Atazanavir/r vs lopinavir/r in treatment-naïve patients: 48 week results

HIV Treat Bull - 2008 March-April;9(3/4):

Although widely used off-label, atazanavir/r is not currently approved in Europe for use in first-line combinations, nor recommended in European guidelines, due to limited data in naïve patients. Results from a large randomised international head-to-head study against lopinavir/r, sponsored by BMS, are therefore important to report.

Jean-Michel Molina from St Louis Hospital, Paris, presented the 48-week analysis from this 96-week CASTLE study. This was a non-inferiority study (10% margin) and the primary endpoint was the proportion of patients with HIV RNA <50 copies/mL at week 48.

The trial randomised 883 treatment-naïve patients to either atazanavir 300 mg / ritonavir 100 mg once-daily or lopinavir/ritonavir 400 mg/100 mg twice-daily, both in combination with fixed-dose tenofovir/FTC once-daily. vBaseline demographics and characteristics included median CD4 count 205 cells/mm³ (range 2-810) with 12% less than 50 cells/mm³; and viral load around 5 log copies/mL (range 2.6-5.9), with 50% patients starting above 100,000 copies/mL. Only around 5% had CDC class C diagnosis, and 12% were coinfected with hepatitis B or C.

Only around 10% of patients discontinued prior to week 48, with a balance between each arm, detailed in Table 1.

Table 1: Patient disposition at week 48 View table

The percentage of patients with viral load <50 copies/mL at week 48 in the atazanavir/r and lopinavir/r arms was 78% vs 76% (estimated difference 1.9, 95% CI –3.6 to 7.4), by intent-to-treat analysis.

Stratified by baseline viral load, the results were 82% vs 81% (<100,000 copies/mL) and 74% vs 72% (>100,000 copies/mL), in the ATZ/r and LPV/r groups respectively, with no statistical difference between arms.

A post-hoc analysis of results by baseline CD4 counts showed no impact for ATZ/r, but a statistically significant poorer response for the LPV/r arm, ranging from 80% <50 copies/mL in patients with >200 CD4 cells/mm³ to 63% for those starting with <50 cells/mm³, p = 0.0085.

CD4 response was similar in each arm (+203 vs + 219 cells/mm³).

Side effects generally reflected the known profile of each drug, with ATZ/r having higher incidence of jaundice, and LPV/r reporting greater GI-related ae’s, that are detailed in Table 2.

Table 2: Adverse events in CASTLE study View table

With laboratory AE’s, grade 3-4 ALT/AST elevations were low (>2%) in both arms.

Lipid profile favoured ATZ/r with fewer patients at week 48 having total cholesterol >240 mg/dL (7% vs 18%), and significantly lower changes from baseline for TC, non HDL and TG (all p<0.0001). Lipid lowering drugs were used by 2% and 7% of the ATZ/r and LPV/r arms respectively.

Comment

The study concluded that atazanavir/r is an appropriate treatment for first line therapy. Regulatory and guidelines committees will hopefully review these data carefully and promptly.

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