Kaletra effective and well tolerated in PI-experienced patients

Ritonavir-boosed lopinavir (Kaletra) is an effective and well tolerated option for patients who have failed one protease inhibitor, according to findings presented this week at the Seventh International Congress on Drug Therapy in HIV Infection in Glasgow.

The Phase III M98-888 study was designed to confirm the efficacy and safety of Kaletra in patients who had experienced failure of a single protease inhibitor-containing drug regimen, but who had not been exposed to non-nucleoside reverse transcriptase inhibitors (NNRTIs).

Two hundred and eighty-eight patients were randomised to receive Kaletra (400mg lopinavir with 100mg ritonavir) twice daily, or to receive protease inhibitors selected by the investigators on the basis of previous drug exposure. Most of the patients had failed a nelfinavir (Viracept) or indinavir (Crixivan)-containing regimen.

As the study was begun in 1999, before the use of low-dose ritonavir (Norvir) to boost protease inhibitor concentrations, the control arm included any single protease inhibitor, a combination of high-dose ritonavir (400mg) with either saquinavir (Invirase) 400mg or indinavir 400mg, or nelfinavir 1250mg with saquinavir 1200mg. Patients in both arms also received nevirapine (Viramune) and two nucleoside reverse transcriptase inhibitors.

After 48 weeks, fewer patients had discontinued treatment in the Kaletra arm than in the control group (24 vs. 43%, p Kaletra arm had viral loads below 400 copies/ml (57 vs. 33%, p 3).

Patients in the Kaletra arm also experienced fewer adverse events than the control patients (5 vs. 12%, p = 0.032). These were mainly gastrointestinal: nausea (7 vs. 16%, p = 0.015) and vomiting (4 vs. 12%, p = 0.016) were both less common in the Kaletra group. However, diarrhoea, and elevations in cholesterol and triglycerides were similar in both groups.

Dr Richard Pollard, presenting, admitted that patients with single protease inhibitor failure but who have never taken an NNRTI would be rare, given current treatment guidelines. Today, NNRTIs or ritonavir-boosted protease inhibitors such as Kaletra are commonly used in first-line anti-HIV therapy.

Similarly, the protease inhibitor combinations chosen for use in the control arm are unlikely to be used today, due to shifts in prescribing recommendations. Nevertheless, these results indicate a possible strong position for Kaletra in antiretroviral regimen sequencing.

Kaletra’s powerful position was also demonstrated in a poster presentation demonstrating the drug’s efficacy after six years of therapy. One hundred patients in the M97-720 study started therapy with a combination of Kaletra, d4T (stavudine, Zerit) and 3TC (lamivudine, Epivir). At the six-year mark, 62% of these patients had viral loads below 50 copies/ml, with a mean CD4 cell count increase of 529 cells/mm³ (Gulick 2004).

Kaletra's manufacturer Abbott Laboratories was recently asked by the US Food and Drug Administration to stop publishing adverts for the product which ask the question: "Where do you see yourself in 5 years?". The FDA pointed out that Kaletra has been licensed for use in the US on the basis of trials lasting no longer than 72 weeks. "These promotional pieces overstate the effectiveness of Kaletra and omit [..] material information about the risks associated with Kaletra in the treatment of HIV infection," the FDA told Abbott.