Longitudinal analysis of the associations between antiretroviral therapy, viraemia and immunosuppression with lipid levels: the D:A:D study.
Antiretroviral (ART) drugs have been associated with higher triglycerides (TG), higher total cholesterol (TC) and lower high-density lipoprotein cholesterol (HDL-C) levels. Associations between lipid levels with HIV viraemia and immunosuppression in the presence of ART remain unclear.



Participants from the D:A:D study with at least one TG/TC/HDL-C measurement were included. Linear mixed effect models were used to determine the association of ART, viral load (VL), nadir and current CD4+T-cell count and previous AIDS diagnosis with lipids.



Of 49,717 participants, 90%, 92% and 80% contributed at least one TG/TC/HDL-C measurement (median follow-up 6.8, 6.8 and 5.0 years, respectively). Predicted mean (95% CI) baseline levels for TG, TC and HDL-C (mmol/l), were 2.10 (2.05, 2.14), 4.94 (4.91, 4.98) and 1.08 (1.07, 1.10), respectively. Lopinavir was associated with the worst TG profile, (27.2% higher levels compared to atazanavir; 95% CI 25.2%, 29.2%), and darunavir had a similar profile as atazanavir. The nucleoside pair lamivudine/tenofovir was associated with the most favourable TG profile (-2.8%; -3.5%, -2.0%) compared with emtricitabine/tenofovir, whereas lamivudine/abacavir (+10.2%; +9.3%, +11.2%) and lamivudine/stavudine (+8.0%; +6.9%, +9.0%), were associated with the worst. Raltegravir was associated with lower TG (-5.2%; -6.4%, -3.9%), and nevirapine had a more favourable HDL-C profile (+11.3%; +10.8%, +11.7%) than efavirenz (+5.3%; 5.0%, 5.7%), compared to atazanavir. Higher VLs were associated with lower TG/TC/HDL-C, whereas higher CD4+T-cell counts were associated with higher TG/TC/HDL-C.



TG, TC and HDL-C levels, which generally improved over time, are dependent on ART, viraemia and, to a lesser extent, immunosuppression.
Research Department of Infection and Population Health, UCL, London, UK.
David A
DA
Kamara
Research Department of Infection and Population Health, UCL, London, UK.
Colette
C
Smith
CHIP, Department of Infectious Diseases, Section 2100, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Lene
L
Ryom
Division of Infectious Diseases, Department of Global Health, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
Peter
P
Reiss
Institute of Social and Preventive Medicine, University of Lausanne, Lausanne, Switzerland.
Martin
M
Rickenbach
Research Department of Infection and Population Health, UCL, London, UK.
Andrew
A
Phillips
Research Department of Infection and Population Health, UCL, London, UK.
Amanda
A
Mocroft
Department of Infectious Diseases, CHU St Pierre Hospital, Brussels, Belgium.
Stephan
S
De Wit
The Kirby Institute for Infection and Immunity in Society, University of New South Wales, Sydney, Australia.
Matthew
M
Law
Department of Health Sciences, San Paolo University Hospital, Milan, Italy.
Antonella d'Arminio
AD
Monforte
University of Bordeaux, ISPED, Centre Inserm U0897-Epidemiologie-Biostatistique, Bordeaux, France.
Francois
F
Dabis
Department of Public Health, Nice University Hospital, Nice, France.
Christian
C
Pradier
CHIP, Department of Infectious Diseases, Section 2100, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Jens D
JD
Lundgren
Research Department of Infection and Population Health, UCL, London, UK.
Caroline
C
Sabin
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000097:blood* / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D007108:Immune Tolerance; D016014:Linear Models; D008055:Lipids / Q000097:blood*; D008137:Longitudinal Studies; D008297:Male; D011446:Prospective Studies; D013997:Time Factors; D014280:Triglycerides / Q000097:blood; D019562:Viral Load; D014766:Viremia / Q000097:blood / Q000188:drug therapy / Q000821:virology
D019380:Anti-HIV Agents; D008076:Cholesterol, HDL; D008055:Lipids; D014280:Triglycerides; D002784:Cholesterol