A. Karim, Q. , A. Karim, S. Frohlich, J. Grobler et al., Effectiveness and Safety of Tenofovir Gel, an Antiretroviral Microbicide, for the Prevention of HIV Infection in Women, Science, vol.329, issue.5996, pp.1168-1174, 2010.
DOI : 10.1126/science.1193748

M. Cohen, Y. Chen, M. Mccauley, T. Gamble, M. Hosseinipour et al., Prevention of HIV-1 Infection with Early Antiretroviral Therapy, New England Journal of Medicine, vol.365, issue.6, pp.493-505, 2011.
DOI : 10.1056/NEJMoa1105243

R. Gray, G. Kigozi, D. Serwadda, F. Makumbi, S. Watya et al., Male circumcision for HIV prevention in men in Rakai, Uganda: a randomised trial, The Lancet, vol.369, issue.9562, pp.657-666, 2007.
DOI : 10.1016/S0140-6736(07)60313-4

J. Baeten, D. Donnell, P. Ndase, N. Mugo, J. Campbell et al., Antiretroviral Prophylaxis for HIV Prevention in Heterosexual Men and Women, New England Journal of Medicine, vol.367, issue.5, pp.399-410, 2012.
DOI : 10.1056/NEJMoa1108524

S. Rerks-ngarm, P. Pitisuttithum, S. Nitayaphan, J. Kaewkungwal, J. Chiu et al., Vaccination with ALVAC and AIDSVAX to Prevent HIV-1 Infection in Thailand, New England Journal of Medicine, vol.361, issue.23, pp.2209-2220, 2009.
DOI : 10.1056/NEJMoa0908492

N. Michael, RV 144 Update: Vaccination with ALVAC and AIDSVAC to prevent HIV-1 infection in Thai adults, 17th Conference on Retroviruses and Opportunistic Infections, 2010.

S. Rerks-ngarm, A. Brown, C. Khamboonruang, P. Thongcharoen, and P. Kunasol, HIV/AIDS preventive vaccine ???prime-boost??? phase III trial: foundations and initial lessons learned from Thailand, AIDS, vol.20, issue.11, pp.1471-1479, 2006.
DOI : 10.1097/01.aids.0000237362.26370.f8

L. Baden and R. Dolin, The Road to an Effective HIV Vaccine, New England Journal of Medicine, vol.366, issue.14, pp.1343-1344, 2012.
DOI : 10.1056/NEJMe1202492

G. Gray, M. Allen, Z. Moodie, G. Churchyard, L. Bekker et al., Safety and efficacy of the HVTN 503/Phambili Study of a clade-B-based HIV-1 vaccine in South Africa: a double-blind, randomised, placebo-controlled test-of-concept phase 2b study, The Lancet Infectious Diseases, vol.11, issue.7, pp.507-515, 2011.
DOI : 10.1016/S1473-3099(11)70098-6

S. Hammer, M. Sobieszczyk, H. Janes, S. Karuna, M. Mulligan et al., Efficacy Trial of a DNA/rAd5 HIV-1 Preventive Vaccine, New England Journal of Medicine, vol.369, issue.22, p.369, 2013.
DOI : 10.1056/NEJMoa1310566

K. Saunders, R. Rudicell, and G. Nabel, The design and evaluation of HIV-1 vaccines, AIDS, vol.26, issue.10, pp.1293-1302
DOI : 10.1097/QAD.0b013e32835474d2

L. Corey, G. Nabel, C. Dieffenbach, P. Gilbert, B. Haynes et al., HIV-1 Vaccines and Adaptive Trial Designs, Science Translational Medicine, vol.3, issue.79, pp.79-92, 2011.
DOI : 10.1126/scitranslmed.3001863

G. Nabel, Designing Tomorrow's Vaccines, New England Journal of Medicine, vol.368, issue.6, pp.551-560, 2013.
DOI : 10.1056/NEJMra1204186

R. Simon, S. Steinberg, M. Hamilton, A. Hildesheim, S. Khleif et al., Clinical Trial Designs for the Early Clinical Development of Therapeutic Cancer Vaccines, Journal of Clinical Oncology, vol.19, issue.6, pp.1848-185419, 2001.
DOI : 10.1200/JCO.2001.19.6.1848

E. Eisenhauer, P. Therasse, J. Bogaerts, L. Schwartz, D. Sargent et al., New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1), European Journal of Cancer, vol.45, issue.2, pp.228-247, 2009.
DOI : 10.1016/j.ejca.2008.10.026

J. Excler, G. Tomaras, and N. Russell, Novel directions in HIV-1 vaccines revealed from clinical trials, Current Opinion in HIV and AIDS, vol.8, issue.5, pp.421-431, 2013.
DOI : 10.1097/COH.0b013e3283632c26

P. Gilbert, D. Grove, E. Gabriel, Y. Huang, G. Gray et al., A Sequential Phase 2b Trial Design for Evaluating Vaccine Efficacy and Immune Correlates for Multiple HIV Vaccine Regimens, Statistical Communications in Infectious Diseases, vol.3, issue.1, p.4, 2011.
DOI : 10.2202/1948-4690.1037

Z. Moodie, A. Rossini, M. Hudgens, P. Gilbert, S. Self et al., Statistical evaluation of HIV vaccines in early clinical trials, Contemporary Clinical Trials, vol.27, issue.2, pp.147-160, 2006.
DOI : 10.1016/j.cct.2005.11.008

H. Streeck, N. Frahm, and B. Walker, The role of IFN-?? Elispot assay in HIV vaccine research, Nature Protocols, vol.61, issue.4, pp.461-469, 2009.
DOI : 10.1186/1479-5876-3-20

J. Currier, V. Ngauy, M. De-souza, S. Ratto-kim, J. Cox et al., Phase I Safety and Immunogenicity Evaluation of MVA-CMDR, a Multigenic, Recombinant Modified Vaccinia Ankara-HIV-1 Vaccine Candidate, PLoS ONE, vol.27, issue.11, p.13983, 2010.
DOI : 10.1371/journal.pone.0013983.s005

F. Garcia, J. Bernaldo-de-quiros, C. Gomez, B. Perdiguero, J. Najera et al., Safety and immunogenicity of a modified pox vector-based HIV/AIDS vaccine candidate expressing Env, Gag, Pol and Nef proteins of HIV-1 subtype B (MVA-B) in healthy HIV-1-uninfected volunteers: A phase I clinical trial (RISVAC02), Vaccine, vol.29, issue.46, pp.8309-8316, 2011.
DOI : 10.1016/j.vaccine.2011.08.098

R. Greenberg, E. Overton, D. Haas, I. Frank, M. Goldman et al., Safety, Immunogenicity, and Surrogate Markers of Clinical Efficacy for Modified Vaccinia Ankara as a Smallpox Vaccine in HIV-Infected Subjects, Journal of Infectious Diseases, vol.207, issue.5, pp.749-758, 2013.
DOI : 10.1093/infdis/jis753

B. Peters, W. Jaoko, E. Vardas, G. Panayotakopoulos, P. Fast et al., Studies of a prophylactic HIV-1 vaccine candidate based on modified vaccinia virus Ankara (MVA) with and without DNA priming: Effects of dosage and route on safety and immunogenicity, Vaccine, vol.25, issue.11, pp.2120-2127, 2007.
DOI : 10.1016/j.vaccine.2006.11.016

E. Sandstrom, C. Nilsson, B. Hejdeman, A. Brave, G. Bratt et al., Broad Immunogenicity of a Multigene, Multiclade HIV???1 DNA Vaccine Boosted with Heterologous HIV???1 Recombinant Modified Vaccinia Virus Ankara, The Journal of Infectious Diseases, vol.198, issue.10, pp.1482-1490, 2008.
DOI : 10.1086/592507

M. Tameris, M. Hatherill, B. Landry, T. Scriba, M. Snowden et al., Safety and efficacy of MVA85A, a new tuberculosis vaccine, in infants previously vaccinated with BCG: a randomised, placebo-controlled phase 2b trial, The Lancet, vol.381, issue.9871, pp.1021-1028, 2013.
DOI : 10.1016/S0140-6736(13)60177-4

S. Vasan, S. Schlesinger, Z. Chen, A. Hurley, A. Lombardo et al., Phase 1 Safety and Immunogenicity Evaluation of ADMVA, a Multigenic, Modified Vaccinia Ankara-HIV-1 B'/C Candidate Vaccine, PLoS ONE, vol.5, issue.1, p.8816, 2010.
DOI : 10.1371/journal.pone.0008816.s002

A. Von-krempelhuber, J. Vollmar, R. Pokorny, P. Rapp, N. Wulff et al., A randomized, double-blind, dose-finding Phase II study to evaluate immunogenicity and safety of the third generation smallpox vaccine candidate IMVAMUNE??, Vaccine, vol.28, issue.5, pp.1209-1216, 2010.
DOI : 10.1016/j.vaccine.2009.11.030

A. Pathan, A. Minassian, C. Sander, R. R. Porter, D. Poulton et al., Effect of vaccine dose on the safety and immunogenicity of a candidate TB vaccine, MVA85A, in BCG vaccinated UK adults, Vaccine, vol.30, issue.38, pp.5616-5624, 2012.
DOI : 10.1016/j.vaccine.2012.06.084

V. Ramanathan, M. Kumar, J. Mahalingam, P. Sathyamoorthy, P. Narayanan et al., A Phase 1 Study to Evaluate the Safety and Immunogenicity of a Recombinant HIV Type 1 Subtype C-Modified Vaccinia Ankara Virus Vaccine Candidate in Indian Volunteers, AIDS Research and Human Retroviruses, vol.25, issue.11, pp.1107-1116, 2009.
DOI : 10.1089/aid.2009.0096

C. Durier, O. Launay, V. Meiffredy, Y. Saidi, D. Salmon et al., Clinical safety of HIV lipopeptides used as vaccines in healthy volunteers and HIV-infected adults, AIDS, vol.20, issue.7, pp.1039-1049, 2006.
DOI : 10.1097/01.aids.0000222077.68243.22

D. Hokey and D. Weiner, DNA vaccines for HIV: challenges and opportunities, Springer Seminars in Immunopathology, vol.74, issue.3, pp.267-279, 2006.
DOI : 10.1007/s00281-006-0046-z

D. Salmon-ceron, C. Durier, C. Desaint, L. Cuzin, M. Surenaud et al., Immunogenicity and safety of an HIV-1 lipopeptide vaccine in healthy adults: a phase 2 placebo-controlled ANRS trial, AIDS, vol.24, issue.14, pp.2211-2223, 2010.
DOI : 10.1097/QAD.0b013e32833ce566

E. Vardas, I. Stanescu, M. Leinonen, K. Ellefsen, G. Pantaleo et al., Indicators of therapeutic effect in FIT-06, a Phase II trial of a DNA vaccine, GTU??-Multi-HIVB, in untreated HIV-1 infected subjects, Vaccine, vol.30, issue.27, pp.4046-4054, 2012.
DOI : 10.1016/j.vaccine.2012.04.007

O. Connell, R. Kim, J. Corey, L. Michael, and N. , Human immunodeficiency virus vaccine trials. Cold Spring Harb Perspect Med, p.7351, 2012.

R. Simon, R. Wittes, and S. Ellenberg, Randomized phase II clinical trials, Cancer Treat Rep, vol.69, pp.1375-1381, 1985.

A. Hoos, G. Parmiani, K. Hege, M. Sznol, H. Loibner et al., A Clinical Development Paradigm for Cancer Vaccines and Related Biologics, Journal of Immunotherapy, vol.30, issue.1, pp.1-15, 2007.
DOI : 10.1097/01.cji.0000211341.88835.ae

K. Gray, K. Legg, A. Sharp, N. Mackie, F. Olarinde et al., Participation in two phase II prophylactic HIV vaccine trials in the UK, Vaccine, vol.26, issue.23, pp.2919-2924, 2008.
DOI : 10.1016/j.vaccine.2008.03.039

D. Asmuth, E. Brown, M. Dinubile, X. Sun, C. Del-rio et al., Vaccine Prime???Boost Regimens, The Journal of Infectious Diseases, vol.201, issue.1, pp.132-141, 2010.
DOI : 10.1086/648591

G. Churchyard, C. Morgan, E. Adams, J. Hural, B. Graham et al., A phase IIA randomized clinical trial of a multiclade HIV-1 DNA prime followed by a multiclade rAd5 HIV-1 vaccine boost in healthy adults (HVTN204) PloS One, p.21225, 2011.

A. Harari, P. Bart, W. Stohr, G. Tapia, M. Garcia et al., An HIV-1 clade C DNA prime, NYVAC boost vaccine regimen induces reliable, polyfunctional, and long-lasting T cell responses, The Journal of Experimental Medicine, vol.3, issue.1, pp.63-77, 2008.
DOI : 10.4049/jimmunol.173.10.6274

S. Brown, W. Gregory, C. Twelves, M. Buyse, F. Collinson et al., Designing phase II trials in cancer: a systematic review and guidance, British Journal of Cancer, vol.4, issue.2, pp.194-199, 2011.
DOI : 10.1038/bjc.2011.235

H. Ray and S. Rai, Operating characteristics of a Simon two-stage phase II clinical trial design incorporating continuous toxicity monitoring, Pharmaceutical Statistics, vol.1, issue.2, pp.170-176, 2012.
DOI : 10.1002/pst.510

O. Launay, C. Durier, C. Desaint, B. Silbermann, A. Jackson et al., Cellular Immune Responses Induced with Dose-Sparing Intradermal Administration of HIV Vaccine to HIV-Uninfected Volunteers in the ANRS VAC16 Trial, PLoS ONE, vol.167, issue.8, p.725, 2007.
DOI : 10.1371/journal.pone.0000725.s002

Y. Levy, K. Ellefssen, W. Stoehr, P. Bart, J. Lelièvre et al., Optimal Priming of Poxvirus Vector-based HIV Vaccine Regimens Requires 3 DNA Injections: Results of the Randomized Multicentre EV03/ANRS Vac20 Phase I/II Trial, 17th Conference on Retroviruses and Opportunistic Infections, 2010.

M. Mcelrath and B. Haynes, Induction of Immunity to Human Immunodeficiency Virus Type-1 by Vaccination, Immunity, vol.33, issue.4, pp.542-554, 2010.
DOI : 10.1016/j.immuni.2010.09.011

H. Virgin and B. Walker, Immunology and the elusive AIDS vaccine, Nature, vol.321, issue.7286, pp.224-231, 2010.
DOI : 10.1038/nature08898

M. Mcelrath, D. Rosa, S. Moodie, Z. Dubey, S. Kierstead et al., HIV-1 vaccine-induced immunity in the test-of-concept Step Study: a case???cohort analysis, The Lancet, vol.372, issue.9653, p.372, 1894.
DOI : 10.1016/S0140-6736(08)61592-5

T. Fleming, One-Sample Multiple Testing Procedure for Phase II Clinical Trials, Biometrics, vol.38, issue.1, pp.143-151, 1982.
DOI : 10.2307/2530297

R. Gray, J. Manola, S. Saxman, J. Wright, J. Dutcher et al., Phase II Clinical Trial Design: Methods in Translational Research from the Genitourinary Committee at the Eastern Cooperative Oncology Group, Clinical Cancer Research, vol.12, issue.7, p.12, 1966.
DOI : 10.1158/1078-0432.CCR-05-1136

A. Hern and R. , Sample size tables for exact single-stage phase II designs, pp.859-866, 2001.

S. Zohar, S. Teramukai, and Y. Zhou, Bayesian design and conduct of phase II single-arm clinical trials with binary outcomes: A tutorial, Contemporary Clinical Trials, vol.29, issue.4, pp.608-616, 2008.
DOI : 10.1016/j.cct.2007.11.005

S. Jung and K. Kim, On the estimation of the binomial probability in multistage clinical trials, Statistics in Medicine, vol.73, issue.6, pp.881-896, 2004.
DOI : 10.1002/sim.1653

J. Bryant and R. Day, Incorporating Toxicity Considerations Into the Design of Two-Stage Phase II Clinical Trials, Biometrics, vol.51, issue.4, pp.1372-1383, 1995.
DOI : 10.2307/2533268

K. Messer, L. Natarajan, E. Ball, and T. Lane, Toxicity-evaluation designs for phase I/II cancer immunotherapy trials, Statistics in Medicine, vol.49, issue.7-8, pp.712-720, 2010.
DOI : 10.1002/sim.3799

A. Kramar and C. Bascoul-mollevi, Early Stopping Rules in Clinical Trials Based on Sequential Monitoring of Serious Adverse Events, Medical Decision Making, vol.29, issue.3, pp.343-350, 2009.
DOI : 10.1177/0272989X08327332

A. Ivanova, B. Qaqish, and M. Schell, Continuous Toxicity Monitoring in Phase II Trials in Oncology, Biometrics, vol.42, issue.2, pp.540-545, 2005.
DOI : 10.1111/j.1541-0420.2005.00311.x

J. Yu, A. Hutson, A. Siddiqui, and M. Kedron, Group sequential control of overall toxicity incidents in clinical trials ??? non-Bayesian and Bayesian approaches, Statistical Methods in Medical Research, vol.51, issue.1, 2012.
DOI : 10.1016/0197-2456(86)90004-8

E. Gehan, The determination of the number of patients required in a preliminary and a follow-up trial of a new chemotherapeutic agent, Journal of Chronic Diseases, vol.13, issue.4, pp.346-353, 1961.
DOI : 10.1016/0021-9681(61)90060-1

R. Simon, Optimal two-stage designs for phase II clinical trials, Controlled Clinical Trials, vol.10, issue.1, pp.1-10, 1989.
DOI : 10.1016/0197-2456(89)90015-9

L. Rubinstein, E. Korn, B. Freidlin, S. Hunsberger, S. Ivy et al., Design Issues of Randomized Phase II Trials and a Proposal for Phase II Screening Trials, Journal of Clinical Oncology, vol.23, issue.28, pp.7199-7206, 2005.
DOI : 10.1200/JCO.2005.01.149

C. Jennison and B. Turnbull, Group Sequential Methods with Applications to Clinical Trials, 2000.

A. Goldman and P. Hannan, Optimal continuous sequential boundaries for monitoring toxicity in clinical trials: a restricted search algorithm, Statistics in Medicine, vol.51, issue.11, pp.1575-1589, 2001.
DOI : 10.1002/sim.713

J. Lee and D. Liu, A predictive probability design for phase II cancer clinical trials, Clinical Trials, vol.14, issue.1, pp.93-106, 2008.
DOI : 10.1177/1740774508089279

H. Jin, Alternative designs of phase II trials considering response and toxicity, Contemporary Clinical Trials, vol.28, issue.4, pp.525-531, 2007.
DOI : 10.1016/j.cct.2007.03.003

P. Thall and S. Cheng, Optimal two-stage designs for clinical trials based on safety and efficacy, Statistics in Medicine, vol.64, issue.7, pp.1023-1032, 2001.
DOI : 10.1002/sim.717

M. Conaway and G. Petroni, Bivariate Sequential Designs for Phase II Trials, Biometrics, vol.51, issue.2, pp.656-664, 1995.
DOI : 10.2307/2532952

P. Brutti, S. Gubbiotti, and V. Sambucini, An extension of the single threshold design for monitoring efficacy and safety in phase II clinical trials, Statistics in Medicine, vol.91, issue.4, pp.1648-1664, 2011.
DOI : 10.1002/sim.4229

H. Ray and S. Rai, Flexible bivariate phase II clinical trial design incorporating toxicity and response on different schedules, Statistics in Medicine, vol.55, issue.2, pp.470-485, 2013.
DOI : 10.1002/sim.5671

A. Hoering, M. Leblanc, and J. Crowley, Seamless Phase I-II Trial Design for Assessing Toxicity and Efficacy for Targeted Agents, Clinical Cancer Research, vol.17, issue.4, pp.640-646, 2011.
DOI : 10.1158/1078-0432.CCR-10-1262

P. Liu, M. Leblanc, and M. Desai, False Positive Rates of Randomized Phase II Designs, Controlled Clinical Trials, vol.20, issue.4, pp.343-352, 1999.
DOI : 10.1016/S0197-2456(99)00009-4

. Richert, Accelerating clinical development of HIV vaccine strategies: methodological challenges and considerations in constructing an optimised multi-arm phase I/II trial design, Trials, vol.15, issue.1, p.68, 2014.
DOI : 10.1016/S0197-2456(99)00009-4

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