HPTN 084-01

HPTN 084-01: Safety, Tolerability, and Acceptability of Long-Acting Cabotegravir (CAB LA) for HIV Prevention Among Adolescent Females

Rationale

HIV continues to disproportionately affect adolescents, with rising mortality in this age group despite progress in other demographics. Adherence challenges with daily oral pre-exposure prophylaxis (PrEP) are especially pronounced among adolescents and young adults, limiting its effectiveness. Expanding adult safety data for long-acting cabotegravir (CAB LA) to include adolescents is crucial for licensing and addressing the unique needs of this vulnerable group.

Primary Objective

To evaluate the safety, tolerability, and acceptability of CAB LA in healthy, HIV-uninfected female adolescents under 18 years old.

Secondary Objectives

1. Assess adherence to and timeliness of CAB LA injections over time.
2. Examine sexual risk behavior patterns among adolescent participants receiving CAB LA.
3. Evaluate CAB LA safety during a 48-week follow-up period after the final injection.

Investigators

• Principal Investigator (IoR): Prof Sinead Delany-Moretlwe
• Sub-Investigators:
  • Dr Carrie-Anne Mathew
  • Dr Elizabeth Roos
  • Dr Nicole Poovan

Sponsors

• Division of AIDS (DAIDS), US National Institute of Allergy and Infectious Diseases (NIAID)
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• US National Institutes of Health (NIH)

Linked Studies and Projects

• Parent Protocol: HPTN 084 – A Phase 3 Double-Blind Safety and Efficacy Study of Long-Acting Injectable Cabotegravir Compared to Daily Oral TDF/FTC for PrEP in HIV-Uninfected Women.

Abstract

CAB LA For HIV Prevention In African Cisgender Female Adolescents (HPTN 084-01)

Sybil Hosek, Erica L.Hamilton, Julie Ngo, Yuqing Jiao, Brett Hanscom, Sinead Delany-Moretlwe, Nyaradzo M.Mgodi, Bekezela Siziba, Ishana Naidoo, Brenda G.Mirembe, Betty Kamira, Mark A.Marzinke, Cynthia McCoig, Hans Spiegel, Lynda Stranix-Chibanda. CROI, Seattle, Washington 19-22 February,2023

Background: While adolescents represent a key population in need of HIV prevention worldwide, daily oral TDF/FTC pre-exposure prophylaxis (PrEP) confers adherence challenges that limit effectiveness. This single arm, open-label Phase 2b safety study (HPTN 084-01) examined the safety, tolerability and acceptability of long-acting injectable cabotegravir (CAB-LA) among adolescent cisgender females in South Africa, Uganda and Zimbabwe.

Methods: Sexually active, HIV-uninfected females under 18 years of age, willing to use reliable long-acting contraception and weighing at least 35kg were eligible to participate. Parental/guardian consent was required for participation unless youth were considered emancipated minors. Step 1 involved a 5-week oral CAB 30mg QD lead-in, followed by 5 intramuscular gluteal injections of 3 mL (600 mg) of CAB-LA administered at weeks 5, 9, 17, 25 and 33 (Step 2). Participants then switched to daily oral TDF/FTC for 48 weeks of follow-up (Step 3) or opted to continue CAB-LA via open label extension (HPTN 084 OLE). We present safety data, injection tolerability, product acceptability, and adverse events (AEs) of special interest (Table 1).

Results: From November 2020-August 2021, 69 individuals were screened and 55 were enrolled (mean age=16, age range 12-17; 100% Black African). At baseline, most had a primary sexual partner in the past month (71%), 22% reported transactional sex, 31% had genitourinary chlamydia and 7% had gonorrhea. Fifty-two (95%) of participants completed Step 1 and 2; two participants discontinued during Step 1 for AEs unrelated to CAB and 1 participant who started Step 2 stopped CAB-LA after 3 injections due to incident pregnancy. There were no product-related serious AEs nor discontinuations from product due to AEs. No one acquired HIV on study. CAB-LA injections were well tolerated overall. Fourteen participants (26%) experienced 20 injection site reactions (ISR) – all Grade 1 or 2. For acceptability, 62% of participants reported via survey that they would consider using CAB-LA for HIV prevention in the future and 94% of participants went on to continue CAB-LA via HPTN 084 OLE.

Conclusions: CAB LA for HIV PrEP was found to be safe, tolerable and acceptable to sexually active adolescent females under the age of 18 in 3 African countries. Concurrent evaluation of CAB-LA for adolescents and adults has allowed for simultaneous licensure in several countries to date, expanding the HIV prevention options available to youth in circumstances of heightened risk.

Latest Update:

November 2024

For more about HPTN 084-01 please email rhicomms@wrhi.ac.za