Clinical trial NCT00641641: The Effect of Raltegravir on HIV Decay During Primary and Chronic Infection
Official title: An Open Label Study to Examine the Characteristics of HIV Decay Following Introduction of Combination Antiretroviral Therapy Including Raltegravir During Primary and Chronic HIV Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: HIV Infection
Keywords: Viral compartments
integrase inhibitor therapy
viral species
Lead sponsor: Kirby Institute
Sponsor class: OTHER_GOV
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2008-03-24
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Mean Change From Baseline Plasma HIV RNA (Log Copies/mL)
timeFrame: 12 times within 48 weeks.
Secondary outcomes:
Other outcomes:
Locations:
city: Darlinghurst, Sydney
country: Australia
facility: St Vincent's Hospital
state: New South Wales
city: Sydney
country: Australia
facility: 407 Doctors
state: New South Wales
city: Sydney
country: Australia
facility: Holdsworth House Medical Practice
state: New South Wales
city: Sydney
country: Australia
facility: Taylor Square Private Clinic
state: New South Wales
Study officials:
affiliation: Kirby Institute
name: Anthony Kelleher, MBBS (Hons) PhD, FRACP, FRCPA
role: PRINCIPAL_INVESTIGATOR
References:
citation: Koelsch KK, Boesecke C, McBride K, Gelgor L, Fahey P, Natarajan V, Baker D, Bloch M, Murray JM, Zaunders J, Emery S, Cooper DA, Kelleher AD; PINT study team. Impact of treatment with raltegravir during primary or chronic HIV infection on RNA decay characteristics and the HIV viral reservoir. AIDS. 2011 Nov 13;25(17):2069-78. doi: 10.1097/QAD.0b013e32834b9658.
citation: Murray JM, McBride K, Boesecke C, Bailey M, Amin J, Suzuki K, Baker D, Zaunders JJ, Emery S, Cooper DA, Koelsch KK, Kelleher AD; PINT STUDY TEAM. Integrated HIV DNA accumulates prior to treatment while episomal HIV DNA records ongoing transmission afterwards. AIDS. 2012 Mar 13;26(5):543-50. doi: 10.1097/QAD.0b013e328350fb3c.
citation: Hey-Cunningham WJ, Murray JM, Natarajan V, Amin J, Moore CL, Emery S, Cooper DA, Zaunders J, Kelleher AD, Koelsch KK; PINT study team. Early antiretroviral therapy with raltegravir generates sustained reductions in HIV reservoirs but not lower T-cell activation levels. AIDS. 2015 May 15;29(8):911-9. doi: 10.1097/QAD.0000000000000625.