Long-term LDL-cholesterol trajectories in virologically suppressed HIV patients: effect of liver fibrosis and statin use.

Background: HIV infection and initiation of highly active antiretroviral therapy (HAART) alter low-density lipoprotein- cholesterol (LDL-c). HIV infection is also associated with increased incidence and progression of liver fibrosis even in the absence of hepatitis C (HCV) co-infection. However, it is unclear whether liver fibrosis modifies LDL-c serum levels over time and whether the anti-inflammatory effect of statins protects against fibrosis progression.

Methods: We used the US VA HIV Clinical Case Registry to generate a medication exposure model for HAART and statins. We identified all HCV-negative patients who initiated HAART after 1/1/2003, and had at least three LDL-c and liver fibrosis index-4 (FIB-4) measurements over time. We selected LDL-c and FIB-4 values recorded during periods of viral suppression (HIV-1 RNA<500 copies/mL) and HAART use ratio >80% (days on HAART/days since HAART initiation). We fit fractional polynomials curves stratified by FIB-4 category and current statin use at the time of LDL-c measurement. We used multilevel linear regression to assess the effect of FIB-4 on LDL-c changes over time adjusting for age, time since HAART initiation, initial LDL-c level, sex, race, statin prescription and CD4 count. We used the same methods to assess the effect statin use ratio quartiles and LDL-c on FIB-4 score changes.

Results: The analysis included 2551 individuals with an average of 8 LDL-c and 5 FIB-4 measurements per person. Overall, LDL-c decreased by 0.7 (0.6, 1.1) mg/dl with each additional year on HAART. Higher FIB-4 (indicating greater likelihood of liver fibrosis) was associated with lower LDL-c over time regardless of statin use (see Figures 1 and 2).  Compared to those with FIB-4<1.45, average LDL-c was 7.9 (5.5-10.4) mg/dL lower in patients with FIB-4>3.25 (advanced fibrosis), and 2.3 (1.4-3.3) mg/dL lower in those with FIB-4 between 1.45-3.25. Statin use ratio was not significantly associated with FIB-4 changes over time regardless of initial LDL-c.

Conclusion: Among HIV-infected patients with suppressed viremia on stable HAART, LDL-c declined over time regardless of statin use and the decline was greater in those with higher liver fibrosis score. FIB-4 score changes did not differ by statin use categories.