Immediate Initiation of Antiretroviral Therapy During "Hyperacute" HIV Infection

Although ART decreases HIV-associated mortality, it does not appear to completely restore
immune health, for reasons that remain unclear. In addition, while HIV prevention approaches
have led to significant successes in decreasing the incidence of new HIV infection over the
past few years, the epidemic continues to grow both locally and globally. While complete
eradication may not currently be feasible, a "functional cure" in which patients are able to
indefinitely maintain undetectable viral loads in the absence of therapy may be an attainable
immediate goal. Studying patients with early HIV infection and immediate ART will provide a
unique opportunity to investigate the pathophysiology of the earliest stages of HIV infection
and may help identify the virologic/immunologic predictors of a functional cure.

Inclusion Criteria:

1. Willing and able to provide written informed consent

2. Male or female, age ≥18 years

3. Acute HIV infection with a negative or indeterminate HIV-1 antibody test and plasma
HIV-1 RNA > 40 cp/ml, OR clinical history consistent with new HIV infection in the
last 90 days.

4. Antiretroviral therapy untreated or recently initiated (within 7 days)

5. Participant must be able to comply with the dosing instructions for study drug
administration and able to complete the study schedule of assessments.

6. All participants must agree not to participate in a conception process (eg, active
attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization)..

7. When participating in sexual activity that could lead to pregnancy, female
participants must agree to use a double barrier method of contraception for at least
two weeks after discontinuation of study drug.

Exclusion Criteria:

1. Known severe kidney disease (CrCl < 60 ml/min via Cockcroft-Gault method)

2. Known severe hepatic impairment (Child-Pugh Class C)

3. Unstable liver disease (as defined by the presence of ascites, encephalopathy,
coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice),
known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic
gallstones)

4. Participants with anticipated need for Hepatitis C virus (HCV) therapy during study

5. Concurrent treatment with dofetilide, oxcarbazepine, phenytoin, phenobarbital,
carbamazepine, St. John's wort, or metformin

6. Serious illness requiring systemic treatment and/or hospitalization in the preceding
90 days prior to study enrollment

7. Concurrent treatment with immunomodulatory drugs, or exposure to any immunomodulatory
drugs in the preceding 90 days prior to study enrollment (e.g. IL-2, interferon-alpha,
methotrexate, cancer chemotherapy)

8. Concurrent treatment with investigational drugs, or exposure to any investigational
drugs in the preceding 90 days prior to study enrollment

9. Active drug or alcohol use or dependence that, in the opinion of the Principal
Investigator, would interfere with adherence to study requirements

10. Known allergy/sensitivity or any hypersensitivity to components of study drug(s) or
their formulation

11. Pregnant or breastfeeding women.

12. For participants who agree to colorectal biopsy

13. Known blood coagulation disorder

14. Platelets < 50,000/mm^3

15. PTT > 2x upper limit of normal

16. INR > 1.3

17. Use of aspirin, NSAIDs, Plavix, Coumadin, or other blood thinners that cannot be
stopped for clinical reasons for 5 days before and after each colorectal biopsy

18. Inflammatory colitis (e.g., Crohn's disease and/or ulcerative colitis) and/or any
contraindications to sigmoidoscopy or colorectal biopsy such as peritonitis, active
diverticulitis, or recent bowel surgery