Integrase Inhibitor '572 Tested Against Raltegravir-Resistant HIV
GlaxoSmithKline (GSK) has licensed an anti-HIV integrase inhibitor discovered by the Shionogi Corporation in Japan. Because of these arrangements, this drug has the complex code name S/GSK1349572 and for now is increasingly referred to simply as '572 by researchers.
In lab experiments '572 has activity against HIV that is resistant to raltegravir, the only currently approved integrase inhibitor.
Researchers tested '572 in HIV-positive volunteers who had HIV that was resistant to raltegravir. Participants either substituted '572 in place of raltegravir or started taking '572 if they had already quit raltegravir. All participants had HIV that was also resistant to drugs from the three commonly used groups of anti-HIV medicines:
- protease inhibitors
For the first 11 days of the study, participants received 50 mg once daily of '572 and no other drugs. After this period they also received an optimized background regimen based on resistance testing and medical history. This study is called Viking and so far only results from the first 11 days have been released.
The average profile of the 27 participants enrolled at the start of the study was as follows:
- 2 females, 25 males
- age -- 45 years
- CD4+ count -- 110 cells
- viral load -- 30,000 copies/ml
- duration of taking ART -- 14 years
Examples of prior ART used included these drugs, which were used by the following proportion of participants:
- etravirine (Intelence) -- 70%
- T-20 (Fuzeon, enfurvirtide) -- 81%
- darunavir (Prezista) -- 85%
- maraviroc (Celsentri) -- 37%
That most of these potent drugs were commonly used suggests that the study group represented heavily pre-treated patients.
After 11 days, 21 out of 27 participants (78%) had their viral load fall to 400 copies/ml or less or had their viral load fall by 0.7 log.
Participants in this study had weak immune systems and sometimes it is difficult to separate drug side effects from symptoms of HIV disease in this population. Despite this, investigators determined that the following side effects were caused by '572:
- mild diarrhea -- one person
- mild nausea -- one person
- moderate fatigue and problems falling asleep -- one person
- moderate diarrhea -- one person
Two participants had severely elevated levels of pancreatic enzymes; it is not yet certain if this is due to exposure to '572. However, no serious or life-threatening complications occurred after exposure to '572.
Long-term results from Viking are needed to assess the benefit of '572 in raltegravir-resistant people.
- Eron J, Durant J, Poizot-Martin I, et al. Activity of a next generation integrase inhibitor (INI), S/GSK1349572, in subjects with HIV exhibiting raltegravir resistance: initial results of VIKING study (ING112961). In: Program and abstracts of the 18th International Conference on AIDS, 18-23 July 2010, Vienna, Austria. Abstract MOAB0105.