Boosting atazanavir in treatment-naive patients, and impact on lipids after switching from lopinavir/r

3 September 2007. Related: Conference reports, Antiretrovirals, IAS 4th Sydney 2007.

Simon Collins, HIV i-Base

Although atazanavir/r is widely used in treatment-naive patients, and widely used as a choice of switch drug in patients experiencing tolerability problems with efavirenz or lopinavir/r, there is limited data in naive patients (and for whom it still not indicated in Europe).

Malan and colleagues presented 96 week results from the BMS-089 study comparing atazanavir 400mg QD to atazanavir 300mg QD boosted by 100mg ritonavir in approximately 200 treatment-naive individuals. All patients received 3TC and the extended release once-daily d4T that never become commercially available. [1]

Confirming the US and European recommendations to use boosted atazanavir in treatment-experienced patients, virological suppression to <50 copies/mL was greater in the ATZ/r arm (TLOVR 65% vs 55%, difference estimate 9.8 (95% CI: -3.4 to 23.1). Virological failure occurred more frequently in the unboosted arm (in 20 vs 5 patients), with higher rates of resistance (M184V occurring in 11/20 vs 1/5 patients and I50I/L or N88N/S occurring in 5/20 and 1/5 patients in the unboosted and boosted arms respectively).

CD4 increases were higher in the unboosted arm (+315 vs +276 cells/mm3), though this difference was not statistically significant.

Greater increases in lipids occurred when ritonavir was used: total cholesterol increased by +0.18 vs +0.52 mmol/L (p<0.01); LDL by +0.36 vs +0.70 mmol/L (p<0.05); and HDL by +0.59 vs + 0.85 mmol/L (p=NS), in the ATZ and ATV/r arms respectively, but this generally occurred in the first 48 weeks of treatment. 48 week results from this study were presented at the 13th CROI in 2006. [2]

Horberg and colleagues from Kaiser Permanente presented results from a retrospective analysis of 443 patients using unboosted- (n=69) and boosted-atazanavir (n=374). [3]

All patients were treatment-naive, and adherence was reported at approximately 80% for each group. Viral suppression to <400 copies/mL was 54% in the unboosted vs 78% in the boosted patients.

Elion and colleagues, presented results from a GSK study of once-daily atazanavir/ritonavir plus abacavir/3TC in 111 treatment-naive patients, half of whom had baseline CD4 counts <200 cellsmm3 and viral load >100,000 copies/mL. [4]

In this study, 87% patients reported viral suppression to <50 copies/mL at week 48. 16 subjects (14%) prematurely discontinued: lost to follow-up (5), consent withdrawal (5), adverse event (3), protocol violation (1), non-compliance (1), and virologic failure (1).

Further data on impact of the boosting ritonavir dose on lipids was presented by Mallola and colleagues from University Hospital Clinic, Barcelona, in virologically suppressed patients randomised to either continue on lopinavir/r (n=127) or switch to atazanavir/r (n=121). [5]

There were no significant differences in continued efficacy: treatment failure occurred in 20% vs 17% and virological failure occurred in 6.3% vs 5% in the LPV/r and ATV/r arms respectively. CD4 changes from baseline were similar in both arms (around 40 cells/mm3). Adverse events leading to study drug discontinuation was 5% in both arms and changes in ALT/AST were also similar.

While fasting cholesterol and triglyceride both reduced in the atazanavir/r arm by -9% and -29% (by -19 and -51 mg/dL respectively) compared to no change in the LPV/r arm, neither HDL or LDL changes (both reduced, by -6% and -7% respectively) were reported as significantly improving.

While the percentage of patients above NCEP guidelines for lipid lowering treatment was higher for TC, TG and LDL in patients using LPV/r, the number of patients with HDL <40 mg/dL doubled from 16% to 32% in patients using ATV/r. See Table 1. The number of patients with LDLc >130 mg/dL even increased by +5% from 20% to 25% in the ATV/r arm (though by +10% in the LPV/r arm). Use of lipid lowering drugs did not significantly change during the study.

Table 1: Percentage above NCEP treatment recommended levels

References:

1. Malan N, Krantz E, David N et al. Efficacy and safety of atazanavir-based therapy in antiretroviral naive HIV-1 infected subjects, both with and without ritonavir: 96-week results from AI424089. 4th IAS Conference, Sydney, 2007. Abstract WEPEB024.
   http://www.ias2007.org/pag/Abstracts.aspx?AID=3725
2. Malan N et al. 13th CROI; Denver, Colorado; February 5-8, 2006. Abstract 107LB.
   http://www.aegis.org/conferences/croi/2006/107lb.html
3. Horberg M, Klein D, Hurley L et al. Efficacy and safety of non-boosted to ritonavir-boosted atazanavir among antiretroviral naive patients. 4th IAS Conference, Sydney, 2007. Abstract WEPEB025.
   http://www.ias2007.org/pag/Abstracts.aspx?SID=155&AID=2098
4. Elion R, DeJesus E, Sension M et al. Once-daily abacavir/lamivudine (ABC/3TC) and boosted atazanavir (ATV/RTV) in antiretroviral-naive HIV-1 infected subjects: 48-week results from COL102060 (SHARE). 4th IAS Conference, Sydney, 2007. Abstract WEPEB033.
   http://www.ias2007.org/pag/Abstracts.aspx?AID=410
5. Mallolas J, Podzamczer D, Domingo P et al. Efficacy and safety of switching from lopinavir/r (LPV/r) to atazanavir/r (ATV/r) in patients with virologic suppression receiving a LPV/r containing HAART: the ATAZIP study. 4th IAS Conference, Sydney, 2007. Abstract WEPEB117LB.
   http://www.ias2007.org/pag/Abstracts.aspx?AID=5499