Prevention and Treatment Continuum for Youth at HIV Risk, Acutely Infected and With Established HIV Infection

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.

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