HPV Test-and-Treat-Strategy Versus Cytology-based Strategy for Prevention of CIN2+ in HIV-Infected Women

• Detection of high risk (hr)-HPV by the Abbott Real Time high-risk HPV assay (aHPV) at study visits. [ Time Frame: 26-130 weeks post randomization ] [ Designated as safety issue: No ]
• Cervical cytology results at study visits. [ Time Frame: 26-130 weeks post randomization ] [ Designated as safety issue: No ]
• Time to CIN2+ diagnosis by biopsy, as determined by local review at a DAIDS-assessed laboratory. [ Time Frame: 26-130 weeks post randomization ] [ Designated as safety issue: No ]
• CIN3+ (CIN3 or invasive cancer) by biopsy 26 weeks post randomization through 130 weeks post randomization, as determined by local review at a DAIDS-assessed laboratory. [ Time Frame: 26-130 weeks post randomization ] [ Designated as safety issue: No ]
• Early study discontinuation rates and reasons. [ Time Frame: 0-130 weeks post randomization ] [ Designated as safety issue: Yes ]

Women sometimes develop cancer in an area called the cervix, which is the opening to the uterus, or womb. Women who have HIV are more likely to get this kind of cancer than women who do not have HIV. Nearly all of these cancers are caused by another virus, called human papilloma virus (or HPV). Other times, the cause of this cancer is not known.

The investigators are looking for a better way to prevent cervical cancer. This study is comparing two different methods to prevent cancer of the cervix in women who have HIV. This study will also see if these methods are safe and tolerable in women who have HIV.

• Procedure: cervical cryotherapy
  Participants will undergo cervical cryotherapy within 7 days after study entry. The cryotherapy consists of two 3-minute freezes separated by 5 minutes of thawing.
• Procedure: Loop Electrosurgical Excision Procedure (LEEP)
  Participants found to have CIN2+ by biopsy at any point during the study will be offered LEEP, an electro-surgical procedure used to treat high-grade cervical dysplasia.

• Experimental: Arm A: Immediate cryotherapy (HPV test-and-treat)
  Participants in Arm A (HPV test-and-treat) will undergo cervical cryotherapy at entry. Post entry, participants in Arm A will be seen at regular intervals for the collection of cervical specimens, cytology, and as needed cervical colposcopy, directed biopsies, and LEEP.
  Interventions:

  • Procedure: cervical cryotherapy
  • Procedure: Loop Electrosurgical Excision Procedure (LEEP)
• Experimental: Arm B: cytology-based strategy
  Participants in Arm B will follow a cytology-based management plan involving three steps- cytology, colposcopy with directed biopsies, and LEEP (as needed).
  Intervention: Procedure: Loop Electrosurgical Excision Procedure (LEEP)
• Experimental: Arm C : Ineligible for randomization to Arm A or B
  Participants will be eligible for Arm C under the conditions noted in the inclusion criteria. Participants in Arm C will undergo colposcopy and directed biopsies at entry. If CIN2+ is found by biopsy, then LEEP will be performed and a follow-up visit 26 weeks after these procedures will be scheduled for the collection of cervical specimens, cytology, and as needed cervical colposcopy, directed biopsies, and LEEP. After the week 26 visit, Arm C participants will go off study.
  Intervention: Procedure: Loop Electrosurgical Excision Procedure (LEEP)

Inclusion Criteria:

• HIV-1 infection.
• Certain laboratory values obtained within 30 days prior to study entry (more information can be found in the protocol).
• For candidates suitable for cervical cryotherapy, hr-HPV detected by aHPV within 30 days prior to study entry.
• For women without hr-HPV detected by the aHPV assay, presence of lesions on visual inspection or HSIL cervical cytology. These participants are not eligible for randomization to Arms A or B and will be followed in Arm C.
• Suitable candidate for cervical cryotherapy (as defined in the protocol). Unsuitable participants are not eligible for randomization to Arms A or B and will be followed in Arm C.
• For participants of reproductive potential, negative pregnancy test within 48 hours prior to study entry.
• Must agree not to participate in a conception process (e.g. active attempt to get pregnant or in vitro fertilization), or use at least one reliable contraceptive if participating in sexual activity, from time of study entry until 12 weeks after study entry.
• If recently gave birth, must be at least 12 weeks postpartum.
• Ability and willingness of participant or legal guardian/representative to provide written informed consent.

Exclusion Criteria:

• Current or prior history of cervical, vaginal, or vulvar cancer.
• Prior cervical cryotherapy, LEEP, cervical conization, or total or partial hysterectomy.
• Cervical, vaginal, or vulvar lesions that are suspicious on clinical exam for cancer.
• Visual evidence of bacterial STIs or suspicion of pelvic inflammatory disease.
• Prior vaccination with an HPV vaccine.
• Hemophilia.
• Currently on anticoagulation therapy other than acetylsalicylic acid.
• Serious illness requiring systemic treatment and/or hospitalization within 21 days prior to study entry.
• Active drug or alcohol use or dependence or any other condition that, in the opinion of the site investigator, would interfere with the participant's ability to adhere to study requirements.