Impact of antiretroviral therapy (ART), immunosuppression and viraemia on lipid levels: the D:A:D study
Authors: Kamara D , Sabin C , Reiss P , Rickenbach M , Smith C , De Wit S , Law M , Mocroft A , Pradier C , Lundgren J 
Published: November 2012

Purpose of the study

To investigate the impact of ART, HIV viremia and immunosuppression on triglyceride (TG), total cholesterol (TC) and high density lipoprotein cholesterol (HDL‐C) levels.

Methods

We considered the cross‐sectional associations between TG, TC and HDL‐C (mmol/l; first available measurement on/after enrolment in the D:A:D study) and use of ART, HIV viral load (VL; copies/ml), and CD4 count (cells/mm3) measured at the same time. TG was log10 transformed to ensure normality. Analyses were performed using linear regression and adjusted for other factors known to impact lipid levels (table footnote). ART and VL status were combined (off ART&VL >100,000, off ART&VL <100,000, on ART&VL <500, on ART&VL >500), current and nadir CD4 count were categorised as <200, 200–349, 350–499 and >500.

Summary of results

44,322/49,734 participants in the D:A:D Study (89.1%) contributed a TG measurement (median; IQR 1.52; 1.00–2.45), 45,169 (90.8%) a TC measurement (4.80; 4.00–5.70) and 38,604 (77.6%) a HDL‐C measurement (1.12; 0.90–1.40). Most participants were male (74%), of white ethnicity (51%), without AIDS (78%), were not receiving lipid‐lowering drugs (4%) and were ART experienced (61%) with 47% previously exposed to PIs, 61% previously exposed to NRTIs and 29% previously exposed to NNRTIs. The median (IQR) age, current CD4 count and CD4 nadir were 38 (36–45) years, 400 (242–590) cells/µl and 240 (100–410) cells/µl respectively. Compared to those on ART with a suppressed VL, all lipids were lower for those off ART (Table); non‐suppressive ART was also associated with lower TC and HDL‐C levels (no impact on TG). A low current CD4 count was associated with lower lipid levels, whereas a low nadir CD4 count was associated with higher TC and TG levels. Prior AIDS diagnosis was associated with higher TG and TC, but lower HDL‐C levels.

Impact of ART, immunosuppression and viraemia, on TG, TC and HDL‐C (mmol/l)

Average impact on log10TG*†

Average inpact on TC*
Average impact on HDL‐C*

ART and VL

Off ART … VL≥100000
−0.09 (−0.10,−0.08)
<0.001
−0.55 (−0.60,−0.51)
<0.001
−0.14 (−0.16,−0.13)
<0.001

Off ART … VL<100000
−0.04 (−0.06,−0.03)
<0.001
−0.85 (−0.91,−0.78)
<0.001
−0.31 (−0.33,−0.29)
<0.001

On ART … VL<500
Ref

Ref

Ref

On ART … VL≥500
0.00 (−0.01, 0.00)
0.38
−0.40 (−0.44,−0.36)
<0.001
−0.16 (−0.17,−0.15)
<0.001

CD4 count

<200
−0.03 (−0.04,−0.02)
<0.001
−0.33 (−0.39,−0.28)
<0.001
−0.04 (−0.06,−0.02)
<0.001

200–349
−0.02 (−0.03,−0.01)
<0.001
−0.11 (−0.15,−0.06)
<0.001
0.00 (−0.01, 0.02)
0.72

350–499
Ref

Ref

Ref

500+
0.04 (0.03, 0.04)
<0.001
0.12 (0.08, 0.16)
<0.001
−0.02 (−0.03,−0.00)
0.02

Nadir CD4 Count

<200
0.07 (0.06, 0.08)
<0.001
0.19 (0.14, 0.24)
<0.001
−0.05 (−0.06,−0.03)
<0.001

200–349
0.02 (0.01, 0.03)
<0.001
0.01 (−0.03, 0.06)
0.57
−0.03 (−0.05,−0.02)
<0.001

350–499
Ref

Ref

Ref

500 +
0.00 (−0.02, 0.01)
0.33
0.03 (−0.02, 0.09)
0.23
0.04 (0.02, 0.06)
<0.001

Prior AIDS
0.05 (0.05, 0.06)
<0.001
0.11 (0.08, 0.15)
<0.001
−0.03 (−0.04,−0.01)
<0.001

estimates included are mutually adjusted for each other and for the following demographic variables: age; gender; mode of infection; ethnicity; body mass index; smoking; family history of CVD; diabetes; use of lipid lowering drugs; co‐infection with hepatitis C; participating cohort; and year of entry into study.

TG is log10 transformed. Thus, the results presented for TG reflect relative rather than absolute effects. For example, lipid levels for those off ART … VL ≥100000 are 9% lower than those on ART … VL < 500.

Conclusion

Although specific drug classes were not considered, lipid levels are considerably higher in those on a suppressive ART regimen. The higher TC/TG and lower HDL‐C levels seen among those with low nadir CD4 count and with a prior AIDS diagnosis suggests severe immunosuppression may be associated with dyslipidaemia over the long‐term.