NCT01315353

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

Completed NA Results posted Last updated 11 May 2018

What this trial tests

NA trial testing Cervical Cryotherapy in HIV-1 Infection in 467 participants. Completed in 1 February 2017.

Timeline

4 April 2012

Primary endpoint
1 February 2017

1 February 2017

Quick facts

Lead sponsor	Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections
Phase	NA
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	467
Start date	4 April 2012
Primary completion	1 February 2017
Estimated completion	1 February 2017
Sites	13 locations across Zimbabwe, Haiti, South Africa, Peru, Malawi, Botswana, India

Drugs / interventions tested

• Cervical Cryotherapy
• Loop Electrosurgical Excision Procedure (LEEP)

Conditions studied

• HIV-1 Infection — all drugs for HIV-1 Infection →

Sponsor

Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections

Who can join

18 and older, female only, with HIV-1 Infection. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Cumulative Rate of Cervical Intraepithelial Neoplasia (CIN2+) (CIN2, CIN3 or Invasive Cancer) by Week 130 Primary · Weeks 26, 52, 78, 104 and 130 post randomization

The Kaplan-Meier estimate of the cumulative rate of CIN2+ (CIN2, CIN3 or invasive cancer) by week 130. Time to CIN2+ was computed as the number of weeks between randomization and the week 26 to week 130 biopsy week when CIN2+ was first detected. For those who did not develop CIN2+, event time was censored at the latest among the following: time of last biopsy or last colposcopy or last pap smear. CIN2+ diagnosis by biopsy was determined by local review at a DAIDS-assessed laboratory.

Group	Value	95% CI
Arm A: Immediate Cryotherapy (HPV Test-and-treat)	24.9	16.9 – 32.9
Arm B: Cytology-based Strategy	26.5	18.3 – 34.7

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

Time to CIN2+ was computed as the number of weeks between randomization and the week 26 to week 130 biopsy week when CIN2+ was first detected. For those who did not develop CIN2+, event time was censored at the latest among the following: time of last biopsy or last colposcopy or last pap smear. The 10th percentile of the time to CIN2+ (the number of weeks at which 10% of participants had had CIN2+ diagnosis) is presented in the data table below.

Group	Value	95% CI
Arm A: Immediate Cryotherapy (HPV Test-and-treat)	31	28 – 66
Arm B: Cytology-based Strategy	30	27 – 87

Cumulative Rate of CIN3+ (CIN3 or Invasive Cancer) by Week 130. Secondary · Weeks 26, 52, 78, 104 and 130 post randomization

The Kaplan-Meier estimate of the cumulative rate of CIN3+ (CIN3 or invasive cancer) by week 130. Time to CIN3+ was computed as the number of weeks between randomization and the week 26 to week 130 biopsy week when CIN3+ was first detected. For those who did not develop CIN3+, event time was censored at the latest among the following: time of last biopsy or last colposcopy or last pap smear. CIN3+ diagnosis by biopsy was determined by local review at a DAIDS-assessed laboratory.

Group	Value	95% CI
Arm A: Immediate Cryotherapy (HPV Test-and-treat)	12.7	6.8 – 18.6
Arm B: Cytology-based Strategy	17.1	10.0 – 24.3

Number of Participants Who Discontinued Study Early. Secondary · 0 to 130 weeks post randomization

The number of participants who did not complete the study.

Group	Value	95% CI
Arm A: Immediate Cryotherapy (HPV Test-and-treat)	29
Arm B: Cytology-based Strategy	23

Number of Participants With Abnormal Cytology Results at Study Visits. Secondary · Weeks 26, 52, 78, 104 and 130 post randomization

Number of participants with abnormal (ASCUS: atypical squamous cells; undetermined significance, ASC-H: atypical squamous cells; favor high-grade squamous intra-epithelial lesion, LSIL: low-grade squamous intraepithelial lesion/mild dysplasia/HPV, HSIL: high-grade squamous intraepithelial lesion/moderate or severe dysplasia/carcinoma in situ/features of invasion; squamous cell carcinoma) cytology results.

Week 26: With Abnormal Cytology

Group	Value	95% CI
Arm A: Immediate Cryotherapy (HPV Test-and-treat)	80
Arm B: Cytology-based Strategy	75

Week 52: With Abnormal Cytology

Group	Value	95% CI
Arm A: Immediate Cryotherapy (HPV Test-and-treat)	80
Arm B: Cytology-based Strategy	72

Week 78: With Abnormal Cytology

Group	Value	95% CI
Arm A: Immediate Cryotherapy (HPV Test-and-treat)	63
Arm B: Cytology-based Strategy	64

Week 104: With Abnormal Cytology

Group	Value	95% CI
Arm A: Immediate Cryotherapy (HPV Test-and-treat)	57
Arm B: Cytology-based Strategy	62

Week 130: With Abnormal Cytology

Group	Value	95% CI
Arm A: Immediate Cryotherapy (HPV Test-and-treat)	33
Arm B: Cytology-based Strategy	46

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

Number of participants with hr-HPV (HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68) as detected by the Abbott Real Time high-risk HPV assay. Specimens for weeks 52, 78, 104 and 130 were not tested due to insufficient funding.

Week 26: With hr-HPV Detected

Group	Value	95% CI
Arm A: Immediate Cryotherapy (HPV Test-and-treat)	74
Arm B: Cytology-based Strategy	78

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

Number of participants with hr-HPV (HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68) as detected by the Xpert HPV assay. Specimens for weeks 52, 78, 104 and 130 were not tested due to insufficient funding.

Week 26: With hr-HPV Detected

Group	Value	95% CI
Arm A: Immediate Cryotherapy (HPV Test-and-treat)	64
Arm B: Cytology-based Strategy	68

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

Number of participants with hr-HPV (HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68) as detected by the Roche Linear Array HPV Genotyping test. Specimens for weeks 52, 78, 104 and 130 were not tested due to insufficient funding.

Week 26: With hr-HPV Detected

Group	Value	95% CI
Arm A: Immediate Cryotherapy (HPV Test-and-treat)	74
Arm B: Cytology-based Strategy	73

Percentage of Participants With Targeted Adverse Events (AEs) Reported Post Cryotherapy in Arm A. Secondary · 4 weeks post cryotherapy

Cryotherapy was performed in Arm A within 7 days of study entry. Targeted AEs four weeks after cryotherapy is provided in the data table below. The AE categories are not mutually exclusive. A participant may have experienced AEs and may be counted in more than one category.

Profuse watery vaginal discharge

Group	Value	95% CI
Arm A: Immediate Cryotherapy (HPV Test-and-treat)	20

Mild cervical bleeding

Group	Value	95% CI
Arm A: Immediate Cryotherapy (HPV Test-and-treat)	15

Heavy odorous discharge

Group	Value	95% CI
Arm A: Immediate Cryotherapy (HPV Test-and-treat)	13

Cervical infection

Group	Value	95% CI
Arm A: Immediate Cryotherapy (HPV Test-and-treat)	5

Mild watery vaginal discharge

Group	Value	95% CI
Arm A: Immediate Cryotherapy (HPV Test-and-treat)	4

Lower Abdominal Pain

Group	Value	95% CI
Arm A: Immediate Cryotherapy (HPV Test-and-treat)	3

Severe cramps or abdominal pain requiring parenter

Group	Value	95% CI
Arm A: Immediate Cryotherapy (HPV Test-and-treat)	3

Moderate Watery Vaginal Discharge

Group	Value	95% CI
Arm A: Immediate Cryotherapy (HPV Test-and-treat)	2

Percentage of Participants With Targeted AEs Reported Post LEEP. Secondary · 4 weeks post LEEP

LEEP was performed on participants who had CIN2+. For Arm A participants, LEEP was available starting at week 26; for Arms B and C, LEEP was available starting at study entry. Targeted AEs four weeks after LEEP is provided in the data table below. The AE categories are not mutually exclusive. A participant may have experienced AEs and may be counted in more than one category.

Cervical bleeding

Group	Value	95% CI
Arm A: Immediate Cryotherapy (HPV Test-and-treat)	50
Arm B: Cytology-based Strategy	21
Arm C : Ineligible for Randomization to Arm A or B	22

Vaginal discharge

Group	Value	95% CI
Arm A: Immediate Cryotherapy (HPV Test-and-treat)	12
Arm B: Cytology-based Strategy	15
Arm C : Ineligible for Randomization to Arm A or B	31

Cramps or abdominal pain requiring parenteral meds

Group	Value	95% CI
Arm A: Immediate Cryotherapy (HPV Test-and-treat)	12
Arm B: Cytology-based Strategy	6
Arm C : Ineligible for Randomization to Arm A or B	13

Vaginal Bleeding

Group	Value	95% CI
Arm A: Immediate Cryotherapy (HPV Test-and-treat)	4
Arm B: Cytology-based Strategy	3
Arm C : Ineligible for Randomization to Arm A or B	13

Cervical infection

Group	Value	95% CI
Arm A: Immediate Cryotherapy (HPV Test-and-treat)	0
Arm B: Cytology-based Strategy	3
Arm C : Ineligible for Randomization to Arm A or B	2

Metrorrhagia

Group	Value	95% CI
Arm A: Immediate Cryotherapy (HPV Test-and-treat)	4
Arm B: Cytology-based Strategy	0
Arm C : Ineligible for Randomization to Arm A or B	0

Pelvic inflammatory disease

Group	Value	95% CI
Arm A: Immediate Cryotherapy (HPV Test-and-treat)	0
Arm B: Cytology-based Strategy	3
Arm C : Ineligible for Randomization to Arm A or B	0

Adverse events — posted to ClinicalTrials.gov

Time frame: AEs reported from entry visit to off study visit (at week 130 or earlier).. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

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

Serious: 5/145 (3%)

Deaths: 2/145

Arm B: Cytology-based Strategy

Serious: 2/143 (1%)

Deaths: 1/143

Arm C: Ineligible for Randomization to Arm A or B

Serious: 5/177 (3%)

Deaths: 0/177

Serious adverse events (9 terms)

Reaction	System	Arm A: Immediate Cryothera…	Arm B: Cytology-based Stra…	Arm C: Ineligible for Rand…
Vaginal haemorrhage	Reproductive system and breast disorders	—	—	—
Localised infection	Infections and infestations	—	—	—
Cervix carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—
Cervix carcinoma stage 0	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—
Squamous cell carcinoma of the cervix	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—
Abortion spontaneous	Pregnancy, puerperium and perinatal conditions	—	—	—
Foetal death	Pregnancy, puerperium and perinatal conditions	—	—	—
Cervical dysplasia	Reproductive system and breast disorders	—	—	—
Cervix haemorrhage uterine	Reproductive system and breast disorders	—	—	—

Other adverse events (9 terms — click to expand)

Reaction	System	Arm A: Immediate Cryothera…	Arm B: Cytology-based Stra…	Arm C: Ineligible for Rand…
Vaginal discharge	Reproductive system and breast disorders	—	—	—
Cervicitis	Infections and infestations	—	—	—
Bacterial vaginosis	Infections and infestations	—	—	—
Cervical dysplasia	Reproductive system and breast disorders	—	—	—
Abdominal pain lower	Gastrointestinal disorders	—	—	—
Vulvovaginal candidiasis	Infections and infestations	—	—	—
Vaginal haemorrhage	Reproductive system and breast disorders	—	—	—
Cervicitis trichomonal	Infections and infestations	—	—	—
Pregnancy	Pregnancy, puerperium and perinatal conditions	—	—	—

Most-reported serious reactions: Vaginal haemorrhage, Localised infection, Cervix carcinoma, Cervix carcinoma stage 0, Squamous cell carcinoma of the cervix, Abortion spontaneous, Foetal death, Cervical dysplasia.

Data from ClinicalTrials.gov NCT01315353 adverse events section.

Sponsor's own description

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.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

1. Improving diagnostic capability for HPV disease internationally within the NIH-NIAID Division of AIDS Clinical Trial Networks.
   Godfrey CC, Michelow PM, Godard M, Sahasrabuddhe VV, et al · · 2013 · cited 7× · PMID 24225757 · DOI 10.1309/ajcpibis19qiyhjy
2. A Randomized Clinical Trial of Human Papillomavirus Test-and-Treat as Compared to Cytology-Based Screening for Prevention of Cervical Cancer Among Women With Human Immunodeficiency Virus: AIDS Clinical Trials Group Protocol A5282.
   Wilkin T, Chen H, Sahasrabuddhe V, Matining R, et al · · 2022 · cited 4× · PMID 35294524 · DOI 10.1093/cid/ciac213
3. Extensive cervical lesion and treatment outcomes in women with HIV/HPV co-infection.
   Mngqibisa R, Chen H, Godfrey C, Sebitloane M, et al · · 2024 · cited 1× · PMID 39736742 · DOI 10.1186/s12981-024-00693-6