Kaletra monotherapy - more encouraging results

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HIV-positive patients who have suppressed their HIV viral load to undetectable levels for at least six months using traditional potent HIV therapy can safely and effectively switch to Kaletra (lopinavir/ritonavir) monotherapy and maintain undetectable viral load in the longer term, according to interim results from the KalMo study presented to the Sixteenth International AIDS Conference in Toronto on Tuesday August 15th. The study randomised patients who had achieved an undetectable viral load, and had no previous virological failure, to either continue with their multi-drug therapy or to switch to Kaletra monotherapy. After 48 weeks patients in both arms of the study had similar outcomes and, importantly, those taking Kaletra monotherapy did not have a higher risk of experiencing virological failure.

Although antiretroviral therapy can mean a longer and healthier life, it is expensive and can cause long-term side-effects. There is therefore interest in developing simplified anti-HIV treatment regimens that involve exposure to fewer antiretroviral drugs. A possible candidate for this treatment approach is the boosted protease inhibitor Kaletra as it is potent and has a high genetic barrier against the emergence of drug-resistant HIV.

The KalMo study is a 96-week open-label, randomised study that includes HIV-positive individuals who achieved a viral load below 80 copies/ml using conventional multi-drug anti-HIV treatment and have no previous virological failure. The study is being carried out at two centres in Brazil. The study recruited patients with CD4 cell counts above 200 cells/mm3 who had achieved viral load suppression on triple combination therapy for at least six months.

Glossary

monotherapy

Taking a drug on its own, rather than in combination with other drugs.

nucleoside

A precursor to a building block of DNA or RNA. Nucleosides must be chemically changed into nucleotides before they can be used to make DNA or RNA. 

diarrhoea

Abnormal bowel movements, characterised by loose, watery or frequent stools, three or more times a day.

virological suppression

Halting of the function or replication of a virus. In HIV, optimal viral suppression is measured as the reduction of viral load (HIV RNA) to undetectable levels and is the goal of antiretroviral therapy.

boosting agent

Booster drugs are used to ‘boost’ the effects of protease inhibitors and some other antiretrovirals. Adding a small dose of a booster drug to an antiretroviral makes the liver break down the primary drug more slowly, which means that it stays in the body for longer times or at higher levels. Without the boosting agent, the prescribed dose of the primary drug would be ineffective.

Participants were randomised to either continue with multi-drug therapy or to switch to Kaletra monotherapy. Interim data results based on 48-week data were presented to the Toronto conference.

A total of 60 patients were enrolled to the study, with patients in each arm being comparable at baseline. Only one patient was taking Kaletra prior to randomisation. Nineteen patients who were randomised to Kaletra had been taking an non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen previously. Participants had high CD4 cell counts (552 cells/mm3 in the Kaletra arm, 514 in the continued multi-drug arm), and had been taking antiretroviral therapy for approximately three and a half years.

At week 48, by intent-to-treat, non-completer equals failure analysis, 86% (26/30) of patients in the monotherapy arm had a viral load below 80 copies/ml compared to 83% (25/30) in the multi-drug treatment arm. This difference was not statistically significant. There was one virological failure (defined as a rebound of viral load above 1000 copies/ml) in each arm. The individual with virological failure in the monotherapy arm subsequently had their viral load re-suppressed to below 80 copies/ml after their therapy was intensified by the addition of 3TC (lamivudine, Epivir) and tenofovir (Viread). No resistance mutations were detected in either patient. A second patient in the Kaletra arm experienced a viral load blip above 80 copies/ml, but the patient's viral subsequently fell back below 80 copies without any change in treatment.

There were no significant differences at week 48 between the two arms with regard to CD4 cell count, blood lipids, and body shape change. No serious laboratory abnormalities were observed in either arm of the study. However, one patient in the monotherapy arm withdrew from the study because of diarrhoea (a recognised side-effect of Kaletra), and two individuals in the multi-drug arm changed therapy because of side-effects. Sixty-six per cent of patients in the Kaletra arm reported mild to moderate diarrhoea compared to 16% in the continued multi-drug arm. Five treatment modifications took place in the continued HAART arm due to nucleoside analogue toxicities such as peripheral neuropathy.

“Switching from various triple antiretroviral regimens to lopinavir/ritonavir monotherapy in patients who were virologically suppressed and without a history of previous virologic failure, was effective, safe and well tolerated through 48 weeks”, conclude the investigators.

References

Nunes EP et al. 48-week efficacy and safety results of simplification to single agent lopinavir/ritonavir regimen in patients suppressed below 80 copies/ml on HAART - the KalMo study. Sixteenth International AIDS Conference, Toronto, abstract TuAb0103, 2006.