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^[3][4][5][6]. These lipid changes are mild in the majority of patients and only rarely lead to treatment discontinuation^[7][8]. 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^[9]. The low-dose ritonavir, rather than the lopinavir in Kaletra drives the increases in blood cholesterol and triglyceride levels^[10]. Kaletra is also associated with insulin resistance and the development of type II diabetes^[11]. For more details, see Body fat and metabolic changes whilst on treatment.

The other key side-effect associated with Kaletra is elevated liver enzyme levels, which occurs most commonly among individuals coinfected with hepatitis B or C^[12][13][14]. 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^[15]. 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^[16].