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Metabolic profiles of individuals switched to second-line antiretroviral therapy after failing standard first-line therapy for treatment of HIV-1 infection in a randomized, controlled trial

Yao, AH; Moore, CL; Lim, PL; Molina, J-M; Madero, JS; Kerr, S; Mallon, PW; ... SECOND-LINE study group, .; + view all (2018) Metabolic profiles of individuals switched to second-line antiretroviral therapy after failing standard first-line therapy for treatment of HIV-1 infection in a randomized, controlled trial. Antiviral Therapy , 23 pp. 21-32. 10.3851/IMP3171. Green open access

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Abstract

BACKGROUND: To investigate metabolic changes associated with second-line antiretroviral therapy (ART) following virological failure of first-line ART. METHODS: SECOND-LINE was an open-label randomized controlled trial. Participants were randomized 1:1 to receive ritonavir-boosted lopinavir (LPV/r) with 2-3 nucleoside/nucleotide reverse transcriptase inhibitors (N(t)RTI-group) or raltegravir (RAL-group) Two hundred and ten participants had a dual energy X-ray absorptiometry (DXA)-scan at baseline, week 48 and 96. We categorized participants according to second-line ART backbone: 1. thymidine analogue (ta-NRTI)+lamivudine/emtricitabine (3[F]TC) [ta-NRTI group]; 2. tenofovir (TDF)+3[F]TC [TDF group]; 3. TDF+ta-NRTI+/-3[F]TC [TDF+ta-NRTI group]; 4. RAL. Changes in fasted total cholesterol, LDL-cholesterol, HDL-c, TC/HDL-cholesterol ratio, triglycerides and glucose from baseline to week 96 were examined. We explored the association between metabolic and DXA-assessed soft-tissue changes. Linear regression methods were used. RESULTS: We analyzed 454 participants. Participants in RAL group had greater TC increases TC (adjusted mean difference (aMD)=0.65, 95%CI 0.33, 0.96), LDL-c (aMD=0.38, 95%CI 0.15, 0.61) and glucose (aMD = 0.47, 95%CI -0.01, 0.92) compared to TDF group, and had greater increases in TC (aMD=0.65, 95%CI 0.28, 1.03), HDL-c (aMD=0.12, 95%CI 0.02, 0.23) and LDL-c (aMD=0.41, 95%CI 0.13, 0.69;) compared to TDF+ta-NRTI group. TC/HDL ratio and triglycerides increased in all groups without significant differences between groups. A 1kg increase in trunk fat mass was associated with an increase in TC. CONCLUSIONS: We observed metabolic changes of limited clinical significance in the relatively young population enrolled in this study. However, the metabolic changes observed may have greater clinical significance in older people living with HIV or those with other concomitant cardiovascular risks.

Type: Article
Title: Metabolic profiles of individuals switched to second-line antiretroviral therapy after failing standard first-line therapy for treatment of HIV-1 infection in a randomized, controlled trial
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.3851/IMP3171
Publisher version: http://doi.org/10.3851/IMP3171
Language: English
Additional information: © 2017 International Medical Press. This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology
URI: https://discovery.ucl.ac.uk/id/eprint/1556726
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