ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01315353
Recruitment Status : Completed
First Posted : March 15, 2011
Results First Posted : May 11, 2018
Last Update Posted : May 11, 2018
Sponsor:
Collaborator:
National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by (Responsible Party):
AIDS Clinical Trials Group

Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition: HIV-1 Infection
Interventions: Procedure: Cervical Cryotherapy
Procedure: Loop Electrosurgical Excision Procedure (LEEP)

  Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Participants were enrolled from April 2012 to June 2014 from 7 different countries.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Arm A: Immediate Cryotherapy (HPV Test-and-treat)

Participants in Arm A (HPV test-and-treat) had cervical cryotherapy at entry. Post entry, participants in Arm A were seen at regular intervals for the collection of cervical specimens, cytology, and as needed, cervical colposcopy, directed biopsies, and LEEP.

Cervical Cryotherapy: Participants had cervical cryotherapy within 7 days after study entry. The cryotherapy consists of two 3-minute freezes separated by 5 minutes of thawing.

Loop Electrosurgical Excision Procedure (LEEP): Participants found to have CIN2+ by biopsy post-entry had LEEP, an electro-surgical procedure used to treat high-grade cervical dysplasia.

Arm B: Cytology-based Strategy

Participants in Arm B followed a cytology-based management plan involving three steps- cytology, colposcopy with directed biopsies, and LEEP (as needed).

Loop Electrosurgical Excision Procedure (LEEP): Participants found to have CIN2+ by biopsy at any point during the study had LEEP, an electro-surgical procedure used to treat high-grade cervical dysplasia.

Arm C : Ineligible for Randomization to Arm A or B

Participants were eligible for Arm C under the conditions noted in the inclusion criteria. Participants in Arm C had colposcopy and directed biopsies at entry. If CIN2+ is found by biopsy, then LEEP was performed and a follow-up visit 26 weeks after these procedures was 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 went off study.

Loop Electrosurgical Excision Procedure (LEEP): Participants found to have CIN2+ by biopsy at any point during the study had LEEP, an electro-surgical procedure used to treat high-grade cervical dysplasia.


Participant Flow:   Overall Study
    Arm A: Immediate Cryotherapy (HPV Test-and-treat)   Arm B: Cytology-based Strategy   Arm C : Ineligible for Randomization to Arm A or B
STARTED   145   143   179 
COMPLETED   116   120   166 
NOT COMPLETED   29   23   13 
Death                2                1                0 
Withdrawal by Subject                2                6                1 
Lost to Follow-up                13                6                6 
Unwilling to adhere to requirements                5                5                4 
Site closing                7                4                0 
Taken off study by site in error                0                1                0 
Inadvertent randomization/assignment                0                0                2 



  Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent to treat: All eligible participants were included in the analysis.

Reporting Groups
  Description
Arm A: Immediate Cryotherapy (HPV Test-and-treat)

Participants in Arm A (HPV test-and-treat) had cervical cryotherapy at entry. Post entry, participants in Arm A were seen at regular intervals for the collection of cervical specimens, cytology, and as needed, cervical colposcopy, directed biopsies, and LEEP.

Cervical Cryotherapy: Participants had cervical cryotherapy within 7 days after study entry. The cryotherapy consists of two 3-minute freezes separated by 5 minutes of thawing.

Loop Electrosurgical Excision Procedure (LEEP): Participants found to have CIN2+ by biopsy post-entry had LEEP, an electro-surgical procedure used to treat high-grade cervical dysplasia.

Arm B: Cytology-based Strategy

Participants in Arm B followed a cytology-based management plan involving three steps- cytology, colposcopy with directed biopsies, and LEEP (as needed).

Loop Electrosurgical Excision Procedure (LEEP): Participants found to have CIN2+ by biopsy at any point during the study had LEEP, an electro-surgical procedure used to treat high-grade cervical dysplasia.

Arm C : Ineligible for Randomization to Arm A or B

Participants were eligible for Arm C under the conditions noted in the inclusion criteria. Participants in Arm C had colposcopy and directed biopsies at entry. If CIN2+ is found by biopsy, then LEEP was performed and a follow-up visit 26 weeks after these procedures was 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 went off study.

Loop Electrosurgical Excision Procedure (LEEP): Participants found to have CIN2+ by biopsy at any point during the study had LEEP, an electro-surgical procedure used to treat high-grade cervical dysplasia.

Total Total of all reporting groups

Baseline Measures
   Arm A: Immediate Cryotherapy (HPV Test-and-treat)   Arm B: Cytology-based Strategy   Arm C : Ineligible for Randomization to Arm A or B   Total 
Overall Participants Analyzed 
[Units: Participants]
 145   143   177   465 
Age 
[Units: Participants]
Count of Participants
       
Participants Analyzed   145   143   177   465 
<=18 years      0   0.0%      0   0.0%      0   0.0%      0   0.0% 
Between 18 and 65 years      145 100.0%      143 100.0%      175  98.9%      463  99.6% 
>=65 years      0   0.0%      0   0.0%      2   1.1%      2   0.4% 
Age 
[Units: Years]
Median (Inter-Quartile Range)
       
Participants Analyzed   145   143   177   465 
   38 
 (32 to 42) 
 34 
 (29 to 39) 
 36 
 (32 to 42) 
 36 
 (31 to 41) 
Sex: Female, Male 
[Units: Participants]
Count of Participants
       
Participants Analyzed   145   143   177   465 
Female      145 100.0%      143 100.0%      177 100.0%      465 100.0% 
Male      0   0.0%      0   0.0%      0   0.0%      0   0.0% 
Race/Ethnicity, Customized 
[Units: Participants]
Count of Participants
       
Participants Analyzed   145   143   177   465 
Black Non-Hispanic      106  73.1%      107  74.8%      156  88.1%      369  79.4% 
Hispanic (Regardless of Race)      11   7.6%      9   6.3%      6   3.4%      26   5.6% 
Asian, Pacific Islander      28  19.3%      27  18.9%      15   8.5%      70  15.1% 
Region of Enrollment 
[Units: Participants]
Count of Participants
       
Haiti         
Participants Analyzed   145   143   177   465 
Haiti   3   3   16   22 
Malawi         
Participants Analyzed   145   143   177   465 
Malawi   35   37   23   95 
Botswana         
Participants Analyzed   145   143   177   465 
Botswana   8   7   45   60 
South Africa         
Participants Analyzed   145   143   177   465 
South Africa   40   41   55   136 
Zimbabwe         
Participants Analyzed   145   143   177   465 
Zimbabwe   20   19   17   56 
Peru         
Participants Analyzed   145   143   177   465 
Peru   11   9   6   26 
India         
Participants Analyzed   145   143   177   465 
India   28   27   15   70 
CD4+ T-cell Count [1] [2] 
[Units: Cells/mm^3]
Median (Inter-Quartile Range)
       
Participants Analyzed   108   106   146   360 
   529 
 (386 to 687) 
 479 
 (330 to 649) 
 568 
 (391 to 728) 
 521 
 (381 to 699) 
[1] CD4+ T-cell count at entry.
[2] Includes participants with non-missing entry CD4+ T-cell counts.
Nadir CD4+ T-Cell Count [1] [2] 
[Units: Participants]
Count of Participants
       
Participants Analyzed   134   135   167   436 
<=50 cells/mm^3      16  11.9%      15  11.1%      13   7.8%      44  10.1% 
51-100 cells/mm^3      12   9.0%      19  14.1%      17  10.2%      48  11.0% 
101-200 cells/mm^3      33  24.6%      34  25.2%      34  20.4%      101  23.2% 
201-500 cells/mm^3      61  45.5%      57  42.2%      70  41.9%      188  43.1% 
>500 cells/mm^3      12   9.0%      10   7.4%      33  19.8%      55  12.6% 
[1] Nadir CD4+ T-cell count at screening.
[2] Included participants with non-missing nadir CD4+ T-cell count.
HIV-1 RNA [1] 
[Units: Participants]
Count of Participants
       
Participants Analyzed   145   143   177   465 
<LLQ      93  64.1%      85  59.4%      116  65.5%      294  63.2% 
>=LLQ      52  35.9%      58  40.6%      61  34.5%      171  36.8% 
[1] Entry HIV-1 RNA value categorized as below the assay's corresponding lower limit of quantification (<LLQ) or otherwise (>=LLQ).
Antiretroviral Therapy (ART) Use [1] 
[Units: Participants]
Count of Participants
       
Participants Analyzed   145   143   177   465 
Not taking any ART      25  17.2%      22  15.4%      35  19.8%      82  17.6% 
Taking any ART      120  82.8%      121  84.6%      142  80.2%      383  82.4% 
[1] Participants status of ART use at screening.


  Outcome Measures

1.  Primary:   Cumulative Rate of Cervical Intraepithelial Neoplasia (CIN2+) (CIN2, CIN3 or Invasive Cancer) by Week 130   [ Time Frame: Weeks 26, 52, 78, 104 and 130 post randomization ]

2.  Secondary:   Time to CIN2+ Diagnosis by Biopsy, as Determined by Local Review at a DAIDS-assessed Laboratory.   [ Time Frame: Weeks 26, 52, 78, 104 and 130 post randomization ]

3.  Secondary:   Cumulative Rate of CIN3+ (CIN3 or Invasive Cancer) by Week 130.   [ Time Frame: Weeks 26, 52, 78, 104 and 130 post randomization ]

4.  Secondary:   Number of Participants Who Discontinued Study Early.   [ Time Frame: 0 to 130 weeks post randomization ]

5.  Secondary:   Number of Participants With Abnormal Cytology Results at Study Visits.   [ Time Frame: Weeks 26, 52, 78, 104 and 130 post randomization ]

6.  Secondary:   Number of Participants With High Risk (hr)-HPV by the Abbott Real Time High-risk HPV Assay (aHPV) at Study Visits.   [ Time Frame: Weeks 26, 52, 78, 104 and 130 post randomization ]

7.  Secondary:   Number of Participants With High Risk (hr)-HPV by the Xpert HPV Assay at Study Visits.   [ Time Frame: Weeks 26, 52, 78, 104 and 130 post randomization ]

8.  Secondary:   Number of Participants With High Risk (hr)-HPV by the Roche Linear Array HPV Genotyping Test at Study Visits.   [ Time Frame: Weeks 26, 52, 78, 104 and 130 post randomization ]

9.  Secondary:   Percentage of Participants With Targeted Adverse Events (AEs) Reported Post Cryotherapy in Arm A.   [ Time Frame: 4 weeks post cryotherapy ]

10.  Secondary:   Percentage of Participants With Targeted AEs Reported Post LEEP.   [ Time Frame: 4 weeks post LEEP ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information

Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: ACTG Clinicaltrials.gov Coordinator
Organization: ACTG Network Coordinating Center, Social and Scientific Systems, Inc.
phone: (301) 628-3313
e-mail: ACTGCT.Gov@s-3.com



Responsible Party: AIDS Clinical Trials Group
ClinicalTrials.gov Identifier: NCT01315353     History of Changes
Other Study ID Numbers: ACTG A5282
1U01AI068636 ( U.S. NIH Grant/Contract )
First Submitted: March 14, 2011
First Posted: March 15, 2011
Results First Submitted: February 1, 2018
Results First Posted: May 11, 2018
Last Update Posted: May 11, 2018