Reduced-Dose HPV Vaccine for Women with HIV

(NOVA-HIV Trial)

Recruiting at 11 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether women living with HIV (WLWH) can receive two doses of a nonavalent HPV (9vHPV) vaccine instead of the usual three to protect against HPV, a virus that can lead to cervical cancer. The researchers aim to determine if the reduced-dose schedule generates an immune response as effectively as the standard schedule. Women aged 18-45 in Canada who have HIV, have not received an HPV vaccine before, and have a uterine cervix might be suitable for this study. This research will help identify the best vaccination strategy for this vulnerable group and inform global health policies for preventing cervical cancer. As a Phase 4 trial, it involves an FDA-approved vaccine, ensuring safety and effectiveness, and helps understand how it benefits more patients.

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 is the safety track record for the Nonavalent HPV vaccine?

Research has shown that the nonavalent HPV vaccine, known as Gardasil 9, has undergone safety testing in various groups, including women with HIV. Studies have found that this vaccine is generally well-tolerated, with most side effects being mild, such as pain at the injection site, headaches, or fatigue. Serious side effects are rare.

The FDA approved Gardasil 9 in 2014, indicating it has passed numerous safety checks for use in the general population. In women aged 16-26, further research has confirmed its safety and effectiveness. For women with HIV, studies indicate that the vaccine is safe, though more research may be needed to confirm these findings in this group.

Overall, the vaccine appears safe, with a strong track record in various studies. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about the reduced-dose HPV vaccine protocols for women with HIV because they explore more flexible dosing schedules that could make vaccination more convenient and accessible. Unlike the standard three-dose schedule given at 0, 2, and 6 months, the experimental approach investigates extending the intervals to two doses at 0 and 6 months, with a third dose at 12 months. This extended schedule could simplify logistics and improve adherence, especially for individuals who may have difficulty attending multiple appointments in a shorter timeframe. Additionally, if proven effective, this approach could help optimize resource allocation, making it a promising strategy for broader public health impact.

What evidence suggests that this trial's treatments could be effective for women with HIV?

Research has shown that the nonavalent HPV vaccine effectively creates a strong immune response in women living with HIV (WLWH). Studies have found that the vaccine is safe and helps protect against HPV, which is crucial for preventing cervical cancer. This trial will compare two dosing schedules: the routine three-dose schedule and an extended two-dose schedule with a third dose given later. Although limited information exists on using fewer doses for WLWH, the vaccine has proven very effective in similar groups. This research aims to determine if two doses can work as well as the usual three doses. Earlier findings suggest that even with fewer doses, the vaccine can still provide strong protection, facilitating broader global vaccination access. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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).

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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]

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]

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]

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]

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]

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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05495906

A Study of Reduced Dosing of the Nonavalent HPV ... This randomized clinical trial will enrol WLWH aged 18-45 from across Canada who have not previously received an HPV vaccine.

2. withpower.com withpower.com/trial/phase-3-hiv-infections-8-2022-b0ec2

Reduced-Dose HPV Vaccine for Women with HIV 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.

3. nature.com nature.com/articles/s41598-021-83727-7

Efficacy and safety of human papillomavirus vaccination in ... Prophylactic HPV vaccines may also benefit HIV + patients, however, little is known about their safety and efficacy in this population.

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0264410X18313264

Immunogenicity and safety of a mixed vaccination ... The results show the mixed HPV vaccination schedules used in this study are immunogenic and have an acceptable safety profile.

5. 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.

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

GARDASIL 9 safety and side effects GARDASIL 9 may not fully protect everyone, nor will it protect against diseases caused by other HPV types or against diseases not caused by HPV. GARDASIL 9 does ...

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

Human Papillomavirus (HPV) Vaccine Safety Gardasil 9 (human papillomavirus 9-valent vaccine, recombinant; 9vHPV) was approved by FDA for use in 2014. The safety of Gardasil 9 was studied in clinical ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8496244/

Update on Safety and Efficacy of HPV Vaccines Final efficacy, immunogenicity, and safety analyses of a nine-valent human papillomavirus vaccine in women aged 16–26 years: a randomised, double-blind trial.

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11359547/

Safety and Immunogenicity of the Nonavalent Human ... The objectives were to evaluate the safety and immunogenicity of the nonavalent human papillomavirus (nHPV) vaccine in adult Spanish women living with HIV ( ...

10. aetna.com aetna.com/cpb/medical/data/700_799/0726.html

Human Papillomavirus (HPV) Vaccine Final efficacy, immunogenicity, and safety analyses of a nine-valent human papillomavirus vaccine in women aged 16-26 years: A randomised, double-blind trial.