GSK744: 24-week results with oral integrase inhibitor planned for once-monthly injections
1 December 2013. Related: Conference reports, Antiretrovirals, EACS 14 Brussels 2013.
Simon Collins, HIV i-Base
Early results were also presented at EACS 2013 for ViiV Healthcare’s follow-up compound to dolutegravir, which currently has the development name GSK-744. [1]
Previous results with this integrase inhibitor have reported a sufficiently long half-life with both IV and SC injectible formulations to support once-monthly dosing both in therapeutic and PrEP prevention studies.
Viral efficacy results from the LATTE study were from using the oral formulation of GSK-744 in combination with tenofovir/FTC. Participants who become undetectable by week 24, roll over to use dual therapy with oral GSK-744 plus oral rilpivirine, out to 96 weeks. [2]
The first part of the study was a randomised open label dose finding study comparing 10 mg, 30 mg and 60 mg of GSK-744 to a control arm of efavirenz plus tenofovir/FTC. Approximately 60 patients were in each arm.
Baseline median CD4 count was approximately 400 cells/mm3 with mean viral load or 4.2 – 4.4 log copies/mL Again, no data on the range or variance for the baseline data were included in the presentation, limiting the ability to interpret the results, although broadly people were in early HIV infection.
At week 24, viral load reductions in the 10 mg, 30 mg, 60 mg and control arms were -2.53, -2.53, -2.50 and -1.88 log copies/mL, respectively The percentage of patients (95% CI) with viral suppression to <50 copies/mL was 88% (80%, 96%), 85% (76%, 94%), 87% (78%, 95%) and 74% (63%, 85%), respectively.
Future development will go forward using the 30 mg dose.
Comment
Given the approximate -2.2 log reductions seen following 10 days of monotherapy with GSK-744 and that tenofovir and FTC are included for six months with such a low baseline viral load, it is difficult to understand why a higher percentage of people had an undetectable viral load.
While ART is generally getting better, the target should be for near-100%.
References:
- Margolis D et al. Once-daily oral GSK1265744 (GSK744) as part of combination therapy in antiretroviral naïve adults: 24-week safety and efficacy results from the LATTE study (LAI116482). 14th EACS, 2013, Brussels. Oral abstract PS7.1.
http://www.eacsmobile.org/libraryEntry/show/38282193537098395 - LATTE Study. Clinicaltrials.gov.
http://clinicaltrials.gov/show/NCT01641809