A randomized, placebo-controlled, dose-escalation study to determine the safety, tolerability, and immunogenicity of an HPV-16 therapeutic vaccine in HIV-positive participants with oncogenic HPV infection of the anus.
OBJECTIVE
Study aimed to assess safety, tolerability, and immunogenicity of novel therapeutic HPV-16 E6E7 ISCOMATRIX vaccine for treatment of human papilloma virus (HPV)-related anal intraepithelial neoplasia in HIV-infected men who have sex with men with moderate immunosuppression.


METHODS
Randomized, multicenter, blinded, placebo-controlled, dose-escalating study investigating 3 different doses of vaccine and different dose schedule. Primary objective to determine safety and tolerability, including clinical status, maintenance of virological control, and CD4 cell count for more than 252 days.


RESULTS
Thirty-five men who have sex with men enrolled; median age 47 years; current CD4 count 627 cells per milliliter; nadir CD4 count 154 cells per milliliter; 94% current antiretrovirals; 100% high-risk HPV types; 69% abnormal anal cytology; and 34% anal intraepithelial neoplasia 1-3 on high-resolution anoscopy. No dose-limiting toxicities or serious adverse events in HPV-16 vaccine recipients. Most HPV-16 vaccine recipients reported moderate/severe short-term injection site reactions and systemic reactions including headache, myalgia, and fatigue. CD4 cell counts remained stable. Five participants had transiently detectable viral loads. Ninety-six percent of vaccine recipients had at least a 4-fold increase in HPV-16 antibody from prevaccination levels. Seventy-one percent had at least a 3-fold increase in interferon-gamma responses to E6E7 peptides.


CONCLUSIONS
The novel therapeutic HPV-16 E6E7 ISCOMATRIX vaccine seemed safe and reasonably well tolerated. The therapeutic vaccine induces strong and durable antibody responses and moderate interferon-gamma levels that fell to prevaccination levels by week 24.
Anderson
Jonathan S
JS
National Centre In HIV Epidemiology and Clinical Research, University of New South Wales, Sydney, Australia. janderson@nchecr.unsw.edu.au
Hoy
Jennifer
J
Hillman
Richard
R
Barnden
Megan
M
Eu
Beng
B
McKenzie
Andrew
A
Gittleson
Charmaine
C
D000276:Adjuvants, Immunologic; D000328:Adult; D000914:Antibodies, Viral; D001005:Anus Neoplasms / Q000150:complications / Q000628:therapy*; D002784:Cholesterol; D004306:Dose-Response Relationship, Immunologic; D004334:Drug Administration Schedule; D004338:Drug Combinations; D015658:HIV Infections / Q000150:complications*; D052162:Human papillomavirus 16; D006801:Humans; D008297:Male; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000150:complications / Q000628:therapy*; D053918:Papillomavirus Vaccines / Q000627:therapeutic use*; D010743:Phospholipids; D012503:Saponins
D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D004338:Drug Combinations; C493786:ISCOMATRIX; D053918:Papillomavirus Vaccines; D010743:Phospholipids; D012503:Saponins; D002784:Cholesterol