Reduced-Dose HPV Vaccine for Women with HIV

(NOVA-HIV Trial)

Recruiting at 9 trial locations

Overseen By Deborah Money, MD

Age: 18 - 65

Sex: Female

Trial Phase: Phase 4

Sponsor: University of British Columbia

Disqualifiers: Pregnancy, Allergy to vaccine, 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 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

450 Participants Needed

Trial Summary

What is the purpose of this trial?

There are very little data on human papillomavirus (HPV) vaccination among the 18 million women living with HIV (WLWH) globally, who constitute a population most vulnerable to HPV and the resultant cervical cancer. Particularly, there are no data to date on reduced-dose schedules of nonavalent HPV (9vHPV) vaccination in WLWH and there are very little data on the 9vHPV vaccine in this population overall. It is critical to examine the 9vHPV vaccine in WLWH now because the quadrivalent HPV (4vHPV) vaccine has been discontinued. Additionally, in order to reach the World Health Organization's global goal of cervical cancer elimination, we must determine the role of various HPV prevention strategies in this important population including reduced vaccine dosing which can drastically increase the feasibility of HPV vaccination programs globally. This randomized clinical trial will enrol WLWH aged 18-45 from across Canada who have not previously received an HPV vaccine. Participants will be randomized 1:1 to receive 3 doses of 9vHPV vaccine at the routine vaccine schedule of 0/2/6 months or 2 doses at an expanded schedule of 0/6 months with a third dose at month 12 to adhere to current recommendations for WLWH. We will compare the immune response generated to two versus three doses of 9vHPV vaccine and will follow participants for 2 years to examine the immune response over time. This study, which builds upon our team's prior work on HPV vaccination in WLWH, will determine whether two doses of 9vHPV vaccine can be used in WLWH instead of three, and will examine additional aspects of HPV vaccination in WLWH including the immune response to three doses, vaccine safety and efficacy, and attitudes towards self-collected HPV samples in this population. These data will inform global public health policy and programming and will inform the global strategy for cervical cancer elimination.

Do I need to stop my current medications to join the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your healthcare provider.

What data supports the effectiveness of the treatment Nonavalent HPV vaccine, Gardasil 9, Human Papillomavirus 9-valent Vaccine, Recombinant for women with HIV?

The nine-valent HPV vaccine, Gardasil 9, is generally safe and has been shown to be effective in preventing diseases caused by HPV types included in the vaccine, especially in individuals without prior HPV exposure. However, the effectiveness of HPV vaccines in HIV-infected individuals is inconsistent, with some studies showing reduced effectiveness in this group. ^{1 2 3 4 5}

Is the reduced-dose HPV vaccine safe for women with HIV?

The HPV vaccine, including Gardasil 9, has been shown to be generally safe in both HIV-infected and uninfected individuals, with common side effects being local pain and headache. Serious adverse events are rare, and the vaccine's safety profile is favorable, with a low rate of serious issues reported. ^{4 5 6 7 8}

How is the reduced-dose HPV vaccine different for women with HIV?

The reduced-dose HPV vaccine, Gardasil 9, is unique because it targets nine different types of HPV, including high-risk types that can lead to cancer, and is being studied specifically for its effectiveness and safety in women with HIV, who may have different immune responses compared to the general population. ^{3 4 5 9 10}

Eligibility Criteria

This trial is for women aged 18-45 living with HIV in Canada who have a cervix and haven't had an HPV vaccine before. They must be able to consent, not pregnant or agree to avoid pregnancy during the study, and have no allergies to the vaccine ingredients.

Inclusion Criteria

Living with HIV

I have a cervix.

Exclusion Criteria

I have received an HPV vaccine in the past.

I am unable to understand and agree to the study details on my own.

Allergy to the vaccine or its components

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either 3 doses of 9vHPV vaccine at 0/2/6 months or 2 doses at 0/6 months with a third dose at month 12

12 months

Multiple visits for vaccine administration

Follow-up

Participants are monitored for immune response and safety for 2 years

24 months

Regular follow-up visits

Treatment Details

Interventions

• Nonavalent HPV vaccine

Trial Overview The study tests if two doses of the Nonavalent HPV Vaccine are as effective as three in generating an immune response in women living with HIV. Participants will either follow a routine schedule (0/2/6 months) or an expanded one (0/6 months plus a third dose at month 12).

Participant Groups

Group I: Extended schedule Experimental Treatment 1 Intervention

Two doses of 9vHPV vaccine at an expanded dosing schedule of 0/6 months with a third dose given at month 12

Group II: Routine schedule Active Control 1 Intervention

Three doses of 9vHPV vaccine at the routine dosing schedule of 0/2/6 months

Nonavalent HPV vaccine is already approved in United States, Canada, European Union, Switzerland for the following indications:

Approved in United States as Gardasil 9 for:

• Cervical cancer
• Vulvar cancer
• Vaginal cancer
• Anal cancer
• Oropharyngeal cancer
• Other head and neck cancers
• Genital warts

Approved in Canada as Gardasil 9 for:

• Cervical cancer
• Vulvar cancer
• Vaginal cancer
• Anal cancer
• Oropharyngeal cancer
• Other head and neck cancers
• Genital warts

Approved in European Union as Gardasil 9 for:

• Cervical cancer
• Vulvar cancer
• Vaginal cancer
• Anal cancer
• Oropharyngeal cancer
• Other head and neck cancers
• Genital warts

Approved in Switzerland as Gardasil 9 for:

• Cervical cancer
• Vulvar cancer
• Vaginal cancer
• Anal cancer
• Oropharyngeal cancer
• Other head and neck cancers
• Genital warts

Who Is Running the Clinical Trial?

University of British Columbia

Lead Sponsor

Trials

1,506

Recruited

2,528,000+

Findings from Research

Individuals with HIV are at a higher risk for HPV infection and related cancers, but their immune response to HPV vaccination is often weaker and declines faster than in HIV-negative individuals.

Current HPV vaccines, particularly Gardasil 4, show inconsistent efficacy in HIV-positive individuals, suggesting a need for further research into optimal vaccination strategies, especially considering that Cervarix may offer better immunogenicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HPV vaccination in HIV infection. Lacey, CJ.[2020]

HPV infection and related diseases are increasingly prevalent among HIV-infected women, highlighting the need for effective prevention strategies as these individuals live longer lives.

HPV vaccines are safe and effective in preventing HPV-related diseases, especially in those without prior HPV exposure, but there are significant barriers to vaccination that need to be addressed for HIV-infected women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human papillomavirus vaccination in HIV-infected women: need for increased coverage. Kojic, EM., Rana, AI., Cu-Uvin, S.[2018]

The 3-dose quadrivalent HPV vaccine series was found to be immunogenic and safe in young women aged 16-23 who are infected with HIV, with 100% seroconversion rates for HPV types 6, 11, 16, and 18 among those on antiretroviral therapy (ART).

While immune responses were generally robust, participants not taking ART had lower geometric mean titers for HPV-16 and HPV-18 compared to a historical group of HIV-negative women, indicating that ART may enhance vaccine efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunogenicity and safety of the human papillomavirus 6, 11, 16, 18 vaccine in HIV-infected young women. Kahn, JA., Xu, J., Kapogiannis, BG., et al.[2022]

The quadrivalent HPV vaccine demonstrated high immunogenicity in both HIV-infected (85% seroconversion) and HIV-negative adolescents and young adults (91% seroconversion), indicating it is effective for both populations.

The vaccine was found to be generally safe and well tolerated, with local pain and headache being the most common side effects, suggesting it can be a beneficial preventive measure against HPV-related diseases in HIV-infected individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and immunogenicity of a quadrivalent human papillomavirus vaccine in HIV-infected and HIV-negative adolescents and young adults. Giacomet, V., Penagini, F., Trabattoni, D., et al.[2015]

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 HPV vaccine demonstrated a nearly 100% seroconversion rate in HIV-infected individuals, significantly increasing antibody levels against HPV types 16 and 18 compared to placebo, indicating strong immunogenicity.

There were no significant differences in severe adverse events or changes in CD4+ T-cell counts and HIV viral load between the vaccine and placebo groups, suggesting that the HPV vaccine is safe for use in people with HIV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of human papillomavirus vaccination in HIV-infected patients: a systematic review and meta-analysis. Zizza, A., Banchelli, F., Guido, M., et al.[2021]

In a study of 266,647 doses of Gardasil-9® administered in Puglia, Italy, only 22 adverse events following immunization (AEFIs) were reported, resulting in a low reporting rate of 8.25 per 100,000 doses, indicating a favorable safety profile for the vaccine.

Out of the 22 reported AEFIs, only 5 were classified as serious, with 2 leading to hospitalization; however, only 2 serious AEFIs were consistently associated with the vaccine, suggesting that the benefits of Gardasil-9® outweigh the risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-Life Safety Profile of the 9-Valent HPV Vaccine Based on Data from the Puglia Region of Southern Italy. Di Lorenzo, A., Berardi, P., Martinelli, A., et al.[2022]

The quadrivalent HPV vaccine (Gardasil) effectively stimulated HPV-specific immune responses in HIV-infected young adults undergoing antiretroviral therapy, showing significant increases in various T lymphocyte populations after three doses.

The immune response in HIV-infected individuals was comparable to that of healthy controls, suggesting that the vaccine is both safe and effective in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human papilloma virus vaccination induces strong human papilloma virus specific cell-mediated immune responses in HIV-infected adolescents and young adults. Rainone, V., Giacomet, V., Penagini, F., et al.[2018]

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]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

HPV vaccination in HIV infection. [2020]

2. England pubmed.ncbi.nlm.nih.gov

Human papillomavirus vaccination in HIV-infected women: need for increased coverage. [2018]

3. United States pubmed.ncbi.nlm.nih.gov

Immunogenicity and safety of the human papillomavirus 6, 11, 16, 18 vaccine in HIV-infected young women. [2022]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Safety and immunogenicity of a quadrivalent human papillomavirus vaccine in HIV-infected and HIV-negative adolescents and young adults. [2015]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Safety of 9-valent human papillomavirus vaccine administered to males and females in routine use. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of human papillomavirus vaccination in HIV-infected patients: a systematic review and meta-analysis. [2021]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Real-Life Safety Profile of the 9-Valent HPV Vaccine Based on Data from the Puglia Region of Southern Italy. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Human papilloma virus vaccination induces strong human papilloma virus specific cell-mediated immune responses in HIV-infected adolescents and young adults. [2018]

9. Czech Republic pubmed.ncbi.nlm.nih.gov

[Nine-valent HPV vaccine - new generation of HPV vaccine]. [2018]

10. United States 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. [2019]