Coverage of 2007 ICAAC
(Interscience Conference on Antimicrobial Agents and Chemotherapy)

September 17–20, 2007, Chicago, Illinois

Recent study shows exceptional potency of new integrase inhibitor

September 19, 2007

Results from a study of the soon-to-be approved integrase inhibitor (II) Isentress (raltegravir) presented at the 47th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) being held in Chicago reinforce the importance of combining it with two or more active drugs.

The data were from the second part of a phase II, dose ranging study. In the initial period of the study, treatment experienced volunteers were randomly assigned to one of three doses (200, 400 or 600mg) or a placebo—all taken twice daily. Everyone was also given optimized background therapy, or a combination of the best available anti-HIV drugs, chosen with the help of resistance testing. In the second part of the study, everyone was offered open label (they knew what they were taking) 400mg Isentress when they had completed the initial 24 week period.

Overall Isentress proved to be potent and durable. The table below shows the percentage of people in each group with HIV levels below 400 and below 50 at both 24 and 48 weeks. People taking any of the three doses of Isentress were much more likely to have undetectable HIV levels at both 24 and 48 weeks than those taking the placebo.

 

Table 1
Original Randomized Treatment Group	% with HIV RNA (copies/mL)
	< 400 copies		< 50 copies
	Week 24	Week 48	Week 24	Week 48
Isentress 200mg	70	69	65	64
Isentress 400mg	71	64	56	46
Isentress 600mg	71	71	67	53
Placebo	16	13	13	9

Almost everyone (35 of 36) whose viral loads went up during the study showed evidence of resistance to Isentress. Importantly the people at the most risk of treatment failure were those who had no active drugs in their background regimen. This further highlights the importance of combining Isentress with two or more active drugs, whenever possible.

As seen in other studies of Isentress, the drug was generally well tolerated, with similar rates of side effects between the people taking Isentress and those taking the placebo.

As reported here, the antiviral advisory committee to the Food and Drug Administration (FDA) unanimously recommended that Isentress receive accelerated approval for treatment of drug resistant HIV. Full approval could come in October. For people who need it to construct a viable drug regimen, Isentress is currently available through an expanded access program.

The results of this study are more good news for a drug that has seen almost nothing but. The drug appears exceptionally potent, as well as generally well tolerated. While much is understood about Isentress, it will take long term study and real world use to fully understand the drug. Currently it is clear that Isentress is a powerful and tolerable option for people with extensive treatment experience and resistance to multiple anti-HIV drugs. Along with (darunavir) approved in 2006, Selzentry (maraviroc) approved just weeks ago and etravirine (TMC-125) which is available through expanded access and is likely to gain approval next year, this is a golden opportunity for people with drug resistant HIV to build truly effective and durable regimens.