Treatment of Acute HIV With Emtricitabine, Tenofovir and Efavirenz (CID 0805)

CID 0805 - Treatment of Acute HIV Infection With a Once Daily Regimen of Emtricitabine, Tenofovir and Efavirenz - A Pilot Study of Response to Therapy and HIV Pathogenesis

This is a pilot study of treatment of acute HIV infection with a once daily regimen of Emtricitabine, Tenofovir and Efavirenz. The primary objectives of this study are:

1. To determine the safety and tolerability, and the virologic and immunologic efficacy of FTC, TDF, and efavirenz given once daily to patients with acute HIV infection.
2. To assess the impact of once daily therapy combined with a standardized adherence program on treatment adherence, virologic suppression, and rate of viral load decline in blood and infectious fluids (semen, cervico-vaginal secretions).
3. To define the prevalence of genotypic and phenotypic resistance to antiretroviral agents among persons diagnosed with acute HIV infection in the Southeastern United States.

Hypothesis: Once daily ART with fixed dose combination FTC/TDF/EFV will reduce viral replication to <200 copies RNA/ml plasma in blood and other body compartments in patients with acute HIV infection, reducing infectivity. The treatment regimen will be well tolerated during treatment follow-up. A coordinated program of counseling and support will facilitate adherence and promote successful therapy. Prevalence of transmitted drug resistant HIV-1 will be assessed.

Study Design: Dual-center, prospective, single-arm pilot study of FTC/TDF/EFV in patients with acute HIV infection. Study sites will be members of the Duke-UNC Acute HIV Infection Study Consortium. Patients will be followed intensively for 96 weeks.

Inclusion Criteria:

1. Diagnosis of acute HIV infection as defined by protocol.

2. The following laboratory parameters verified within 30 days of study entry:

   • Bilirubin </= 3.0mg/dL
   • ALT/AST </= 10 X upper limit of normal
   • Absolute neutrophil count (ANC) >/= 500cells/mm3
   • Platelet count >/= 25,000 cells/mm3
   • Hemoglobin >/= 8.5g/dL for men and >/= 8.0 g/dL for women
   • 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)

3. All women of child-bearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of bHCG) within 72 hours prior to start of study medication. WOCBP is defined as any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy), who is not postmenopausal (defined as amenorrhea >/=12 consecutive months), or is on hormone replacement therapy (HRT) with documented plasma follicle-stimulating hormone level >/=35mLU/mL. Women who are using oral, implanted, or injectable contraceptive hormones or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy or practicing abstinence or where partner is sterile (e.g., vasectomy), should be considered to be of child bearing potential;

4. Be willing to use two effective forms of contraception throughout study. Barrier contraception should always be used in combination with other methods of contraception (oral or other hormonal contraceptives);

5. Weigh >/= 40 kg;

Exclusion Criteria:

1. A life expectancy less than twelve months.

2. Women who are pregnant or breastfeeding.

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

4. WOCBP who are unwilling or unable to use two acceptable methods to avoid pregnancy for the entire study period

5. WOCBP using a prohibited contraceptive method

6. Hypersensitivity to any component of the formulation of study drugs.

7. A clinically important illness not explicitly excluded by the protocol, a physical or psychiatric disability, or a laboratory abnormality that might place the patient at increased risk by being exposed to the medications in this study or which might confound the interpretation of this investigation.

8. Proven or suspected acute hepatitis within 30 days prior to study entry (this excludes liver inflammation related to acute HIV infection).

9. Intractable diarrhea (>/=6 loose stools/day for at least 7 consecutive days) within 30 days prior to study entry or vomiting lasting more than 4 days within one month prior to dosing (this excludes symptoms attributed to acute HIV infection).

10. An active AIDS-defining opportunistic infection or disease (for the purpose of this study, a CD4 count </=200 cells/mm3 in the absence of any other AIDS-defining indicator condition is not considered an AIDS-defining event. AIDS-defining events occurring during the acute HIV infection syndrome period such as Candida esophagitis will be considered on a case-by-case basis and will not be automatically considered exclusionary).

11. Inability to communicate effectively with study personnel.

12. Current alcohol or recreational drug use which in the investigator's opinion interferes with the subject's ability to comply with dosing schedule and protocol evaluations or increases the risk of developing pancreatitis.

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

14. Difficulty swallowing capsules/tablets.

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

16. Treatment with immune-modulating agents (within 30 days of initiating study treatment) such as cyclosporine and systemic corticosteroids. Routine vaccinations are allowed.

17. Therapy with agents with significant systemic neurotoxic pancreotropic or cytotoxic potential within 3 months of study start, or the need for such therapy is expected at the time of enrollment.

18. Therapy with nephrotoxic agents (aminoglycosides, IV amphotericin, cidofovir, IV pentamidine, cisplatin other agents with nephrotoxic potential), adefovir or probenecid. These agents must be discontinued at least 30 days prior to starting study medications. Brief course of aminoglycosides within 30 days of enrollment may be allowed after discussion with Study Chairs.

19. Concomitant Medications:

    • The following medications are expressly prohibited during the course of the trial: Astemizole, cisapride, ergot derivatives, hydroxyurea, midazolam, thalidomide, triazolam, vincristine, zalcitabine, ribavirin, doxorubicin, Voriconazole, St. John's wort or any medications that are contraindicated for concomitant use as described in the current product information packet insert for the ARV therapies used.