TY - JOUR

T1 - Changes in Cardiovascular Disease Risk Factors With Immediate Versus Deferred Antiretroviral Therapy Initiation Among HIV-Positive Participants in the START (Strategic Timing of Antiretroviral Treatment) Trial

AU - Baker, Jason V

AU - Sharma, Shweta

AU - Achhra, Amit C

AU - Bernardino, Jose Ignacio

AU - Bogner, Johannes R

AU - Duprez, Daniel

AU - Emery, Sean

AU - Gazzard, Brian

AU - Gordin, Jonathan

AU - Grandits, Greg

AU - Phillips, Andrew N

AU - Schwarze, Siegfried

AU - Soliman, Elsayed Z

AU - Spector, Stephen A

AU - Tambussi, Giuseppe

AU - Lundgren, Jens

AU - INSIGHT (International Network for Strategic Initiatives in Global HIV Trials) START (Strategic Timing of Antiretroviral Treatment) Study Group

N1 - © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

PY - 2017/5/22

Y1 - 2017/5/22

N2 - INTRODUCTION: HIV infection and certain antiretroviral therapy (ART) medications increase atherosclerotic cardiovascular disease risk, mediated, in part, through traditional cardiovascular disease risk factors.METHODS AND RESULTS: We studied cardiovascular disease risk factor changes in the START (Strategic Timing of Antiretroviral Treatment) trial, a randomized study of immediate versus deferred ART initiation among HIV-positive persons with CD4+ cell counts >500 cells/mm3. Mean change from baseline in risk factors and the incidence of comorbid conditions were compared between groups. The characteristics among 4685 HIV-positive START trial participants include a median age of 36 years, a CD4 cell count of 651 cells/mm3, an HIV viral load of 12 759 copies/mL, a current smoking status of 32%, a median systolic/diastolic blood pressure of 120/76 mm Hg, and median levels of total cholesterol of 168 mg/dL, low-density lipoprotein cholesterol of 102 mg/dL, and high-density lipoprotein cholesterol of 41 mg/dL. Mean follow-up was 3.0 years. The immediate and deferred ART groups spent 94% and 28% of follow-up time taking ART, respectively. Compared with patients in the deferral group, patients in the immediate ART group had increased total cholesterol and low-density lipoprotein cholesterol and higher use of lipid-lowering therapy (1.2%; 95% CI, 0.1-2.2). Concurrent increases in high-density lipoprotein cholesterol with immediate ART resulted in a 0.1 lower total cholesterol to high-density lipoprotein cholesterol ratio (95% CI, 0.1-0.2). Immediate ART resulted in 2.3% less BP-lowering therapy use (95% CI, 0.9-3.6), but there were no differences in new-onset hypertension or diabetes mellitus.CONCLUSIONS: Among HIV-positive persons with preserved immunity, immediate ART led to increases in total cholesterol and low-density lipoprotein cholesterol but also concurrent increases in high-density lipoprotein cholesterol and decreased use of blood pressure medications. These opposing effects suggest that, in the short term, the net effect of early ART on traditional cardiovascular disease risk factors may be clinically insignificant."CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00867048.

AB - INTRODUCTION: HIV infection and certain antiretroviral therapy (ART) medications increase atherosclerotic cardiovascular disease risk, mediated, in part, through traditional cardiovascular disease risk factors.METHODS AND RESULTS: We studied cardiovascular disease risk factor changes in the START (Strategic Timing of Antiretroviral Treatment) trial, a randomized study of immediate versus deferred ART initiation among HIV-positive persons with CD4+ cell counts >500 cells/mm3. Mean change from baseline in risk factors and the incidence of comorbid conditions were compared between groups. The characteristics among 4685 HIV-positive START trial participants include a median age of 36 years, a CD4 cell count of 651 cells/mm3, an HIV viral load of 12 759 copies/mL, a current smoking status of 32%, a median systolic/diastolic blood pressure of 120/76 mm Hg, and median levels of total cholesterol of 168 mg/dL, low-density lipoprotein cholesterol of 102 mg/dL, and high-density lipoprotein cholesterol of 41 mg/dL. Mean follow-up was 3.0 years. The immediate and deferred ART groups spent 94% and 28% of follow-up time taking ART, respectively. Compared with patients in the deferral group, patients in the immediate ART group had increased total cholesterol and low-density lipoprotein cholesterol and higher use of lipid-lowering therapy (1.2%; 95% CI, 0.1-2.2). Concurrent increases in high-density lipoprotein cholesterol with immediate ART resulted in a 0.1 lower total cholesterol to high-density lipoprotein cholesterol ratio (95% CI, 0.1-0.2). Immediate ART resulted in 2.3% less BP-lowering therapy use (95% CI, 0.9-3.6), but there were no differences in new-onset hypertension or diabetes mellitus.CONCLUSIONS: Among HIV-positive persons with preserved immunity, immediate ART led to increases in total cholesterol and low-density lipoprotein cholesterol but also concurrent increases in high-density lipoprotein cholesterol and decreased use of blood pressure medications. These opposing effects suggest that, in the short term, the net effect of early ART on traditional cardiovascular disease risk factors may be clinically insignificant."CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00867048.

KW - Adult

KW - Anti-HIV Agents/administration & dosage

KW - Cardiovascular Diseases/epidemiology

KW - Comorbidity/trends

KW - Cyclic N-Oxides

KW - Drug Administration Schedule

KW - Female

KW - Follow-Up Studies

KW - Global Health

KW - HIV

KW - HIV Infections/drug therapy

KW - Humans

KW - Male

KW - Mercaptoethanol/analogs & derivatives

KW - Risk Assessment

KW - Risk Factors

KW - Time Factors

U2 - 10.1161/JAHA.116.004987

DO - 10.1161/JAHA.116.004987

M3 - Journal article

C2 - 28533305

VL - 6

JO - Journal of the American Heart Association

JF - Journal of the American Heart Association

SN - 2047-9980

IS - 5

M1 - e004987

ER -