Dolutegravir in Reservoirs

The purpose of this study is to find out how well the HIV medication dolutegravir gets into
different parts of the body: including blood plasma, special blood cells, and rectal tissue.
Specifically, investigators want to compare how fast dolutegravir lowers the HIV viral load
in these three different sites. In addition, investigators seek to learn if there are any
differences in how dolutegravir acts in males and females. Results of this study will provide
more information about HIV medications and their limitations. In the future, this could help
create better HIV medications that can get into these hard-to-reach places and eventually
cure HIV infection.

The primary aim of this study is to validate the integrated population PK-VD model that
quantitatively describes the relationship between dolutegravir (DTG) exposure and HIV viral
decay in blood plasma. The second aim of this study is to develop an integrated population
pharmacokinetic-viral dynamic (PK-VD) model to describe the relationship between DTG exposure
and HIV viral decay in peripheral blood mononuclear cells and rectal tissue reservoir sites.
The third aim is exploratory and will investigate sex differences in DTG penetration into
blood plasma, peripheral blood mononuclear cells and rectal tissue reservoirs reservoirs as
well as its impact on the rectal microbiome.

Inclusion Criteria:

- Antiretroviral naïve. Participants will be classified as ARV-naïve if they meet any of
the following criteria: 1) No ARVs for ≥ 6 months and never taken HIV medications for
≥ 30 consecutive days, 2) Females that only took ARVs during pregnancy and have been
off ARVs for ≥ 6 months prior to enrollment, or 3) Persons whose only exposure to ARVs
was "monotherapy"(meaning they were taking only one class of ARVs) before the advent
of HAART.

- Plasma HIV-1 RNA >1000 copies/mL

- Creatinine Clearance >50 mL/min, as calculated by the Cockcroft-Gault equation within
90 days of screen

- Liver function testing, including alanine aminotransferase (ALT), aspartate
aminotransferase (AST), and alkaline phosphatase < 5 times upper limit of normal
within 90 days of screen

- Intact gastrointestinal tract

- Able and willing to give informed consent

- Willing and eligible to initiate ARV therapy with Triumeq, DTG + Truvada (TDF/FTC), or
DTG + Descovy (FTC/TAF)

- Agree to receive from their provider and pay for a prescribed supply of the drug,
Tivicay® (dolutegravir/DTG), with either Triumeq, or Truvada or Descovy as determined
by their primary HIV provider.

- Agree to take the prescribed medication by mouth.

- Agree that they (the participant) is responsible for bringing these medications
with them to their study visits.

- Willing to undergo serial blood and rectal tissue sampling

- Female participants' must be willing to have a pregnancy test done at each visit.

Female participants of childbearing potential (FCB) must agree to either commit to
continued abstinence from heterosexual intercourse or to use a reliable form of birth
control such as oral contraceptive pills, intrauterine device, Nexplanon, Depo Provera,
permanent sterilization, or another acceptable method, as determined by the investigator
for the duration of the study. FCB are defined as sexually mature women who have not
undergone hysterectomy or bilateral oophorectomy or have not been naturally postmenopausal
for at least 24 consecutive months (i.e have had menses at any time in preceding 24 months)

Exclusion Criteria:

- Pregnant or attempting to conceive now or during the course of the study

- Palpable abnormality on digital rectal exam

- Severe perianal disease requiring surgery or prohibiting the ability to safely perform
anoscopy with biopsies, in investigator's opinion

- Taking concurrent medications that interfere with DTG (see Table 2)

- Bleeding diathesis

- Platelet count <50,000 mm3

- Medical condition that interferes with conduct of study, in investigator's opinion