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Background:  High rates of early virologic failure have been reported in naive patients receiving triple NUC combinations containing tenofovir (TDF), with either lamivudine (LAM) and didanosine, or LAM and abacavir (ABC). However, a daily zidovudine (ZDV), LAM, ABC, and TDF regimen showed acceptable virologic success rate, and the resistance pattern (less K65R or M184V) suggested a role of ZDV in resistance modulation in this quadruple NUC combination.

Methods:  This pilot prospective cohort study was conducted in the HIV outpatient clinic at Strasbourg University Hospital. Treatment-naïve subjects were offered a fixed-dose combination of ZDV/LAM (300 mg/150 mg) twice daily, and TDF 300 mg daily. CD4 cells count and HIV-1 viral load were assessed at baseline, after 1 and 2 months of treatment, and then every 2 months. Early virologic response was evaluated after 1 or 2 weeks of treatment.

Results:  Between April 2002 and September 2004, 36 patients were included (30 males, 6 females; median age of 39 years [22 to 73]); 2 had an AIDS diagnosis. At baseline, median CD4 count was 230/mm³ (69 to 425/mm³), 13 subjects had CD4 < 200/mm³, median HIV-1 viral load was 4.9 log (3.14 to > 5.89 log), and 16 had a viral load > 5 log. Median follow-up was 8 months (1 week to 27 months). On treatment analysis showed a median HIV RNA decrease after 1 to 2 weeks of treatment of –1.57 log, and after 1 month of –2.36 log (first quartile, –1.44 to –2.06 log; fourth quartile, –2.69 to –3.18 log). Of 29 patients, 26 had a viral load < 1000 copies/mL at month 1. At month 6, 18 of 20 (90%) had viral load < 50 copies/mL, as did 9 of 13 (69%) after 12 months. Median time to HIV RNA < 50 copies/mL was 2 months (1 to 24 weeks). Median CD4 count increase at month 6 was + 85/mm³. Of 32 treatment interruptions, 5 (16%) occurred because of side effects (abdominal pain and nausea in 3 and anemia in 2, probably due to ZDV). During the first 12 months of treatment, 4 viral failures occurred (due to poor compliance), 1 with K65R mutation, 2 with M184V + 2 or 3 TAMS, and 1 with 2 TAMS. Two of them successfully changed the ARV treatment; the others remained on ZDV + LAM + TDF, with low viral loads.

Conclusions:  Combination of ZDV + LAM + TDF in treatment-naïve HIV-infected subjects induces a rapid and sustained HIV RNA decrease, associated with a good immunologic response and good safety profile. Despite recent recommendations on triple NUC drugs association, the results of this evaluation suggest that this triple NUC combination should be further evaluated.

Keywords: tenofovir; triple NUCs combination; resistance mutation