A Randomised, Open-label, 96-week Study Comparing the Safety and Efficacy of Three Different Combination Antiretroviral Regimens as Initial Therapy for HIV Infection.

The primary objective of this study is to compare the virological efficacy, as measured by the time-weighted mean change from baseline plasma HIV-RNA, and safety, of three strategic regimens of initial antiretroviral therapy (ART) containing a fixed dose formulation of tenofovir and emtricitabine, with either efavirenz or ritonavir boosted atazanavir or zidovudine plus abacavir. (Primary comparisons are regimen I versus II and I versus III as described below).

I. tenofovir (TDF) + emtricitabine (FTC) + efavirenz (EFV) II. tenofovir (TDF) + emtricitabine (FTC) + ritonavir/atazanavir (r/ATV) III. tenofovir (TDF) + emtricitabine (FTC) + zidovudine (ZDV) + abacavir (ABC)

Secondary objectives of this study will be to undertake a range of analyses including but not limited to the following,

1. Percentage of patients < 50 copies HIV RNA/mL (and < 400 copies/mL) at week 48 and week 96 between treatment arms.
2. Time to confirmed (first of two consecutive) plasma HIV-1 RNA < 50 copies/mL (and < 400 copies/mL) between treatment arms.
3. Time to virologic failure defined as confirmed plasma HIV-1 RNA > 50 copies/mL (and 400 copies/mL) after confirmed < 50 copies/mL (where time = 0 if patient never achieves plasma virus load < 50 or <400 copies/mL).
4. Mean change from baseline of absolute CD4+ T cell count at weeks 48 and 96 between treatment arms.
5. Time to change in randomly assigned therapy (all reasons individually and on aggregate) between treatment arms.
6. Time to first virologic failure (defined as #3 above) or cessation of randomly assigned antiretroviral therapy.
7. Mean change from baseline Lipodystrophy Case Definition score at weeks 48 and 96 between treatment arms.
8. Mean change from baseline in peripheral and central adipose tissue, as measured by CT and DEXA at weeks 48 and 96 between treatment arms.
9. Mean change from baseline in fasting lipid and glycemic parameters at weeks 48 and 96 between treatment arms.
10. Comparison of total number of patients with any serious adverse events (SAEs), and the cumulative incidence of SAEs, between treatment arms.
11. Comparison of total number of patients with any adverse events (AEs), and the cumulative incidence of AEs, associated with cessation of randomly assigned therapy between treatment arms.
12. Patterns of genotypic HIV resistance associated with virological treatment failure across treatment arms.
13. Describe aspects of immune reconstitution disease.
14. Adherence to therapy and associations with virologic outcomes between treatment arms.
15. Comparison of quality of life between treatment arms.

Following the result of the scheduled week 48 data analysis, the protocol steering committee amended the study protocol as follows: