Baseline cardiovascular risk in the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial

Abstract

Introduction The Strategic Timing of AntiRetroviral Treatment (START) trial has recruited antiretroviral-naïve individuals with high CD4 cell counts from all world regions. We describe the distribution of cardiovascular (CVD) risk factors, overall and by geographic region, at study baseline. Methods The distribution of CVD risk factors was assessed and compared by geographic region among START participants who had baseline electrocardiogram (n=4019; 11% North America; 36% Europe/Australia/Israel; 26% South America; 4% Asia; 23% Africa; median age 36 years; 26% females). Results About 58.3% (n=2344) of the participants had at least one CVD risk factor and 18.9% (n=761) had two or more. The most common CVD risk factors were current smoking (32%), hypertension (19.3%) and obesity (16.5%). There were significant differences in the prevalence of CVD risk factors among geographic regions. The prevalence of at least one risk factor across regions was as follows: 70.0% North America, 65.1% Europe/Australia/Israel, 49.4% South America, 37.0% Asia, and 55.8% Africa (p-value<0.001). Significant regional differences were also observed when risk factors were used as part of the Framingham and D:A:D risk scores or used to define favourable risk profile. Conclusions CVD risk factors are common among START participants, and their distribution varies by geographic region. Better understanding of how and why CVD risk factors develop in people with HIV and their geographical distributions could shed light on appropriate strategies for CVD prevention and may inform the interpretation of the results of START as CVD is expected to be a major fraction of the primary endpoints observed.

Cardiovascular disease risk among Chinese antiretroviral-naïve adults with advanced HIV disease

“…Given the younger age of populations with HIV in China (68.4% of patients in our cohort were less than 40 years), the FRS and D:A:D risk equations are more widely applicable compared with tools such as the ACC/AHA ASCVD Risk Score, which applies to individuals ≥40 years of age. The prevalence of patients with 10-year CVD risk ≥10% in our cohort was 4.5% based upon the FRS, which is on par with that reported previously among other studies among Asian (6.5%) and African HIV-positive patients (3.6%) [10, 33] and lower compared with rates observed among individuals with HIV in Western countries (19.6–21.1%) [10]. The lower CVD risk in Asia and Africa in the START trial may reflect younger age and lower hypertension and obesity rates for the former, and higher proportion of women and low smoking and dyslipidemia rates in the latter.…”

Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection

“…The results support global goals set by the World Health Organization and the Joint United Nations Programme on HIV/AIDS to expand the use of antiretroviral therapy to all HIV-positive patients in order to improve their health and as part of efforts to reduce the future spread of HIV. 22-24,47,48 …”

Why START? Reflections that led to the conduct of this large long‐term strategic HIV trial

“…• For 2.4% of participants the HIV RNA level was 50 copies/mL or lower [31]. • Approximately 19% of participants had two or more cardiovascular risk factors; 32% of participants reported smoking [32]. • Chronic kidney disease, defined as eGFR < 60 mL/min/ 1.73 m 2 or dipstick proteinuria 1 + or greater, was present in 6.2% of participants [33].…”

“…Below we highlight some characteristics of this unique cohort of individuals who were ART naïve and had CD4 cell counts > 500 cells/μL at study entry. The median age of the cohort was 36 years and 27% were women. The median CD4 cell count was 651 cells/μL and the median HIV RNA was 12 754 HIV‐1 RNA copies/mL . For 2.4% of participants the HIV RNA level was 50 copies/mL or lower . Approximately 19% of participants had two or more cardiovascular risk factors; 32% of participants reported smoking . Chronic kidney disease, defined as eGFR < 60 mL/min/1.73 m 2 or dipstick proteinuria 1 + or greater, was present in 6.2% of participants . Approximately 17% of participants reported condomless sex with a serodiscordant partner in the 2 months prior to randomization . There was substantial geographical diversity in carrying out routine screening for transmitted ART‐resistant virus, with screening much more likely to occur in resource‐rich areas of the world . Quality of life was mostly favourable; the average of the visual analogue scale of overall current health was 80.9 out of 100 . Changes in neurocognitive test performance will be compared for the immediate and deferred ART groups in 608 participants. At entry about 20% of participants had at least mild neurocognitive impairment . Changes in arterial elasticity will be compared for the immediate and deferred ART groups in 331 participants.…”