October 27, 2008
Several posters were presented at the joint 2008 ICAAC/IDSA meeting in Washington, DC on the use of the protease inhibitor (PI), Lexiva (fosamprenavir). The studies looked at long-term follow-up from the KLEAN study, as well as 3 studies investigating different dosings of the drug.
Lexiva is recommended by the Federal Guidelines as a preferred PI when boosted with Norvir (ritonavir) as part of a person's first HIV regimen. The drug can also be used without Norvir by people who have never taken PIs.
The first poster was an analysis of long-term results from KLEAN. This was a head-to-head comparison of boosted Lexiva to Kaletra (lopinavir + ritonavir) both taken with the fixed dose combination pill Epzicom (abacavir + lamivudine/3TC). Results from KLEAN have been presented at various conferences. This is the first presentation of results after 144 weeks.
The results were mostly good for Lexiva. After 144 weeks, 83% of people taking Lexiva had HIV levels below 400 copies, compared to 70% of those on Kaletra. An even larger difference was seen when looking at the proportion of people with HIV levels below 50, with 77% for Lexiva and only 55% for Kaletra.
On average people taking Kaletra did gain more CD4 cells, averaging 335 compared to 300 for Lexiva. This is the latest in a number of studies that have shown Kaletra to be somewhat better than other HIV drugs in terms of increasing CD4 counts.
There were also more side effects among people taking Lexiva. Overall, 42% of those on Lexiva reported some side effect compared to 27% for Kaletra. There was no difference in more serious grade 3 or 4 adverse events, with 24% for Lexiva vs. 23% for Kaletra.
The second poster reported on efficacy and side effects of two dosing schedules for Lexiva. Just over 200 people were studied, with half taking 1,400mg Lexiva + 100mg Norvir once a day, and the others taking 700mg Lexiva + 100mg Norvir twice daily. Everyone also took Epzicom.
Two dosing methods were equally good at reducing HIV levels. After 24 weeks, 73% of people taking Lexiva once daily had HIV levels below 50 copies, compared to 76% taking it twice a day. People on Lexiva once a day gained slightly more CD4 cells, averaging 114 compared to 99 for the twice a day group.
There were some differences in terms of side effects. Overall, 22% of the once daily group reported side effects, compared to 31% in the twice daily group. There was more diarrhea and greater changes in blood fats among people taking Lexiva twice a day. This difference might be due to the higher amount of Norvir taken. Hypersensitivity reactions were somewhat more common in the once daily group. HLA testing accurately predicts the risk of this reaction.
The next study looked at the risk of resistance in people who saw their HIV levels rise while taking one of two doses of Lexiva: 1,400mg + either 100 or 200mg Norvir, once a day each along with Epzicom. There was no evidence of PI resistance in people who met the criteria for virologic failure.
The last poster was an analysis of the same study that compared the safety and efficacy of those two doses of Lexiva. After 96 weeks, significantly more people taking 100mg Norvir + Lexiva had undectable HIV: 78% vs. 53%. There was no difference when people who left the study or were lost to follow-up were excluded. This shows that the difference was likely due to tolerance issues rather than the potency of the regimens. However, there were no major differences in the frequency or type of side effects reported between the groups.
While none of these studies add much to our understanding of Lexiva, they do augment the evidence that it's a potent and well tolerated option for people wanting to take a boosted PI. A few years ago, Kaletra stood alone as the preferred boosted PI. Now a number of head-to-head studies have shown most of the widely used PIs are equivalent to Kaletra, including Lexiva.