Longitudinal analysis of the associations between antiretroviral therapy, viraemia and immunosuppression with lipid levels: the D:A:D study

David A Kamara; Colette Smith; Lene Ryom; Peter Reiss; Martin Rickenbach; Andrew Phillips; Amanda Mocroft; Stephan De Wit; Matthew Law; Antonella d'Arminio Monforte; Francois Dabis; Christian Pradier; Jens D Lundgren; Caroline Sabin

doi:10.3851/IMP3051

Longitudinal analysis of the associations between antiretroviral therapy, viraemia and immunosuppression with lipid levels: the D:A:D study

David A Kamara, Colette Smith, Lene Ryom, Peter Reiss, Martin Rickenbach, Andrew Phillips, Amanda Mocroft, Stephan De Wit, Matthew Law, Antonella d'Arminio Monforte, Francois Dabis, Christian Pradier, Jens D Lundgren, Caroline Sabin

Department of Immunology and Microbiology

12 Citations (Scopus)

Abstract

Background: 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. Methods: 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. Results: 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 proile, (27.2% higher levels compared to atazanavir; 95% CI 25.2%, 29.2%), and darunavir had a similar proile as atazanavir. The nucleoside pair lamivudine/tenofovir was associated with the most favourable TG proile (-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 proile (+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. Conclusions: TG, TC and HDL-C levels, which generally improved over time, are dependent on ART, viraemia and, to a lesser extent, immunosuppression.

Original language	English
Journal	Antiviral Therapy
Volume	21
Issue number	6
Pages (from-to)	495-506
Number of pages	12
ISSN	1359-6535
DOIs	https://doi.org/10.3851/IMP3051
Publication status	Published - 2016

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Kamara, D. A., Smith, C., Ryom, L., Reiss, P., Rickenbach, M., Phillips, A., Mocroft, A., De Wit, S., Law, M., Monforte, A. DA., Dabis, F., Pradier, C., Lundgren, J. D., & Sabin, C. (2016). Longitudinal analysis of the associations between antiretroviral therapy, viraemia and immunosuppression with lipid levels: the D:A:D study. Antiviral Therapy, 21(6), 495-506. https://doi.org/10.3851/IMP3051

Kamara, DA, Smith, C, Ryom, L, Reiss, P, Rickenbach, M, Phillips, A, Mocroft, A, De Wit, S, Law, M, Monforte, ADA, Dabis, F, Pradier, C, Lundgren, JD & Sabin, C 2016, 'Longitudinal analysis of the associations between antiretroviral therapy, viraemia and immunosuppression with lipid levels: the D:A:D study', Antiviral Therapy, vol. 21, no. 6, pp. 495-506. https://doi.org/10.3851/IMP3051

@article{3ea5a3512d804b0da132be3f036db1b9,

title = "Longitudinal analysis of the associations between antiretroviral therapy, viraemia and immunosuppression with lipid levels: the D:A:D study",

abstract = "Background: 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. Methods: 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. Results: 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 proile, (27.2% higher levels compared to atazanavir; 95% CI 25.2%, 29.2%), and darunavir had a similar proile as atazanavir. The nucleoside pair lamivudine/tenofovir was associated with the most favourable TG proile (-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 proile (+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. Conclusions: TG, TC and HDL-C levels, which generally improved over time, are dependent on ART, viraemia and, to a lesser extent, immunosuppression.",

author = "Kamara, {David A} and Colette Smith and Lene Ryom and Peter Reiss and Martin Rickenbach and Andrew Phillips and Amanda Mocroft and {De Wit}, Stephan and Matthew Law and Monforte, {Antonella d'Arminio} and Francois Dabis and Christian Pradier and Lundgren, {Jens D} and Caroline Sabin",

year = "2016",

doi = "10.3851/IMP3051",

language = "English",

volume = "21",

pages = "495--506",

journal = "Antiviral Therapy",

issn = "1359-6535",

publisher = "International Medical Press",

number = "6",

}

TY - JOUR

T1 - Longitudinal analysis of the associations between antiretroviral therapy, viraemia and immunosuppression with lipid levels

T2 - the D:A:D study

AU - Kamara, David A

AU - Smith, Colette

AU - Ryom, Lene

AU - Reiss, Peter

AU - Rickenbach, Martin

AU - Phillips, Andrew

AU - Mocroft, Amanda

AU - De Wit, Stephan

AU - Law, Matthew

AU - Monforte, Antonella d'Arminio

AU - Dabis, Francois

AU - Pradier, Christian

AU - Lundgren, Jens D

AU - Sabin, Caroline

PY - 2016

Y1 - 2016

N2 - Background: 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. Methods: 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. Results: 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 proile, (27.2% higher levels compared to atazanavir; 95% CI 25.2%, 29.2%), and darunavir had a similar proile as atazanavir. The nucleoside pair lamivudine/tenofovir was associated with the most favourable TG proile (-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 proile (+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. Conclusions: TG, TC and HDL-C levels, which generally improved over time, are dependent on ART, viraemia and, to a lesser extent, immunosuppression.

AB - Background: 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. Methods: 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. Results: 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 proile, (27.2% higher levels compared to atazanavir; 95% CI 25.2%, 29.2%), and darunavir had a similar proile as atazanavir. The nucleoside pair lamivudine/tenofovir was associated with the most favourable TG proile (-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 proile (+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. Conclusions: TG, TC and HDL-C levels, which generally improved over time, are dependent on ART, viraemia and, to a lesser extent, immunosuppression.

U2 - 10.3851/IMP3051

DO - 10.3851/IMP3051

M3 - Journal article

C2 - 27114439

SN - 1359-6535

VL - 21

SP - 495

EP - 506

JO - Antiviral Therapy

JF - Antiviral Therapy

IS - 6

ER -

Longitudinal analysis of the associations between antiretroviral therapy, viraemia and immunosuppression with lipid levels: the D:A:D study

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