the effect of raltegravir on hiv decay during primary and chronic infection

Conditions: HIV Infection

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.

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.

Keywords: viral compartments integrase inhibitor therapy viral species