HTB

GSK572: 24-week results in treatment-naive and raltegravir-experienced patients

Simon Collins, HIV i-Base

Oral presentations in Glasgow presented 24-week data on the pipeline integrase compound S/GSK1349572 (GSK572) in naive and experienced patients. [1, 2]

In general, the promising early results were sustained: 16-week data were presented at the IAS conference in Vienna in July (see HTB August 2010).

The SPRING-1 dose-finding phase 2 study (approximately 50 people in each of 4 arms) in treatment naive patients reported over 90% patients achieving viral suppression <50 copies/mL by 24 weeks compared to 78% in the efavirenz control group. Although this presentation noted that 26% of participants had a baseline viral load >100,000 copies/mL viral load in the remaining 74% patients must have been significantly lower given that median baseline viral load for the whole study was only approximately 25-40,000 copies/mL (4.4–4.6 logs).

Three people had confirmed virological failure (2 rebounds at week 2 and 24 with 572, one failure to achieve >1 log decline at week 4 with efavirenz who later suppressed), with no resistance detected.

No new tolerability concerns were raised, with GSK572 continuing to show a lipid advantage (mean change from baseline in LDL cholesterol was +0.023 vs +0.468 mmol/L in the combined 572 vs efavirenz arms).

CD4 increases were significantly higher in the combined GSK572 arms (median change +172 vs + 110, p=0.008).

The VIKING study reported results from 17/27 raltegravir-experienced patients who continued treatment out to 24 weeks. Baseline median fold change in raltegravir susceptibility for the whole study was 161, range: 0.57- >166. The study design added GSK572 (50 mg once-daily) to the failing combination for 10 days before optimising the combination on day 11 based on phenotypic sensitivity.

Virological responses correlated with phenotypic susceptibility score (PSS): 2/12 (17%) subjects with PSS =0, 4/7 (57%) with PSS=1 and 8/8 (100%) with PSS =2 achieved <400 copies/mL at Week 24. This highlights the imperative to only use integrase inhibitors in combinations in which they are supported by preferably at least two other drugs to which the virus is sensitive.

Importantly, a second cohort following the VIKING protocol is investigating using GSK572 50 mg twice-daily to attempt to overcome the phenotypic resistance at the 50mg dose, supported by PK/PD modeling. [4]

References:

Unless stated otherwise, references are to the Programme and Abstracts of the 10th International Congress on Drug Therapy in HIV Infection, 7–11 November2010, Glasgow, published in Journal of the International AIDS Society 2010, 13(Suppl 4).

  1. Rockstroh J et al. Once-daily S/GSK1349572 combination therapy in antiretroviral-naive adults: rapid and potent 24-week antiviral responses in SPRING-1 (ING112276). 10th International Congress on Drug Therapy in HIV Infection, 7–11 November 2010, Glasgow. Oral abstract O50. Published in Journal of the International AIDS Society 2010, 13(Suppl 4):O50doi:10.1186/1758-2652-13-S4-O50. http://www.jiasociety.org/content/13/S4/O50
  2. Eron J et al. Activity of the integrase inhibitor S/GSK1349572 in subjects with HIV exhibiting raltegravir resistance: week 24 results of the VIKING study (ING112961). 10th International Congress on Drug Therapy in HIV Infection, 7–11 November 2010, Glasgow. Oral abstract O51. Published in Journal of the International AIDS Society 2010, 13(Suppl 4):O50doi:10.1186/1758-2652-13-S4-O51. http://www.jiasociety.org/content/13/S4/O51
  3. GSK572: second-generation integrase inhibitor, 18th World AIDS Conference, Vienna, 2010. HTB August 2010. http://i-base.info/htb/13812
  4. Lovern M et al. PK/PD modeling supports the dose-escalation decision in VIKING. 10th International Congress on Drug Therapy in HIV Infection, 7–11 November 2010, Glasgow. Oral abstract P182. Published in Journal of the International AIDS Society 2010, 13(Suppl 4):O50doi:10.1186/1758-2652-13-S4-P182.
    http://www.jiasociety.org/content/13/S4/P182

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