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Boosted Versus Unboosted Atazanavir After Long-Term Lopinavir
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11th European AIDS Conference
October 24-27, 2007
Madrid
Mark Mascolini
Switching to unboosted atazanavir after long-term lopinavir/ritonavir controlled HIV as well as switching to boosted atazanavir in a 213-person retrospective analysis by Nicola Gianotti and colleagues at Milan's San Raffaele Institute [1]. But because the results do not come from a randomized trial, the boosted and unboosted groups differed in ways that may have affected results.
Gianotti studied 114 people who switched to once-daily boosted atazanavir and 51 who switched to once-daily unboosted atazanavir with a viral load below 50 copies while taking lopinavir/ritonavir. Everyone had at least one follow-up visit after the swap, and follow-up continued until the end of treatment with atazanavir, a switch from boosted to unboosted atazanavir, or vice versa.
At the time of the switch the boosted group had taken lopinavir significantly longer (median 542 versus 473 days, P = 0.043) and had a higher CD4 count (median 474 versus 374 cells, P = 0.004). More importantly, the boosted group had more detectable viral loads while taking lopinavir than the unboosted group. Gianotti figured a median "detectability ratio" (number of detectable loads divided by the number of viral load tests) of 0.57 for the boosted group and 0.38 for the unboosted group (P = 0.005). Perhaps clinicians opted for boosted atazanavir in people whose viral control seemed shaky with lopinavir. The groups did not differ significantly in viral load before starting lopinavir; the medians of 4.21 log for the boosted group and 3.96 log for the unboosted group are both under 20,000 copies.
The boosted and unboosted groups also differed in certain follow-up measures. Significantly higher proportions starting boosted atazanavir backed it up with tenofovir (48.3% versus 14.1%, P < 0.0001), while significantly more starting unboosted atazanavir also switched to AZT (34.4% versus 15.4%, P = 0.003). Despite higher use of AZT in the unboosted group, more of them switched from a thymidine analog-containing backbone to a non-thymidine analog backbone (39.1% versus 18.1%, P = 0.002).
Precisely the same proportion of people changing to boosted and unboosted atazanavir had a viral rebound above 50 copies after the switch, 9%. And rebound rates did not differ significantly when Gianotti figured rates according to whether people shifted to nonthymidine analogs when they started atazanavir. CD4 counts rose significantly after the switch in both atazanavir groups.
Multivariate analysis isolated only one factor that independently predicted a rebound after the switch: Every 10-fold higher viral load when people started lopinavir raised the risk of rebound on atazanavir 2.7 times (95% confidence interval 1.27 to 5.94, P = 0.01). But figuring why a higher load before long-term control with lopinavir would affect control on atazanavir is not easy, especially since the higher "detectability ratio" in the boosted group while they were taking lopinavir did not affect rebound in the multivariate analysis.
Curiously, switching to a thymidine analog-sparing regimen raised the rebound risk 2.76 times, but that correlation fell short of statistical significance (95% confidence interval 0.751 to 10.14, P = 0.126). Other factors that did not influence rebounds in this analysis were age, gender, duration of lopinavir therapy, baseline CD4 count or CD4%, lowest-ever CD4 count, switch to a thymidine analog-sparing regimen, or switch to boosted versus unboosted atazanavir.
Gianotti did not report how many people eventually added ritonavir to atazanavir or how long follow-up lasted. Nor did he present atazanavir blood level data to show how atazanavir troughs compared in the boosted and unboosted groups. A prospective cohort study of 343 atazanavir-treated people by Paris clinicians correlated a 12-hour atazanavir level below 1000 ng/mL and a 24-hour level below 300 ng/mL with virologic failure (adjusted odds ratio 3, P = 0.001) [2]. Earlier work by Italian clinicians suggested an atazanavir trough cutoff of 150 ng/mL, but that proved too low for the French cohort.
The San Raffaele researchers saw no significant difference between the boosted and unboosted groups in total cholesterol or triglyceride changes after the switch, a finding countering the expectation that ritonavir boosting may adversely affect lipids. But significantly more people switching to boosted atazanavir failed to reach the National Cholesterol Education Program triglyceride target.
Reference
1. Gianotti N, Galli L, Seminari E, et al. Boosted or unboosted atazanavir as simplification of lopinavir/r-containing regimens. European AIDS Conference. October 24-27, 2007. Madrid. Abstract PS3/4.
2. Lescure FX, Poirier JM, Guiard-Schmid JB, et al. Atazanavir trough concentration: is 150 ng/mL cut-off for efficacy? Definition of an optimal therapeutic range and analysis of factors of predictive failure. European AIDS Conference. October 24-27, 2007. Madrid. Abstract P4.2/05.
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