Abstract
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. DESIGN:: 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-γ levels that fell to prevaccination levels by week 24.
| Original language | English |
|---|---|
| Pages (from-to) | 371-381 |
| Number of pages | 11 |
| Journal | Journal of Acquired Immune Deficiency Syndromes |
| Volume | 52 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 1 Nov 2009 |
Keywords
- Anal intraepithelial neoplasia
- HIV
- Human papilloma virus
- Randomized controlled trial
- Therapeutic vaccine
Cite this
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A randomized, placebo-controlled, dose-escalation study to determine the safety, tolerability, and immunogenicity of an HPV-16 therapeutic vbaccine in HIV-positive participants with oncogenic HPV infection of the anus. / Anderson, Jonathan S.; Hoy, Jennifer; Hillman, Richard; Barnden, Megan; Eu, Beng; McKenzie, Andrew; Gittleson, Charmaine.
In: Journal of Acquired Immune Deficiency Syndromes, Vol. 52, No. 3, 01.11.2009, p. 371-381.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - A randomized, placebo-controlled, dose-escalation study to determine the safety, tolerability, and immunogenicity of an HPV-16 therapeutic vbaccine in HIV-positive participants with oncogenic HPV infection of the anus
AU - Anderson, Jonathan S.
AU - Hoy, Jennifer
AU - Hillman, Richard
AU - Barnden, Megan
AU - Eu, Beng
AU - McKenzie, Andrew
AU - Gittleson, Charmaine
PY - 2009/11/1
Y1 - 2009/11/1
N2 - 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. DESIGN:: 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-γ levels that fell to prevaccination levels by week 24.
AB - 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. DESIGN:: 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-γ levels that fell to prevaccination levels by week 24.
KW - Anal intraepithelial neoplasia
KW - HIV
KW - Human papilloma virus
KW - Randomized controlled trial
KW - Therapeutic vaccine
UR - http://www.scopus.com/inward/record.url?scp=70350550184&partnerID=8YFLogxK
U2 - 10.1097/QAI.0b013e3181b7354c
DO - 10.1097/QAI.0b013e3181b7354c
M3 - Article
VL - 52
SP - 371
EP - 381
JO - JAIDS
JF - JAIDS
SN - 1525-4135
IS - 3
ER -