The commonest side-effects of Kaletra are diarrhoea and nausea. In the major studies of Kaletra, moderate or severe diarrhoea affected 12 to 27% of participants. Two to 7% of patients interrupted therapy because of diarrhoea, but only 1% of all participants in these trials stopped Kaletra treatment. Diarrhoea and loose stools are most common during the first two months of treatment, but many people experience ongoing problems. Nausea related to lopinavir treatment is also a common reason for interrupting treatment, occurring in 2 to 12% of study participants .
Fatigue, muscle weakness, headache, stomach pain and vomiting are less common side-effects associated with Kaletra in clinical trials.
Body fat changes and metabolic disorders have been associated with the protease inhibitors as a class. After 60 weeks on lopinavir, 7% of HIV-positive individuals in a major international study had developed body fat changes, the same rate of development as seen among people who received nelfinavir (Viracept).1 However in another study, 35% of patients experienced body fat changes after four years on Kaletra. 2
Elevated lipids, including high triglycerides and cholesterol levels, occur amongst 10 to 25% of people on Kaletra, particularly among those with high cholesterol or triglycerides before starting to take the drug.2 3 4 5
These lipid changes are mild in the majority of patients and only rarely lead to treatment discontinuation.6 7 There seems to be no correlation between blood concentrations of lopinavir and the severity of lipid elevations, suggesting that dose reductions are unlikely to moderate lipid increases.8 The low-dose ritonavir, rather than the lopinavir in Kaletra drives the increases in blood cholesterol and triglyceride levels.9 Kaletra is also associated with insulin resistance and the development of type II diabetes.10 For more details, see Metabolic changes while on ART.
The other key side-effect associated with Kaletra is elevated liver enzyme levels, which occurs most commonly among individuals co-infected with hepatitis B or C.2 11 12 As observed for lipid elevations, liver toxicity does not seem to be related to the levels of lopinavir in the blood, suggesting that dose adjustments are unlikely to be of benefit.13 However, liver problems are rare in patients taking Kaletra, with one study finding an incidence of severe liver abnormalities of less than one per 100 person-years of treatment.14
In ACTG 5142, lipoatrophy (defined as a 20% loss of limb fat at week 96), was experienced by 32% of the efavirenz + 2NRTI group, 17% of the Kaletra + 2 NRTI group, and 9% of the Kaletra/efavirenz group.15
When the incidence of lipoatrophy was analysed according to the second nucleoside analogue used, it was most commonly seen in patients who received d4T, 42% compared to 27% in the AZT group. Just 9% of tenofovir-treated patients developed lipoatrophy, a significantly lower proportion than was found in the AZT recipients.
Compared to EFV, LPV had less lipoatrophy when given with an NRTI. When lipoatrophy incidence was analysed according to pairings of drugs, it was evident that tenofovir recipients who received efavirenz were more likely to develop lipoatrophy (12%) than those who received Kaletra (6%). Similarly, AZT recipients who received efavirenz were also at greater risk of lipoatrophy (40% vs 16% for Kaletra recipients). The difference was less pronounced for d4T recipients (51% for efavirenz, 33% for Kaletra).
After 96 weeks those in the nucleoside-sparing arm had experienced an average 18% gain in limb fat (around 1kg), compared to a 9.8% gain in the Kaletra + 2 NRTIs group and a gain of 1.4% in the efavirenz group.
A surprising result was that the NRTI-sparing regimen (LPV+EFV) increased lipids significantly more than did the EFV+2 NRTIs or LPV+2 NRTIs regimens. Triglyceride increases were also greater in LPV compared to EFV+NRTI regimens, but cholesterol changes were not significantly different.
Triglyceride increases were also greater in LPV compared to EFV+NRTI regimens, but cholesterol elevations between the Kaletra and efavirenz arms were similar. The increase in HDL cholesterol was significantly greater in the Kaletra/efavirenz nucleoside-sparing arm.