In treatment-naïve patients with HIV, atazanavir/ritonavir (A/R) once daily shows similar antiviral efficacy to (L/R) twice daily. Thus once daily A/R should be a first line treatment option for these patients as it has a number of advantages over the currently recommended twice-daily L/R. These are the conclusions of the authors of the CASTLE study, published early Online and in an upcoming edition of The Lancet.
Professor Jean-Michel Molina, Hopital Saint-Louis 1, Paris, France, and Dr Graeme Moyle, Chelsea and Westminster Hospital, London, UK, and colleagues did a study of 883 antiretroviral-naïve, HIV infected patients, of which 440 were randomly assigned to receive A/R 300/100mg once daily, while 443 received L/R 400/100mg twice daily (443). Both regimens were in combination with tenofovir / emtricitabine 300/200mg once daily, as is standard. The proportion of patients with viral load less than 50 copies per ml in their blood was measured at 48 weeks.
The researchers found that 78% of patients receiving A/R and 76% of those receiving L/R had achieved the target viral load above by week 48. Increases in the numbers of CD4 cells (part of the immune system) also increased by similar amounts, by 203 cells per μl of blood in the A/R group and by 219 cells per μl in the L/R group. In both groups, 6% of patients had failed on the treatment by the end of the study; and two patients developed resistance mutations to treatment in the A/R group compared with none in the L/R group. Serious adverse events occurred in 12% of A/R patients and 10% of L/R patients; however fewer patients in the A/R group than in the L/R group experienced treatment-related diarrhoea (2% vs 10%), and also nausea (4% vs 8%). Jaundice was seen in 4% of patients in the A/R group but zero patients in the L/R group; while large increases in bilirubin* were seen in 34% of patients in the A/R group but less than 1% of patients in the L/R group.
The authors conclude: "In treatment-naïve patients, atazanavir/ritonavir once-daily demonstrated similar antiviral efficacy to lopinavir/ritonavir twice daily, with less gastrointestinal toxicity but with a higher rate of hyperbilirubinaemia*…the results of this study support the use of once-daily atazanavir/ritonavir as a recommended first-line treatment option, with a number of patient benefits over the currently recommended ritonavir-boosted twice-daily lopinavir for the treatment of HIV-infected antiretroviral-naïve patients."
Professor Jean-Michel Molina, Hopital Saint-Louis 1, Paris, France, currently in Mexico for International AIDS conference, please e-mail to arrange interview E) jean-michel.molina@sls.aphp.fr
Dr Graeme Moyle, Chelsea and Westminster Hospital, London, UK, contact by e-mail only E) graeme.moyle@chelwest.nhs.uk
Notes to editors: *Bilirubin: a yellow pigment that comes from the degradation of haemoglobin and which is detoxified in the liver – high increases (hyperbilirubinaemia) can cause jaundice.
for full study e-mail tony.kirby@lancet.com
Journal
The Lancet