1. What is HPTN 083-01?
HPTN 083-01 is a clinical trial examining whether injectable cabotegravir (CAB) for PrEP (pre-exposure prophylaxis) is a safe and acceptable method of HIV prevention for adolescents assigned male at birth. HPTN 083-01 is a sub-study of a larger clinical trial called HPTN 083. HPTN 083 examines whether injectable CAB works as PrEP, but in men and transgender women 18 years or older.
2. What is PrEP?
PrEP stands for Pre-Exposure Prophylaxis. PrEP is an HIV prevention strategy that uses anti-HIV medications to fight HIV in people who do not have HIV to reduce the risk of HIV. HPTN 083-01 is testing the safety and acceptability of long-acting injectable cabotegravir for PrEP, which is not currently approved for use among adolescents. There are currently three drugs approved for PrEP by the U.S. Food and Drug Administration (FDA):
- Daily oral emtricitabine and tenofovir disoproxil fumarate, sold under the brand name Truvada®
- Daily oral emtricitabine and tenofovir alafenamide, sold under the brand name Descovy®
- Long-acting injectable cabotegravir, sold under the brand name Apretude®
Truvada is approved for PrEP for all adults and adolescents at risk of HIV. Descovy is approved for HIV prevention in adult and adolescent cisgender men and transgender women but has not been studied in other populations. Apretude was recently approved by the U.S. FDA for PrEP in adults and adolescents weighing at least 35 kilograms (77 pounds).
3. What organizations are involved in this study?
The National Institute of Allergy and Infectious Diseases (NIAID) is working with the HIV Prevention Trials Network (HPTN), The Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), and ViiV Healthcare.
4. When and where will 083-01 be done?
This study began enrolling participants in June 2020. There are study sites in Boston, Chicago, Denver, and Memphis.
5. How many people will be in this study and who can join?
This study will be enrolling about 50 adolescents, assigned male at birth, under the age of 18. The total study duration per participant will be approximately 21 months.
6. Why is this study being done?
Before injectable CAB can be approved for PrEP among adolescent males, we need to answer the following questions in this study:
- Is it safe for adolescents assigned male at birth to take CAB pills and CAB injections?
- Is it acceptable and practical for adolescents assigned male at birth to use CAB for PrEP?
- Are injection appointments every eight weeks at the clinic acceptable and convenient for adolescents assigned male at birth?
- What do parents/guardians think about their children using CAB for PrEP?
7. What will happen during the study?
Participants will move through the study in 3 steps:
Step 1: Participants will take one CAB pill every day for five weeks
Step 2: Participants will receive a total of 5 CAB injections over 6 months
Step 3: Participants will come to the clinic for study visits quarterly and have the option to receive Truvada for PrEP for about one year or continue on CAB LA injections
During study visits, participants will also receive physical health examinations, answer questions about their overall health, and receive counseling about HIV prevention and difficulties they may have during the study. Urine, blood, and rectal and oral swabs will be taken at visits throughout the study to test for HIV, Hepatitis, and sexually transmitted infections (STIs); and liver and kidney health and cholesterol.
8. How will participants be supported to take their medication and remember study visits?
Participants will receive support from clinic staff and counselors at each visit. Counselors may ask participants about difficulties that get in the way of attending study visits. Participants will be offered reminders about their visits if desired.
9. Will injectable CAB be tested in adolescent girls?
10. Is injectable CAB safe?
Studies conducted so far in adults have shown CAB to be safe. Safety will continue to be assessed among adults in HPTN 083 and HPTN 084 as well as among adolescents in HPTN 083-01 and HPTN 084-01.
11. Can injectable CAB protect participants from getting infected with HIV?
Results from the HPTN 083 study released at the AIDS 2020: Virtual conference in July showed that a PrEP regimen containing CAB LA was superior to oral Truvada for the prevention of HIV acquisition in 4570 cisgender men and transgender women enrolled in HPTN 083. More information about HPTN 083 is available at giveprepashot.org or hptn.org/research/studies/hptn083.
Participants in HPTN 083 were put into one of two groups by chance (like the flip of a coin):
- Group A: Real CAB drug and Truvada placebo (injection that has real CAB and pill that does not have real TDF/FTC)
- Group B: CAB placebo and real Truvada (injections that do not have real CAB and pill that has real TDF/FTC)
In HPTN 083, both CAB LA and Truvada were very good at preventing new HIV infections. They also found that both CAB LA and daily Truvada pills were safe and well tolerated. The HPTN 083 study found that people who got the CAB LA shots had 2/3 less new HIV infections than people who got daily Truvada pills.
We do not know if CAB can protect adult cisgender women from acquiring HIV. The HPTN 084 (LIFE) study is looking at the safety and efficacy of CAB in adult cisgender women and will continue to be a rigorously conducted study and collect data about the safety and efficacy of CAB LA in cisgender women. More information about HPTN 084 is available at 084life.org or hptn.org/research/studies/hptn084.
12. What do the HPTN 083 results mean for HPTN 083-01?
We are not changing how we are doing HPTN 083-01 because we still need to see if the CAB LA shots are safe and acceptable among youth. We need to find this out if we want CAB LA shots to be approved for use by youth. So, all people in HPTN 083-01 will receive CAB LA shots. This is good news now that we know CAB LA works to prevent HIV infection. HPTN 083-01 and HPTN 084-01 will not show us if CAB works for PrEP among adolescents but will show us if CAB LA shots are safe and acceptable in youth.
13. What HIV preventive care will study participants receive?
HPTN 083-01 study participants will receive HIV prevention counseling, condoms and lubricant, as well as counseling to encourage and support taking the study pills. Participants will be tested for STIs throughout the study and referred for appropriate treatment if an STI is diagnosed. After participants stop getting injections, they will be offered Truvada for PrEP for about a year or access to another CAB study.
14. When are results expected from HPTN 083-01?
We expect to have results in 2023.
15. How is HPTN ensuring the safety of HPTN 083-01 study participants?
Multiple individuals and groups will carefully monitor the safety of HPTN 083-01 study participants. Study sites will report and manage any adverse health outcomes daily, and the study team will monitor safety reports from the sites. In addition, a Clinical Management Committee will assist principal investigators if unexpected safety concerns arise.
Additionally, both a Study Monitoring Committee and an independent Data and Safety Monitoring Board (DSMB) will conduct periodic reviews of participants’ safety. A DSMB is an unbiased group composed of clinical research and medical experts, statisticians, and ethicists who meet periodically during a study to review safety data. The DSMB will alert the study team if anything appears to raise a new safety concern for study participants or if it becomes clear that the study cannot answer one of the questions it was designed to address. If indicated, the DSMB can advise that the study be ended early.
16. What will happen to study participants who acquire HIV infection during the trial?
Being in this study will not increase your risk for acquiring HIV, but a participant could acquire HIV through sex or other activities while in this study. Participants who acquire HIV will stop using their study product, but complete study visits to make sure they are doing okay. The study staff will provide counselling and referral for HIV treatment and other available services, but the study will not pay for this treatment. We will share any test results relevant to treatment decisions. Testing will be done to help select the best drugs to treat the HIV.
17. Does my parent/guardian need to know I am in the study?
Because study participants are still minors, permission from a parent/guardian is needed before they can take part in the study. Once the parent/guardian agrees for the minor to participate, the minor may attend study visits alone. Every effort will be made to keep the study participant’s information private and confidential. No information about the study participant or the participant’s health will be shared with anyone, even the parent/guardian, without talking to the study participant first, except when the participant’s life is thought to be in danger.
18. Where can I find more information?
More information can be found at hptn.org/research/studies/083-01.