March 20, 2002
A common side effect of some highly active antiretroviral therapy (HAART) regimens, particularly those containing protease inhibitors, is the development of higher-than-normal levels of lipids -- cholesterol and triglycerides -- in the blood. Increased levels of lipids could raise the risk of developing cardiovascular disease as well as diabetes. To compare the effect of different HAART regimens on lipid levels and other side effects, researchers at GlaxoSmithKline and elsewhere conducted a study of the following regimens:
Researchers enrolled 258 HIV-positive subjects who did not have diabetes. Before entering the study none of the subjects had previously used anti-HIV drugs. Subjects had the following profile before they began to use the study drugs:
Subjects were monitored for about one year.
Between 39% to 48% of subjects achieved viral loads below the 50 copy mark. The differences in viral load changes between the three study groups was not statistically significant. In general, subjects gained about 150 extra CD4+ cells during the study. Again, there were no significant differences in CD4+ cell increases between the three regimens.
In general, lipid levels remained lowest among those subjects who used three nukes (NRTIs) -- Combivir with abacavir -- than in those who used protease-inhibitor-containing regimens. It is noteworthy that subjects who used d4T were significantly more likely to develop increased levels of lipids than subjects who did not use this nuke.
Nausea was more common among abacavir users and diarrhea was more common among nelfinavir users.
Throughout the study, technicians analyzed blood samples from subjects to measure levels of lactate (lactic acid). This is because higher-than-normal levels of lactate suggests damage to the energy-producing parts of cells called mitochondria. People with high lactate levels may develop the following:
On average, lactate levels were highest in subjects using the nuke d4T than in those who did not use this drug.
The results of the study suggest that over a period of about one year, a combination of AZT, 3TC and abacavir is as beneficial as a protease-containing regimen in HIV-positive people who have never previously used HAART. Moreover, the abacavir combination is significantly less likely to alter lipid levels than a PI-containing combination. Although the study used Combivir and abacavir, all three drugs are available in one tablet sold under the brand name Trizivir. The study is ongoing and further results may be available next year. GlaxoSmithKline and the researchers should be praised for recruiting such a large proportion of women in an HIV/AIDS study.