EACS 2013: GSK1265744 Rapidly Suppresses HIV, Appears Safe At Selected Dose

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The experimental HIV integrase inhibitor GSK1265744 demonstrated rapid and potent antiviral activity and good tolerability for treatment-naive patients in the LATTE study, according to a report at the 14th European AIDS Conference this week in Brussels.

Integrase inhibitors are among the most well-tolerated antiretroviral medications. GSK1265744 (or GSK744 for short), being developed by GlaxoSmithKline, is similar to the recently approved dolutegravir. It is being tested both as a once-daily oral drug and as a long-acting injectable that may allow for once-monthly administration. A recently presented analysis of 8 studies showed that it is safe with no notable safety concerns.

David Margolis from GlaxoSmithKline and colleagues evaluated the safety, tolerability, and efficacy of GSK744 in previously untreated people with HIV.

The Phase 2b LATTE trial started with a 24-week induction phase comparing 3 oral doses of GSK744 plus 2 nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) to inform selection of an optimal dose for further development. At week 24, participants with stable viral suppression discontinued NRTIs and switched to a simplified dual maintenance regimen of GSK744 plus oral rilpivirine (Edurant).

The primary endpoint of this partially-blinded, dose-ranging, multicenter studyis undetectable HIV viral load (<50 copies/mL) at 48 weeks. Margolis reported interim 24-week findings.

This analysis included 243 treatment-naive patients. Almost all were men; Margolis explained that the lack of women was in part due to a restriction on use of hormonal contraception, since drug interactions with GSK744 are not yet known. A majority of participants (about 60%) were white, about 30% were black, and the median age was about 34 years. The median CD4 T-cell count was approximately 410 cells/mm3 and 16% had high baseline viral load (>100,000 copies/mL). About 5% were coinfected with hepatitis C.

Participants were randomly assigned to receive GSK744 at doses of 10 mg, 30 mg or 60 mg, or 600 mg efavirenz, all once daily. They also started on 2 investigator-selected NRTIs, about 60% taking tenofovir/emtricitabine (Truvada) and 40% taking abacavir/lamivudine (Epzicom).

Results

"Oral [GSK744] administered once-daily with 2 NRTIs was associated with a good treatment response," the researchers concluded.

Based on these findings, the 30 mg GSK744 dose was selected. The maintenance phase of LATTE testing GSK744 plus rilpivirine maintenance therapy is currently underway. Results from that part of the trial will prepare the way for a Phase 2b study of combined long-acting injectable formulations of both drugs, which may one day be used as monthly maintenance therapy or pre-exposure prophylaxis (PrEP).

10/19/13

Reference

D Margolis, L Bhatti, G Smith, et al. Once-daily oral GSK1265744 (GSK744) as part of combination therapy in antiretroviral naive adults: 24-week safety and efficacy results from the LATTE study (LAI116482). 14th European AIDs Conference (EACS 2013). Brussels. October 16-19, 2013. Abstract PS7/1.