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.

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.

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.

Limited cohort (n=16) of exclusively male participants treated with a licensed regimen of combination antiretroviral therapy with the primary focus being a detailed examination of virus decay characteristics