once daily 3tc, efavirenz and ddi for hiv infection

Conditions: HIV Infection; AIDS

Summary: poor compliance is thought to be a major cause of treatment failure. the teddi study is a randomised, multi-centre, open-label study in well-controlled treatment-experienced hiv-infected patients to assess compliance with a once-daily regimen of antiretroviral therapy versus continuation of current anti-retroviral regimen delivered at least twice daily.

rationale: 'teddi' will enable a once-daily treatment strategy to be studied and provide information on effectiveness, patient adherence and quality of life and the tolerability of such regimens. hypothesis: the study hypothesis is that an antiretroviral regimen comprising of three agents taken once daily will have higher levels of adherence than a regimen requiring more frequent dosing. primary objective: to determine over 24 weeks the levels of adherence in two groups of hiv-infected subjects randomised to receive either a once daily minimum 3-drug regimen or to continue a minimum 3-drug regimen requiring more frequent dosing. secondary objectives: the secondary objectives of the study will include: * to estimate the proportion of patients with treatment failure where treatment failure is defined as: * hiv-1 rna viral load of \>400 copies/ml on two consecutive occasions more than one month apart, or * discontinuation of treatment for any reason (where subsequent therapy does not comply with the study regimen change guidelines outlined in section 3.3.3) * proportion of patients with plasma hiv-rna less than 50 copies/ml (using an ultrasensitive assay) at 24 and 48 weeks * change from baseline in cd4 cell count at 24 and 48 weeks * changes from baseline in subjects' quality of life at 24 and 48 weeks * changes from baseline based on dass 21 scores at 24 and 48 weeks * incidence and severity of adverse events and abnormal laboratory values (grade 3 \& 4) at 24 and 48 weeks * proportion of patients remaining on assigned treatment study design this is a randomised, open-label, multi-centre, prospective, 48-week study comparing a 3 (or more) drug once-daily antiretroviral regimen with any 3 (or more) drug regimen in which at least 1 drug must be taken at least twice daily. one hundred and twenty (120) subjects will be recruited and randomised in a 1:1 ratio to one of two open-label treatment regimens and will continue to receive randomised treatment until week 24: arm 1: (once daily arm) commence treatment with a once-a-day combination of licensed antiviral medications (such as efv/ddi/3tc, efv/3tc/tdf or atv/3tc/tdf). arm 2: (continuation arm) continue current art (minimum 3-drugs) dosed twice daily or more frequently following week 24, patients will have the option to continue randomised treatment for a further 24 weeks or switch to the once daily treatment arm. in all cases, patients will be followed up for 48 weeks from the baseline visit.

Eligibility criteria:
inclusion criteria: * aged 18 years or more with laboratory evidence of hiv-1 infection * ability to understand and provide written informed consent to participate in the study * stable on current art regimen for at least 3 months prior to screening. * plasma hiv-rna less than 400 copies/ml at the screening visit. * women of child bearing potential must have a negative serum or urine β-hcg pregnancy test within 14 days prior to week -4 (assessment of study eligibility) exclusion criteria: * virological failure of a proposed once daily arm medication * a serious medical condition which may compromise the subject's safety, including an active aids-defining condition within the previous 6 months * known toxicities to any of the proposed once daily arm medications * laboratory abnormalities at screening: * serum creatinine greater than twice the upper limit of normal (2 x upper limit of normal (uln)) * ast, alt or alkaline phosphatase greater than 5 times the uln * lactate greater than 2.5 x uln * haemoglobin less than 9.5 g/dl * women who are pregnant or breast-feeding or who, if of child-bearing potential, are not willing to use adequate contraception (including barrier contraception) * patients who in the investigator's opinion are unlikely to complete the study

Keywords: hiv infection aids adherence mems caps treatment experienced