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Dolutegravir Superior to Raltegravir in ART-Experienced Integrase Inhibitor Naive at 24 Weeks
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20th Conference on Retroviruses and Opportunistic Infections, March 3-6, 2013, Atlanta
Mark Mascolini
After 24 weeks a regimen including the integrase inhibitor dolutegravir proved virologically superior to a raltegravir-based regimen in antiretroviral-experienced people who had never taken an integrase inhibitor [1]. The SAILING trial found half as many virologic failures with dolutegravir as with raltegravir, but among people taking either integrase inhibitor with darunavir/ritonavir, dolutegravir's virologic advantage disappeared. The complete poster is available at the link below.
This double-blind, double-dummy, phase 3 trial randomized antiretroviral-experienced adults with a viral load above 400 copies to 50 mg of dolutegravir once daily or 400 mg of raltegravir twice daily plus investigator-selected background regimens including no more than two antiretrovirals, one of which had to be fully active. No one had taken an integrase inhibitor. The primary endpoint is the proportion of people in the modified intention-to-treat population with a viral load below 50 copies at week 48 by the FDA snapshot analysis. SAILING investigators presented the planned 24-week analysis at the Conference on Retroviruses.
Researchers randomized 354 people to dolutegravir and 361 to raltegravir. Median ages in the two groups were 42 and 43, about one third were women, and about 40% African American. Median CD4 count stood at 205 in the dolutegravir arm and 193 in the raltegravir arm, with respective median viral loads of 4.17 and 4.21 log10 copies/mL; 30% in each group had a viral load above 50,000 copies. Half of the people in each arm had at least triple-class resistance. The most frequently prescribed background drugs were darunavir/ritonavir plus tenofovir and lopinavir/ritonavir plus tenofovir. All background drug choices were evenly distributed between study arms.
Forty-eight people (14%) withdrew from the dolutegravir arm and 61 (17%) from the raltegravir arm. Lack of efficacy accounted for 15 dolutegravir withdrawals (4%) and 23 raltegravir withdrawals (7%).
At week 24 proportions with a viral load below 50 copies in the primary analysis were 79% randomized to dolutegravir and 70% randomized to raltegravir. The adjusted difference of 9.7% favoring dolutegravir (95% confidence interval 3.1% to 15.9%) established the superiority of dolutegravir at this point (P = 0.003).
Researchers counted 53 virologic nonresponders in the dolutegravir arm (15%) and 86 (24%) in the raltegravir arm. Protocol-defined virologic failure rates were 4% with dolutegravir and 9% with raltegravir. Sub-50 response rates were 80% with dolutegravir and 81% with raltegravir among people also taking darunavir/ritonavir and having no primary protease inhibitor mutations. Among people with a baseline viral load above 50,000 copies, sub-50 response rates were 70% with dolutegravir and 53% with raltegravir. Median CD4 gains were similar with dolutegravir (+99) and raltegravir (+93).
Only 2 people randomized to dolutegravir and 4 randomized to raltegravir had serious drug-related adverse events. Overall drug-related adverse events affected 20% assigned to dolutegravir and 23% assigned to raltegravir. Rates of grade 3 or 4 lab abnormalities were low and similar in the two treatment arms.
Reference
1. Pozniak A, Mingrone H, Shuldyakov A, et al. Dolutegravir vs raltegravir in ART-experienced, integrase-naive subjects: 24-week interim results from SAILING (ING111762). 20th Conference on Retroviruses and Opportunistic Infections. March 3-6, 2013. Atlanta. Abstract 179LB. http://www.retroconference.org/2013b/PDFs/179LB.pdf
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