HPV Vaccine Therapy in Reducing High-Grade Cervical Lesions in Patients With HIV and HPV
HPV Vaccine Therapy in Reducing High-Grade Cervical Lesions in Patients With HIV and HPV
This randomized phase III trial studies how well human papillomavirus (HPV) vaccine therapy
 works in reducing high-grade cervical lesions in patients with human immunodeficiency virus
 (HIV) and HPV. Vaccines made from HPV peptides or antigens may help the body build an
 effective immune response to kill the HPV virus and prevent cervical lesions from developing
 or coming back after being removed.
At screening, potential participants will be tested for cervical human papillomavirus (HPV)
 infection (GeneXpert hrHPV assay and HPV DNA PCR) and undergo cervical colposcopy to confirm
 the absence of cervical cancer. If eligible, the participant will be randomized to receive
 either the 9-valent HPV vaccine or saline placebo.

 Participants will return 4 and 26 weeks later for the second dose of vaccine or placebo. At
 week 4, participants will have cervical colposcopy and undergo cryotherapy or loop
 electrosurgical excisional procedure (LEEP) as appropriate. Participants undergoing cervical
 cryotherapy will have cervical biopsies before the treatment. Participants will be followed
 with HPV testing (Gene Xpert and HPV DNA PCR) at weeks 26, 52, 78, and 104, and will have
 cervical cytology and colposcopy with biopsies at weeks 26, 52, and 104.
Inclusion Criteria:

 -  HIV-1 infection, documented by any licensed rapid HIV test or HIV enzyme or
 chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and
 confirmed by a licensed western blot or a second antibody test by a method other than
 the initial rapid HIV and/or E/CIA, or by HIV-1 antigen, plasma HIV-1 RNA viral load,
 or documentation of receipt of antiretroviral therapy; Note: the term "licensed"
 refers to a kit that has been certified or licensed by an oversight body within the
 participating country and validated internally; WHO (World Health Organization) and
 CDC (Centers for Disease Control and Prevention) guidelines mandate that confirmation
 of the initial test result must use a test that is different from the one used for the
 initial assessment; a reactive initial rapid test should be confirmed by either
 another type of rapid assay or an E/CIA that is based on a different antigen
 preparation and/or different test principle (e.g., indirect versus competitive), or a
 western blot or a plasma HIV-1 RNA viral load

 -  HPV positive by the GeneXpert hrHPV assay with HPV16, HPV 18/45, or HPV31/33/35/52/58
 detected; Note: participants who are hrHPV positive with only HPV51/59 or HPV
 39/68/56/66 detected are not eligible

 -  Receipt of ART for at least 180 days prior to randomization

 -  Participants of childbearing potential, defined as a sexually mature woman who: (1)
 has not undergone a hysterectomy or bilateral oophorectomy or (2) has not been
 naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at
 any time in the preceding 24 consecutive months), must have a negative urine or serum
 pregnancy test within 3 weeks prior to enrollment and agree to use an effective form
 of contraception (e.g., barrier contraception or hormonal contraception), delaying
 pregnancy for at least 12 months and ideally for the duration of the study; Note:
 those willing to participate delay pregnancy for at least 6 months, while receiving
 the recombinant human papillomavirus nonavalent (9vHPV) vaccine (or placebo)

 -  If the participant is of childbearing potential, she should be at least 3 months
 postpartum

 -  Karnofsky score >= 70%

 -  Ability to understand and the willingness to sign a written informed consent document

 Exclusion Criteria:

 -  Current sexually transmitted infection (STI) requiring treatment (women may
 participate after adequate treatment, at the discretion of the treating provider)

 -  History of allergic reactions attributed to compounds of similar chemical or biologic
 composition to Gardasil or Gardasil 9

 -  Uncontrolled intercurrent illness that would limit compliance with study requirements

 -  Prior hysterectomy with removal of the cervix

 -  Prior treatment for cervical HSIL

 -  Prior history of cervical, vulvar, or vaginal cancer

 -  Cervical, vulvar, or vaginal lesions suspicious for cancer based on clinical
 appearance (e.g. necrotic, ulcerated, and/or fungating masses), unless biopsies show
 no invasive cancer

 -  Known bleeding diathesis

 -  Prior HPV vaccination

 -  Current or planned use of anticoagulants other than aspirin or non-steroidal
 anti-inflammatory agents