HPV Vaccine for HIV/AIDS

(AGO-Gard Trial)

Overseen By Executive Director, Office of Research Services

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Louisiana State University Health Sciences Center in New Orleans

Must be taking: Antiretrovirals

Must not be taking: Chronic steroids, Immune modulators

Disqualifiers: Pregnancy, Acute illness, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 7

250 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of the Gardasil-9 vaccine in people with HIV, focusing on their immune response. Researchers aim to determine if the vaccine protects against certain HPV infections and maintains protection over time. The trial seeks participants with HIV who have their condition under control and are either new to the Gardasil-9 vaccine or have completed the vaccine series previously. As a Phase 4 trial, the treatment is already FDA-approved and proven effective, allowing researchers to understand its benefits for a broader patient population.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop your current medications. However, you cannot participate if you are taking chronic steroids or immune modulating medications.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are taking chronic steroids or immune-modulating medications.

What is the safety track record for the Gardasil-9 vaccine?

Research has shown that Gardasil-9, the HPV vaccine, is generally safe, with a safety record similar to the earlier version, Gardasil. The most common side effects are mild, such as soreness at the injection site, headaches, and fever. Some individuals might faint after receiving the shot, so sitting or lying down for a while afterward is advisable.

Further studies have confirmed its safety, although rare reports of serious side effects require more investigation. The vaccine is approved for individuals aged 9 to 45, indicating it is usually well-tolerated. This trial aims to assess how well adults with well-controlled HIV respond to the vaccine, but current evidence shows it is generally safe for most people. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about using the Gardasil-9 vaccine for individuals with HIV/AIDS because it targets the prevention of multiple strains of the human papillomavirus (HPV), which is a significant risk for this population. Unlike traditional treatments that manage HPV-related complications, Gardasil-9 aims to prevent these issues from occurring in the first place by triggering an immune response against nine different HPV types. This proactive approach could lead to a reduced incidence of HPV-related cancers and other complications in people with compromised immune systems, offering a new layer of protection that current treatments do not provide.

What evidence suggests that the HPV vaccine is effective for individuals with HIV?

Research shows that Gardasil-9, the HPV vaccine, works very well. Studies have found that over 98% of people who receive the vaccine develop a strong immune response to the targeted HPV types soon after completing the vaccine series. For some HPV-related health issues, the vaccine is up to 99% effective. Importantly, for people with HIV, the vaccine has been proven to trigger an immune response and is safe to use. In this trial, participants in the "Gardasil-9 recipients" arm will receive a 3-dose Gardasil-9 vaccine series. Meanwhile, the "Gardasil vaccine experienced cohort" will be observed to determine Gardasil HPV serum antibody titers in relation to time since vaccine series completion. Long-term research indicates that Gardasil-9 offers lasting protection, maintaining high antibody levels for up to 10 years. This means the vaccine can effectively help prevent HPV-related problems in people with HIV. ^{5 6 7 8 9}

Who Is on the Research Team?

Michael Hagensee, MD

Principal Investigator

Louisiana State University Health Sciences Center

Jennifer E Cameron, PhD

Principal Investigator

Louisiana State University Health Sciences Center

Are You a Good Fit for This Trial?

This trial is for adults with well-controlled HIV (viral load <1,000 copies/mL and CD4+ count >200 cells/ml) who have not previously received the Gardasil-9 vaccine. They must be stable on antiretroviral therapy for at least 3 months. Pregnant women, those acutely ill, on chronic steroids or immune-modulating meds, recent recipients of blood products or vaccines are excluded.

Inclusion Criteria

I have never received the Gardasil-9 vaccine.

Immune intact (CD4+ T cell count in peripheral blood >200 cells/ml)

My HIV is under control with less than 1,000 copies/mL.

Exclusion Criteria

I am taking medication that affects my immune system.

Recipients of other vaccine products within the past month

I am currently pregnant.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Vaccination

Participants receive the 3-dose Gardasil-9 vaccine series at 0, 1, and 6 months

6 months

3 visits (in-person)

Follow-up

Participants are monitored for seroconversion and HPV infection status

18 months

4 visits (in-person)

Cross-sectional Study

Participants with prior Gardasil vaccination are evaluated for serum antibody titers

What Are the Treatments Tested in This Trial?

Interventions

• Human papillomavirus 9-valent vaccine, recombinant

Trial Overview The study tests how effective the Gardasil-9 HPV vaccine is in adults with controlled HIV by measuring their antibody response compared to people without HIV. It also looks at short-term effects on existing HPV-related infections after completing the three-dose vaccine series.

How Is the Trial Designed?

Group I: Gardasil-9 recipients Experimental Treatment 1 Intervention

Participants receive 3-dose Gardasil-9 vaccine series.

Group II: Gardasil vaccine experienced cohort Experimental Treatment 1 Intervention

Observational cohort to determine Gardasil HPV serum antibody titers in relation to time since vaccine series completion.

Human papillomavirus 9-valent vaccine, recombinant is already approved in United States, European Union for the following indications:

Approved in United States as Gardasil 9 for:

• Prevention of cervical, vulvar, vaginal, anal, oropharyngeal and other head and neck cancers caused by HPV types 16, 18, 31, 33, 45, 52, and 58
• Prevention of genital warts caused by HPV types 6 and 11
• Prevention of precancerous or dysplastic lesions caused by HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58

Approved in European Union as Gardasil 9 for:

• Prevention of precancerous growths and cancer in the cervix and anus, and genital warts
• Protection against 9 types of HPV (types 6, 11, 16, 18, 31, 33, 45, 52, and 58)

Who Is Running the Clinical Trial?

Louisiana State University Health Sciences Center in New Orleans

Lead Sponsor

Trials

123

Recruited

42,400+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Published Research Related to This Trial

A study involving 215,965 individuals who received the nine-valent HPV vaccine (HPV9) found no new safety concerns, confirming its established safety profile from previous research.

While some elevated event categories were noted, such as skin disorders and ill-defined conditions, most were either previously known or had other causes, and no deaths were linked to the vaccine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of 9-valent human papillomavirus vaccine administered to males and females in routine use. Hansen, J., Yee, A., Lewis, N., et al.[2023]

The 9-valent HPV vaccine (Gardasil 9®) significantly increases protection against cervical cancer by covering 9 oncogenic HPV types, raising potential protection from about 70% to 90%, based on clinical trials involving young women.

Clinical trials demonstrated that the 9vHPV vaccine has a comparable safety profile and immunogenicity to the original 4-valent vaccine, with a 2-dose regimen showing similar effectiveness in younger boys and girls compared to the standard 3-dose regimen for older women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expanded strain coverage for a highly successful public health tool: Prophylactic 9-valent human papillomavirus vaccine. Zhang, Z., Zhang, J., Xia, N., et al.[2019]

In a study of 569 postpartum inpatients, 23.1% of vaccine-eligible patients received the nine-valent HPV (9vHPV) vaccine during their hospital stay, indicating that integrating vaccination into postpartum care can increase uptake.

The study found that certain demographics, particularly Hispanic, Spanish-speaking, and publicly insured patients, were more likely to receive the vaccine, suggesting that targeted approaches in postpartum care could help reduce vaccination disparities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human Papillomavirus Inpatient Postpartum Vaccination: Clinical Guideline Implementation. Murphy, EC., Alimena, S., Pelletier, A., et al.[2023]

The 9-valent HPV vaccine (9vHPV) is highly immunogenic in females aged 12-26 who previously received the quadrivalent HPV vaccine (qHPV), with over 98% showing seropositivity for additional HPV types 31/33/45/52/58 after the third dose.

While injection-site adverse events were more common in the 9vHPV group (91.1%) compared to placebo (43.9%), systemic adverse events were similar between both groups, indicating that the 9vHPV vaccine is generally well tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and immunogenicity of a 9-valent HPV vaccine in females 12-26 years of age who previously received the quadrivalent HPV vaccine. Garland, SM., Cheung, TH., McNeill, S., et al.[2016]

The 9-valent HPV vaccine (9vHPV) can potentially increase the prevention of cervical cancer from 70% to 90% by covering additional HPV types (31, 33, 45, 52, and 58) not included in earlier vaccines.

In addition to cervical cancer, the 9vHPV vaccine could prevent 85-95% of HPV-related vulvar, vaginal, and anal cancers, highlighting its broad efficacy in reducing the overall cancer burden associated with HPV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

9-Valent HPV vaccine for cancers, pre-cancers and genital warts related to HPV. Pitisuttithum, P., Velicer, C., Luxembourg, A.[2022]

The 9-valent HPV vaccine (9vHPV) was well tolerated in over 15,000 participants aged 9 to 26, with a safety profile similar to the quadrivalent HPV vaccine, showing mostly mild-to-moderate adverse events like injection-site pain and headaches.

Serious adverse events were very rare (0.1%), and the vaccine did not show any significant safety concerns related to pregnancy outcomes, supporting its widespread use for HPV prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Profile of the 9-Valent HPV Vaccine: A Combined Analysis of 7 Phase III Clinical Trials. Moreira, ED., Block, SL., Ferris, D., et al.[2019]

The 9-valent HPV vaccine demonstrated a high efficacy of 92.3% in preventing high-grade cervical, vulvar, and vaginal dysplasia related to HPV types 31, 33, 45, 52, and 58 in a study involving 5,312 participants aged 9-26 years.

The vaccine was well tolerated, with over 99% of recipients developing antibodies for all 9 HPV types, and most adverse events were mild to moderate, supporting its use in vaccination programs in Latin America.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy, immunogenicity, and safety of a 9-valent human papillomavirus vaccine in Latin American girls, boys, and young women. Ruiz-Sternberg, ÁM., Moreira, ED., Restrepo, JA., et al.[2021]

The nine-valent HPV vaccine, Gardasil9, significantly increases the efficacy against cervical cancer from 70% to 90% compared to the quadrivalent vaccine, covering a broader range of HPV types.

Gardasil9 also provides high efficacy (97%) against lesions associated with HPV types 31, 33, 45, 52, and 58, while maintaining similar effectiveness against HPV types 6, 11, 16, and 18 as the quadrivalent vaccine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Nine-valent HPV vaccine - new generation of HPV vaccine]. Fait, T., Dvořák, V., Pilka, R.[2018]

In a study of 167 HIV-infected women, the prevalence of high-risk HPV types was found to be significantly higher in the anus (90%) compared to the cervix (83%), indicating a need for targeted screening and prevention in this population.

The nonavalent HPV vaccine, which targets both high-risk and low-risk HPV types, is supported by the findings as 9v HR-HPV types were prevalent (67% in the anus and 51% in the cervix), highlighting its potential effectiveness in reducing HPV-related disease in HIV-infected women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevalence and Incidence of Anal and Cervical High-Risk Human Papillomavirus (HPV) Types Covered by Current HPV Vaccines Among HIV-Infected Women in the SUN Study. Kojic, EM., Conley, L., Bush, T., et al.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8706722/

Human Papillomavirus Vaccine Efficacy and Effectiveness ... For CIN2+ and CIN3+ associated with HPV 6/11/16/18, the vaccine efficacy was 99% (95% CI = 91% to 100%) and 99% (95% CI = 82% to 100%). The quadrivalent ...

2. fda.gov fda.gov/media/90064/download

Package Insert - GARDASIL 9 1.3 Limitations of Use and Effectiveness​​ GARDASIL 9 has not been demonstrated to provide protection against disease caused by: • HPV types not covered by the ...

3. cdc.gov cdc.gov/vaccines/vpd/hpv/hcp/vaccines.html

HPV Vaccine Efficacy More than 98% of recipients develop an antibody response to HPV types included in the respective vaccines 1 month after completing a full vaccination series.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4825670/

Human Papillomavirus Vaccination in HIV-infected Women This review summarizes available data on the use of the HPV vaccines among HIV infected women. The immunogenicity and safety of the vaccine is highlighted.

5. vaccineadvisor.com vaccineadvisor.com/news/long-term-immunogenicity-effectiveness-observed-with-hpv-vaccine-gardasil-9/

Long-Term Immunogenicity, Effectiveness Observed With ... Gardasil 9 (human papillomavirus [HPV] 9-valent vaccine, recombinant) was associated with sustained HPV-antibody responses through 10 years among boys and ...

6. cdc.gov cdc.gov/vaccine-safety/vaccines/hpv.html

Human Papillomavirus (HPV) Vaccine Safety The safety findings from these pre-licensure studies show that Gardasil 9 has a similar safety profile to Gardasil, an earlier version of the vaccine. The main ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12269663/

Adverse events following 9-valent human papillomavirus ... This VAERS-based analysis supports the established safety of GARDASIL 9 while highlighting rare signals that warrant further investigation.

8. gardasil9.com gardasil9.com/patient-pd/what-is-gardasil-9/safety-and-side-effects/

GARDASIL 9 safety and side effects The most common side effects of GARDASIL 9 include:​​ Fainting can happen after getting an HPV vaccine. Sometimes people who faint can fall and hurt themselves.

9. gardasil9.com gardasil9.com/

GARDASIL®9 (Human Papillomavirus 9-valent Vaccine ... GARDASIL 9 helps protect individuals ages 9 to 45 against the following diseases caused by 9 types of HPV: cervical, vaginal, and vulvar cancers in females.