In July 2020, HPTN researchers launched the first HPTN study to enroll U.S. adolescents under the age of 18 exclusively. HPTN 083-01 evaluates the safety, tolerability, and acceptability of a pre-exposure prophylaxis (PrEP) regimen containing long-acting injectable cabotegravir (CAB LA) for adolescents assigned male at birth. The U.S.-based study is the first collaboration between the HPTN and the Adolescent Medicine Trials Network for HIV/AIDS Interventions, part of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. A companion study, HPTN 084-01, launched in November 2020. Also known as “LIFT,” this study examines whether injectable cabotegravir for PrEP is safe, tolerable, and acceptable for adolescents assigned female at birth under 18 years of age. LIFT is enrolling study participants at sites in South Africa, Uganda, and Zimbabwe.
Why focus HIV prevention research efforts on adolescents? According to UNAIDS, more than half of those newly infected with HIV are between 15 and 24. This population often lacks critical information on protecting themselves from acquiring or transmitting HIV. Many young people are also at high or increased risk due to their social or economic situations.
To better understand the challenges of recruiting participants and educating communities for these two cabotegravir studies, we asked three trial site staffers to share their thoughts and insights on how best to overcome barriers to effective HIV prevention programs targeting young people. Global restrictions instituted in response to the COVID-19 pandemic confounded these challenges during the study start-up period, further complicating access to potential study participants. However, experienced, creative, and dedicated site staff have been unwavering in their commitment to launch these studies successfully.
Adolescent and Young Adult Research project assistant, Ruth M. Rothstein CORE Center at Cook County Health, Chicago
“At the start of the study, most potential study participants were hesitant to enroll over fears they would have to disclose their sexuality to their parents or guardians.”
According to McPherson, some potential study participants in HPTN 083-01 were dissuaded by the study procedures and study locations, including the requirement to have injections or attend a clinical setting for study visits. These challenges further underscore the need to continue building trust and understanding with adolescents regarding clinical research and create environments where they feel safe to participate.
Since the HPTN 083-01 study launched during the COVID-19 pandemic lockdown, existing relationships with healthcare providers and community-based organizations were critical. "We were unable to conduct recruitment in our traditional settings such as health fairs, community events, and youth drop-ins," said McPherson. As a result, McPherson and his site colleagues ramped up social media efforts and Zoom meetings to reach potential study participants. "We're currently in the process of re-branding our social media presence," said McPherson. "This includes new Facebook and Instagram pages, as well as a TikTok account." Zoom was used to share study information with community-based organizations and medical sites that serve adolescents, McPherson said.
Also, adolescents need assurance confidentiality is kept regarding their sexual and reproductive health experiences, said McPherson. "We're currently approved to use self-consent for youth who do not feel comfortable having parents or guardians involved," McPherson said. "Currently, one participant has consented using the self-consent process."
“Religious beliefs were a huge factor in deciding whether a child could join a study. Some churchgoers do not believe in contraception as it is against their religion; therefore, children could not join any research study because of the requirement to be on contraception.”
Community liaison officer, Wits RHI, Johannesburg
While preparing to launch HPTN 084-01 in South Africa, Tshandu learned many parents believed their children could not acquire HIV because they were too young to engage in sexual activities. “Family planning sessions at study clinics helped to demystify myths and misconceptions parents may have about sexual activity among adolescents and HIV prevention research studies,” Tshandu said.
Community engagement coordinator, Johns Hopkins University Research Collaboration, Makerere University, Kampala, Uganda
“After identifying a potential study participant, securing an appointment with the parents would take more than a week depending on availability. Tracing the child’s documents [to verify age] would also take another week or more, as the research team tries to encourage parents or adolescents to travel to their rural home or the care setting where the child was born for birth notes or school reports that indicate age.”
Another significant recruitment challenge in Uganda is verifying age according to protocol-specific requirements. “Parents do not have birth certificates or the equivalent documentation for their children, which is a requirement to join the HPTN 084-01 study,” said Nakyanzi. Study counselors considered several options to overcome this barrier, including a verbal report from the parent(s), determining age by physical appearance, or class reports.
The inclusion of adolescents in HIV prevention research is a critical step in creating a world without HIV. However, recruiting youth in HIV prevention clinical research studies presents a series of unique challenges, particularly during another global pandemic. Identifying those challenges and creating solutions is key to the success of these studies. The HPTN has a longstanding record of community engagement during study development and roll-out. The lessons learned and community insights from HPTN 083-01 and 084-01 remind us that barriers to enrollment are dependent upon the population we are trying to enroll, which further emphasizes the need for targeted community engagement in HIV prevention studies.
Participant recruitment for HPTN 083-01 and HPTN 084-01 will continue through December 2021. Participants will take one cabotegravir pill daily for five weeks, followed by five cabotegravir injections over six months (34 weeks). All participants who have received at least one injection will be followed for 48 weeks after their last injection. During this step, waning levels of cabotegravir will be managed with daily-use oral tenofovir/emtricitabine (TDF/FTC) or the option to remain on CAB LA in HPTN 083-01 or, for participants in HPTN 084-01, the opportunity to join the HPTN 084 CAB open-label extension. Participants will visit the clinic either quarterly (if moving to TDF/FTC) or every two months (if continuing CAB LA) for those 48 weeks after the final injection. The total study duration for each participant will be approximately 1.5 years.
For more information about HPTN 083-01, visit inject2protect.org
For more information about HPTN 084-01, visit lifttrial.org