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

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00604175
• Collaborator: National Institute of Dental and Craniofacial Research (NIDCR) (NIH)
• Enrollment: 319
• Locations: 61
• Arms: 3
• Duration (Months): 57
• Patients Per Site: 5.2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Human papillomavirus (HPV) is the most common sexually transmitted disease in the world. HPV infection can cause genital warts and certain cervical problems, including cervical cancer. HPV infection may be more severe and harder to treat in HIV-infected people. The purpose of this study was to determine whether the quadrivalent HPV vaccine is safe, tolerable, and effective in producing antibodies to HPV in HIV-infected women.

Condition or Disease	Intervention/Treatment	Phase
HIV Infections; Sexually Transmitted Diseases	Biological: Quadrivalent HPV vaccine	Phase 2

Detailed Description

HPV is a DNA virus that affects both men and women. Approximately 90 types of HPV have been identified, 30 of which are sexually transmitted. The most common forms of HPV are types 6, 11, 16, and 18. The quadrivalent HPV vaccine that was tested in this study had been shown in previous studies to be effective in preventing infection with HPV 6, 11, 16, and 18 in healthy young women. According to a report by the Centers for Disease Control and Prevention (CDC), 80% of women will have acquired HPV by the age of 50. HIV infected women have been reported to have a higher prevalence and persistence of HPV infection, as well as an increased risk for abnormal Pap smears and cervical cancer. HPV types 16 and 18 cause the majority of cervical cancers worldwide, and types 6 and 11 are responsible for the majority of cases of genital warts. Vaccinations for preventable infections are particularly important among HIV infected people because people with HIV have compromised immune systems; therefore, any infection is very serious and can potentially be fatal. However, standard vaccination series have not been very successful because a compromised immune system may not produce the desired immune response to a vaccine. The HPV vaccine is designed to protect against infection with HPV types 6, 11, 16, and 18 and has been approved by the FDA for use in women between the ages of 9 and 26. The purpose of this study was to determine whether the quadrivalent HPV vaccine is safe, tolerable, and effective in producing antibodies to HPV in HIV infected females.

The study consisted of single arm evaluations of HPV vaccine immunogenicity and safety in 3 groups based on the study screening CD4 cell count as follows:

• Stratum A: CD4 cell count >350 cells/mm^3

• Stratum B: CD4 cell count >200 to <=350 cells/mm^3

• Stratum C: CD4 cell count <=200 cells/mm^3

In Version 1.0 of the protocol, the target accrual was n=67 participants with screening HIV viral load <=10,000 copies/mL and n=67 participants with HIV viral load >10,000 copies/mL within each CD4 stratum, yielding n=134 in each CD4 stratum. In light of subsequent findings from completed HPV vaccine studies, the sample size was changed to n=94 participants per CD4 stratum in Version 2.0 of the protocol, and stratification by screening HIV viral load was removed. All Stratum A and Stratum B participants were enrolled under protocol Version 1.0.

The study duration was 72 weeks. All participants received HPV vaccine administered by intramuscular injection at baseline, and at Weeks 8 and 24. Following each injection, participants remained at the clinic for 30 minutes of observation for adverse events. A telephone follow-up or a home visit by study staff was performed within 2 days following each injection.

Participants returned to the clinic for visits at Weeks 4, 8, 12, 24, 28, 52, and 72. Most study visits included a physical exam, medication review, blood and urine collection, and answering questions about signs and symptoms since previous visit. Some visits included measurement of HIV viral load and CD4 cell count; collection of endocervical wick, cervical cytobrush and anal swab; and an oral exam. A subset of participants were asked to provide additional blood samples and oral cytobrush specimens.

Study Design

• Study Type: Interventional
• Actual Enrollment: 319 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: A Phase II Study to Evaluate the Immunogenicity and Safety of a Quadrivalent Human Papillomavirus Vaccine in HIV-1-Infected Females
• Study Start Date: Feb 1, 2008
• Actual Primary Completion Date: Jan 1, 2012
• Actual Study Completion Date: Nov 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Stratum A Participants with screening CD4 count >350 cells/mm^3 received 0.5mL of quadrivalent HPV vaccine at baseline and Weeks 8 and 24.	Biological: Quadrivalent HPV vaccine; Quadrivalent HPV (types 6, 11, 16, 18) recombinant vaccine. All participants received the vaccine via intramuscular injection at baseline, Week 8 and Week 24.; Other Names: GARDASIL
Experimental: Stratum B Participants with screening CD4 count >200 to <=350 cells/mm^3 received 0.5mL of quadrivalent HPV vaccine at baseline and Weeks 8 and 24.	Biological: Quadrivalent HPV vaccine; Quadrivalent HPV (types 6, 11, 16, 18) recombinant vaccine. All participants received the vaccine via intramuscular injection at baseline, Week 8 and Week 24.; Other Names: GARDASIL
Experimental: Stratum C Participants with screening CD4 count <=200 cells/mm^3 received 0.5mL of quadrivalent HPV vaccine at baseline and Weeks 8 and 24.	Biological: Quadrivalent HPV vaccine; Quadrivalent HPV (types 6, 11, 16, 18) recombinant vaccine. All participants received the vaccine via intramuscular injection at baseline, Week 8 and Week 24.; Other Names: GARDASIL

Outcome Measures

Primary Outcome Measures

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

   Percentage of participants with HPV6 antibody development from seronegative status (HPV6 antibody titers <20 mMU/mL) at baseline to seropositive (HPV6 antibody titers >=20 mMU/mL) status a month after the completion of HPV vaccination series. HPV serotyping was performed centrally using the competitive Luminex ImmunoAssay (HPV-4, cLIA) on stored serum.

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

   Percentage of participants with HPV11 antibody development from seronegative status (HPV11 antibody titers <16 mMU/mL) at baseline to seropositive (HPV11 antibody titers >=16 mMU/mL) status a month after the completion of HPV vaccination series. HPV serotyping was performed centrally using the competitive Luminex ImmunoAssay (HPV-4, cLIA) on stored serum.

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

   Percentage of participants with HPV16 antibody development from seronegative status (HPV16 antibody titers <20 mMU/mL) at baseline to seropositive (HPV16 antibody titers >=20 mMU/mL) status a month after the completion of HPV vaccination series. HPV serotyping was performed centrally using the competitive Luminex ImmunoAssay (HPV-4, cLIA) on stored serum.

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

   Percentage of participants with HPV18 antibody development from seronegative status (HPV18 antibody titers <24 mMU/mL) at baseline to seropositive (HPV18 antibody titers >=24 mMU/mL) status a month after the completion of HPV vaccination series. HPV serotyping was performed centrally using the competitive Luminex ImmunoAssay (HPV-4, cLIA) on stored serum.

Secondary Outcome Measures

1. HPV6 Antibody Titers Among Those Seronegative for HPV6 at Baseline [Weeks 28, 72]

   HPV antibody titers to type 6 were measured centrally using the competitive Luminex ImmunoAssay (HPV-4, cLIA) on stored serum. The results below the lower limit of detection (LLD) were assigned the values of half the LLD (7 mMU/mL, and after assay change in December 2012, 11 mMU/mL for HPV6). Geometric mean HPV6 titers with 95% CIs were calculated among the subset of participants who were seronegative for HPV6 (<20 mMU/mL) at baseline.

2. HPV11 Antibody Titers Among Those Seronegative for HPV11 at Baseline [Weeks 28, 72]

   HPV antibody titers to type 11 were measured centrally using the competitive Luminex ImmunoAssay (HPV-4, cLIA) on stored serum. The results below the lower limit of detection (LLD) were assigned the values of half the LLD (8 mMU/mL for HPV11). Geometric mean HPV11 titers with 95% CIs were calculated among the subset of participants who were seronegative for HPV11 (<16 mMU/mL) at baseline.

3. HPV16 Antibody Titers Among Those Seronegative for HPV16 at Baseline [Weeks 28, 72]

   HPV antibody titers to type 16 were measured centrally using the competitive Luminex ImmunoAssay (HPV-4, cLIA) on stored serum. The results below the lower limit of detection (LLD) were assigned the values of half the LLD (11 mMU/mL for HPV16). Geometric mean HPV16 titers with 95% CIs were calculated among the subset of participants who were seronegative for HPV16 (<20 mMU/mL) at baseline.

4. HPV18 Antibody Titers Among Those Seronegative for HPV18 at Baseline [Weeks 28, 72]

   HPV antibody titers to type 18 were measured centrally using the competitive Luminex ImmunoAssay (HPV-4, cLIA) on stored serum. The results below the lower limit of detection (LLD) were assigned the values of half the LLD (10 mMU/mL for HPV18). Geometric mean HPV18 titers with 95% CIs were calculated among the subset of participants who were seronegative for HPV18 (<24 mMU/mL) at baseline.

5. Change in Log10 HPV6 Antibody Titers From Baseline Among Those Seropositive for HPV6 at Baseline [Weeks 0, 28, 72]

   Change in log10 HPV6 antibody titers was calculated as log10 HPV6 antibody titers at a later timepoint (Week 28, Week 72) minus log10 HPV6 antibody titers at baseline among those seropositive for HPV6 (>=20 mMU/mL) at baseline. HPV antibody titers to type 6 were measured centrally using the competitive Luminex ImmunoAssay (HPV-4, cLIA) on stored serum. The results below the lower limit of detection (LLD) were assigned the values of half the LLD (7 mMU/mL, and after assay change in December 2012, 11 mMU/mL for HPV6).

6. Change in Log10 HPV11 Antibody Titers From Baseline Among Those Seropositive for HPV11 at Baseline [Weeks 0, 28, 72]

   Change in log10 HPV11 antibody titers was calculated as log10 HPV11 antibody titers at a later timepoint (Week 28, Week 72) minus log10 HPV11 antibody titers at baseline among those seropositive for HPV11 (>=16 mMU/mL) at baseline. HPV antibody titers to type 11 were measured centrally using the competitive Luminex ImmunoAssay (HPV-4, cLIA) on stored serum. The results below the lower limit of detection (LLD) were assigned the values of half the LLD (8 mMU/mL for HPV11).

7. Change in Log10 HPV16 Antibody Titers From Baseline Among Those Seropositive for HPV16 at Baseline [Weeks 0, 28, 72]

   Change in log10 HPV16 antibody titers was calculated as log10 HPV16 antibody titers at a later timepoint (Week 28, Week 72) minus log10 HPV16 antibody titers at baseline among those seropositive for HPV16 (>=20 mMU/mL) at baseline. HPV antibody titers to type 16 were measured centrally using the competitive Luminex ImmunoAssay (HPV-4, cLIA) on stored serum. The results below the lower limit of detection (LLD) were assigned the values of half the LLD (11 mMU/mL for HPV16).

8. Change in Log10 HPV18 Antibody Titers From Baseline Among Those Seropositive for HPV18 at Baseline [Weeks 0, 28, 72]

   Change in log10 HPV18 antibody titers was calculated as log10 HPV18 antibody titers at a later timepoint (Week 28, Week 72) minus log10 HPV18 antibody titers at baseline among those seropositive for HPV18 (>=24 mMU/mL) at baseline. HPV antibody titers to type 18 were measured centrally using the competitive Luminex ImmunoAssay (HPV-4, cLIA) on stored serum. The results below the lower limit of detection (LLD) were assigned the values of half the LLD (10 mMU/mL for HPV18).

9. Number of Participants With Signs and Symptoms of Grade 3 or Higher [From baseline to up to Week 72]

   Number of participants who experienced a sign or symptom of Grade 3 or higher at any time after baseline while on study. Grading of signs and symptoms was according to Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, December 2004.

10. Number of Participants With Laboratory Abnormalities of Grade 3 or Higher [From baseline to up to Week 72]

    Number of participants who experienced a laboratory abnormality of Grade 3 or higher at any time after baseline while on study. Grading of laboratory abnormalities was according to Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, December 2004.

11. Change in Log10 HIV Viral Load (VL) From Baseline [Weeks 0, 4, 12, 28, 52, and 72]

    A blood sample was drawn for local testing to determine the HIV VL. Change in log10 HIV VL was calculated as log10 HIV VL at a later time point (Weeks 4, 12, 28, 52 and 72) minus log10 HIV VL at baseline.

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

    A blood sample was drawn for local testing to determine the CD4 cell count. Change in CD4 cell count was calculated as CD4 cell count at a later time point (Weeks 4, 8, 12, 24, 28, 52 and 72) minus CD4 cell count at baseline.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 13 Years to 45 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• HIV infection

• CD4 count obtained within 45 days prior to study entry

• Karnofsky performance score >=70 on at least one occasion within 45 days prior to study entry

• The following labs within 45 days prior to study entry:

• hemoglobin >8.0 g/dL

• direct bilirubin <2.5 x upper limit of normal (ULN)

• alanine aminotransferase, ALT (SGPT) <3 xULN

• aspartate aminotransferase, AST (SGOT) <3 xULN

• platelet count >=100,000 /mm^3

• Willing to use acceptable forms of contraception for the duration of the study

• Written informed consent from participant or from parent or guardian, if applicable

• If on HAART, then the same regimen for at least 12 weeks prior to study entry with no change within 30 days prior to study entry. (This criterion was removed in Version 2.0 of the protocol.)

• HIV viral load obtained within 45 days prior to study entry (This criterion was removed in Version 2.0 of the protocol.)

Exclusion Criteria:

• Abnormal Pap test with confirmed biopsy results of cervical intraepithelial neoplasia (CIN) II or III or cervical cancer within 180 days prior to study entry

• Vulval intraepithelial neoplasia (VIN) II or III or cancer confirmed by biopsy results within 180 days prior to study entry

• Physician-diagnosed genital warts within 180 days prior to study entry

• Previous cervical dysplasia treatment, including loop electrosurgical excision procedure (LEEP), cervical cryotherapy, cone biopsy, and cervical laser vaporization within 180 days prior to study entry

• Use of any systemic antineoplastic or immunomodulatory treatment, systemic corticosteroids, investigational vaccines, interleukins, interferons, growth factors, or intravenous immunoglobulin (IVIG) within 45 days prior to study entry. Participants who had received standard of care (e.g., hepatitis B, influenza, and tetanus) vaccines were not excluded.

• Known allergy or hypersensitivity to yeast or any components of the vaccine or its formulation

• Current drug or alcohol use or dependence or any other condition that may interfere with study participation

• Serious illness requiring systemic treatment and/or hospitalization within 45 days prior to study entry

• Total hysterectomy. Participants who had undergone partial hysterectomy and had a cervix were not excluded.

• Hemophilia

• Currently on anticoagulation therapy other than acetylsalicylic acid

• Prior vaccination with an HPV vaccine

• Pregnant or breastfeeding

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Alabama Therapeutics CRS	Birmingham	Alabama	United States	35294-2050
2	Usc La Nichd Crs	Alhambra	California	United States	90033
3	University of California, UC San Diego CRS	La Jolla	California	United States	92093-0672
4	Miller Children's Hosp. Long Beach CA NICHD CRS	Long Beach	California	United States	90806
5	University of Southern California CRS	Los Angeles	California	United States	90033-1079
6	UCLA CARE Center CRS	Los Angeles	California	United States	90035
7	Stanford AIDS Clinical Trials Unit CRS	Palo Alto	California	United States	94304-5350
8	UCSD Antiviral Research Center CRS	San Diego	California	United States	92103
9	Ucsf Hiv/Aids Crs	San Francisco	California	United States	94110
10	University of Colorado Hospital CRS	Aurora	Colorado	United States	80045
11	Denver Public Health CRS	Denver	Colorado	United States	80204
12	Georgetown University CRS (GU CRS)	Washington	District of Columbia	United States	20007
13	Howard Univ. Washington DC NICHD CRS	Washington	District of Columbia	United States	20060
14	South Florida CDTC Ft Lauderdale NICHD CRS	Fort Lauderdale	Florida	United States	33316
15	Univ. of Florida Jacksonville NICHD CRS	Jacksonville	Florida	United States	32209
16	Pediatric Perinatal HIV Clinical Trials Unit CRS	Miami	Florida	United States	33136
17	The University of Miami AIDS Clinical Research Unit (ACRU) CRS	Miami	Florida	United States	33136
18	The Ponce de Leon Center CRS	Atlanta	Georgia	United States	30308
19	Mt. Sinai Hosp. Med. Ctr. - Chicago, Womens & Childrens HIV Program	Chicago	Illinois	United States	60608
20	Northwestern University CRS	Chicago	Illinois	United States	60611
21	Rush Univ. Med. Ctr. ACTG CRS	Chicago	Illinois	United States	60612
22	Rush University CRS	Chicago	Illinois	United States	60612
23	Tulane Univ. New Orleans NICHD CRS	New Orleans	Louisiana	United States	70112
24	IHV Baltimore Treatment CRS	Baltimore	Maryland	United States	21201
25	Johns Hopkins University CRS	Baltimore	Maryland	United States	21205
26	Massachusetts General Hospital CRS (MGH CRS)	Boston	Massachusetts	United States	02114
27	Bmc Actg Crs	Boston	Massachusetts	United States	02118
28	Beth Israel Deaconess Med. Ctr., ACTG CRS	Boston	Massachusetts	United States	02215
29	Henry Ford Hosp. CRS	Detroit	Michigan	United States	48202
30	Washington University Therapeutics (WT) CRS	Saint Louis	Missouri	United States	63110-1010
31	Cooper Univ. Hosp. CRS	Camden	New Jersey	United States	08103
32	New Jersey Medical School- Adult Clinical Research Ctr. CRS	Newark	New Jersey	United States	07103
33	Weill Cornell Chelsea CRS	New York	New York	United States	10011
34	NY Univ. HIV/AIDS CRS	New York	New York	United States	10016
35	Columbia P&S CRS	New York	New York	United States	10032-3732
36	Columbia IMPAACT CRS	New York	New York	United States	10032
37	Trillium Health ACTG CRS	Rochester	New York	United States	14607
38	Univ. of Rochester ACTG CRS	Rochester	New York	United States	14642
39	Chapel Hill CRS	Chapel Hill	North Carolina	United States	27599
40	Duke Univ. Med. Ctr. Adult CRS	Durham	North Carolina	United States	27710
41	Greensboro CRS	Greensboro	North Carolina	United States	27401
42	Cincinnati CRS	Cincinnati	Ohio	United States	45219
43	Case CRS	Cleveland	Ohio	United States	44106
44	MetroHealth CRS	Cleveland	Ohio	United States	44109
45	Ohio State University CRS	Columbus	Ohio	United States	43210
46	The Research & Education Group-Portland CRS	Portland	Oregon	United States	97210
47	Penn Therapeutics, CRS	Philadelphia	Pennsylvania	United States	19104
48	Thomas Jefferson Univ. Med. Ctr. CRS	Philadelphia	Pennsylvania	United States	19107
49	University of Pittsburgh CRS	Pittsburgh	Pennsylvania	United States	15213
50	The Miriam Hospital Clinical Research Site (TMH CRS) CRS	Providence	Rhode Island	United States	02906
51	Vanderbilt Therapeutics (VT) CRS	Nashville	Tennessee	United States	37204
52	Trinity Health and Wellness Center CRS	Dallas	Texas	United States	75208
53	Texas Children's Hospital CRS	Houston	Texas	United States	77030-2399
54	Houston AIDS Research Team CRS	Houston	Texas	United States	77030
55	Virginia Commonwealth Univ. Medical Ctr. CRS	Richmond	Virginia	United States	23298
56	University of Washington AIDS CRS	Seattle	Washington	United States	98104-9929
57	Instituto de Pesquisa Clinica Evandro Chagas (IPEC) CRS	Rio de Janeiro		Brazil	21040-900
58	Puerto Rico AIDS Clinical Trials Unit CRS	San Juan		Puerto Rico	00935
59	University of Puerto Rico Pediatric HIV/AIDS Research Program CRS	San Juan		Puerto Rico	00935
60	San Juan City Hosp. PR NICHD CRS	San Juan		Puerto Rico	00936
61	Wits Helen Joseph Hospital CRS (Wits HJH CRS)	Johannesburg	Gauteng	South Africa	2092

Sponsors and Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID)
• National Institute of Dental and Craniofacial Research (NIDCR)

Investigators

• Study Chair: Erna Milunka Kojic, MD, Department of Immunology/Infectious Disease, The Miriam Hospital, Brown University
• Study Chair: Susan Cu-Uvin, MD, Obstetrics-Gynecology and Medicine, The Miriam Hospital, Brown University

Study Documents (Full-Text)

None provided.

More Information

Publications

• Cameron JE, Hagensee ME. Human papillomavirus infection and disease in the HIV+ individual. Cancer Treat Res. 2007;133:185-213. Review.
• Chaturvedi AK, Goedert JJ. Human papillomavirus genotypes among women with HIV: implications for research and prevention. AIDS. 2006 Nov 28;20(18):2381-3.
• De Vuyst H, Franceschi S. Human papillomavirus vaccines in HIV-positive men and women. Curr Opin Oncol. 2007 Sep;19(5):470-5. Review.
• Kojic EM, Cu-Uvin S. Update: human papillomavirus infection remains highly prevalent and persistent among HIV-infected individuals. Curr Opin Oncol. 2007 Sep;19(5):464-9. Review.
• Palefsky J. Human papillomavirus infection in HIV-infected persons. Top HIV Med. 2007 Aug-Sep;15(4):130-3. Review.

• Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• ClinicalTrials.gov Identifier: NCT00604175
• Other Study ID Numbers: A5240; 10393; ACTG A5240
• First Posted: Jan 30, 2008
• Last Update Posted: Nov 4, 2021
• Last Verified: Aug 1, 2015

• Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID): HIV; HPV 6; HPV 11; HPV 16; HPV 18; Vaccine
• Additional relevant MeSH terms: Sexually Transmitted Diseases

Study Results

Participant Flow

Recruitment Details	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 Detail	Participants were enrolled into 3 strata based on screening CD4 cell count: Stratum A: CD4 cell count >350 cells/mm^3 Stratum B: CD4 cell count >200 to <=350 cells/mm^3 Stratum C: CD4 cell count <=200 cells/mm^3

Arm/Group Title	Stratum A	Stratum B	Stratum C
Arm/Group Description	Participants with screening CD4 count >350 cells/mm^3 received 0.5mL of quadrivalent HPV vaccine at baseline and Weeks 8 and 24.	Participants with screening CD4 count >200 to <=350 cells/mm^3 received 0.5mL of quadrivalent HPV vaccine at baseline and Weeks 8 and 24.	Participants with screening CD4 count <=200 cells/mm^3 received 0.5mL of quadrivalent HPV vaccine at baseline and Weeks 8 and 24.
Period Title: Entry Through Week 28
STARTED	130	95	94
COMPLETED	120	92	93
NOT COMPLETED	10	3	1
Period Title: Entry Through Week 28
STARTED	120	92	93
COMPLETED	108	85	89
NOT COMPLETED	12	7	4

Baseline Characteristics

Arm/Group Title	Stratum A	Stratum B	Stratum C	Total
Arm/Group Description	Participants with screening CD4 count >350 cells/mm^3 received 0.5mL of quadrivalent HPV vaccine at baseline and Weeks 8 and 24.	Participants with screening CD4 count >200 to <=350 cells/mm^3 received 0.5mL of quadrivalent HPV vaccine at baseline and Weeks 8 and 24.	Participants with screening CD4 count <=200 cells/mm^3 received 0.5mL of quadrivalent HPV vaccine at baseline and Weeks 8 and 24.	Total of all reporting groups
Overall Participants	127	95	93	315
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	35	38	36	36
Age, Customized (Number) [Number]
13 - 17 years	0 0%	0 0%	1 1.1%	1 0.3%
18 - 24 years	10 7.9%	3 3.2%	7 7.5%	20 6.3%
25 - 29 years	24 18.9%	11 11.6%	12 12.9%	47 14.9%
30 - 34 years	26 20.5%	14 14.7%	20 21.5%	60 19%
35 - 39 years	31 24.4%	26 27.4%	24 25.8%	81 25.7%
40 - 45 years	36 28.3%	41 43.2%	29 31.2%	106 33.7%
Sex: Female, Male (Count of Participants)
Female	127 100%	95 100%	93 100%	315 100%
Male	0 0%	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Number) [Number]
White, Non-Hispanic	19 15%	9 9.5%	8 8.6%	36 11.4%
Black, Non-Hispanic	67 52.8%	59 62.1%	51 54.8%	177 56.2%
Hispanic (Regardless of Race)	39 30.7%	25 26.3%	32 34.4%	96 30.5%
Asian, Pacific Islander	2 1.6%	0 0%	1 1.1%	3 1%
Unknown	0 0%	2 2.1%	1 1.1%	3 1%
Region of Enrollment (Number) [Number]
United States	113 89%	80 84.2%	69 74.2%	262 83.2%
Brazil	11 8.7%	6 6.3%	11 11.8%	28 8.9%
South Africa	3 2.4%	9 9.5%	13 14%	25 7.9%
HIV Antiretroviral Therapy (ART) Status (Number) [Number]
On ART	58 45.7%	71 74.7%	80 86%	209 66.3%
Not on ART	69 54.3%	24 25.3%	13 14%	106 33.7%
CD4 Cell Count (Cells/mm^3) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [Cells/mm^3]	519	287	154	310
Nadir CD4 Cell Count (Cells/mm^3) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [Cells/mm^3]	368	176	41	179
HIV Viral Load (Number) [Number]
<=10,000 copies/mL	71 55.9%	69 72.6%	61 65.6%	201 63.8%
>10,000 copies/mL	56 44.1%	25 26.3%	32 34.4%	113 35.9%
Unknown	0 0%	1 1.1%	0 0%	1 0.3%
Human Papillomavirus Type 6 (HPV6) Serostatus (Number) [Number]
Seronegative	66 52%	60 63.2%	56 60.2%	182 57.8%
Seropositive	54 42.5%	35 36.8%	37 39.8%	126 40%
Unknown	7 5.5%	0 0%	0 0%	7 2.2%
Human Papillomavirus Type 11 (HPV11) Serostatus (Number) [Number]
Seronegative	99 78%	72 75.8%	74 79.6%	245 77.8%
Seropositive	22 17.3%	23 24.2%	19 20.4%	64 20.3%
Unknown	6 4.7%	0 0%	0 0%	6 1.9%
Human Papillomavirus Type 16 (HPV16) Serostatus (Number) [Number]
Seronegative	77 60.6%	65 68.4%	67 72%	209 66.3%
Seropositive	44 34.6%	30 31.6%	26 28%	100 31.7%
Unknown	6 4.7%	0 0%	0 0%	6 1.9%
Human Papillomavirus Type 18 (HPV18) Serostatus (Number) [Number]
Seronegative	92 72.4%	83 87.4%	73 78.5%	248 78.7%
Seropositive	29 22.8%	12 12.6%	20 21.5%	61 19.4%
Unknown	6 4.7%	0 0%	0 0%	6 1.9%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With HPV6 Antibody Development From Seronegative Status at Baseline to Seropositive Status a Month After Completion of HPV Vaccination Series
Description	Percentage of participants with HPV6 antibody development from seronegative status (HPV6 antibody titers <20 mMU/mL) at baseline to seropositive (HPV6 antibody titers >=20 mMU/mL) status a month after the completion of HPV vaccination series. HPV serotyping was performed centrally using the competitive Luminex ImmunoAssay (HPV-4, cLIA) on stored serum.
Time Frame	Week 28

Outcome Measure Data

Analysis Population Description

Per-protocol analysis including all participants seronegative to HPV6 at baseline who completed the vaccination series per protocol and had HPV6 titer available at Week 28.

Arm/Group Title	Stratum A	Stratum B	Stratum C
Arm/Group Description	Participants with screening CD4 count >350 cells/mm^3 received 0.5mL of quadrivalent HPV vaccine at baseline and Weeks 8 and 24.	Participants with screening CD4 count >200 to <=350 cells/mm^3 received 0.5mL of quadrivalent HPV vaccine at baseline and Weeks 8 and 24.	Participants with screening CD4 count <=200 cells/mm^3 received 0.5mL of quadrivalent HPV vaccine at baseline and Weeks 8 and 24.
Measure Participants	54	50	45
Number (95% Confidence Interval) [Percentage of participants]	96.3 75.8%	100.0 105.3%	84.4 90.8%

2. Primary Outcome

Title	Percentage of Participants With HPV11 Antibody Development From Seronegative Status at Baseline to Seropositive Status a Month After Completion of HPV Vaccination Series
Description	Percentage of participants with HPV11 antibody development from seronegative status (HPV11 antibody titers <16 mMU/mL) at baseline to seropositive (HPV11 antibody titers >=16 mMU/mL) status a month after the completion of HPV vaccination series. HPV serotyping was performed centrally using the competitive Luminex ImmunoAssay (HPV-4, cLIA) on stored serum.
Time Frame	Week 28

Outcome Measure Data

Analysis Population Description

Per-protocol analysis including all participants seronegative to HPV11 at baseline who completed the vaccination series per protocol and had HPV11 titer available at Week 28.

Arm/Group Title	Stratum A	Stratum B	Stratum C
Arm/Group Description	Participants with screening CD4 count >350 cells/mm^3 received 0.5mL of quadrivalent HPV vaccine at baseline and Weeks 8 and 24.	Participants with screening CD4 count >200 to <=350 cells/mm^3 received 0.5mL of quadrivalent HPV vaccine at baseline and Weeks 8 and 24.	Participants with screening CD4 count <=200 cells/mm^3 received 0.5mL of quadrivalent HPV vaccine at baseline and Weeks 8 and 24.
Measure Participants	86	59	62
Number (95% Confidence Interval) [Percentage of participants]	97.7 76.9%	98.3 103.5%	91.9 98.8%

3. Primary Outcome

Title	Percentage of Participants With HPV16 Antibody Development From Seronegative Status at Baseline to Seropositive Status a Month After Completion of HPV Vaccination Series
Description	Percentage of participants with HPV16 antibody development from seronegative status (HPV16 antibody titers <20 mMU/mL) at baseline to seropositive (HPV16 antibody titers >=20 mMU/mL) status a month after the completion of HPV vaccination series. HPV serotyping was performed centrally using the competitive Luminex ImmunoAssay (HPV-4, cLIA) on stored serum.
Time Frame	Week 28

Outcome Measure Data

Analysis Population Description

Per-protocol analysis including all participants seronegative to HPV16 at baseline who completed the vaccination series per protocol and had HPV16 titer available at Week 28.

Arm/Group Title	Stratum A	Stratum B	Stratum C
Arm/Group Description	Participants with screening CD4 count >350 cells/mm^3 received 0.5mL of quadrivalent HPV vaccine at baseline and Weeks 8 and 24.	Participants with screening CD4 count >200 to <=350 cells/mm^3 received 0.5mL of quadrivalent HPV vaccine at baseline and Weeks 8 and 24.	Participants with screening CD4 count <=200 cells/mm^3 received 0.5mL of quadrivalent HPV vaccine at baseline and Weeks 8 and 24.
Measure Participants	67	56	56
Number (95% Confidence Interval) [Percentage of participants]	98.5 77.6%	98.2 103.4%	92.9 99.9%

4. Primary Outcome

Title	Percentage of Participants With HPV18 Antibody Development From the Seronegative Status at Baseline to Seropositive Status a Month After Completion of HPV Vaccination Series
Description	Percentage of participants with HPV18 antibody development from seronegative status (HPV18 antibody titers <24 mMU/mL) at baseline to seropositive (HPV18 antibody titers >=24 mMU/mL) status a month after the completion of HPV vaccination series. HPV serotyping was performed centrally using the competitive Luminex ImmunoAssay (HPV-4, cLIA) on stored serum.
Time Frame	Week 28

Outcome Measure Data

Analysis Population Description

Per-protocol analysis including all participants seronegative to HPV18 at baseline who completed the vaccination series per protocol and had HPV18 titer available at Week 28.

Arm/Group Title	Stratum A	Stratum B	Stratum C
Arm/Group Description	Participants with screening CD4 count >350 cells/mm^3 received 0.5mL of quadrivalent HPV vaccine at baseline and Weeks 8 and 24.	Participants with screening CD4 count >200 to <=350 cells/mm^3 received 0.5mL of quadrivalent HPV vaccine at baseline and Weeks 8 and 24.	Participants with screening CD4 count <=200 cells/mm^3 received 0.5mL of quadrivalent HPV vaccine at baseline and Weeks 8 and 24.
Measure Participants	78	71	61
Number (95% Confidence Interval) [Percentage of participants]	91.0 71.7%	84.5 88.9%	75.4 81.1%

5. Secondary Outcome

Title	HPV6 Antibody Titers Among Those Seronegative for HPV6 at Baseline
Description	HPV antibody titers to type 6 were measured centrally using the competitive Luminex ImmunoAssay (HPV-4, cLIA) on stored serum. The results below the lower limit of detection (LLD) were assigned the values of half the LLD (7 mMU/mL, and after assay change in December 2012, 11 mMU/mL for HPV6). Geometric mean HPV6 titers with 95% CIs were calculated among the subset of participants who were seronegative for HPV6 (<20 mMU/mL) at baseline.
Time Frame	Weeks 28, 72

Outcome Measure Data

Analysis Population Description

All eligible participants who received at least one vaccine and were seronegative for HPV6 (HPV6-) at baseline (the number of participants analyzed) and had HPV6 titer available at the respective follow-up week. Strata A; B; C. Week 28: n=60; 58; 52. Week 72: n=55; 53; 53.

Arm/Group Title	Stratum A/Baseline HPV6-	Stratum B/Baseline HPV6-	Stratum C/Baseline HPV6-
Arm/Group Description	Participants with screening CD4+ count >350 cells/mm^3 (Stratum A) who were seronegative for HPV6 at baseline.	Participants with screening CD4+ count >200 to <=350 cells/mm^3 (Stratum B) who were seronegative for HPV6 at baseline.	Participants with screening CD4+ count<=200 cells/mm^3 (Stratum C) who were seronegative for HPV6 at baseline.
Measure Participants	66	60	56
HPV6 titers at Week 28 (n=60; 58; 52)	462.3	349.2	137.1
HPV6 titers at Week 72 (n=55; 53; 53)	112.8	79.9	43.0

6. Secondary Outcome

Title	HPV11 Antibody Titers Among Those Seronegative for HPV11 at Baseline
Description	HPV antibody titers to type 11 were measured centrally using the competitive Luminex ImmunoAssay (HPV-4, cLIA) on stored serum. The results below the lower limit of detection (LLD) were assigned the values of half the LLD (8 mMU/mL for HPV11). Geometric mean HPV11 titers with 95% CIs were calculated among the subset of participants who were seronegative for HPV11 (<16 mMU/mL) at baseline.
Time Frame	Weeks 28, 72

Outcome Measure Data

Analysis Population Description

All eligible participants who received at least one vaccine and were seronegative for HPV11 (HPV11-) at baseline (the number of participants analyzed) and had HPV11 titer available at the respective follow-up week. Strata A; B; C. Week 28: n=93; 70; 71. Week 72: n=83; 66; 69.

Arm/Group Title	Stratum A/Baseline HPV11-	Stratum B/Baseline HPV11-	Stratum C/Baseline HPV11-
Arm/Group Description	Participants with screening CD4+ count >350 cells/mm^3 (Stratum A) who were seronegative for HPV11 at baseline.	Participants with screening CD4+ count >200 to <=350 cells/mm^3 (Stratum B) who were seronegative for HPV11 at baseline.	Participants with screening CD4+ count<=200 cells/mm^3 (Stratum C) who were seronegative for HPV11 at baseline.
Measure Participants	99	72	74
HPV11 at Week 28 (n=93; 70; 71)	476.5	417.2	205.1
HPV11 at Week 72 (n=83; 66; 69)	122.3	85.1	52.9

7. Secondary Outcome

Title	HPV16 Antibody Titers Among Those Seronegative for HPV16 at Baseline
Description	HPV antibody titers to type 16 were measured centrally using the competitive Luminex ImmunoAssay (HPV-4, cLIA) on stored serum. The results below the lower limit of detection (LLD) were assigned the values of half the LLD (11 mMU/mL for HPV16). Geometric mean HPV16 titers with 95% CIs were calculated among the subset of participants who were seronegative for HPV16 (<20 mMU/mL) at baseline.
Time Frame	Weeks 28, 72

Outcome Measure Data

Analysis Population Description

All eligible participants who received at least one vaccine and were seronegative for HPV16 (HPV16-) at baseline (the number of participants analyzed) and had HPV16 titer available at the respective follow-up week. Strata A; B; C. Week 28: n=73; 63; 64. Week 72: n=63; 59; 64.

Arm/Group Title	Stratum A/Baseline HPV16-	Stratum B/Baseline HPV16-	Stratum C/Baseline HPV16-
Arm/Group Description	Participants with screening CD4+ count >350 cells/mm^3 (Stratum A) who were seronegative for HPV16 at baseline.	Participants with screening CD4+ count >200 to <=350 cells/mm^3 (Stratum B) who were seronegative for HPV16 at baseline.	Participants with screening CD4+ count<=200 cells/mm^3 (Stratum C) who were seronegative for HPV16 at baseline.
Measure Participants	77	65	67
HPV16 at Week 28 (n=73; 63; 64)	1199.9	1117.1	570.8
HPV16 at Week 72 (n=63; 59; 64)	248.9	170.4	98.3

8. Secondary Outcome

Title	HPV18 Antibody Titers Among Those Seronegative for HPV18 at Baseline
Description	HPV antibody titers to type 18 were measured centrally using the competitive Luminex ImmunoAssay (HPV-4, cLIA) on stored serum. The results below the lower limit of detection (LLD) were assigned the values of half the LLD (10 mMU/mL for HPV18). Geometric mean HPV18 titers with 95% CIs were calculated among the subset of participants who were seronegative for HPV18 (<24 mMU/mL) at baseline.
Time Frame	Weeks 28, 72

Outcome Measure Data

Analysis Population Description

All eligible participants who received at least one vaccine and were seronegative for HPV18 (HPV18-) at baseline (the number of participants analyzed) and had HPV18 titer available at the respective follow-up week. Strata A; B; C. Week 28: n=86; 80; 69. Week 72: n=75; 73; 69.

Arm/Group Title	Stratum A/Baseline HPV18-	Stratum B/Baseline HPV18-	Stratum C/Baseline HPV18-
Arm/Group Description	Participants with screening CD4+ count >350 cells/mm^3 (Stratum A) who were seronegative for HPV18 at baseline.	Participants with screening CD4+ count >200 to <=350 cells/mm^3 (Stratum B) who were seronegative for HPV18 at baseline.	Participants with screening CD4+ count<=200 cells/mm^3 (Stratum C) who were seronegative for HPV18 at baseline.
Measure Participants	92	83	73
HPV18 at Week 28 (n=86; 80; 69)	175.0	170.8	93.6
HPV18 at Week 72 (n=75; 73; 69)	41.9	40.6	20.8

9. Secondary Outcome

Title	Change in Log10 HPV6 Antibody Titers From Baseline Among Those Seropositive for HPV6 at Baseline
Description	Change in log10 HPV6 antibody titers was calculated as log10 HPV6 antibody titers at a later timepoint (Week 28, Week 72) minus log10 HPV6 antibody titers at baseline among those seropositive for HPV6 (>=20 mMU/mL) at baseline. HPV antibody titers to type 6 were measured centrally using the competitive Luminex ImmunoAssay (HPV-4, cLIA) on stored serum. The results below the lower limit of detection (LLD) were assigned the values of half the LLD (7 mMU/mL, and after assay change in December 2012, 11 mMU/mL for HPV6).
Time Frame	Weeks 0, 28, 72

Outcome Measure Data

Analysis Population Description

All eligible participants who received at least one vaccine and were seropositive for HPV6 (HPV6+) at baseline (the number of participants analyzed) and had HPV6 titer available at the respective follow-up week. Strata A; B; C. Week 28: n=52; n=33; n=36. Week 72: n=43; 31; 35.

Arm/Group Title	Stratum A/Baseline HPV6+	Stratum B/Baseline HPV6+	Stratum C/Baseline HPV6+
Arm/Group Description	Participants with screening CD4+ count >350 cells/mm^3 (Stratum A) who were seropositive for HPV6 at baseline.	Participants with screening CD4+ count >200 to <=350 cells/mm^3 (Stratum B) who were seropositive for HPV6 at baseline.	Participants with screening CD4+ count<=200 cells/mm^3 (Stratum C) who were seropositive for HPV6 at baseline.
Measure Participants	54	35	37
Change in HPV6 at Week 28 (n=52; 33; 36)	1.12	1.10	0.97
Change in HPV6 at Week 72 (n=43; 31; 35)	0.73	0.70	0.44

10. Secondary Outcome

Title	Change in Log10 HPV11 Antibody Titers From Baseline Among Those Seropositive for HPV11 at Baseline
Description	Change in log10 HPV11 antibody titers was calculated as log10 HPV11 antibody titers at a later timepoint (Week 28, Week 72) minus log10 HPV11 antibody titers at baseline among those seropositive for HPV11 (>=16 mMU/mL) at baseline. HPV antibody titers to type 11 were measured centrally using the competitive Luminex ImmunoAssay (HPV-4, cLIA) on stored serum. The results below the lower limit of detection (LLD) were assigned the values of half the LLD (8 mMU/mL for HPV11).
Time Frame	Weeks 0, 28, 72

Outcome Measure Data

Analysis Population Description

All eligible participants who received at least one vaccine and were seropositive for HPV11 (HPV11+) at baseline (the number of participants analyzed) and had HPV11 titer available at the respective follow-up week. Strata A; B; C. Week 28: n=20; 21; 17. Week 72: n=17; 18; 19.

Arm/Group Title	Stratum A/Baseline HPV11+	Stratum B/Baseline HPV11+	Stratum C/Baseline HPV11+
Arm/Group Description	Participants with screening CD4+ count >350 cells/mm^3 (Stratum A) who were seropositive for HPV11 at baseline.	Participants with screening CD4+ count >200 to <=350 cells/mm^3 (Stratum B) who were seropositive for HPV11 at baseline.	Participants with screening CD4+ count<=200 cells/mm^3 (Stratum C) who were seropositive for HPV11 at baseline.
Measure Participants	22	23	19
Change in HPV11 at Week 28 (n=20; 21; 17)	1.32	1.42	0.60
Change in HPV11 at Week 72 (n=17; 18; 19)	0.93	0.89	0.43

11. Secondary Outcome

Title	Change in Log10 HPV16 Antibody Titers From Baseline Among Those Seropositive for HPV16 at Baseline
Description	Change in log10 HPV16 antibody titers was calculated as log10 HPV16 antibody titers at a later timepoint (Week 28, Week 72) minus log10 HPV16 antibody titers at baseline among those seropositive for HPV16 (>=20 mMU/mL) at baseline. HPV antibody titers to type 16 were measured centrally using the competitive Luminex ImmunoAssay (HPV-4, cLIA) on stored serum. The results below the lower limit of detection (LLD) were assigned the values of half the LLD (11 mMU/mL for HPV16).
Time Frame	Weeks 0, 28, 72

Outcome Measure Data

Analysis Population Description

All eligible participants who received at least one vaccine and were seropositive for HPV16 (HPV16+) at baseline (the number of participants analyzed) and had HPV16 titer available at the respective follow-up week. Strata A; B; C. Week 28: n=40; 28; 24. Week 72: n=37; 25; 24.

Arm/Group Title	Stratum A/Baseline HPV16+	Stratum B/Baseline HPV16+	Stratum C/Baseline HPV16+
Arm/Group Description	Participants with screening CD4+ count >350 cells/mm^3 (Stratum A) who were seropositive for HPV16 at baseline.	Participants with screening CD4+ count >200 to <=350 cells/mm^3 (Stratum B) who were seropositive for HPV16 at baseline.	Participants with screening CD4+ count<=200 cells/mm^3 (Stratum C) who were seropositive for HPV16 at baseline.
Measure Participants	44	30	26
Change in HPV16 at Week 28 (n=40; 28; 24)	1.65	1.29	1.06
Change in HPV16 at Week 72 (n=37; 25; 24)	1.28	0.97	0.53

12. Secondary Outcome

Title	Change in Log10 HPV18 Antibody Titers From Baseline Among Those Seropositive for HPV18 at Baseline
Description	Change in log10 HPV18 antibody titers was calculated as log10 HPV18 antibody titers at a later timepoint (Week 28, Week 72) minus log10 HPV18 antibody titers at baseline among those seropositive for HPV18 (>=24 mMU/mL) at baseline. HPV antibody titers to type 18 were measured centrally using the competitive Luminex ImmunoAssay (HPV-4, cLIA) on stored serum. The results below the lower limit of detection (LLD) were assigned the values of half the LLD (10 mMU/mL for HPV18).
Time Frame	Weeks 0, 28, 72

Outcome Measure Data

Analysis Population Description

All eligible participants who received at least one vaccine and were seropositive for HPV18 at baseline (the number of participants analyzed) and had HPV18 titer available at the respective follow-up week. Strata A; B; C. Week 28: n=27; 11; 19. Week 72: n=25; 11; 19.

Arm/Group Title	Stratum A/Baseline HPV18+	Stratum B/Baseline HPV18+	Stratum C/Baseline HPV18+
Arm/Group Description	Participants with screening CD4+ count >350 cells/mm^3 (Stratum A) who were seropositive for HPV18 at baseline.	Participants with screening CD4+ count >200 to <=350 cells/mm^3 (Stratum B) who were seropositive for HPV18 at baseline.	Participants with screening CD4+ count<=200 cells/mm^3 (Stratum C) who were seropositive for HPV18 at baseline.
Measure Participants	29	12	20
Change in HPV18 at Week 28 (n=27; 11; 19)	1.02	0.89	0.85
Change in HPV18 at Week 72 (n=25; 11; 19)	0.57	0.20	0.14

13. Secondary Outcome

Title	Number of Participants With Signs and Symptoms of Grade 3 or Higher
Description	Number of participants who experienced a sign or symptom of Grade 3 or higher at any time after baseline while on study. Grading of signs and symptoms was according to Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, December 2004.
Time Frame	From baseline to up to Week 72

Outcome Measure Data

Analysis Population Description

All eligible participants who received at least one vaccine.

Arm/Group Title	Stratum A	Stratum B	Stratum C
Arm/Group Description	Participants with screening CD4 count >350 cells/mm^3 received 0.5mL of quadrivalent HPV vaccine at baseline and Weeks 8 and 24.	Participants with screening CD4 count >200 to <=350 cells/mm^3 received 0.5mL of quadrivalent HPV vaccine at baseline and Weeks 8 and 24.	Participants with screening CD4 count <=200 cells/mm^3 received 0.5mL of quadrivalent HPV vaccine at baseline and Weeks 8 and 24.
Measure Participants	127	95	93
Number [Participants]	20 15.7%	20 21.1%	16 17.2%

14. Secondary Outcome

Title	Number of Participants With Laboratory Abnormalities of Grade 3 or Higher
Description	Number of participants who experienced a laboratory abnormality of Grade 3 or higher at any time after baseline while on study. Grading of laboratory abnormalities was according to Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, December 2004.
Time Frame	From baseline to up to Week 72

Outcome Measure Data

Analysis Population Description

All eligible participants who received at least one vaccine.

Arm/Group Title	Stratum A	Stratum B	Stratum C
Arm/Group Description	Participants with screening CD4 count >350 cells/mm^3 received 0.5mL of quadrivalent HPV vaccine at baseline and Weeks 8 and 24.	Participants with screening CD4 count >200 to <=350 cells/mm^3 received 0.5mL of quadrivalent HPV vaccine at baseline and Weeks 8 and 24.	Participants with screening CD4 count <=200 cells/mm^3 received 0.5mL of quadrivalent HPV vaccine at baseline and Weeks 8 and 24.
Measure Participants	127	95	93
Number [Participants]	10 7.9%	7 7.4%	12 12.9%

15. Secondary Outcome

Title	Change in Log10 HIV Viral Load (VL) From Baseline
Description	A blood sample was drawn for local testing to determine the HIV VL. Change in log10 HIV VL was calculated as log10 HIV VL at a later time point (Weeks 4, 12, 28, 52 and 72) minus log10 HIV VL at baseline.
Time Frame	Weeks 0, 4, 12, 28, 52, and 72

Outcome Measure Data

Analysis Population Description

N=315 eligible participants who initiated intervention and had HIV VL available at Week 0 and the respective follow-up week. Strata A; B; C. Week 4: n=123; 89; 88. Week 12: n=118; 89; 90. Week 28: n=118; 91; 87. Week 52: n=109; 85; 82. Week 72: n=105; 81; 83.

Arm/Group Title	Stratum A	Stratum B	Stratum C
Arm/Group Description	Participants with screening CD4 count >350 cells/mm^3 received 0.5mL of quadrivalent HPV vaccine at baseline and Weeks 8 and 24.	Participants with screening CD4 count >200 to <=350 cells/mm^3 received 0.5mL of quadrivalent HPV vaccine at baseline and Weeks 8 and 24.	Participants with screening CD4 count <=200 cells/mm^3 received 0.5mL of quadrivalent HPV vaccine at baseline and Weeks 8 and 24.
Measure Participants	127	95	93
Change in log10 HIV VL at Week 4 (n=123; 89; 88)	0	0	0
Change in log10 HIV VL at Week 12 (n=118; 89; 90)	0	0	0
Change in log10 HIV VL at Week 28 (n=118; 91; 87)	0	0	0
Change in log10 HIV VL at Week 52 (n=109; 85; 82)	0	0	0
Change in log10 HIV VL at Week 72 (n=105; 81; 83)	0	0	0

16. Secondary Outcome

Title	Change in CD4 Cell Count From Baseline
Description	A blood sample was drawn for local testing to determine the CD4 cell count. Change in CD4 cell count was calculated as CD4 cell count at a later time point (Weeks 4, 8, 12, 24, 28, 52 and 72) minus CD4 cell count at baseline.
Time Frame	Weeks 0, 4, 8, 12, 24, 28, 52 and 72

Outcome Measure Data

Analysis Population Description

N=315 eligible participants who initiated intervention and had data available at Week 0 and the respective follow-up week. Strata A; B; C. Week 4: n=122; 92; 88. Week 8: n=119; 92; 90. Week 12: n=115; 87; 90. Week 24: n=117; 85; 88. Week 28: n=114; 89; 87. Week 52: n=108; 85; 87. Week 72: 105; 85; 88.

Arm/Group Title	Stratum A	Stratum B	Stratum C
Arm/Group Description	Participants with screening CD4 count >350 cells/mm^3 received 0.5mL of quadrivalent HPV vaccine at baseline and Weeks 8 and 24.	Participants with screening CD4 count >200 to <=350 cells/mm^3 received 0.5mL of quadrivalent HPV vaccine at baseline and Weeks 8 and 24.	Participants with screening CD4 count <=200 cells/mm^3 received 0.5mL of quadrivalent HPV vaccine at baseline and Weeks 8 and 24.
Measure Participants	127	95	93
Change in CD4 count at Week 4 (n=122; 92; 88)	31	-3	5
Change in CD4 count at Week 8 (n=119; 92; 90)	21	-8	13
Change in CD4 count at Week 12 (n=115; 87; 90)	5	-3	13
Change in CD4 count at Week 24 (n=117; 85; 88)	12	27	12
Change in CD4 count at Week 28 (n=114; 89; 87)	35	37	17
Change in CD4 count at Week 52 (n=108; 85; 87)	6	49	40
Change in CD4 count at Week 72 (n=105; 85; 88)	31	65	46

Adverse Events

Time Frame	From baseline to up to Week 72
Adverse Event Reporting Description	The protocol required reporting of signs and symptoms and laboratory abnormalities of >=Grade 2 and all grades of fever. The DAIDS Adverse Event (AE) Grading Table, Version 1.0, December 2004 (Clarification, August 2009) was used for grading of AEs. Expedited adverse event reporting followed Version 2.0 of the DAIDS Expedited Adverse Event Manual.
Arm/Group Title	Stratum A		Stratum B		Stratum C
Arm/Group Description	Participants with screening CD4 count >350 cells/mm^3 received 0.5mL of quadrivalent HPV vaccine at baseline and Weeks 8 and 24.		Participants with screening CD4 count >200 to <=350 cells/mm^3 received 0.5mL of quadrivalent HPV vaccine at baseline and Weeks 8 and 24.		Participants with screening CD4 count <=200 cells/mm^3 received 0.5mL of quadrivalent HPV vaccine at baseline and Weeks 8 and 24.
All Cause Mortality
	Stratum A		Stratum B		Stratum C
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Stratum A		Stratum B		Stratum C
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/127 (4.7%)		2/95 (2.1%)		6/93 (6.5%)
Blood and lymphatic system disorders
Neutropenia	0/127 (0%)		1/95 (1.1%)		0/93 (0%)
Gastrointestinal disorders
Acute abdomen	0/127 (0%)		0/95 (0%)		1/93 (1.1%)
General disorders
Chest pain	0/127 (0%)		0/95 (0%)		1/93 (1.1%)
Multi-organ failure	0/127 (0%)		0/95 (0%)		1/93 (1.1%)
Infections and infestations
Infection	0/127 (0%)		0/95 (0%)		1/93 (1.1%)
Lobar pneumonia	1/127 (0.8%)		0/95 (0%)		1/93 (1.1%)
Pneumocystis jiroveci pneumonia	0/127 (0%)		0/95 (0%)		1/93 (1.1%)
Pneumonia	0/127 (0%)		0/95 (0%)		2/93 (2.2%)
Injury, poisoning and procedural complications
Brain herniation	1/127 (0.8%)		0/95 (0%)		0/93 (0%)
Investigations
Liver function test abnormal	1/127 (0.8%)		0/95 (0%)		0/93 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Intraductal proliferative breast lesion	1/127 (0.8%)		0/95 (0%)		0/93 (0%)
Non-Hodgkin's lymphoma	1/127 (0.8%)		0/95 (0%)		0/93 (0%)
Nervous system disorders
Migraine	0/127 (0%)		1/95 (1.1%)		0/93 (0%)
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous	1/127 (0.8%)		0/95 (0%)		0/93 (0%)
Other (Not Including Serious) Adverse Events
	Stratum A		Stratum B		Stratum C
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	96/127 (75.6%)		71/95 (74.7%)		82/93 (88.2%)
Blood and lymphatic system disorders
Lymphadenopathy	4/127 (3.1%)		2/95 (2.1%)		5/93 (5.4%)
Gastrointestinal disorders
Abdominal pain	11/127 (8.7%)		8/95 (8.4%)		12/93 (12.9%)
Abdominal pain upper	5/127 (3.9%)		1/95 (1.1%)		7/93 (7.5%)
Diarrhoea	6/127 (4.7%)		3/95 (3.2%)		15/93 (16.1%)
Leukoplakia oral	1/127 (0.8%)		0/95 (0%)		5/93 (5.4%)
Nausea	14/127 (11%)		6/95 (6.3%)		15/93 (16.1%)
Vomiting	13/127 (10.2%)		4/95 (4.2%)		16/93 (17.2%)
General disorders
Chest pain	4/127 (3.1%)		5/95 (5.3%)		8/93 (8.6%)
Chills	5/127 (3.9%)		2/95 (2.1%)		5/93 (5.4%)
Fatigue	4/127 (3.1%)		6/95 (6.3%)		15/93 (16.1%)
Injection site pain	4/127 (3.1%)		6/95 (6.3%)		3/93 (3.2%)
Oedema peripheral	9/127 (7.1%)		2/95 (2.1%)		5/93 (5.4%)
Pyrexia	15/127 (11.8%)		12/95 (12.6%)		22/93 (23.7%)
Infections and infestations
Bronchitis	10/127 (7.9%)		5/95 (5.3%)		4/93 (4.3%)
Herpes simplex	5/127 (3.9%)		3/95 (3.2%)		5/93 (5.4%)
Herpes zoster	0/127 (0%)		7/95 (7.4%)		2/93 (2.2%)
Oral candidiasis	1/127 (0.8%)		2/95 (2.1%)		7/93 (7.5%)
Upper respiratory tract infection	7/127 (5.5%)		6/95 (6.3%)		2/93 (2.2%)
Urinary tract infection	9/127 (7.1%)		6/95 (6.3%)		7/93 (7.5%)
Vaginitis bacterial	11/127 (8.7%)		12/95 (12.6%)		11/93 (11.8%)
Vulvovaginal candidiasis	22/127 (17.3%)		8/95 (8.4%)		11/93 (11.8%)
Vulvovaginitis trichomonal	5/127 (3.9%)		5/95 (5.3%)		1/93 (1.1%)
Investigations
Alanine aminotransferase increased	2/127 (1.6%)		7/95 (7.4%)		6/93 (6.5%)
Aspartate aminotransferase increased	3/127 (2.4%)		9/95 (9.5%)		8/93 (8.6%)
Blood bilirubin increased	6/127 (4.7%)		6/95 (6.3%)		6/93 (6.5%)
Blood creatinine increased	4/127 (3.1%)		1/95 (1.1%)		10/93 (10.8%)
Blood sodium decreased	0/127 (0%)		0/95 (0%)		5/93 (5.4%)
Haemoglobin decreased	2/127 (1.6%)		5/95 (5.3%)		15/93 (16.1%)
Neutrophil count decreased	10/127 (7.9%)		7/95 (7.4%)		18/93 (19.4%)
White blood cell count decreased	0/127 (0%)		2/95 (2.1%)		14/93 (15.1%)
Metabolism and nutrition disorders
Decreased appetite	5/127 (3.9%)		1/95 (1.1%)		8/93 (8.6%)
Musculoskeletal and connective tissue disorders
Arthralgia	6/127 (4.7%)		5/95 (5.3%)		4/93 (4.3%)
Back pain	12/127 (9.4%)		8/95 (8.4%)		7/93 (7.5%)
Myalgia	7/127 (5.5%)		0/95 (0%)		6/93 (6.5%)
Pain in extremity	16/127 (12.6%)		10/95 (10.5%)		11/93 (11.8%)
Nervous system disorders
Dizziness	4/127 (3.1%)		3/95 (3.2%)		6/93 (6.5%)
Headache	17/127 (13.4%)		11/95 (11.6%)		13/93 (14%)
Paraesthesia	3/127 (2.4%)		0/95 (0%)		6/93 (6.5%)
Pregnancy, puerperium and perinatal conditions
Pregnancy	4/127 (3.1%)		5/95 (5.3%)		3/93 (3.2%)
Psychiatric disorders
Anxiety	2/127 (1.6%)		2/95 (2.1%)		6/93 (6.5%)
Depression	9/127 (7.1%)		4/95 (4.2%)		7/93 (7.5%)
Insomnia	3/127 (2.4%)		2/95 (2.1%)		5/93 (5.4%)
Renal and urinary disorders
Dysuria	7/127 (5.5%)		1/95 (1.1%)		5/93 (5.4%)
Reproductive system and breast disorders
Menorrhagia	2/127 (1.6%)		3/95 (3.2%)		5/93 (5.4%)
Vaginal discharge	24/127 (18.9%)		8/95 (8.4%)		11/93 (11.8%)
Vulvovaginal pruritus	17/127 (13.4%)		4/95 (4.2%)		4/93 (4.3%)
Respiratory, thoracic and mediastinal disorders
Cough	17/127 (13.4%)		12/95 (12.6%)		24/93 (25.8%)
Dyspnoea	3/127 (2.4%)		8/95 (8.4%)		14/93 (15.1%)
Nasal congestion	5/127 (3.9%)		2/95 (2.1%)		11/93 (11.8%)
Oropharyngeal pain	4/127 (3.1%)		4/95 (4.2%)		11/93 (11.8%)
Rhinorrhoea	1/127 (0.8%)		2/95 (2.1%)		8/93 (8.6%)
Wheezing	2/127 (1.6%)		1/95 (1.1%)		5/93 (5.4%)
Skin and subcutaneous tissue disorders
Erythema	2/127 (1.6%)		5/95 (5.3%)		1/93 (1.1%)
Pruritus	5/127 (3.9%)		3/95 (3.2%)		6/93 (6.5%)
Skin lesion	8/127 (6.3%)		1/95 (1.1%)		5/93 (5.4%)
Vascular disorders
Hypertension	0/127 (0%)		5/95 (5.3%)		4/93 (4.3%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

In accordance with the Clinical Trials Agreement between NIAID (DAIDS) and company collaborators, NIAID (DAIDS) provides companies with a copy of any abstract, press release, or manuscript prior to submission for publication with sufficient time for company review and comment. The publication/other disclosure can be delayed for up to 30 additional business days for manuscripts and five (5) business days for abstracts, to preserve U.S. or foreign patent or other intellectual property rights.