Background: Atazanavir is a once-daily protease inhibitor (PI) that does not increase TC, LDL, or TG levels in antiretroviral-naïve subjects. Atazanavir and saquinavir have complementary resistance profiles and favorable pharmacokinetic interactions. This protocol evaluated the safety, tolerability, and efficacy of dual PI therapy with atazanavir (400 or 600 mg qd)/saquinavir (1200 mg qd), or ritonavir (400 mg BID)/saquinavir (400 mg BID) + 2 nucleoside reverse transcriptase inhibitors (NRTIs) after virologic failure on a prior regimen.

Methods: Randomized, active-controlled, blinded study in 85 adults with HIV RNA 1000-100,000 copies/mL and CD4 ³100 cells/mm³.

Results: Efficacy and lipid results at week 48 are summarized in the table. There were fewer discontinuations for treatment-related adverse events in the atazanavir/saquinavir treatment groups (atazanavir 400 mg, n=3 [9%]; 600 mg, 3 [11%]) compared with the ritonavir/saquinavir treatment group (7 [30%]).

                                                                                                                                                    Atazanavir/Saquinavir qd                               Ritonavir/Saquinavir BID 
                                                                                                                                                            400 mg (n=34)           600 mg (n=28)        400 mg (n=23)

Mean change from baseline at week 48; randomized subjects      HIV RNA log₁₀ c/mL (SE)              –1.44 (0.25)                –1.19 (0.22)            –1.66 (0.23)

CD4 cells/mm³ (n)                                                                                                                                     109 (24)                       55 (26)                   149 (36)

TC                                                                                                                                                             1 (181; 21)             –5 (199; 16)          11 (202; 11)

Fasting LDL                                                                                                                                            –1 (110;15)             –7 (108;11)            23 (117; 6)             

Fasting TG                                                                                                                                              –5 (223; 15)           –27 (177; 11)          93 (191; 7)

Conclusions: In subjects who have failed a prior regimen, atazanavir/saquinavir once daily was safe and well tolerated, and it rapidly and durably suppressed HIV RNA and durably increased CD4. Atazanavir/saquinavir once daily lowered TC, LDL, and TG levels from baseline, whereas ritonavir/saquinavir twice daily produced prompt, marked, and sustained increases. The ability to improve serum lipid profiles in treatment-experienced subjects suggests that atazanavir may reduce the risk of cardiovascular events in this population.