Safety of and Immune Response to the Human Papillomavirus (HPV) Vaccine in HIV-Infected Women

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00604175
First received: January 17, 2008
Last updated: July 22, 2014
Last verified: July 2014
Results First Received: July 15, 2013  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Prevention
Conditions: HIV Infections
Sexually Transmitted Diseases
Intervention: Biological: Quadrivalent HPV vaccine

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
319 HIV-infected women 13-45 years of age were recruited in US, South Africa and Brazil between March 2008 and July 2011 for participation in this study.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment

Participants were enrolled into 3 strata based on screening CD4 cell count:

  • Stratum A: CD4 cell count >350 cells/mm3
  • Stratum B: CD4 cell count >200 to <=350 cells/mm3
  • Stratum C: CD4 cell count <=200 cells/mm3

Reporting Groups
  Description
Stratum A Participants with screening CD4 count >350 cells/mm3 received 0.5mL of quadrivalent HPV vaccine at baseline and Weeks 8 and 24.
Stratum B Participants with screening CD4 count >200 to <=350 cells/mm3 received 0.5mL of quadrivalent HPV vaccine at baseline and Weeks 8 and 24.
Stratum C Participants with screening CD4 count <=200 cells/mm3 received 0.5mL of quadrivalent HPV vaccine at baseline and Weeks 8 and 24.

Participant Flow:   Overall Study
    Stratum A     Stratum B     Stratum C  
STARTED     130     95     94  
COMPLETED     120 [1]   92 [1]   93 [1]
NOT COMPLETED     10     3     1  
Death                 2                 0                 0  
Withdrawal by Subject                 1                 0                 0  
Lost to Follow-up                 4                 3                 0  
Ineligible                 1                 0                 0  
Did not start intervention                 2                 0                 1  
[1] Completed 28 weeks of the study (the primary endpoint time point).



  Baseline Characteristics
  Hide 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.
All participants, except 4: one was found to be ineligible after enrollment (Stratum A) and 3 failed to start intervention (2 in Stratum A, 1 in Stratum B).

Reporting Groups
  Description
Stratum A Participants with screening CD4 count >350 cells/mm3 received 0.5mL of quadrivalent HPV vaccine at baseline and Weeks 8 and 24.
Stratum B Participants with screening CD4 count >200 to <=350 cells/mm3 received 0.5mL of quadrivalent HPV vaccine at baseline and Weeks 8 and 24.
Stratum C Participants with screening CD4 count <=200 cells/mm3 received 0.5mL of quadrivalent HPV vaccine at baseline and Weeks 8 and 24.
Total Total of all reporting groups

Baseline Measures
    Stratum A     Stratum B     Stratum C     Total  
Number of Participants  
[units: participants]
  127     95     93     315  
Age  
[units: years]
Median ( Inter-Quartile Range )
  35  
  ( 29 to 40 )  
  38  
  ( 33 to 42 )  
  36  
  ( 31 to 40 )  
  36  
  ( 30 to 41 )  
Age, Customized  
[units: Participants]
       
13 - 17 years     0     0     1     1  
18 - 24 years     10     3     7     20  
25 - 29 years     24     11     12     47  
30 - 34 years     26     14     20     60  
35 - 39 years     31     26     24     81  
40 - 45 years     36     41     29     106  
Gender  
[units: Participants]
       
Female     127     95     93     315  
Male     0     0     0     0  
Race/Ethnicity, Customized [1]
[units: Participants]
       
White, Non-Hispanic     19     9     8     36  
Black, Non-Hispanic     67     59     51     177  
Hispanic (Regardless of Race)     39     25     32     96  
Asian, Pacific Islander     2     0     1     3  
Unknown     0     2     1     3  
Region of Enrollment  
[units: Participants]
       
United States     113     80     69     262  
Brazil     11     6     11     28  
South Africa     3     9     13     25  
HIV Antiretroviral Therapy (ART) Status  
[units: Participants]
       
On ART     58     71     80     209  
Not on ART     69     24     13     106  
CD4 Cell Count  
[units: Cells/mm3]
Median ( Inter-Quartile Range )
  519  
  ( 418 to 664 )  
  287  
  ( 246 to 344 )  
  154  
  ( 86 to 188 )  
  310  
  ( 197 to 498 )  
Nadir CD4 Cell Count  
[units: Cells/mm3]
Median ( Inter-Quartile Range )
  368  
  ( 234 to 482 )  
  176  
  ( 64 to 261 )  
  41  
  ( 20 to 108 )  
  179  
  ( 47 to 314 )  
HIV Viral Load [2]
[units: Participants]
       
<=10,000 copies/mL     71     69     61     201  
>10,000 copies/mL     56     25     32     113  
Unknown     0     1     0     1  
Human Papillomavirus Type 6 (HPV6) Serostatus [3]
[units: Participants]
       
Seronegative     66     60     56     182  
Seropositive     54     35     37     126  
Unknown     7     0     0     7  
Human Papillomavirus Type 11 (HPV11) Serostatus [4]
[units: Participants]
       
Seronegative     99     72     74     245  
Seropositive     22     23     19     64  
Unknown     6     0     0     6  
Human Papillomavirus Type 16 (HPV16) Serostatus [5]
[units: Participants]
       
Seronegative     77     65     67     209  
Seropositive     44     30     26     100  
Unknown     6     0     0     6  
Human Papillomavirus Type 18 (HPV18) Serostatus [6]
[units: Participants]
       
Seronegative     92     83     73     248  
Seropositive     29     12     20     61  
Unknown     6     0     0     6  
[1] Race/ethnicity, self-reported (NIH categories).
[2] A blood sample was drawn for HIV viral load testing by local laboratories. The assays used were Roche Amplicor Monitor HIV RT PCR, Roche UltraSensitive HIV RT PCR, bDNA (Versant HIV-1 RNA 3.0, 3rd), Roche COBAS AmpliPrep/Taqman HIV and Abbott RealTime HIV-1.
[3] HPV serotyping was performed centrally using the competitive Luminex ImmunoAssay (HPV-4, cLIA) on stored serum. Seronegative status was defined as HPV6 antibody titers <20 mMU/mL and seropositive as HPV6 antibody titers >=20 mMU/mL.
[4] HPV serotyping was performed centrally using the competitive Luminex ImmunoAssay (HPV-4, cLIA) on stored serum. Seronegative status was defined as HPV11 antibody titers <16 mMU/mL and seropositive as HPV11 antibody titers >=16 mMU/mL.
[5] HPV serotyping was performed centrally using the competitive Luminex ImmunoAssay (HPV-4, cLIA) on stored serum. Seronegative status was defined as HPV16 antibody titers <20 mMU/mL and seropositive as HPV16 antibody titers >=20 mMU/mL.
[6] HPV serotyping was performed centrally using the competitive Luminex ImmunoAssay (HPV-4, cLIA) on stored serum. Seronegative status was defined as HPV18 antibody titers <24 mMU/mL and seropositive as HPV18 antibody titers >=24 mMU/mL.



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Percentage of Participants With HPV6 Antibody Development From Seronegative Status at Baseline to Seropositive Status a Month After Completion of HPV Vaccination Series   [ Time Frame: Week 28 ]

2.  Primary:   Percentage of Participants With HPV11 Antibody Development From Seronegative Status at Baseline to Seropositive Status a Month After Completion of HPV Vaccination Series   [ Time Frame: Week 28 ]

3.  Primary:   Percentage of Participants With HPV16 Antibody Development From Seronegative Status at Baseline to Seropositive Status a Month After Completion of HPV Vaccination Series   [ Time Frame: Week 28 ]

4.  Primary:   Percentage of Participants With HPV18 Antibody Development From the Seronegative Status at Baseline to Seropositive Status a Month After Completion of HPV Vaccination Series   [ Time Frame: Week 28 ]

5.  Secondary:   HPV6 Antibody Titers Among Those Seronegative for HPV6 at Baseline   [ Time Frame: Weeks 28, 72 ]

6.  Secondary:   HPV11 Antibody Titers Among Those Seronegative for HPV11 at Baseline   [ Time Frame: Weeks 28, 72 ]

7.  Secondary:   HPV16 Antibody Titers Among Those Seronegative for HPV16 at Baseline   [ Time Frame: Weeks 28, 72 ]

8.  Secondary:   HPV18 Antibody Titers Among Those Seronegative for HPV18 at Baseline   [ Time Frame: Weeks 28, 72 ]

9.  Secondary:   Change in Log10 HPV6 Antibody Titers From Baseline Among Those Seropositive for HPV6 at Baseline   [ Time Frame: Weeks 0, 28, 72 ]

10.  Secondary:   Change in Log10 HPV11 Antibody Titers From Baseline Among Those Seropositive for HPV11 at Baseline   [ Time Frame: Weeks 0, 28, 72 ]

11.  Secondary:   Change in Log10 HPV16 Antibody Titers From Baseline Among Those Seropositive for HPV16 at Baseline   [ Time Frame: Weeks 0, 28, 72 ]

12.  Secondary:   Change in Log10 HPV18 Antibody Titers From Baseline Among Those Seropositive for HPV18 at Baseline   [ Time Frame: Weeks 0, 28, 72 ]

13.  Secondary:   Number of Participants With Signs and Symptoms of Grade 3 or Higher   [ Time Frame: From baseline to up to Week 72 ]

14.  Secondary:   Number of Participants With Laboratory Abnormalities of Grade 3 or Higher   [ Time Frame: From baseline to up to Week 72 ]

15.  Secondary:   Change in Log10 HIV Viral Load (VL) From Baseline   [ Time Frame: Weeks 0, 4, 12, 28, 52, and 72 ]

16.  Secondary:   Change in CD4 Cell Count From Baseline   [ Time Frame: Weeks 0, 4, 8, 12, 24, 28, 52 and 72 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide 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
  Hide More Information

Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Clinicaltrials.gov Coordinator
Organization: Center for Biostatistics in AIDS Research, Harvard School of Public Health
phone: 617-432-2829
e-mail: CBAR.ClinicalTrials.Gov@sdac.harvard.edu


Publications:

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00604175     History of Changes
Other Study ID Numbers: A5240, 10393, ACTG A5240
Study First Received: January 17, 2008
Results First Received: July 15, 2013
Last Updated: July 22, 2014
Health Authority: United States: Food and Drug Administration