Study of New ViiV HIV Integrase Inhibitor Yields Encouraging Early Results

At the Tenth International Congress on Drug Therapy in HIV Infection in Glasgow from November 7-11, it was reported by the National AIDS Treatment Advocates Project (NATAP) that the experimental integrase inhibitor S/GSK1349572 "proved a potent HIV suppressor at three doses tested in antiretroviral-naive people. Through 24 weeks in this partially blinded comparison with efavirenz, 572 (as it is called for short) had a better safety profile than efavirenz."

572 is an integrase inhibitor that can be taken once daily, without the need for boosting with Norvir (ritonavir), and it appears to have minimal side effects. In addition, the daily dose is small enough that it could easily be combined with other drugs into a single pill.

"The multicenter European/US SPRING-1 study randomized 205 previously untreated [treatment-naive] people to 10, 25, or 50 mg of 572 once daily or to efavirenz [Sustiva], each with tenofovir/emtricitabine [Truvada/Emtriva] (taken by two thirds) or abacavir/lamivudine [Ziagen/Epivir]," according to the report. The participants in the study were mostly white males, their average age was about 37, and their average CD4 count was 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).

The percentage of people with undetectable viral loads (less than 50 copies per/ml) at 24 weeks was 96 percent with the 10 mg dose, 90 percent with the 25 mg dose and 92 percent with the 50 mg dose. Only 78 percent of those taking efavirenz had viral loads under 50 copies by week 24. 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.

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.

Roughly 20 percent of people taking efavirenz had a moderate to severe side effect, compared with 10 percent of those taking one of the three doses of 572.

The researchers counted seven serious adverse events with 572 (5%) and four (8%) with efavirenz. No serious events in the 572 group were attributed to the integrase inhibitor, while one in the efavirenz group (a suicide attempt) was attributed to efavirenz. Two people taking 572 (1%) and four 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).

This Phase 2 study will continue for 96 weeks. Also, Phase 3 studies of 572 are either currently under way or will be soon.