 years old.

Thirty-nine HIV-1-infected men were prospectively tested for HIV seminal shedding after the initiation of highly active antiretroviral therapy. HIV RNA drastically decreased in the semen of all men, but low levels remained detectable in three men at month 18. Proviral HIV DNA became undetectable in the seminal cells of all men after 18 months. HIV-infected cells in the male genital compartment may come from the intermittent passage of blood lymphocytes, rather than constituing a major local reservoir.