Metabolic complications, including dyslipidemias, continue to be a challenging aspect of the daily care of HIV-infected patients. Even before the initiation of therapy, significant effects on total cholesterol (TC) and triglycerides (TG) are seen in most HIV-infected patients.

Today, we know that with chronic HIV disease and no therapy, TC usually decreases and TG usually become elevated. On the other hand, therapy with several antiretrovirals of most classes have resulted in different and complex dyslipidemias.

Protease inhibitors (PIs) have been associated with increases in TC, TG and LDL cholesterol (LDL-C), but with little impact on HDL cholesterol (HDL-C). Recently, several studies conducted with different PIs have found that these lipid level alterations observed when the PI class is used are different depending on which PI is used.

APV 30002 (better known as the SOLO trial) was one of the registrational studies for fosamprenavir (FPV, 908, Lexiva, Telzir). In this study, antiretroviral-naive patients were randomized to receive once-daily fosamprenavir boosted with ritonavir (RTV, Norvir) or twice-daily nelfinavir (NFV, Viracept), both in combination with abacavir (ABC, Ziagen) and lamivudine (3TC, Epivir). Substantial increases in HDL-C were observed at 48 weeks of therapy.

Based on these results, Dr. Jeffrey Nadler, from the University of South Florida in Tampa, Fla., evaluated the lipid parameters observed in his previously presented trial, APV 30001 (the NEAT study). This was also a registrational study conducted in naive patients, in which 249 subjects were randomized to receive unboosted fosamprenavir or nelfinavir, both taken twice-daily in combination with abacavir and lamivudine.

For the NEAT study, fasting samples were collected at baseline and at weeks 8, 16, 24 and 48. Fasting lipid measurements were based on the intent-to-treat observed population at each time point and compared to the National Cholesterol Education Program (NCEP)'s clinical guidelines for cholesterol. The mean fasting lipid values were similar between the fosamprenavir and nelfinavir groups, with relatively low mean HDL-C at baseline. By week 8 the fosamprenavir twice-daily arm showed greater increases in HDL-C than the nelfinavir twice-daily arm. This trend continued over the 48-week course of the study.

The changes in TC/HDL-C ratio were minimal between baseline and week 48 for fosamprenavir (-1%) and mildly elevated for nelfinavir (+12%). On the other hand, there were no significant differences in the LDL-C parameters between the 2 arms of this study at 48 weeks. Similarly, the increases in TC were similar between both groups.

Dr. Nadler concludes that the fosamprenavir group had a favorable 37% increase in mean change in HDL-C compared with a mean change of 22% in the nelfinavir arm. There was also an increasing number of patients experiencing a normalization of HDL-C within the fosamprenavir twice-daily arm compared to the nelfinavir twice-daily arm over 48 weeks. So, in general, the patients taking fosamprenavir in this study had minimal changes in their TG and TC/HDL-C ratio, and had a favorable increase in their HDL-C levels.

This is an interesting observation, in my opinion, given the fact that HDL-C is considered an independent risk factor for the development of coronary heart disease. According to the NCEP guidelines, an increase in HDL-C over 60 mg/dL is considered a "negative risk," which means that its presence removes 1 risk factor from the total risk factor count.

So, over the long term, treatment with fosamprenavir (either unboosted, as it was in this analysis, or boosted, as it was in the previous analysis) may have a beneficial impact on HDL-C, which could potentially result in decreasing patients' risk factors for coronary artery disease. Unfortunately, though, the short-term (48-week) impact appears modest. The immediate clinical relevance is also called into question by the fact that the proportion of patients who received any lipid-lowering agent during the course of this study was the same for both the fosamprenavir and nelfinavir groups.