Acute HIV Infection, HIV Infections
Conditions
Keywords
Acute HIV, HIV, Acute Infections, Acute Infection
Brief summary
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.
Detailed description
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.
Interventions
DRUGefavirenz, emtricitabine, and tenofovir
Once daily ART with emtricitabine, tenofovir DF and efavirenz
Sponsors
Bristol-Myers Squibb
Gilead Sciences
University of North Carolina, Chapel Hill
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Without Virologic Failure at Week 24 | HIV RNA level prior to or at week 24 following enrollment | Number of participants with a HIV RNA level \<200 copies/mL at week 24 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Without Virologic Failure at Week 48 | HIV RNA level at week 48 following enrollment | HIV RNA level \<50 copies/mL at week 48 |
| Number of Participants With HIV RNA Suppression at Week 96 | HIV RNA level at 96 weeks following enrollment | Number of participants wtih HIV RNA level \<50 copies/mL at week 96 |
| Number of Participants With Baseline Genotypic Resistance to Antiretroviral Medications | At enrollment | Prevalence of any of the surveillance drug resistance mutations associated with resistance to antiretroviral medications listed by the World Health Organization |
| Number of Participants With Baseline Genotypic Resistance to One or More Antiretroviral Drugs in the Study Treatment | At enrollment | Baseline genotypic resistance defined as presence of any surveillance drug resistance mutation to any drug in the study treatment listed by the World Health Organization |
| Time to HIV RNA Suppression <50 Copies/mL | Number of days from start of study treatment until HIV RNA suppression, assessed through week 96 | Number of days from ART initiation to HIV RNA suppression \<50 copies/mL |
Countries
United States
Participant flow
Recruitment details
Individuals with acute HIV (AHI) detected via a statewide AHI screening program in publicly funded sites and primary care sites are reported to the NC Department of Health and Human Services (DHHS). DHHS staff immediately refer acute cases to HIV care. From Jan 2005 and Dec 2011, all AHI cases referred to UNC and Duke were offered enrollment.
Pre-assignment details
This was a single-arm, open-label study of emtricitabine/tenofovir/efavirenz started at enrollment. All participants received the same study treatment. Study treatment was not delayed for baseline resistance testing. Participants with transmitted baseline resistance to any drug in the regimen were followed on study on an alternative regimen.
Participants by arm
| Arm | Count |
|---|---|
| Acute HIV Infection Treatment Group This study was a dual-center, single-arm open-label study of the safety and efficacy of once daily, FTC/TDF/EFZ administered to participants with acute HIV infection | 92 |
| Total | 92 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Acute HIV Infection Treatment Group |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 91 Participants |
| Age, Continuous | 27 years |
| CD4 cell count | 487 cells/mm^3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 90 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| HIV RNA level | 614898 copies/mL |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 54 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 38 Participants |
| Region of Enrollment United States | 92 Participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 81 Participants |
| sexually transmitted diseases within 8 weeks prior to diagnosis | 14 Participants |
| Sexual risk group Female | 11 Participants |
| Sexual risk group Heterosexual Male | 9 Participants |
| Sexual risk group Men who have sex with men | 72 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 90 |
| other Total, other adverse events | 52 / 90 |
| serious Total, serious adverse events | 0 / 90 |
Outcome results
Primary
Number of Participants Without Virologic Failure at Week 24
Number of participants with a HIV RNA level \<200 copies/mL at week 24
Time frame: HIV RNA level prior to or at week 24 following enrollment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Acute HIV Infection Treatment Group | Number of Participants Without Virologic Failure at Week 24 | 81 Participants |
Secondary
Number of Participants With Baseline Genotypic Resistance to Antiretroviral Medications
Prevalence of any of the surveillance drug resistance mutations associated with resistance to antiretroviral medications listed by the World Health Organization
Time frame: At enrollment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Acute HIV Infection Treatment Group | Number of Participants With Baseline Genotypic Resistance to Antiretroviral Medications | 17 Participants |
Secondary
Number of Participants With Baseline Genotypic Resistance to One or More Antiretroviral Drugs in the Study Treatment
Baseline genotypic resistance defined as presence of any surveillance drug resistance mutation to any drug in the study treatment listed by the World Health Organization
Time frame: At enrollment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Acute HIV Infection Treatment Group | Number of Participants With Baseline Genotypic Resistance to One or More Antiretroviral Drugs in the Study Treatment | 71 Participants |
Secondary
Number of Participants With HIV RNA Suppression at Week 96
Number of participants wtih HIV RNA level \<50 copies/mL at week 96
Time frame: HIV RNA level at 96 weeks following enrollment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Acute HIV Infection Treatment Group | Number of Participants With HIV RNA Suppression at Week 96 | 65 Participants |
Secondary
Number of Participants Without Virologic Failure at Week 48
HIV RNA level \<50 copies/mL at week 48
Time frame: HIV RNA level at week 48 following enrollment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Acute HIV Infection Treatment Group | Number of Participants Without Virologic Failure at Week 48 | 71 Participants |
Secondary
Time to HIV RNA Suppression <50 Copies/mL
Number of days from ART initiation to HIV RNA suppression \<50 copies/mL
Time frame: Number of days from start of study treatment until HIV RNA suppression, assessed through week 96
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Acute HIV Infection Treatment Group | Time to HIV RNA Suppression <50 Copies/mL | 105 days |