Clinical trial NCT03205696: Prevention and Treatment Continuum for Youth at HIV Risk, Acutely Infected and With Established HIV Infection
Official title: A Comprehensive Community-Based Strategy to Optimize the HIV Prevention and Treatment Continuum for Youth at HIV Risk, Acutely Infected and With Established HIV Infection
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Human Immunodeficiency Virus
Lead sponsor: University of California, Los Angeles
Sponsor class: OTHER
Collaborators: name: Los Angeles LGBT Center
name: Tulane University
First posted: 2017-07-02
Enrollment: 101
Sex: ALL
Minimum age (years): 12
Maximum age (years): 24
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Our study will be recruiting youth between the ages of 12 and 24 years with newly diagnosed HIV infection (Acute /Recent or Established HIV). The study is open to all patients within this age group with a new diagnosis of HIV infection, including pregnant women. This study will include adolescents who are displaced and living in shelters or in the streets. These homeless youth will include African American Gay, Bisexual, and Transgendered Youth (GBTY), who are very susceptible to substance abuse, juvenile justice contact, and acquisition of HIV and other sexually transmitted infections (STI).

Brief summary: This is a strategic prospective cohort study which will measure the effects of early intensive antiretroviral therapy (ART) on the establishment and persistence of HIV-1 reservoirs and HIV-1-specific immunity in acutely /recently HIV infected youth aged 12 to 24 years as compared to newly diagnosed youth with established infection \> 6 months. Participants with newly diagnosed acute /recent HIV-1 infection will be offered enrollment into the study with immediate initiation of ART which is the current standard of care.

Detailed description: Adolescents who are displaced and living in shelters or in the streets constitute an extremely vulnerable population for acquisition of HIV infection worldwide. In the U.S., homeless youth, particularly African American Gay, Bisexual, and Transgendered Youth (GBTY), are very susceptible to substance abuse, juvenile justice contact, and acquisition of HIV and other sexually transmitted infections (STI). The displaced adolescent population is not generally amenable to routine clinic follow-up in hospital settings and potentially more easily identified through mobile outreach efforts. HIV prevalence in this group can be as high as 5.3%. While HIV incidence is unknown, high rates of concurrent exposures to other STIs, substance abuse, and survival sex suggest acute infection is likely high. Pediatric studies of HIV perinatally infected infants treated very early with potent antiretroviral therapy as well as studies of adult cohorts treated during acute infection, have shown that very early treatment of HIV is associated with control and decrease in viral reservoir burden, which is likely predictive of long term HIV control. Although early treatment has not yet been demonstrated to induce a functional cure, it has been associated with an extended period of complete viral quiescence, also known as HIV drug free remission. No studies of this kind have enrolled significant numbers of adolescents. Some studies suggest HIV reservoirs from adolescents who were recently HIV infected may be more pliable and responsive to early combined antiretroviral treatment (cART) than that of adults. Prolonged control of HIV through cART initiated following established HIV infection does not appear to impact viral reservoir size. HIV remission is not attainable in this scenario following treatment interruption, even after many years of undetectable plasma virus levels while on cART. We hypothesize that very early antiretroviral treatment of adolescents with acute HIV infection will be associated with decreased viral reservoir size, and viral reservoir size will be significantly different between adolescents with acute, recent or established HIV infection. To evaluate our hypothesis, we propose to capitalize on a current community-based strategy to initiate very prompt antiretroviral treatment many times the very day of diagnosis of HIV infection. Patients with newly diagnosed HIV infection will be offered antiretroviral treatment immediately or within a very short time by our collaborating clinical sites, and through the present study will be monitored periodically for assessment of virus load and HIV reservoir assays.

Eligibility criteria: Inclusion Criteria:

1. Male or female participants age 12 to 24 years.
2. A positive HIV diagnostic assay following a negative HIV diagnostic assay obtained in the previous study visit (if subjects are enrolled in the high risk cohort study- Project 3) or within the last six months if not followed in Study 3. A positive HIV test at baseline for subjects who are included as part of the recently diagnosed arm. HIV diagnostic assays include POC rapid tests including 4th generation rapid assays, GeneXpert HIV qualitative assays, HIV antibody assays, and HIV RNA or DNA PCR assays.
3. Ability and willingness to provide written informed consent.
4. Willingness to initiate ART
5. Willingness of treating clinician to follow DHHS guidelines for antiretroviral naïve adolescents and adults

Exclusion Criteria:

1. Prior ART use.
2. Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
3. Any acute, chronic, or recent and clinically significant medical condition that, in the opinion of the site investigator, would interfere with adherence to study requirements or jeopardize the safety or rights of the participant.
4. Chronic or recurrent use of medications that modify host immune response, e.g., oral or parenteral steroids, cancer chemotherapy.
5. Clinical treatment with an ARV regimen less effective than those recommended by DHHS HIV clinical guidelines.
6. Enrollment on a experimental ARV regimen

Primary outcomes:
measure: Amount of cell-associated HIV-1 DNA
timeFrame: 12 months
Secondary outcomes:
measure: Evaluate HIV-1-specific CD4+ and CD8+ T-cells
timeFrame: 12 and 24 months
measure: Assess the amount of unspliced HIV-1 RNA
timeFrame: 12 and 24 months
measure: Assess cell-associated HIV-1 RNA to DNA ratio
timeFrame: 12 and 24 months
measure: Assess the decay of HIV proviral DNA
timeFrame: 24 months
measure: Assess the time to undetectable HIV RNA
timeFrame: 24 months
measure: Evaluate demographic and behavioral factors associated with sustained adherence to ART
timeFrame: 24 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of California, Los Angeles
state: California
city: Los Angeles
country: United States
facility: Los Angeles LGBT Center
state: California
city: New Orleans
country: United States
facility: Tulane University
state: Louisiana
Study officials:
affiliation: University of California, Los Angeles
name: Karin Nielsen, M.D.
role: STUDY_CHAIR
References: