October 27, 2008
Two posters presented at the joint 2008 ICAAC/IDSA meeting in Washington, DC presented follow-up data from two small studies of the boosted protease inhibitor (PI) Kaletra used as monotherapy. While most people taking Kaletra alone were able to maintain good control of HIV replication, the rates of failure were higher than those seen in recent studies of traditional three-drug combinations.
The IMANI-2 study was an open label, single arm study of people taking Kaletra alone as their first HIV regimen. Earlier results found 79% of people with HIV levels below 75 copies after 48 weeks. This poster presented follow-up results after 96 weeks.
After 96 weeks, 74% of people had HIV levels below 75 copies. Four had detectable levels of HIV, with three of those being below 1,000 copies. Twelve had detectable HIV levels at some point in the study, which returned to below 75. The authors speculated this was due to adherence issues. Importantly no primary PI mutations were detected in people with replicating HIV.
Another poster looked at three years of follow-up from the OK04 study, which compared Kaletra monotherapy to a traditional HAART regimen of Kaletra + 2 NRTIs. Results from an earlier time point found Kaletra monotherapy to be equivalent to Kaletra + 2 NRTIs after 96 weeks. A published paper from this study in the Journal of AIDS showed that while significantly more people taking traditional three-drug HAART had HIV levels below 50 at 48 weeks (95% vs. 81%), the difference was not quite large enough to be considered inferior.
This poster looked at a total of 100 people who were followed for 144 weeks after being randomized to take Kaletra alone in OK04. Of those, 70% continued to have HIV levels below 50 copies. Most who had HIV levels rise during the study were able to re-suppress HIV replication by adding 2 NRTIs.
Studies of traditional three-drug HAART regimens conducted years ago often saw similar rates of people with HIV levels below the limit of detection: around 70%. While study-to-study comparisons are always problematic, most studies of HAART regimens conducted these days result in higher rates of treatment success, more in the neighborhood of 80-90%.
While the authors of these two posters claim their results support larger studies of Kaletra monotherapy, Project Inform believes they show that Kaletra monotherapy is less likely to fully suppress HIV replication than Kaletra + 2 NRTIs, and it does not merit further study. We feel further study of this strategy is likely to put volunteers at an unacceptably high risk of treatment failure.