Novel Kivexa‐based regimens in early courses of treatment for HIV infection

Background As the long‐term efficacy of antiretroviral therapy regimens is confirmed, we need to identify additional combinations with long‐term safety and potency, while also favoring simplicity of administration. In this light, we have undertaken a review of the use of abacavir/lamivudine (Kivexa, KVX)‐based regimens using integrase or CCR5 inhibitors as the third agent. Methods A retrospective chart review was undertaken, with informed patient consent. We identified all the patients in whom KVX was prescribed (following appropriate HLA‐B5701 screening) with either raltegravir (RGV) or maraviroc (MVC) as initial therapy or as a switch from another regimen for reasons other than virologic failure. Virologic efficacy over 48 weeks was evaluated, along with specific drug‐associated toxicity, adherence, and regimen modifications. Results A total of 38 patients (5 women) were evaluated, 24 on KVX/RGV, 13 on KVX/MVC, 1 on KVX/RGV/MVC. This was used as initial therapy in drug‐naïve subjects in three cases, and was selected as a modification of previous (current or not) therapy in 35 cases. Switches included replacement of the third agent with RGV or MVC (n=13), replacement of the NRTI backbone with KVX (n=13) or both. In all cases, the change was implemented to address a current or previous medication‐associated toxicity, most commonly to address jaundice (n=8), diarrhea (n=5) or reduced renal function (n=5). Patients were predominantly MSMs (n=17) or IDUs (n=13) with a mean baseline CD4 cell count of 363 cells/mm 3 , and plasma viral load of 46407 copies/mL (20 with full suppression at time of study entry). At 48 weeks, 34/38 (89%) achieved or maintained full suppression, with a mean CD4 count of 553 cells/mm 3 . Virologic failure with the development of the M184V mutation was observed in 3/4 non‐suppressed patients, and a loss of CCR5 tropism and RGV resistance were observed in one case each, all in the context of reduced adherence. There were no treatment discontinuations for toxicity and no medication‐associated serious adverse events. Conclusion KVX‐based regimens are safe and effective alternatives to more commonly used regimens in clinical practice, and offer the benefit of good long‐term tolerability and little or no need to enhance follow‐up for laboratory‐based abnormalities. Consideration should be given to non‐NNRTI and non‐PI‐based regimens to address issues of toxicity and simplification without apparent loss of efficacy.