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Background:  Enfuvirtide (ENF) is the first HIV fusion inhibitor. We sought to determine whether the addition of a third viral target (HIV fusion) would confer an increase in viral decay rates compared with ART aimed at 2 targets alone (HIV reverse transcriptase and protease).

Methods:  Previously 22 patients had been enrolled in ENF PK studies, but prior to that naïve to ART or with exposure to only NRTI, were randomized to receive either saquinavir (SQV 1000) mg twice daily + RTV 200 mg twice daily + efavirenz (EFV) 600 mg daily, or the same ART with the addition of ENF 90 mg subcutaneously twice daily. The primary endpoints were the viral decay rates (first phase, second phase, and overall) calculated over the first 12 weeks of therapy. HIV RNA was assessed at day –7, 0, 2, 4, 6, 8, 10 14, 21, 28, 42, 56, 70, and 84. HIV RNA measurements were analyzed using 1-phase and 2-phase decay models to determine first and second phase viral decay rates. HIV RNA was measured to 5 copies/mL by a modified Roche Amplicor ultrasensitive assay. Plasma PK levels of SQV (Cmin) and EFV (Cmid-dose) were monitored at days 14, 28, 56, and 84. Differences in viral decay rates were assessed using Student’s t-test.

Results:  For the 2-target and 3-target arm the calculated rate of loss of productively infected cells (first phase decline, d was 1.03 ± 0.58 day^-1 and 0.71 ± 0.27 day^-1, respectively (p = 0.13). The calculated rate of loss of long-lived productively infected cells (second phase decline, m for the 2-target and 3-target arms arm was 0.066 ± 0.038 day^-1 and 0.039 ± 0.014 day^-1, respectively (p = 0.05). Using only the early data in the 1-phase model the estimated first phase viral decline (d) was 0.62 ± 0.34 day^-1 and 0.51 ± 0.16 day^-1 for the 2-target and 3-target arms respectively (p = 0.34). For a model independent assessment of the effect of the addition of ENF, decline in HIV RNA was compared between days 2 and 8 (first phase), days 8 and 28 (second phase), and days 2 and 28 (overall). There was no difference between arms (all p values > 0.2). SQV Cmin and EFV Cmid-dose values at days 14 and 28 were all above the accepted therapeutic levels. 9/11 (81%) of patients in both arms achieved HIV RNA < 50 copies/mL by week 24.

Conclusions:  The addition of ENF did not produce significant differences in the decay rates of plasma HIV RNA compared to therapy with boosted SQV and EFV alone in these PI- and NNRTI-naïve patients.

Keywords: decay; enfuvirtide; dynamics