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Study Clarifies Risk of Switch to Raltegravir From Suppressive PI
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International HIV and Hepatitis Drug Resistance Workshop, June 8-12, 2010, Dubrovnik, Croatia
Mark Mascolini
Switching from a protease inhibitor (PI) to raltegravir did not appear to compromise continued viral suppression in a 222-person randomized trial--as long as people did not have a record of nucleoside resistance mutations [1].
The results clarify the meaning of the SWITCHMRK trials, in which people replacing suppressive lopinavir/ritonavir with raltegravir had a higher 24-week failure rate than people who continued the PIs [2], but apparently because many patients had taken a failing nucleoside regimen. Archived nucleoside mutations would put raltegravir at a disadvantage in SWITCHMRK, because raltegravir has a lower barrier to resistance than lopinavir/ritonavir and because everyone who entered the trials had controlled HIV with the PIs plus nucleosides. The new study is not definitive, however, because there was no control group who continued their PI.
Vincent Soriano and colleagues at Madrid's Carlos III Hospital selected patients at their center who had a viral load below 50 copies for more than 24 weeks while taking a PI regimen. The investigators randomly assigned patients 2-to-1 to switch to 800 mg of raltegravir once daily or 400 mg twice daily. People on the twice-daily regimen switched to once-daily raltegravir if they had an undetectable viral load after 3 months.
Among 222 people who completed 24 weeks of follow-up at the time of this analysis, 87% were men, age averaged 46 years, and time on antiretroviral therapy averaged 102 months. Ninety-three people (42%) had taken a one- or two-drug regimen, and 150 (68%) had at least one previous virologic failure. Seventy-four people (33%) had a record of resistance to nucleosides. CD4 count averaged 574 when the switch to raltegravir occurred. Most people switched from atazanavir (48%), lopinavir (28%), or fosamprenavir (13%). About two thirds took tenofovir/emtricitabine with raltegravir, and about one third took abacavir/lamivudine.
Thirteen people (6%) had virologic failure within 24 weeks, including 12 (6%) in the once-daily raltegravir group and 1 (3%) in the twice-daily group, a nonsignificant difference (P = 0.18). Twelve people with virologic failure (16%) had prior nucleoside resistance, and only 1 person with virologic failure had no record of nucleoside resistance (1%), a significant difference (P < 0.001). In univariate analysis, prior nucleoside resistance raised the risk of raltegravir failure 28.45 times (95% confidence interval 3.62 to 222.56, P = 0.001).
Twelve people with virologic failure on raltegravir had an earlier virologic failure, while raltegravir failed in 1 person without an earlier failure, but that difference fell short of statistical significance (P = 0.08). Raltegravir failure rates did not differ significantly between people with and without a history of one- or two-drug therapy.
CD4 count climbed by a median of 32 cells after the switch to raltegravir. Total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol all fell significantly during 24 weeks of raltegravir therapy. Alanine aminotransferase fell by a median of 1 IU/L after the switch, but that change was not significant (P = 0.08).
References
1. Vispo E, Barreiro P, Blanco F, et al. Impact of prior NRTI failure in the ODIS trial, a study conducted in HIV+ patients on undetectable viraemia on protease inhibitors who switched to raltegravir once daily versus twice daily. International HIV and Hepatitis Drug Resistance Workshop. June 8-12, 2010. Dubrovnik, Croatia. Abstract 97.
2. Eron JJ, Young B, Cooper DA, et al. Switch to a raltegravir-based regimen versus continuation of a lopinavir-ritonavir-based regimen in stable HIV-infected patients with suppressed viraemia (SWITCHMRK 1 and 2): two multicentre, double-blind, randomised controlled trials. Lancet. 2010;375:396-407.
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