Background: Alterations in serum lipids after initiation of highly active antiretroviral therapy (HAART) have been widely reported. Limited data are available to evaluate the relative effect of HIV-1 infection and antiretroviral therapy (ART) on these lipid abnormalities.

Methods: Longitudinal analysis of data and sera from HIV-infected men in the Multicenter AIDS Cohort Study (MACS) were performed to describe changes in serum lipids during the course of HIV-1 infection and during treatment with ART. Mean levels of total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), apolipoprotein A (ApoA), and apolipoprotein B (ApoB) were measured 1) at 5 time-points for 50 men who were HIV-seroconverters (SC) and later initiated HAART (pre-SC, pre-HAART, and 3 time-points post-HAART), and 2) at 2 time-points for 496 seroprevalent (SP) HIV-infected men who initiated either mono-or combination ART (n = 291) and/or HAART (n = 205).

Results: Prior to HIV-1 infection, the mean TC, HDL-C and LDL-C for the 50 SC were similar to NHANES III for adult men. After HIV-infection (mean 7.8 ±2.6 yrs), notable declines in TC (-31 mg/dL, 95% CI: -51, -19), HDL-C (-12 mg/dL, 95% CI: -18, -6), LDL-C (-21 mg/dl, 95% CI: -44, 4) and Apo A (-17 mg/dL, 95% CI: -27, -6) were observed. After approximately 3 yrs of HAART (PI-containing in 48/50), there were large increases in mean serum TC and LDL-C (51 and 21 mg/dl, respectively); however, the mean changes from the pre-SC baseline were 20 (95% CI: -1, 40) and 0 (95% CI: -23, 24) mg/dl, respectively. Mean HDL-C remained below pre-infection baseline levels throughout the post-HAART period. SP men initiating HAART had notably larger increases in TC (28 mg/dl, 95% CI: 23, 28) and LDL-C (15 mg/dl, 95% CI: 11, 18) compared to men initiating mono/combination ART (TC -6 mg/dl, 95% CI: -10, -2; LDL-C -6 mg/dl, 95% CI: -9, -3).

Conclusions: HIV-infection results in reductions in TC, HDL-C, and LDL-C. HAART initiation is associated with increases in TC and LDL-C, but not HDL-C. The increase in TC (20 mg/dl) seen after HAART (11.6 yrs after pre-SC baseline) in our 50 SC men is commensurate with aging (NHANES III). In this cohort, the majority of the increase in TC and LDL-C observed after approximately 3 yrs of HAART appears to represent a return to pre-infection serum lipid levels in combination with an expected increase due to aging; however, longer follow up is needed.