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Raltegravir Rescue Regimens Do Well With or Without a PI
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5th IAS Conference on HIV Pathogenesis, Treatment and Prevention, July 19-22, 2009, Cape Town
Mark Mascolini
People with heavy antiretroviral experience starting raltegravir in the US expanded-access program responded well--at least for 12 weeks--regardless of whether their background regimen included a protease inhibitor (PI), according to results of a record analysis by investigators at 15 sites [1]. A higher genotypic sensitivity score (GSS) before starting raltegravir with or without a PI predicted a good 12-week virologic response.
The BENCHMRK trials established the potency of the integrase inhibitor raltegravir in treatment-experienced people [2]. But only 7% of BENCHMRK participants took darunavir/ritonavir before entering the trial, and about one third took those PIs for the first time with raltegravir [3]. Overall, 60% of BENCHMRK participants had at least one active PI in their background regimen [3].
To figure out whether an active PI is a critical ingredient of raltegravir-based rescue regimens, US researchers checked regimens and responses in 442 people who took raltegravir with or without a PI in Merck's expanded-access program for the drug. To be eligible for expanded access, people had to have (1) a detectable viral load and (2) resistance to nucleosides, nonnucleosides, and PIs or intolerance to existing antiretrovirals. Everyone in this analysis had at least 12 weeks of follow-up while taking raltegravir. The investigators figured GSS for each background regimen by using the Stanford HIV database tool.
The expanded-access group included 332 people taking a PI (almost all boosted by ritonavir) and 110 taking no PI. The PI group had significantly more drugs in their new regimen (median 4.1 versus 3.8, P = 0.0004), and significantly more new antiretrovirals in their regimen (median 2.5 versus 2.3, P = 0.014). But median GSS was similar in both groups (1.8 with PI, 1.7 without PI), meaning the background regimen of half of these people had good activity against their resistant virus. When these people started raltegravir, their viral load averaged about 20,000 copies and their CD4 count averaged 180. Both study groups were racially diverse with no significant differences between groups.
After 12 weeks of follow-up involving 373 people, almost 90% in both groups had a viral load below 400 copies and over 65% had a load under 75 copies. Those response rates remained steady in the 19 people tracked to 24 weeks. Median time to a viral load below 400 copies did not differ significantly between the groups (7.5 weeks with PI, 7.4 weeks without PI, P = 0.19). Thirteen of 332 people (3.9%) in the PI group and 4 of 110 (3.6%) in the no-PI group had a virologic rebound above 75 copies.
Statistical analysis considering GSS, number of antiretrovirals in the raltegravir regimen, and number of new antiretrovirals in that regimen determined that a higher (better) GSS significantly predicted a viral load below 400 or 75 copies at week 12 (P = 0.039). But number of antiretrovirals in the regimen and using or not using a PI did not predict 12-week virologic response. CD4 gains were similar with and without a PI in the background regimen.
References
1. Skiest D, Cohen C, Barker D, et al. Raltegravir without a protease inhibitor is highly efficacious in heavily pre-treated individuals. 5th IAS Conference on HIV Pathogenesis, Treatment and Prevention. July 19-22, 2009. Cape Town. Abstract MOPEB072.
2. Steigbigel RT, Cooper DA, Kumar PN, et al. Raltegravir with optimized background therapy for resistant HIV-1 infection. N Engl J Med. 2008;359:339-354.
3. Cooper DA, Steigbigel RT, Gatell JM, et al. Subgroup and resistance analyses of raltegravir for resistant HIV-1 infection. N Engl J Med. 2008;359:355-365.
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