The longest clinical study of any HIV treatment – seven years (360 weeks) – of Kaletra (lopinavir/ritonavir)-based therapy study results demonstrated patients taking Kaletra in combination with other antiretroviral agents maintained an undetectable viral load (amount of virus in the blood) of less than 50 copies per millilitre, as measured by HIV RNA.
This data, presented at the 9th European AIDS Conference (EACS), demonstrated that most patients taking a Kaletra-based regimen as initial therapy for HIV infection showed sustained antiviral response. Of the 19 patients who met criteria for resistance testing and had resistance testing results available through week 360, none demonstrated primary protease inhibitor (PI) resistance.
"This impressive seven-year Kaletra data, which demonstrates sustainable treatment without resistance for most patients new to therapy, is a hallmark of the importance of research and development in the area of HIV," said Robert Murphy, M.D., practicing physician and professor, and director of clinical research in biodefense and infectious diseases, Division of Infectious Diseases, Northwestern University, Feinberg School of Medicine, Chicago, Illinois.
Data from the randomized, uncontrolled, open-label, prospective phase II study of 100 treatment-naive patients taking Kaletra in combination with lamivudine (3TC) and stavudine (d4T) show that 59 percent of patients (59/100) had an undetectable viral load (HIV RNA less than 50 copies per millilitre) and 61 percent (61/100) had HIV RNA less than 400 copies per millilitre, using an intent-to-treat analysis, which categorizes any patient who does not complete the study as a treatment failure. Of the 62 patients remaining on treatment at week 360, 98 per cent (61/62) had HIV RNA less than 400 copies per millilitre.
A total of 33 samples from 29 subjects were submitted for resistance testing. Genotypic drug resistance testing failed for 10 subjects whose median HIV-1 RNA was 575 copies/mL. Of the 19 patients who had resistance data available through 360 weeks, none demonstrated evidence of resistance to lopinavir (0/19) or stavudine (0/19). Three patients (3/19) demonstrated lamivudine resistance. Correspondingly, no evidence of phenotypic resistance to any PI was observed.
Patients in this open-label study, in which there was no comparator group, were initially given one of three doses of Kaletra in addition to the nucleoside analogues stavudine and lamivudine. After 48 weeks of therapy, all patients were converted to the same dose of Kaletra (400/100 mg twice-daily) with stavudine and lamivudine.
Kaletra was generally well tolerated through 360 weeks of therapy. The most frequent adverse events were diarrhoea and nausea. At week 360, Grade 3 or Grade 4 cholesterol and triglyceride values were observed in 2 per cent and 3 per cent of patients, respectively.
The low viral loads were accompanied by increases in CD4 cell counts. Average CD4 cell count increase from baseline to week 360 was 501 cells per cubic millimetre for all patients remaining in the study.
"Over the years, this study has helped us better understand the benefit Kaletra brings to patients new to therapy," said Scott Brun, M.D., divisional vice president, Infectious Disease Development, Abbott." Abbott remains committed to conducting research that adds value to the understanding of HIV and its treatment for clinicians and patients."