Incidence of cardiovascular disease in people living with HIV has increased as overall survival has improved because of combination antiretroviral therapy (cART). Arterial stiffness is a composite indicator of cardiovascular disease risk independent of traditional risk factors. We aimed to synthesize the evidence on the relation of HIV and of cART to arterial stiffness. Medline, Embase, CINAHL, PubMed, and Cochrane Libraries were systematically searched for studies relating HIV/cART to arterial stiffness until June 2019. A standardized extraction form was used to collect data from published reports. Random-effects meta-analyses were performed to produce standardized mean differences and 95% CIs from studies reporting carotid-femoral pulse wave velocity. We retrieved 995 citations. Seventy-four studies (N=18 711 participants/13 119 with HIV) were included: 59 cross-sectional, 9 cohort, and 6 randomized trials. In meta-analyses of 17 studies, arterial stiffness was found to be elevated overall in individuals with HIV relative to controls (standardized mean difference, 0.44 m/s [95% CI, 0.25–0.63]) and in cART-treated versus untreated individuals with HIV (standardized mean difference, 0.35 m/s [95% CI, 0.13–0.57]). Several studies suggested that cumulative exposure to cART is associated with a continual increase in arterial stiffness. However, early initiation of treatment might improve arterial stiffness later in life. The results highlight the need for monitoring of cardiovascular risk in this population. The cross-sectional nature of most studies (59/74) mainly allowed for the exploration of associations; large longitudinal studies are needed to confirm the observed associations and establish causality between HIV/cART and arterial stiffness.

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Introduction: Accurate comparisons of carotid--femoral pulse wave velocity (cfPWV) within and across studies require standardized procedures. Guidelines suggest reporting the average of at least two cfPWV measurements; if the difference exceeds 0.5 m/s, a third measurement should be taken, and the median reported. Another method involves repeating measurements until two values are within 0.5 m/s. However, in many studies, duplicate measurements are averaged irrespective of the difference between readings. We evaluated the impact of these methods on the reported cfPWV value. Methods: Measurements of cfPWV (SphygmoCor) from five studies included individuals spanning a wide age range, with or without comorbid conditions, and pregnant women. In participants with at least three high-quality measurements, differences between the median value (MED) and the average of the first two cfPWV measurements (AVG1) and the average of two cfPWV measurements within 0.5 m/s (AVG2) were evaluated using paired t-tests and Bland--Altman plots. Results: Participants’ mean age was 50 ± 14 years and BMI was 28.0 ± 5.5 kg/m2 (N = 306, 79% women). The overall mean difference was −0.10 m/s (95% CI 0.17 to −0.04) between MED and AVG1, and 0.11 m/s (95% CI 0.05--0.17) between MED and AVG2. The absolute difference exceeded 0.5 m/s in 34% (MED-AVG1) and 22% (MED-AVG2) of participants, and 1 m/s in 8% of participants (both MED-AVG1 and MED-AVG2). Scatter around the bias line increased with higher mean cfPWV values. Conclusion: Although the overall mean difference in cfPWV between protocols was not clinically relevant, large variation led to absolute differences exceeding 0.5 m/s in a large proportion of participants.

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Objective:Incidence of cardiovascular disease (CVD) in people living with human immunodeficiency virus (HIV) infection has increased as overall survival has improved due to combination antiretroviral therapy (cART). Arterial stiffness is a composite indicator of CVD risk independent of traditional risk factors. We therefore aimed to synthesize the evidence on the effect of HIV and of cART on arterial stiffness.Design and Methods:We conducted a systematic review of Medline/PubMed, Embase, CINAHL, and the Cochrane Library, searched independently by two reviewers using a predefined search strategy, for studies relating HIV/cART to arterial stiffness until June 2019. Studies were limited to humans and publication in English or French. A standardized extraction form was used to collect data from published reports. Random-effects meta-analyses were performed to produce standardized mean differences (SMDs) and 95% confidence intervals (CIs) from studies reporting carotid-femoral pulse wave velocity.Results:We retrieved 995 citations. Seventy-four studies (N = 18,711 participants/13,119 with HIV) were included: 59 cross-sectional, 9 cohort studies and 6 randomized controlled trials. In meta-analyses of 17 studies, arterial stiffness was found to be increased overall in individuals with HIV relative to healthy controls (SMD 0.44 m/s; 95% CI, 0.25–0.63) and in cART-treated versus untreated individuals with HIV (SMD 0.35 m/s; 95% CI, 0.13–0.57). Several studies suggested that cumulative exposure to cART is associated with a continual increase in arterial stiffness. However, early initiation of treatment might improve arterial stiffness later in life by negating the effect of the HIV.Conclusions:Evidence suggests that HIV infection is associated with increased arterial stiffness, while cART is linked to a further increase, highlighting the need for monitoring of CVD risk in this population, and the need for development of novel treatments. The cross-sectional nature of most studies (59/74) mainly allowed for the exploration of associations. Large longitudinal studies are needed to confirm the observed relationships and establish causality between HIV/cART and arterial stiffness.