Important note: Information in this article was accurate in November 2000. The state of the art may have changed since the publication date.
The product Kaletra, also known as ABT-378/r or lopinavir, is a combination of two protease inhibitors: lopinavir with a small amount of ritonavir (Norvir). The purpose of ritonavir is to boost levels of lopinavir to very high levels. Hopefully these high levels of lopinavir will make it difficult for HIV to develop drug resistance. Since the amount of ritonavir used with lopinavir is small, ritonavir does not have any significant anti-HIV activity in this formulation.
Reports from several doctors suggest that combination therapy that includes lopinavir has helped their patients with AIDS recover from hard-to-treat infections and gain weight. The manufacturer of lopinavir, Abbott Laboratories, recently released results from experiments on 100 HIV+ people who did not have AIDS. Used in combination with the nucleoside analogues (nukes) 3TC and d4T, lopinavir caused CD4+ counts to rise by more than 200 cells after one year. As well, viral load fell below the 50 copy mark in 75% of subjects given the standard dose of lopinavir along with 3TC and d4T. These improvements were sustained for at least one year.
Common side effects associated with lopinavir combination therapy included the following:
As well, some subjects had higher-than-normal levels of fatty substances (lipids) in their blood. In other studies of lopinavir, some subjects developed painfully swollen pancreas glands, a complication called pancreatitis.
Long-term studies are needed to find out if lopinavir is associated with an increased risk of developing cardiovascular disease, diabetes, thinning bones and other potential complications of anti-HIV therapy.
Lopinavir can be stored at room temperature if used up within two months. This product is to be taken with meals twice daily, usually every 12 hours in combination with other anti-HIV drugs. Since lopinavir contains ritonavir, drug interactions may be similar to those seen with ritonavir.
Researchers enrolled 100 subjects (4 female, 96 male) who, on average, had the following profile at the start of the study:
It is important to note that no subject had used anti-HIV drugs before entering this study. Eleven subjects tested positive for hepatitis B or C virus. The researchers divided subjects into smaller groups and gave them different doses of lopinavir in combination with ritonavir as well as the two nukes 3TC and d4T.
Over the course of the study, all doses of lopinavir seemed equally effective at suppressing viral load. In general, combination therapy was able to reduce viral load below the 50 copy mark in at least 80% of subjects. No dose was associated with an increased risk of virologic failure, that is, a viral load above the 400 copy mark.
On average, there were large increases detected in CD4+ cell counts. Nearly one year after the study began, CD4+ counts rose, on average, by more than 200 cells.
The most common side effects included the following:
As lopinavir is a relatively new drug, its long-term side effects when used in combination therapy are not clear at this time. Since lopinavir can increase levels of fatty substances in the blood, the drug has the potential to increase the risk of cardiovascular disease in some people.
Increased liver enzyme levels in the blood were detected in some subjects - most of whom were also infected with hepatitis B and/or C viruses. The researchers stated that liver enzyme levels returned to their pre-study levels with continued use of lopinavir.
1. Murphy RL, Brun S, Hicks C, et al. ABT-378/ritonavir plus stavudine and lamivudine for the treatment of antiretroviral-naive adults with HIV-1 infection: 48 week results. AIDS 2001 Jan 5;15(1):F1-9
2. Anonymous. Abbott Laboratories gains FDA approval for HIV treatment Kaletra (lopinavir/ritonavir), formerly known as ABT-378/r. Press release. September 15, 2000.
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