HIV Viremia and Persistence in Acutely HIV-Infected Patients Treated With Darunavir/Ritonavir and Etravirine

Study Design

This is a multicenter, single arm, 48-week open-label pilot study of DRV/R & ETR in acute HIV
infection. Study sites will be members of the Duke-UNC Acute HIV Infection Study Consortium.
If baseline resistance is detected after treatment begins (e.g. evidence of pre-existing
baseline resistance (genotypic or phenotypic) that may adversely affect the efficacy of the
study regimen), the patient may elect to alter treatment as per best clinical practice. The
new regimen will not be provided by the study, but will be obtained for the participant
through available clinical resources.

After patients are identified with acute HIV infection, they will be offered the opportunity
to participate in the study. Patients will also be offered the opportunity to co-enroll in
CHAVI 001 and 012, studies that follow the virological and immunological response of patients
with AHI, regardless of the initiation of ART. An overall consent form will be signed for
study participation, and separate informed consents with signatures will be obtained for
optional studies. Patients will be eligible for participation after signing the overall
consent - agreeing to participate in studies of other compartment specimens is not required
for enrollment. At the initial visit, patient eligibility will be confirmed with appropriate
laboratory testing (see "STUDY POPULATION"). When eligibility is verified, entry laboratory
studies will be obtained, and the participants will be started on DRV/r, and ETR. All
participants will be followed at regular intervals thereafter as specified in the schedule of
evaluations. Participants meeting criteria for virologic failure will be offered the
opportunity to switch to the best available regimen as selected by their HIV provider.

Hypothesis

Combination therapy with DRV/R & ETR will suppress plasma viremia and improve immunologic
function in antiretroviral (ART)-naïve, acutely HIV-infected (AHI) patients, and will limit
replication in HIV-1 cellular compartments.

Inclusion Criteria:

1. Documentation of Acute HIV Infection as defined above.

2. Men and women age ≥18 years.

3. Participants will be ART naïve, defined as ≤14 days of antiretroviral treatment at any
time prior to entry. The only exceptions are: Post-exposure prophylaxis (PEP) provided
the patient was documented as HIV-1 negative at least 3-6 months after completion of
the PEP treatment.

4. Screening HIV-1 RNA >1,000 copies/mL obtained within 30 days at study entry.

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

6. Absolute neutrophil count >500/mm3

7. Hemoglobin > 8.5 g/dL for men and > 8.0 g/dL for women

8. Platelet count >50,000/mm3

9. AST (SGOT) ≤2.5 x ULN

10. ALT (SGPT) ≤2.5 x ULN

11. Total bilirubin <2.5 x ULN

12. Calculated creatinine clearance (Cockcroft-Gault formula) > 30mL/min:

- CrCl = (140-age) x body weight (kg) (x 0.85 if female)

- Serum creatinine [mg/dL] x (72)

13. For women of reproductive potential, a negative serum or urine pregnancy test within 7
days prior to initiating antiretroviral study medications. Reproductive potential is
defined as females who have reached menarche and have not been post-menopausal for at
least 24 consecutive months, or have not undergone surgical sterilization (e.g.,
hysterectomy, bilateral oophorectomy, or salpingotomy). Acceptable documentation of
surgical sterilization includes patient-reported history.

14. If participating in sexual activity that could lead to pregnancy, female study
patients must use at least one form of contraception, which could consist only of a
barrier method. All patients must continue to use contraception for 6 weeks after
stopping the study medications. Acceptable methods of contraception include: condoms
(male or female) with or without spermicidal agent, diaphragm or cervical cap with
spermicide, or IUD. Female volunteers not of reproductive potential are not required
to use contraception.

15. Ability and willingness of patient to give written informed consent.

Exclusion Criteria:

1. Women who are pregnant or breast-feeding.

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

3. Women of reproductive potential who are unwilling or unable to use acceptable methods
to avoid pregnancy for the entire study period

4. Use of immunomodulators (e.g., interleukins, interferons, cyclosporine), 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.

5. Known allergy/sensitivity to study drugs or their formulations.

6. Difficulty swallowing capsules/tablets.

7. Inability to communicate effectively with study personnel.

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

9. 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.

10. Any active psychiatric illness including schizophrenia, severe depression, or severe
bipolar affective disorder that, in the opinion of the investigator, could confound
the analysis of the neurological examination or neuropsychological test results.

11. Active brain infection (except for HIV-1), brain neoplasm, space-occupying brain
lesion requiring acute or chronic therapy. Participants with any fungal meningitis,
parasitic infection, or CNS lymphoma are excluded from participation.

12. 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.

13. Known cardiac conduction disease.

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

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

16. A life expectancy less than twelve months.

17. Acute Viral Hepatitis, including, but not limited to, Hepatitis A, B, or C

18. Chronic Hepatitis B Infection documented by a detectable serum Hepatitis B surface
antigen (HBsAg) or plasma HBV DNA