Background: The optimal strategy for patients (pts) failing combination nucleoside analogues (NRTI) is not known. This study investigated the use of ritonavir boosted indinavir with efavirenz alone in pts failing NRTI therapy.

Methods: This single arm, open label study, switched pts failing combination NRTI therapy (HIV RNA > 1000 c/ml) to indinavir/ritonavir 800/100 mg bid with efavirenz 600 mg qd. Efficacy was determined by HIV RNA and CD4⁺ responses. Blood samples were collected in a fasted state. Analysis is by intention to treat. Medians (IQR) and means (SD) are expressed.

Results: The study enrolled 61 pts (38 males, 23 females; mean weight 56.5 [9.7] kg). The mean duration of previous combination NRTI therapy was 4.1 (1.2) years. At baseline, the median log₁₀ HIV RNA was 4.09 (3.75–4.61) c/ml and median CD4⁺ was 169 (59.5–277) cells/mm³. At wk 48, the mean log₁₀ HIV RNA decline from baseline was –2.29 (0.950) and the median CD4⁺ rise from baseline was 116 (47.5–179). At wk 48, 53 pts (87%) had HIV RNA < 50 copies/ml. There was one AIDS progression event on study (TB). Two (2) pts permanently ceased therapy (one to receive rifampicin based TB therapy and the other due to NNRTI resistance). Drug interruptions occurred in 10 pts (16 %) as a result of study medication related adverse events. Serious (grade 3 or 4) adverse events (SAE) related to study medication occurred in 15 pts (25%). The most common SAE was hypertriglyceridemia, which occurred in 9 (15%) pts. Lipid disturbances were common, with median rise in triglycerides of 185 (117.8–298.5) mg/dl and total cholesterol of 93 (38.8–126.8) mg/dl. At wk 48, 38 pts (62%) had fasted total cholesterol > 240 mg/dl. Three (3) pts (5%) developed clinical nephrolithiasis on study of whom 2 required therapy interruption. All 3 pts had at least 1 recurrent episode of nephrolithiasis. Eight (8) pts (13 %) recorded a creatinine > 1.40 mg/dl at wk 48. There were 23 pts (38%) with rash at least possibly attributable to efavirenz, but no pt ceased or interrupted therapy due to rash.

Conclusions: Indinavir/ritonavir 800/100 mg BID with efavirenz 600 mg QD provided an excellent virological and immunological response in pts who had virologically failed combination NRTI therapy. The regimen was well tolerated, although most pts developed an abnormal lipid profile. Nephrotoxicity occurred but did not necessitate permanent discontinuation of therapy.