Mechanisms of Lipid Elevations Associated With the Treatment of Patients With HIV Infection

Peter J. Piliero, MD

In This Article

PI-Related Lipid and Other Metabolic Abnormalities in HIV-Infected Patients

The syndrome of lipodystrophy that occurs in PI-treated patients was initially described in 1997. Although apparently multifactorial and not unique to the PI-treated population, this syndrome is particularly common in these patients.[17,18,19] Characteristics of HIV-associated lipodystrophy include fat loss in the cheeks and temples and an abnormal redistribution of fat from the periphery to the neck, upper back ("buffalo hump"), breasts (in women), chest, and visceral abdomen, as well as over the mastoid processes.[17] The reported prevalence of this syndrome varies, as its definition is not standardized. A study of 148 HIV-infected men and 47 healthy men identified lipodystrophy in 64% (74/116) of the PI-treated patients and only 3% (1/32) of the PI-naive patients (P = .0001).[20] Onset of lipodystrophy has been associated with all of the currently available PIs and has been reported to occur after a median of 10 months of therapy.[21,22]

Hypertriglyceridemia is the principal feature of PI-associated dyslipidemia. Increases in TC levels are significant but usually less marked.[23] Although the hypertriglyceridemia is usually moderate, the elevations in TG can be substantial, reportedly rising as high as 5957 mg/dL (67.25 mmol/L).[24] PI-associated dyslipidemia was first observed with ritonavir and has since been seen with all other current PIs.[22,25,26,27] In a phase 2 study of ritonavir, TG levels increased 200% to 300%, whereas TC levels rose to 30% to 40% above baseline levels. Hypertriglyceridemia and hypercholesterolemia persisted throughout the 32-week trial.[28] In patients treated with a combination of saquinavir and ritonavir, PI therapy-related dyslipidemia developed within 2 weeks, with TG levels peaking after 4 weeks.[29] Other PI-induced lipid abnormalities include an increase in the ratio of TC to high-density lipoprotein (HDL) cholesterol. Since the dyslipidemia in patients treated with PI-containing HAART regimens is more pronounced in women, it may partially negate the atheroprotective effects of female gender.[30]

Patients treated with PIs may also develop insulin resistance.[21] The relationship between PI therapy and glucose metabolism was studied in a cross-sectional controlled study of HIV-infected patients.[31] Compared with PI-naive patients, PI-treated patients had significantly decreased insulin sensitivity on insulin tolerance testing (P < .001), and 54% also had abnormal glucose tolerance. Results showed peripheral insulin resistance in all PI-treated patients with impaired oral glucose tolerance or diabetes-defining oral glucose tolerance test results, as well as in approximately one third of PI-treated patients having normal glucose tolerance. Insulin sensitivity was normal in all of the PI-naive patients.