Safety and Efficacy of Fixed Dose Combination Dolutegravir/Abacavir/Lamivudine FDC Initiated During Acute HIV Infection

The study will be conducted at the University of North Carolina in Chapel Hill, NC and Duke
University in Durham, NC. All forty (40) participants will be enrolled for 96 weeks and will
receive DTG/3TC/ABC FDC.

We propose to evaluate the efficacy and time to viral suppression with DTG/3TC/ABC FDC as
initial therapy for AHI (acute HIV infection), as well as the feasibility of prompt
administration using a rapid HLA-B57 (human leukocyte antigen) screening antibody assay. In
addition to validating the restriction of RCI (resting cell infection) by ART (antiretroviral
therapy) including a DTG-based regimen initiated during AHI, we will seek correlations
between low RCI, residual GALT (gastrointestinal associated lymphoid tissue) HIV expression,
and measures of immune activation. We hypothesize that rapid reduction in plasma viremia with
this regimen will limit the area under the pre-ART viral load curve, and thus reduce the
latent reservoir size as measured by a viral outgrowth assay one to two years following ART
start, and as compared with the latent reservoir size in acutely infected individuals started
on regimens without an integrase inhibitor based regimen. In addition, we will examine the
longitudinal impact of the proposed integrase-based regimen initiated during the acute period
on immune activation through week 96. If residual viral expression and persistent immune
dysfunction is related to the burden of the latent viral reservoir (and presumably its
periodic activation) these abnormalities should be ameliorated by early ART with rapid viral
suppression. Finally, we will evaluate dolutegravir levels in plasma and GALT and whether
rapid viral suppression with the proposed dolutegravir-based ART regimen impacts HIV RNA
levels in GALT.

Inclusion Criteria

1. Documentation of Acute HIV infection at or within 30 days of study entry.

2. Men and women age ≥18 years.

3. ART naive, defined as ≤14 days of antiretroviral treatment at any time prior to entry.
The only exceptions are:

- Pre-exposure prophylaxis (PrEP) and documented as HIV-1 negative at least 1 month
prior to AHI diagnosis during PrEP, and

- Post-exposure prophylaxis (PEP) provided the participant was documented as HIV-1
negative at least 3-6 months following completion of PEP treatment.

4. Lab values obtained within 30 days prior to study entry:

- Absolute neutrophil count >500/mm3

- Hemoglobin > 8.5 g/dL for men and > 8.0 g/dL for women

- Platelet count >50,000/mm3

- Lipase ≤ 3 X upper limit of normal (ULN), single repeat test is allowed to
determine eligibility

- Calculated creatinine clearance (Cockcroft-Gault formula) ≥ 50mL/min:

CrCl = (140-age) x body weight (kg) (x 0.85 if female) Serum creatinine [mg/dL] x (72)

5. Testing for HBsAg is pending. Note: Participants who test positive for HBsAg will be
terminated from the study prior to starting study treatment.

6. Testing for HLA-B57 and/or HLA-B*5701 is pending. Note: Participants who test positive
for HLA-B*5701 will be terminated from the study prior to starting study treatment.

7. A female is eligible to enter and participate in the study if she:

- Is of non-childbearing potential defined as either post-menopausal (12 months of
spontaneous amenorrhea and ≥ 45 years of age) or physically incapable of becoming
pregnant with documented tubal ligation, hysterectomy or bilateral oophorectomy;
or,

- Is of child-bearing potential, with a negative pregnancy test at screening and at
enrollment, who agrees to use one of the methods of contraception listed below.

- Complete abstinence from intercourse from 2 weeks prior to administration of
study medication, throughout the study, and for at least 2 weeks after
discontinuation of all study medication;

- Double barrier method (male condom/spermicide, male condom/diaphragm,
diaphragm/spermicide);

- Approved hormonal contraception - used alone is not considered a sufficient form
of contraception for the study see Protocol Appendix 1 for a listing of examples
of approved hormonal contraception;

- Any intrauterine device (IUD) with published data showing that the expected
failure rate is <1% per year; see Protocol Appendix 2 for a listing of IUDs
meeting this criterion;

- Male partner sterilization confirmed prior to the female participant's entry into
the study, and this male is the sole partner for that patient;

- Any other method with published data showing that the expected failure rate is
<1% per year.

- Any contraception method must be used consistently, in accordance with the
approved product label and for at least 2 weeks after discontinuation of the
study medication.

8. Ability and willingness of participant to give written informed consent.

Exclusion Criteria

1. ALT ≥ 5 times Upper Limit of Normal (≥5xULN)

2. AST ≥ 3x ULN

3. Bilirubin ≥1.5x ULN (with >35% direct bilirubin)

4. Women who are breast-feeding.

5. Women with a positive pregnancy test on enrollment or prior to study drug
administration.

6. History or presence of allergy to the study drugs or their components.

7. Requires or is anticipated to require any of the prohibited concomitant therapy:
barbiturates, dofetilide, modafinil, oxcarbazepine, pioglitazone, pimozide, rifampin,
rifapentine, phenytoin, phenobarbital, carbamazepine, and St. John's wort.

- Dofetilide is prohibited, as DTG may inhibit its renal tubular secretion
resulting in increased dofetilide concentrations and potential for toxicity.

8. Unable to discontinue any current medications that are excluded during study
treatment.

9. Use of immunomodulators (e.g., interleukins, interferons, cyclosporine), radiation
therapy, HIV vaccine, systemic cytotoxic chemotherapy, or investigational therapy
within 30 days prior to study entry.

- Prednisone at a daily dose of 10 mg or less (physiologic replacement dose) is
permitted.

10. Treatment with radiation therapy or cytotoxic chemotherapeutics agents within 28 days
prior to screening or has an anticipated need for these agents during the study.

11. Administration of an HIV-1 immunotherapeutic vaccine within 90 days prior to
screening.

12. Prior treatment with any other experimental drug for any indication (within 30 days of
initiating study treatment).

13. Difficulty swallowing capsules/tablets.

14. Inability to communicate effectively with study personnel.

15. Incarceration; prisoner recruitment and participation are not permitted.

16. Active drug or alcohol use or dependence that, in the opinion of the site
investigator, would interfere with adherence to study requirements or confound the
analysis of study endpoints.

17. Any condition (including but not limited to alcohol and drug use) or any active
clinically significant disease or findings during screening of medical history or
physical examination, which, in the opinion of the Investigator would interfere with
patient safety or compliance.

18. Serious illness requiring systemic treatment and/or hospitalization until patient
either completes therapy or is clinically stable on therapy, in the opinion of the
site investigator, for at least 7 days prior to study entry.

NOTE: Oral candidiasis, vaginal candidiasis, mucocutaneous herpes simplex, and other
minor illnesses (as judged by the site investigator) have no restriction.

19. A life expectancy less than twelve months.

20. Acute viral hepatitis, including, but not limited to, hepatitis A, B, or C.

21. History of myocardial infarction or diagnosis of coronary artery disease.

22. History of ongoing or clinically relevant pancreatitis within the previous 6 months.

23. Chronic hepatitis C infection with an anticipated need for treatment during the study
period (through week 96).

24. Chronic hepatitis B infection (see inclusion criteria 5).

25. Evidence for moderate to severe hepatic impairment (as defined by the presence of
cirrhosis, ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or
gastric varices, persistent jaundice or Child-Pugh class B or greater hepatic
impairment).

26. Evidence of biliary abnormalities (with the exception of Gilbert's syndrome or
asymptomatic gallstones).

27. Any verified grade 4 laboratory abnormality with exception of ALT as defined in
exclusion criteria 1