Kaletra "Monotherapy" Safe and Efficacious for Treatment-Naive Patients

This was the first presentation of prospective data on Kaletra (LPV/r, lopinavir/ritonavir) alone for the treatment of HIV infection. Kaletra monotherapy for HIV infection is probably not even on the radar screen of most HIV physicians. For years, monotherapy for HIV infection has been considered to be the nexus of antiretroviral evil. This bold new study from Dr. Joseph Gathe suggests that in the case of highly potent Kaletra, monotherapy may be enough.

But is this really monotherapy? LPV/r is a combination of low-dose ritonavir and standard-dose lopinavir. These two agents are co-formulated, but the plasma levels of ritonavir are below the range considered to be adequate for antiretroviral activity. Thus, in treatment guidelines, it is considered to be one agent and typically combined with two nucleoside reverse transcriptase inhibitors (NRTIs). This study suggests that perhaps LPV/r alone will do the trick and the NRTIs may be spared.

This current study was based on an observation from one of the early phase II studies of LPV/r in which some patients received three weeks of LPV/r monotherapy. It was noted that in these patients the decay in HIV-RNA levels was rapid and no different from the patients who received LPV/r and two NRTIs.

This pilot study enrolled 30 antiretroviral treatment-naive patients (28 male, two female) with a mean CD4 count of 169 cells/mcL and a mean HIV-RNA of 262,020 copies/mL. They were treated with LPV/r three capsules BID (four capsules BID for a weight > 70 kg).

Of the 30 patients, by week 24, eight had dropped out of the study. The reasons for discontinuation are shown below:

Lost to follow-up2
Adverse events2
Non adherence1
Hepatitis B1
Virologic failure1

Remarkably, 21 of the 22 patients who reached week 24 of the follow-up were noted to have a HIV-RNA <400 copies/mL. The one patient with virologic failure had a HIV-RNA level of 1,510 copies/mL at week 24. Genotypic resistance testing showed the L63P protease mutation and the phenotype showed wild type virus. Although not reported on the poster, Dr. Gathe indicated that about 50 percent of the patients had HIV-RNA levels <50 copies/mL.

The mean CD4 count increase at week 24 was 219 cells/mcL. Overall, adverse effects were minimal and treatment was well tolerated.

These are not the only data with boosted protease inhibitor (PI) "monotherapy" for the treatment of HIV infection. There was a presentation at the Paris IAS meeting of boosted indinavir (IDV, Crixivan) alone for HIV (click here for a summary of that presentation). In that study, patients on indinavir/r-based therapy with undetectable plasma HIV-RNA had the NRTIs stopped and continued to demonstrate control of HIV replication out to 48 weeks.

This pilot study of LPV/r monotherapy in treatment-naive patients showed very impressive results for a treatment strategy that, at first blush, sounds improbable. There was tremendous interest in this poster at the meeting, with a standing room only flock of attendees surrounding Dr. Gathe and his poster.

The use of a streamlined regimen with a boosted PI alone would offer the promise of more affordable therapy. There would also be less risk of toxicity by avoiding NRTIs altogether. If this novel approach for the treatment of HIV infection is validated by additional studies, it has the potential to transform HIV treatment as we know it today.

Read the poster of the abstract covered in this article.