Acute HIV Infection in Youth: Protocol for the Adolescent Trials Network 147 (ATN147) Comprehensive Adolescent Research and Engagement Studies (CARES) Study

Abstract

BackgroundEarly treatment studies have shown that prompt treatment of HIV with combination antiretroviral therapy (cART) can limit the size of latent viral reservoirs, thereby providing clinical and public health benefits. Studies have demonstrated that adolescents have a greater capacity for immune reconstitution than adults. Nevertheless, adolescents who acquired HIV through sexual transmission have not been included in early treatment studies because of challenges in identification and adherence to cART.ObjectiveThis study aimed to identify and promptly treat with cART youth aged 12 to 24 years in Los Angeles and New Orleans who have acute, recent, or established HIV infection, as determined by Fiebig stages 1 to 6 determined by viral RNA polymerase chain reaction, p24 antigen presence, and HIV-1 antigen Western blot. The protocol recommends treatment on the day of diagnosis when feasible. Surveillance and dedicated behavioral strategies are used to retain them in care and optimize adherence. Through serial follow-up, HIV biomarkers and response to antiretroviral therapy (ART) are assessed. The study aims to assess viral dynamics, decay and persistence of viral reservoirs over time, and correlate these data with the duration of viral suppression.MethodsA total of 72 youth (36 acutely infected and 36 treatment naïve controls) are enrolled across clinical sites using a current community-based strategy and direct referrals. Youth are prescribed ART according to the standard of care HIV-1 management guidelines and followed for a period of 2 years. Assessments are conducted at specific time points throughout these 2 years of follow-up for monitoring of adherence to ART, viral load, magnitude of HIV reservoirs, and presence of coinfections.ResultsThe study began enrolling youth in July 2017 across study sites in Los Angeles and New Orleans. As of September 30, 2018, a total of 37 youth were enrolled, 12 with recently acquired, 16 with established HIV infection as determined by Fiebig staging, and 9 pending determination of Fiebig status. Recruitment and enrollment are ongoing.ConclusionsWe hypothesize that the size of the HIV reservoir and immune activation markers will be different across groups treated with cART, that is, those with acute or recent HIV infection and those with established infection. Adolescents treated early who are virally suppressed will have diminished HIV reservoirs than those with established infection. These youth may be potential candidates for a possible HIV vaccine and additional HIV remission intervention trials. Our study will inform future studies of viral remission strategies.International Registered Report Identifier (IRRID)DERR1-10.2196/10807

Strategies to Treat and Prevent HIV in the United States for Adolescents and Young Adults: Protocol for a Mixed-Methods Study

“…One of the major innovations in this program project is to monitor the outcomes over time for youth identified and treated with ARV soon after HIV infection. Our acute infection research protocol, which has been described in detail elsewhere [6], is based on our team’s successful Cure research with pediatric populations [5]. One of the biggest challenges we face is identifying a sufficiently large pool (N=36) of youth in the acute infection phase; in the first 15 months, we have identified 13 youths.…”

“…In addition, measures of virus persistence in latent reservoirs, based on digital drop polymerase chain reaction detection of proviral DNA, estimate the replication-competent reservoir size among acutely infected YLH, which is compared with that among treatment-naïve YLH who were infected more than 90 days prior to antiretroviral therapy initiation. Additional details on Protocol 147, including power calculations for sample sizes, have been provided by Nielsen-Saines et al [6].…”

“…This paper summarizes the rationale behind these studies, including the recruitment, retention, assessment, and intervention strategies common across them. Individual protocol papers in this volume outline each specific trial [6-8]. The integrated data analytic protocols [9] and strategies for monitoring sexually transmitted infections (STI) across the studies [10] are concurrently available.…”

Model-Based Methods to Translate Adolescent Medicine Trials Network for HIV/AIDS Interventions Findings Into Policy Recommendations: Rationale and Protocol for a Modeling Core (ATN 161)

“…Comprehensive Adolescent Research and Engagement Studies [54], a comprehensive community-based project that aims to optimize the HIV prevention and treatment continuum for at-risk and acutely infected youth as well as youth with established HIV infection.…”

Community-Based, Point-of-Care Sexually Transmitted Infection Screening Among High-Risk Adolescents in Los Angeles and New Orleans: Protocol for a Mixed-Methods Study

“…We also intend to evaluate other treatment outcomes such as cure rates, reinfection rates, and partner treatment rates. For objectives of other components of the ATN CARES study, refer to other ATN CARES protocol papers [20-24]. For specific power analyses, refer to the ATN CARES paper by Swendeman et al [22].…”