HPV Vaccine Therapy in Reducing High-Grade Cervical Lesions in Patients With HIV and HPV

Inclusion Criteria:

• HIV-1 infection, documented by any licensed rapid HIV test or HIV enzyme orchemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry andconfirmed by a licensed western blot or a second antibody test by a method otherthan the initial rapid HIV and/or E/CIA, or by HIV-1 antigen, plasma HIV-1 RNA viralload, or documentation of receipt of antiretroviral therapy; Note: the term "licensed" refers to a kit that has been certified or licensed by an oversight bodywithin the participating country and validated internally; WHO (World HealthOrganization) and CDC (Centers for Disease Control and Prevention) guidelinesmandate that confirmation of the initial test result must use a test that isdifferent from the one used for the initial assessment; a reactive initial rapidtest should be confirmed by either another type of rapid assay or an E/CIA that isbased 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, orHPV31/33/35/52/58 detected; Note: participants who are hrHPV positive with onlyHPV51/59 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 beennaturally postmenopausal for at least 24 consecutive months (i.e., has had menses atany time in the preceding 24 consecutive months), must have a negative urine orserum pregnancy test within 3 weeks prior to enrollment and agree to use aneffective form of contraception (e.g., barrier contraception or hormonalcontraception), delaying pregnancy for at least 12 months and ideally for theduration of the study; Note: those willing to participate delay pregnancy for atleast 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 monthspostpartum

• Karnofsky score >= 70%

• Ability to understand and the willingness to sign a written informed consentdocument

Exclusion Criteria:

• Current sexually transmitted infection (STI) requiring treatment (women mayparticipate after adequate treatment, at the discretion of the treating provider)

• History of allergic reactions attributed to compounds of similar chemical orbiologic composition to Gardasil or Gardasil 9

• Uncontrolled intercurrent illness that would limit compliance with studyrequirements

• 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 clinicalappearance (e.g. necrotic, ulcerated, and/or fungating masses), unless biopsies showno invasive cancer

• Known bleeding diathesis

• Prior HPV vaccination

• Current or planned use of anticoagulants other than aspirin or non-steroidalanti-inflammatory agents