Once-daily Kaletra as safe and effective as twice-daily dosing

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Lopinavir/ritonavir (Kaletra) taken once-daily as part of a combination antiretroviral regimen worked as well as the approved twice-daily dose in previously treated patients but led to better adherence, researchers reported on Tuesday at the Fifth International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention in Cape Town, South Africa.

Past studies have shown that once-daily and twice-daily Kaletra work equally well in people starting treatment for the first time. Study M06-802 was designed to see whether this was also the case for treatment-experienced patients. There had been previous concerns that once-daily Kaletra might be less effective in treatment-experienced patients.

The study included 599 patients currently taking antiretroviral therapy with a viral load above 1000 copies/ml. There were no significant baseline demographic differences between patients in the two arms of the study. About one-third were women, and whites, blacks, and Hispanics were all well represented in this international trial.

Glossary

treatment-experienced

A person who has previously taken treatment for a condition. Treatment-experienced people may have taken several different regimens before and may have a strain of HIV that is resistant to multiple drug classes.

tolerability

Term used to indicate how well a particular drug is tolerated when taken by people at the usual dosage. Good tolerability means that drug side-effects do not cause people to stop using the drug.

non-inferiority trial

A clinical trial which aims to demonstrate that a new treatment is not worse than another. While the two drugs may have comparable results in terms of virological response, the new drug may have fewer side-effects, be cheaper or have other advantages. 

nucleotide reverse transcriptase inhibitor

Family of antiretrovirals which includes tenofovir disoproxil and tenofovir alafenamide. It may be abbreviated to NtRTI or NRTI. It is often said that nucleotide reverse transcriptase inhibitors work in a similar way to nucleoside reverse transcriptase inhibitors, but approach from a different angle.

nucleotide

A building block of DNA or RNA, chemical structures that store genetic information. 

At the time of randomisation, median HIV viral load was about 4000 copies/ml and median CD4 cell count was 254 cells/mm3. Resistance tests showed that the patients had an average of one major mutation conferring resistance to protease inhibitors.

Participants were randomly assigned in equal numbers to take either a once-daily dose of Kaletra (800 mg of lopinavir plus 200 mg of ritonavir) or twice-daily doses of the drug (400 mg of lopinavir 100 mg ritonavir).

Both groups took Kaletra in combination with two nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), which were selected according to the patient’s treatment history and resistance profile.

After 48 weeks of treatment, 55% of patients taking once-daily Kaletra had an undetectable viral load below 50 copies/ml, compared with 52% of those taking the twice-daily dose. This indicated that once-daily Kaletra was non-inferior to twice-daily dosing in previously treated patients.

When the researchers looked at the data in different waysfor example, either including or excluding participants who stopped treatment earlythe effectiveness of once-daily and twice-daily dosing remained similar. Both regimens worked similarly in patients with more HIV drug-resistance mutations.

The researchers found that CD4 cell count increases were also comparable, 135 cells/mm3 in the once-daily group vs. 122 cells/mm3 in the twice-daily group.

Participants received Kaletra in pill bottles with electronic caps that allowed the investigators to determine whether patients took their medication as prescribed. Taking the drug once-daily was associated with significantly better adherence than twice-daily dosing.

Overall, the once-daily and twice-daily Kaletra doses were similarly well tolerated. Comparable proportions of participants (78%) in both arms completed the study, and most drop-outs were due to reasons other than adverse events. Side effects led 5% of patients taking the once-daily dose and 7% of those taking twice-daily doses to withdraw from the study.

About one-quarter of participants in both groups experienced side-effects. The most commonly reported Kaletra-associated side-effects were diarrhoea (14% in the once-daily arm vs. 11% in the twice-daily arm) and nausea (3% vs. 7%, respectively). Similar proportions in both groups had elevated cholesterol (about 7%) and triglycerides (about 5%).

The investigators concluded that once-daily and twice-daily Kaletra had similar efficacy and tolerability in treated-experienced patients, but the less frequent dose led to better adherence.

Further information

A powerpoint presentation by Sharlaa Badal-Faesen and a webcast of the conference session in which it was presented are available on the IAS 2009 website.