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

Volumn 11, Issue 7, 2011, Pages 507-515

  Gray, Glenda E ^a   Allen, Mary ^b   Moodie, Zoe ^c   Churchyard, Gavin ^d   Bekker, Linda Gail ^e   Nchabeleng, Maphoshane ^f   Mlisana, Koleka ^g   Metch, Barbara ^c   de Bruyn, Guy ^a   Latka, Mary H ^d,h,i   Roux, Surita ^e   Mathebula, Matsontso ^f   Naicker, Nivashnee ^g   Ducar, Constance ^c   Carter, Donald K ^c   Puren, Adrien ^j   Eaton, Niles ^c   McElrath, M Julie ^c   Robertson, Michael ^a   Corey, Lawrence ^c   Kublin, James G ^c   more..

^a UNIVERSITY OF THE WITWATERSRAND   (South Africa)

^b NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES   (United States)

^c USA   (United States)

^d AURUM INSTITUTE   (South Africa)

^e UNIVERSITY OF CAPE TOWN   (South Africa)

^f SEFAKO MAKGATHO HEALTH SCIENCES UNIVERSITY   (South Africa)

^g UNIVERSITY OF KWAZULU NATAL   (South Africa)

^h Department of Medicine   (United States)

ⁱ NATIONAL INSTITUTE FOR COMMUNICABLE DISEASES   (South Africa)

^j MERCK RESEARCH LABORATORIES   (United States)

more..

Author keywords

[No Author keywords available]

Indexed keywords

GAMMA INTERFERON; HUMAN IMMUNODEFICIENCY VIRUS VACCINE; PLACEBO;

ADENOVIRUS 5; ADULT; ALANINE AMINOTRANSFERASE BLOOD LEVEL; ANEMIA; ANTIBODY TITER; ARTHRALGIA; ARTICLE; CHILL; CIRCUMCISION; CLADISTICS; COMPUTER AIDED DESIGN; CONTROLLED STUDY; COUGHING; CYTOKINE RELEASE; DIARRHEA; DIZZINESS; DOUBLE BLIND PROCEDURE; DRUG EFFICACY; DRUG SAFETY; ENZYME LINKED IMMUNOSPOT ASSAY; FATIGUE; FEMALE; FOLLOW UP; GENITAL HERPES; GENITAL SYSTEM DISEASE; HEADACHE; HEMOGLOBIN BLOOD LEVEL; HERPES SIMPLEX VIRUS 2; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS 1 INFECTION; HYPERTENSION; IMMUNOGENICITY; INCIDENCE; INFLUENZA; INJECTION SITE PAIN; LEUKOPENIA; MAJOR CLINICAL STUDY; MALAISE; MALE; MOUTH PAIN; MYALGIA; NAUSEA; NEUTROPENIA; OUTCOME ASSESSMENT; PERIPHERAL BLOOD MONONUCLEAR CELL; PHARYNGITIS; PHASE 2 CLINICAL TRIAL; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; RASH; SEXUAL BEHAVIOR; SIDE EFFECT; SKIN DISEASE; SKIN INFECTION; SOUTH AFRICA; T LYMPHOCYTE; TREATMENT DURATION; UPPER RESPIRATORY TRACT INFECTION; URINARY TRACT INFECTION; VACCINATION; VIRUS LOAD; VOMITING;

ADOLESCENT; ADULT; AIDS VACCINES; COHORT STUDIES; DOUBLE-BLIND METHOD; FEMALE; HIV INFECTIONS; HIV-1; HUMANS; IMMUNITY, CELLULAR; INTERFERON-GAMMA; MALE; PROPORTIONAL HAZARDS MODELS; RNA, VIRAL; SOUTH AFRICA; YOUNG ADULT;

EID: 79959301474     PISSN: 14733099     EISSN: 14744457     Source Type: Journal    
DOI: 10.1016/S1473-3099(11)70098-6     Document Type: Article

References (33)

1. Report on the global AIDS epidemic 2008, UNAIDS, Joint United Nations Programme on HIV/AIDS, Geneva.
2. Shisana O, Rehle T, Simbayi L, et al. South African national HIV prevalence, incidence, behaviour and communication survey 2008: a turning tide among teenagers? 2009, HSRC Press, Cape Town.
3. Klein MR Kinetics of Gag-specific cytotoxic T lymphocyte responses during the clinical course of HIV-1 infection: a longitudinal analysis of rapid progressors and long-term asymptomatics. J Exp Med 1995, 181:1365-1372.
4. Harrer T, Harrer E, Kalams SA, et al. Strong cytotoxic T cell and weak neutralizing antibody responses in a subset of persons with stable nonprogressing HIV type 1 infection. AIDS Res Hum Retroviruses 1996, 12:585-592.
5. Kalams SA, Buchbinder SP, Rosenberg ES, et al. Association between virus-specific cytotoxic T-lymphocyte and helper responses in human immunodeficiency virus type 1 infection. J Virol 1999, 73:6715-6720.
6. Shiver JW, Fu TM, Chen L, et al. Replication-incompetent adenoviral vaccine vector elicits effective anti-immunodeficiency-virus immunity. Nature 2002, 415:331-335.
7. Shiver JW, Emini EA Recent advances in the development of HIV-1 vaccines using replication-incompetent adenovirus vectors. Annu Rev Med 2004, 55:355-372.
8. Ramsburg E, Rose NF, Marx PA, et al. Highly effective control of an AIDS virus challenge in macaques by using vesicular stomatitis virus and modified vaccinia virus Ankara vaccine vectors in a single-boost protocol. J Virol 2004, 78:3930-3940.
9. Rosenberg ES, Billingsley JM, Caliendo AM, et al. Vigorous HIV-1-specific CD4+ T cell responses associated with control of viremia. Science 1997, 278:1447-1450.
10. Priddy FH, Brown D, Kublin J, et al. Safety and immunogenicity of a replication-incompetent adenovirus type 5 HIV-1 clade B gag/pol/nef vaccine in healthy adults. Clin Infect Dis 2008, 46:1769-1781.
11. Tobery TW, Dubey SA, Anderson K, et al. A comparison of standard immunogenicity assays for monitoring HIV type 1 gag-specific T cell responses in Ad5 HIV Type 1 gag vaccinated human subjects. AIDS Res Hum Retroviruses 2006, 22:1081-1090.
12. Buchbinder SP, Mehrotra DV, Duerr A, et al. Efficacy assessment of a cell-mediated immunity HIV-1 vaccine (the Step Study): a double-blind, randomised, placebo-controlled, test-of-concept trial. Lancet 2008, 372:1881-1893.
13. Bredell H, Martin DP, Van Harmelen J, et al. HIV type 1 subtype C gag and nef diversity in southern Africa. AIDS Res Hum Retroviruses 2007, 23:477-481.
14. Woodman Z, Williamson C HIV molecular epidemiology: transmission and adaptation to human populations. Curr Opin HIV AIDS 2009, 4:247-252.
15. Nwanegbo E, Vardas E, Gao W, et al. Prevalence of neutralizing antibodies to adenoviral serotypes 5 and 35 in the adult populations of The Gambia, South Africa, and the United States. Clin Diagn Lab Immunol 2004, 11:351-357.
16. Mast TC, Kierstead L, Gupta SB, et al. International epidemiology of human pre-existing adenovirus (Ad) type-5, type-6, type-26 and type-36 neutralizing antibodies: correlates of high Ad5 titers and implications for potential HIV vaccine trials. Vaccine 2010, 28:950-957.
17. Ferrari G, Humphrey W, McElrath MJ, et al. Clade B-based HIV-1 vaccines elicit cross-clade cytotoxic T lymphocyte reactivities in uninfected volunteers. Proc Natl Acad Sci USA 1997, 94:1396-1401.
18. Coplan PM, Gupta SB, Dubey SA, et al. Cross-reactivity of anti-HIV-1 T cell immune responses among the major HIV-1 clades in HIV-1-positive individuals from 4 continents. J Infect Dis 2005, 191:1427-1434.
19. Aste-Amezaga M, Bett AJ, Wang F, et al. Quantitative adenovirus neutralization assays based on the secreted alkaline phosphatase reporter gene: application in epidemiologic studies and in the design of adenovector vaccines. Hum Gene Ther 2004, 15:293-304.
20. Ashley RL, Militoni J, Lee F, Nahmias A, Corey L Comparison of Western blot (immunoblot) and glycoprotein G-specific immunodot enzyme assay for detecting antibodies to herpes simplex virus types 1 and 2 in human sera. J Clin Microbiol 1988, 26:662-667.
21. de Bruyn G, Martinson NA, Nkala BD, et al. Uptake of male circumcision in an HIV vaccine efficacy trial. J Aquir Immune Defic Syndr 2009, 51:108-110.
22. Malhotra U, Nolin J, Horton H, et al. Functional properties and epitope characteristics of T-cells recognizing natural HIV-1 variants. Vaccine 2009, 27:6678-6687.
23. Dubey S, Clair J, Fu TM, et al. Detection of HIV vaccine-induced cell-mediated immunity in HIV-seronegative clinical trial participants using an optimized and validated enzyme-linked immunospot assay. J Aquir Immune Defic Syndr 2007, 45:20-27.
24. Hochberg Y A sharper Bonferroni procedure for multiple tests of significance. Biometrika 1988, 75:800-802.
25. Gilbert PB, Wei LJ, Kosorok MR, Clemens JD Simultaneous inferences on the contrast of two hazard functions with censored observations. Biometrics 2002, 58:773-780.
26. Moodie Z, Price L, Gouttefangeas C, et al. Response definition criteria for ELISPOT assays revisited. Cancer Immunol Immunother 2010, 59:1489-1501.
27. McElrath MJ, De Rosa SC, Moodie Z, et al. HIV-1 vaccine-induced immunity in the test-of-concept Step Study: a case-cohort analysis. Lancet 2008, 372:1894-1905.
28. Freeman EE, Weiss HA, Glynn JR, Cross PL, Whitworth JA, Hayes RJ Herpes simplex virus 2 infection increases HIV acquisition in men and women: systematic review and meta-analysis of longitudinal studies. AIDS 2006, 20:73-83.
29. Corey L, Wald A, Celum CL, Quinn TC The effects of herpes simplex virus-2 on HIV-1 acquisition and transmission: a review of two overlapping epidemics. J Aquir Immune Defic Syndr 2004, 35:435-445.
30. Corey L Synergistic copathogens-HIV-1 and HSV-2. N Engl J Med 2007, 356:854-856.
31. Weiss HA, Buve A, Robinson NJ, et al. The epidemiology of HSV-2 infection and its association with HIV infection in four urban African populations. AIDS 2001, 15(suppl 4):S97-S108.
32. Ramjee G, Williams B, Gouws E, Van Dyck E, De Deken B, Karim SA The impact of incident and prevalent herpes simplex virus-2 infection on the incidence of HIV-1 infection among commercial sex workers in South Africa. J Aquir Immune Defic Syndr 2005, 39:333-339.
33. Morrison CS, Richardson BA, Mmiro F, et al. Hormonal contraception and the risk of HIV acquisition. AIDS 2007, 21:85-95.