Impact of randomized antiretroviral therapy initiation on glucose metabolism.

TitleImpact of randomized antiretroviral therapy initiation on glucose metabolism.
Publication TypeJournal Article
Year of Publication2014
AuthorsErlandson KMace, Kitch D, Tierney C, Sax PE, Daar ES, Melbourne KM, Ha B, McComsey GA
JournalAIDS
Volume28
Issue10
Pagination1451-61
Date Published2014 Jun 19
ISSN1473-5571
KeywordsAdolescent, Adult, Anti-HIV Agents, Antiretroviral Therapy, Highly Active, Blood Glucose, Double-Blind Method, Energy Metabolism, Female, HIV Infections, Humans, Male, Prospective Studies, Young Adult
Abstract

OBJECTIVE: Prior studies have found that early HIV protease inhibitors contribute to glucose dysregulation. Few randomized trials have evaluated glucose indices in antiretroviral-naive individuals on newer antiretroviral therapy (ART).

METHODS: A5224s was a substudy of A5202, a prospective trial of 1857 ART-naive participants randomized to blinded abacavir-lamivudine (ABC/3TC) or tenofovir DF-emtricitabine (TDF/FTC) with open-label efavirenz (EFV) or atazanavir-ritonavir (ATV/r). Analyses used two-sample t-tests, Spearman correlation coefficients and linear regression.

RESULTS: A5224s included 269 nondiabetic individuals: 85% men, 47% white non-Hispanic, baseline median age 38 years, HIV-1 RNA 4.6 log10 copies/ml and CD4 cell count 233 cells/μl. Overall, significant 96-week increases occurred in fasting glucose, insulin and the homeostatic model assessment of insulin resistance (HOMA-IR), P ≤ 0.004. Assignment to EFV (versus ATV/r) resulted in significantly greater glucose increase [mean difference 4.4; 95% confidence interval (CI) 1.3, 7.5 mg/dl; P = 0.006] but not insulin or HOMA-IR (P ≥ 0.72). Glucose indices were not significantly different between ABC/3TC and TDF/FTC arms, P ≥ 0.18. Significant correlations were detected between changes in glucose indices and changes in BMI; all r ≥ 0.23, P ≤ 0.001. In multivariable analyses, in addition to the EFV effect, higher baseline HIV-1 RNA and greater BMI change were significant independent factors associated with greater glucose increase.

CONCLUSION: Changes in glucose metabolism were not significantly different between TDF/FTC and ABC/3TC-based regimens. A small but significantly greater increase in glucose was observed in those assigned to EFV. As glucose dysregulation may increase with time on ART, longer term studies will be needed to further clarify the clinical significance of these findings.

DOI10.1097/QAD.0000000000000266
Alternate JournalAIDS
PubMed ID24637543
PubMed Central IDPMC4167596
Grant ListAI068634 / AI / NIAID NIH HHS / United States
AI38855 / AI / NIAID NIH HHS / United States
R01 AI065348 / AI / NIAID NIH HHS / United States
U01AI068636 / AI / NIAID NIH HHS / United States
UL1 RR 025005 / RR / NCRR NIH HHS / United States
UL1 TR000042 / TR / NCATS NIH HHS / United States
UM1 AI068634 / AI / NIAID NIH HHS / United States
UM1 AI068636 / AI / NIAID NIH HHS / United States
UM1 AI069412 / AI / NIAID NIH HHS / United States
UM1 AI069424 / AI / NIAID NIH HHS / United States
UM1 AI069432 / AI / NIAID NIH HHS / United States
UM1 AI106701 / AI / NIAID NIH HHS / United States