Treatment intensification with abacavir in HIV-infected patients with at least 12 weeks previous lamivudine/zidovudine treatment

Objectives: To demonstrate that lamivudine and zidovudine, given separately (lamivudine/zidovudine) or as a single combination tablet (Combivir(TM)), had equivalent efficacy. To evaluate the safety and antiretroviral activity of intensification with abacavir in patients treated with lamivudine/zidov udine for greater than or equal to 12 weeks. Design: A 12-week, equivalence study of lamivudine/ zidovudine versus Combi vir. Patients who completed this study could enter a 48-week, intensificati on study of Combivir plus abacavir. Methods: In the equivalence study, treatment-naive patients were assessed f or HIV-1 RNA, CD4 cell count and genotype. The same assessments plus phenot ype were made in the intensification study. Serious adverse events were rec orded in the equivalence study and all adverse events in the intensificatio n study. Results: Lamivudine/zidovudine (n=40) and Combivir (n=35) gave equivalent r eductions in plasma HIV-1 RNA levels at week 12. An identical proportion of patients (74%) in each treatment group harboured virus with the M184V muta tion after 12 weeks. Fifty-two patients entered the intensification study a nd 44 completed 48 weeks of treatment. At the time of intensification with abacavir, all 35 patients with evaluable isolates harboured HIV-1 containin g M184V. Addition of abacavir to Combivir led to further decreases in plasm a HIV-1 RNA and increases in CD4 cell counts compared with the start of int ensification (P<0.001 at week 48). After 48 weeks of triple therapy, multi- nucleoside resistance mutations at codons 69 and 151 were not detected in a ny patients. All treatment regimens were generally well tolerated. Conclusion: Lamivudine/zidovudine and Combivir have equivalent antiretrovir al activity over 12 weeks. Adding abacavir to Combivir can be a safe and ef fective therapeutic option for patients, including those harbouring virus w ith the M184V mutation.