dolutegravir antiretroviral strategy to promote improvement and reduce drug exposure

Conditions: HIV Infection

Summary: hiv-1 infected subjects with cd4 nadir \> 200 cells/mm3, no history of virologic failure and plasma hiv rna \ 50 copies/ml before or at week 24

design hiv-1 infected subjects with cd4 nadir \> 200 cells/mm3, no history of virologic failure and plasma hiv rna \ 50 copies/ml before or at week 24 all subjects will undergo routine monitoring including plasma hiv-1 rna, cd4/cd8 count, hematology, chemistry and fasting lipids. resistance testing will be done in all patients who experience virologic failure. single-copy hiv-1 assay will be done to quantify residual viremia. duration 48 weeks sample size 90 subjects population hiv-1-infected men and women, 18 years and older, with cd4 nadir \> 200 cells/mm3, no baseline resistance, no history of virologic failure, and hiv rna \<50 copies/ml for at least 48 weeks prior to study entry while on any dhhs recommended or alternative three-drug regimen regimen subjects will be randomized (1:1) to: arm 1: dolutegravir 50 mg plus lamivudine 300 mg once daily or arm 2: continue current dhhs recommended or alternative three-drug antiretroviral regimen

Eligibility criteria:
inclusion criteria: * hiv-1 infection * hiv-1 rna \<50 copies/ml on all measurements within 48 weeks prior to study entry while on any dhhs recommended or alternative three-drug antiretroviral regimen. (a history of switching for simplification and/or tolerability is allowed. at least two measurements within the previous 48 weeks are required prior to study screening.) * no history of virologic failure, defined as consecutive hiv rna \> 50 copies/ml after 12 months of initiating art. an isolated (non-consecutive) hiv rna \> 50 copies/ml (but less than 400 copies/ml) is permitted after 12 months of initiating art but not in the 48-week window prior to study entry. * screening plasma hiv rna \< 20 copies/ml using the cobas ampliprep/cobas taqman hiv-1 test v2.0, obtained within 45 days prior to study entry * nadir cd4 count \>200 cells/mm * pretreatment genotype documenting no mutations in the protease or reverse transcriptase genes * no known resistance to integrase inhibitors * laboratory values obtained within 45 days prior to study entry: anc \>750 hemoglobin \>10 g/dl platelets \>50,000 calculated creatinine clearance (crcl) \>50 ml/min * negative serum or urine pregnancy test * men and women age greater or equal to 18 years. * ability to continue current regimen (i.e, have uninterrupted access) * no evidence of chronic hepatitis b exclusion criteria: * serious illness or aids-related complication within 21 days of screening requiring systemic treatment and/or hospitalization * treatment within 30 days prior to study entry with immune modulators * vaccination within 7 days * active hcv treatment or anticipated need for treatment within study period. (hcv infection alone is not exclusionary) * unstable liver disease or severe hepatic impairment * known allergy or hypersensitivity to dtg or lamivudine. * active drug or alcohol use or dependence that could interfere with adherence to study requirements * alt (alanine aminotransferase) \>5 x uln (upper limit of normal) or alt \>3 x uln and total bilirubin \>1.5 x uln (with 35% direct bilirubin)