Digital Health Feedback System (DHFS) for Longitudinal Monitoring of ARVs Used in HIV Pre-exposure Prophylaxis (PrEP)

This study is a prospective single arm open label intervention study over 12 weeks using the
DHFS with participants initiating or continuing HIV PrEP. The study intervention has an
initiation (Phase 1), persistence (Phase 2) and follow-up period up to 96 weeks. In phase 1
participants will use the DHFS with close follow-up incorporating visits with directly
observed ingestions. In Phase 2 the participants utilize the DHFS in their natural setting
with sporadic study visits until 12 weeks. Eligible HIV seronegative participants will
receive an ingestible sensor enabled oral antiretroviral (IS-ARV) of TDF/FTC (Truvada®). The
study will be conducted at the UCSD AVRC. Participants will be recruited from UCSD AVRC, UCSD
Owen Clinic, related or affiliated UCSD primary care programs or community primary care
clinics. Following the 12 week intervention participants will undergo HIV testing and
continuation on HIV PrEP and followed for up to 96 weeks. The primary outcome will be an
accurate measure of adherence i.e. the number of doses of selected IS-ARVs ingested, as
captured by the DHFS, over the number of doses prescribed, adjusted for positive detection
accuracy (PDA), defined as the percentage of detected sensors that have been administered
under direct observation.The investigators will also assess the acceptability and feasibility
of longitudinal monitoring in real time of the ingestion rate utilizing the DHFS. In addition
the investigators will evaluate the ability of the DHFS to identify participants whose
longitudinal medication taking and timing patterns in the first 12 weeks of ARV treatment
puts them at risk for HIV infection as far out as 96 weeks from start of treatment.

Pharmacokinetic Substudy

• To obtain TDF/FTC serum levels data comparing co-encapsulated IS-Truvada formulation to
native Truvada® as supplemental information to dissolution studies.

A subset of 12 participants prescribed IS-Truvada®:(tenofovir disoproxil
fumarate/emtiritabine) for PrEP will be enrolled in a PK sub-study to provide supplementary
data to dissolution studies conducted by Gilead Sciences on the co-encapsulated IS-Truvada
formulation. On Day 14 of treatment, when drug concentrations are expected to be close to
steady state, sub-study participants will have a PK profile for Tenofovir and Emtricitabine
obtained over a single dosing interval (at time 0 (pre-dose Ctrough), 2, 4, 6, 8 and 24
hours). Participants will be seen at the AVRC in a fasting state prior to taking their dose
of IS-Truvada® and will remain fasting for 2 hours after the observed ingestion. The time and
date of the previous doses of IS-Truvada® will be recorded by and available from the DHFS
prior to initiating the PK procedures. The following day, Day 15, the participant will return
to the AVRC in a fasting state. The 24 hour plasma sample will be drawn. Participants will
then receive an observed dose of native Truvada. Participants will remain fasting for 2 hours
after the observed ingestion and will have plasma samples drawn at 2, and 4 hours after
ingestion.

Samples will be analyzed for tenofovir and emtricitabine drug concentration levels either
individually or in batches at the central specialized laboratory.

Inclusion Criteria:

1. Adult non-pregnant HIV-seronegative participants who are starting or continuing HIV
PrEP with IS-TDF/FTC (Truvada®), who are able to use the DHFS mobile device, and to
tolerate a wearable sensor patch

2. Laboratory values obtained by screening laboratories within 14 days of entry:

- Absolute neutrophil count (ANC) ≥ 1,000/mm3.

- Hemoglobin ≥ 9.0 g/dL.

- Platelet count ≥ 75,000/mm3.

- AST (SGOT), ALT (SGPT), and alkaline phosphatase ≤ 3 x ULN.

- Estimated GFR by Cockcroft-Gault equation of >50 ml/min, if starting treatment
with Truvada®(TDF/FTC).

- HIV Ag/Ab test negative

- Hepatitis B serology negative

3. Females of childbearing potential must agree to use an acceptable form of
contraception throughout the protocol.

4. Basic competency in understanding written and verbal information as it applies to DHFS
use. English and Spanish will be used for study documents and communication.

5. Willing to follow all protocol requirements.

6. No symptoms or clinical suspicion of acute HIV infection.

Exclusion Criteria:

1. Female who is pregnant, breast-feeding, or of childbearing potential and declines to
use contraception throughout the study period.

2. Use of any of the prohibited medications or other non-informed medications within 30
days of study entry (Day 0).

3. Known allergy/sensitivity to any of the study drugs.

4. Known sensitivity to skin adhesives.

5. Serious medical (serious infection or acute therapy for other medical illness) or
psychiatric illness requiring systemic treatment and/or hospitalization until
participant either completes therapy or is clinically stable on therapy, in the
opinion of the investigators, for at least 30 days prior to study entry (Day 0).

6. Active drug or alcohol use, or dependence, or other conditions that, in the opinion of
the site investigators, would significantly interfere with ability to follow to study
requirements.