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New S/GSK Integrase Inhibitor Looks Good at 24 Weeks in Phase 2 Trial
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Tenth International Congress on Drug Therapy in HIV Infection, November 7-11, 2010, Glasgow
Mark Mascolini
S/GSK1349572 proved a potent HIV suppressor at three doses tested in antiretroviral-naive people [1]. Through 24 weeks in this partially blinded comparison with efavirenz, 572 (as it is called for short) had a better safety profile than efavirenz.
The multicenter European/US SPRING-1 study randomized 205 previously untreated people to 10, 25, or 50 mg of 572 once daily or to efavirenz, each with tenofovir/emtricitabine (taken by two thirds) or abacavir/lamivudine. Median age of the study group was 37 (range 20 to 79), 86% were men, and 80% were white. Pretreatment viral load averaged 4.46 log (about 30,000 copies) and pretreatment CD4 count 342.
The investigators defined virologic failure as (1) a confirmed rebound above 400 copies following a sub-400 load, (2) a confirmed rebound of at least 0.5 log from the lowest load recorded, (3) a confirmed load above 400 at week 24 without suppression, or (4) less than a 10-fold viral load drop at week 4 (unless the load was below 400 copies).
At week 24 sub-50-copy rates in this time-to-loss-of-virologic-response analysis were 96% (51 of 53) with 10 mg of 572, 90% (46 of 51) with 25 mg, 92% (47 of 51) with 50 mg, and 78% (39 of 50) with efavirenz. Six people in the efavirenz group (12%) had a suboptimal virologic response and 5 (10%) quit or changed from efavirenz for other reasons. Six people in the combined 572 groups (4%) had a poor virologic response and five (3%) stopped or switched from 572 for other reasons. No integrase mutations arose upon virologic failure of 572.
CD4 counts climbed by medians of 158 in the 10-mg 572 group, 206 in the 25-mg group, 167 in the 50-mg group, and 110 in the efavirenz group.
There were 10 grade 2 to 4 drug-related side effects in the combined 572 groups (6%) and 10 (20%) with efavirenz. The researchers counted 7 serious adverse events with 572 (5%) and 4 (8%) with efavirenz. No serious events in the 572 group were attributed to the integrase inhibitor, while 1 in the efavirenz group (a suicide attempt) was attributed to efavirenz. Two people taking 572 (1%) and 4 taking efavirenz (8%) stopped treatment because of side effects. Low-density lipoprotein cholesterol rose 0.023 mmol/L in the 572 group and 0.468 mmol/L with efavirenz (about 1 and 18 mg/dL).
Study participants will continue on their randomized regimen until week 96.
Reference
1. Rockstroh J, Felizarta F, Maggiolo F, et al. Once-daily S/GSK1349572 combination therapy in antiretroviral-naive adults: rapid and potent 24-week antiviral response in SPRING-1 (ING11276). Tenth International Congress on Drug Therapy in HIV Infection. November 7-11, 2010. Glasgow. Abstract O434.
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