HIV Infection
Conditions
Keywords
Viral compartments, integrase inhibitor therapy, viral species
Brief summary
The purpose of this study is to measure the decay characteristics of HIV in the blood of patients after taking a combination of anti-HIV drugs, which includes a new class of anti-HIV drug, an integrase inhibitor. This study explores how this new combination of therapy reduces virus in various compartments of the body and immune system.
Detailed description
The study is an open-label study of 3-years duration. This study will be conducted at 4 study sites in Sydney, Australia. Sixteen participants will be recruited comprising 8 participants diagnosed with primary HIV infection (Cohort A) and 8 individuals with chronic HIV infection (Cohort B). All patients must be antiretroviral therapy (ART) naïve and will commence a regimen of combination ART consisting of tenofovir disoproxil fumarate and emtricitabine (TDF/FTC; Truvada) plus the integrase inhibitor, raltegravir. Subjects will be followed for three years with intensive quantification of both plasma RNA and cell associated DNA viral species.
Interventions
DRUGTenofovir + emtricitabine + raltegravir.
TDF 300mg once daily + FTC 200mg once daily + RAL 400mg twice daily.
Sponsors
Merck Sharp & Dohme LLC
Kirby Institute
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
* Age at least 18 years. * Provision of written, informed consent. * Screening plasma HIV RNA \> 10,000 copies/mL. * Screening CD4+ T lymphocyte count \> 100 x 10\^6)/L. * No previous antiretroviral therapy. * Haemoglobin \> 115 g/L (female) or \> 130 g/L (male). * Absolute neutrophil count \> 1 x 10\^9/L. * Platelet count \> 100 x 10\^9/L * Serum bilirubin \< 1.5 x ULN. * Serum alkaline phosphatase \< 3 X ULN. * Serum aspartate aminotransferase (AST) \< 3 X ULN. * Serum alanine aminotransferase (ALT) \< 3 X ULN. * Creatinine clearance \> 50mL/min (Creatinine clearance (mL/min) =140 - age x weight creatinine Multiply the result by 1.2 for men). Cohort A: Primary HIV infection: Documented acute or early infection diagnosed by: Acute infection: \< 3 bands on Western Blot and any one of: i. positive p24 antigen ii. positive proviral DNA Early infection: i. Positive detuned or BED ELISA result OR ii. Previously negative serology within 6 months of confirmed positive serology. Cohort B: Chronic HIV infection: Documented HIV-infection of at least 12 months duration.
Exclusion criteria
* Pregnancy or breastfeeding. * Receipt of investigational products within 1 month of study entry. * Receipt of any of the following within 6 months of study entry: * interferon alpha or gamma * oral corticosteroids (inhaled or topical corticosteroids are permitted) * cyclosporin * alkylating agents * other immunosuppressive agents * rifampin * phenytoin * phenobarbital * Documented genotypic (IAS 2007) resistance to tenofovir or emtricitabine from any HIV drug resistance test. * Any medications contraindicated with Truvada or raltegravir. * Significant intercurrent illnesses apart from HIV infection such as viral hepatitis (diagnosed by core hepatitis B antigen and/or positive hepatitis B PCR or positive hepatitis C PCR) or any other condition which in the opinion of the investigator would compromise participation in the study. * History of non-traumatic osteoporotic fracture.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline Plasma HIV RNA (Log Copies/mL) | 12 times within 48 weeks. | change was calculated as the mean of 12 assessments minus the baseline value |
Countries
Australia
Participant flow
Recruitment details
Patients were recruited at 5 clinical centres in Sydney
Pre-assignment details
A screening period of less than 42 days prior to commencement of study drugs was employed
Participants by arm
| Arm | Count |
|---|---|
| Drug Intervention Tenofovir+emtricitabine+raltegravir | 16 |
| Total | 16 |
Baseline characteristics
| Characteristic | Drug Intervention |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 16 Participants |
| Region of Enrollment Australia | 16 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 16 |
| serious Total, serious adverse events | 0 / 16 |
Outcome results
Primary
Mean Change From Baseline Plasma HIV RNA (Log Copies/mL)
change was calculated as the mean of 12 assessments minus the baseline value
Time frame: 12 times within 48 weeks.
Population: Intention to treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Drug Intervention | Mean Change From Baseline Plasma HIV RNA (Log Copies/mL) | 5.4 log copies/mL plasma | Standard Deviation 0.6 |