In a study using ultra-sensitive viral load testing, most people who switched from combination therapy to Kaletra monotherapy were found to have extremely low HIV viral loads at 48 weeks, comparable to those on Kaletra plus two nucleoside analogues.
Monotherapy (treatment with a single antiretroviral drug) is contrary to all established HIV treatment guidelines, which call for a combination of at least three antiretrovirals. However, recent studies have shown that standard-dose Kaletra (lopinavir/ritonavir) alone, without accompanying nucleosides, keeps viral loads undetectable in a large percentage of HIV-positive people. This surprising result has led to more in-depth studies of Kaletra monotherapy.
The OK (Only Kaletra) study
The new analysis (described below) follows up on the earlier “OK” (Only Kaletra) study, a “proof-of-concept pilot trial” which enrolled 42 HIV-positive adults at hospitals in Spain. All participants were receiving standard-dose Kaletra (400/100mg twice daily) plus two nucleoside analogues, and their viral loads were undetectable by standard tests (less than 50 copies/mL). (None had any history of treatment failure on protease inhibitors.) Participants were randomised to either continue treatment unchanged, or to stop their “nukes” and continue on Kaletra alone. After 48 weeks, 95% of the triple-therapy group still had undetectable viral loads, versus 81% of the monotherapy group. Researchers noted “significantly worse adherence” in those whose viral loads rebounded on monotherapy.
Ultra-sensitive analysis
In the new findings, published in the journal AIDS, researchers from the University of Pittsburgh joined members of the original study team to do further analysis. An ultra-sensitive test (a modified Roche Amplicor HIV-1 RNA assay), which could measure viral levels as low as 3 copies/mL, was used on blood samples stored from the original participants. (Where values below 3 copies/mL were observed, analytical methods were used to calculate values between 0 and 3 copies/mL.)
Out of the 42 participants, 37 continued on treatment up to 48 weeks with viral loads below 50 copies/mL. The ultra-sensitive test found that, for these people, viral load levels remained essentially unchanged over the 48 weeks. Measured viral loads, in copies/mL, were as follows:
| Time point | Kaletra only | Triple therapy |
| Beginning | 5.1 | 3.0 |
| Week 4 | 4.5 | 2.9 |
| Week 8 | 3.3 | 2.9 |
| Week 12 | 1.9 | 1.0 |
| Week 24 | 3.7 | 3.6 |
| Week 48 | 2.8 | 1.6 |
There was actually no statistically significant difference between these monotherapy and triple-therapy values, even when people whose treatment “failed” were included in the analysis.
The researchers concluded that “the level of persistent viremia did not change after discontinuing NRTI [nucleoside] therapy in subjects who remained suppressed Kaletra monotherapy as a standard treatment option, they stated that “continued use of NRTI may prove to be unnecessary in 80 – 90% of patients after successful induction therapy”, and that “cautious evaluation” and “careful identification of appropriate patients for this strategy” is warranted.
References:
McKinnon J et al. The level of persistent HIV viremia does not increase after successful simplification of maintenance therapy to lopinavir/ritonavir alone. AIDS. 20: 2331-2335, 2006.
Arribas J et al. Lopinavir/ritonavir as single-drug therapy for maintenance of HIV-1 viral suppression: 48-week results of a randomized, controlled, open-label, proof-of-concept pilot trial (OK study). J Acquir Immune Defic Syndr. 40: 280-287, 2005.