Predictors of Time to Viremia With an Analytic Treatment Interruption

The HIV field has made a dramatic shift to an emphasis on finding a cure for HIV.

However, there is no agreed upon test of cure, or even what the definition of a cure might
be. The investigator believes the most reliable test of cure will be an analytic treatment
interruption (ATI) with time to viremia as a standard measure of the impact of an
intervention on the degree to which the reservoir has been depleted. This is rational as
modeling studies utilizing ATI data point to reservoir size as an important predictor of time
to viremia(1) and other studies have shown that levels of HIV DNA(2) and cell associated HIV
RNA(3) prior to starting antiretroviral therapy (ART) are associated with time-to-rebound.
However, these studies used a limited sampling strategy to determine when viremia rebounded
and it is likely that greater sensitivity in measures of time-to rebound will be needed to
accurately assess the impact of an intervention. The investigators have tested an ATI
strategy where plasma HIV is sampled three times each week and ART is resumed once the virus
becomes detectable. In this small, pilot study, the investigators sampled lymph nodes, GALT,
plasma, and PBMC before, during, and after the ATI and found the time-to-rebound was 14 days
(range 5 to 30 days) and that total years of ART exposure was associated with the
time-to-rebound (4). The investigators propose a similar study that includes more intensive
blood and lymphoid tissue sampling to identify factors that predict time to-rebound to
provide a necessary foundation for future studies that utilize a treatment interruption as a
test of efficacy for curative interventions.

Inclusion Criteria:

1. HIV-infected individuals who have been on ART therapy for at least two years

2. Male or Female, aged 18 years or older

3. Documented evidence of CD4+ T cell count ≥ 300 cells/µl for 12 months prior to study
entry

4. BMI ≤ 30 or evidence by ultrasound or physical exam of peripheral inguinal lymph
node(s) that is/are surgically accessible

5. Documented plasma HIV RNA levels below level of quantification <20 to <40 copies
RNA/mL depending on the assay) ≥ 24 months (a single measurement above the level of
detection but < 200 copies/ml will be allowed)

6. Willing to switch to an ART regimen consisting of dolutegravir and either
tenofovir/emtricitabine or abacavir/lamivudine to avoid drugs with a long-half life
that would expose the participant to a period of mono-therapy when the drugs are
stopped.

7. Women of child bearing potential and men with partners of child bearing potential must
agree to use effective contraception during protocol

8. Able to provide voluntary written consent.

Exclusion Criteria

1. ART was initiated during acute infection (within first 6 months of infection)

2. Planning or current pregnancy or breastfeeding

3. History and/or presence of any clinically significant disease or disorder, such as
cardiovascular, pulmonary, renal, hepatic, neurological, gastrointestinal and
psychiatric/mental disease/disorder, which, in the opinion of the enrolling physician,
may put the participant at risk because of participation in the study, influence the
results of the study, or affect the participant's ability to participate in the study.

4. Inability to comply with study procedures per enrolling physician discretion.