Association Between Exposure to Antiretroviral Drugs and the Incidence of Hypertension in HIV-Positive Persons

The Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) Study

CI Hatleberg; L Ryom; A d'Arminio Monforte; E Fontas; P Reiss; O Kirk; W El-Sadr; A Phillips; S de Wit; F Dabis; R Weber; M Law; JD Lundgren; C Sabin; on behalf of the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) Study Group

Disclosures

HIV Medicine. 2018;19(9):605-618. 

In This Article

Abstract and Introduction

Abstract

Objectives: Previous studies have suggested that hypertension in HIV-positive individuals is associated primarily with traditional risk factors such as older age, diabetes and dyslipidaemia. However, controversy remains as to whether exposure to antiretroviral (ARV) drugs poses additional risk, and we investigated this question in the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) cohort.

Methods: The incidence of hypertension [systolic blood pressure (BP) > 140 and/or diastolic BP > 90 mmHg and/or initiation of antihypertensive treatment] was determined overall and in strata defined by demographic, metabolic and HIV-related factors, including cumulative exposure to each individual ARV drug. Predictors of hypertension were identified using uni- and multivariable Poisson regression models.

Results: Of 33 278 included persons, 7636 (22.9%) developed hypertension over 223 149 person-years (PY) [incidence rate: 3.42 (95% confidence interval (CI) 3.35-3.50) per 100 PY]. In univariable analyses, cumulative exposure to most ARV drugs was associated with an increased risk of hypertension. After adjustment for demographic, metabolic and HIV-related factors, only associations for nevirapine [rate ratio 1.07 (95% CI: 1.04–1.13) per 5 years] and indinavir/ritonavir [rate ratio 1.12 (95% CI: 1.04–1.20) per 5 years] remained statistically significant, although effects were small. The strongest independent predictors of hypertension were male gender, older age, black African ethnicity, diabetes, dyslipidaemia, use of lipid-lowering drugs, high body mass index (BMI), renal impairment and a low CD4 count.

Conclusions: We did not find evidence for any strong independent association between exposure to any of the individual ARV drugs and the risk of hypertension. Findings provide reassurance that screening policies and preventative measures for hypertension in HIV-positive persons should follow algorithms used for the general population.

Introduction

Over the last two decades, cardiovascular disease (CVD) has emerged as a leading cause of morbidity and mortality in HIV-positive individuals.[1–3] The increased prevalence of CVD is a consequence of increased life expectancy resulting from the widespread use of effective combination antiretroviral therapy (cART),[1–3] the high prevalence of traditional CVD risk factors (including hypertension)[4–6] and the contribution of HIV-related factors.[7–9]

The prevalence of hypertension is higher in HIV-positive than HIV-negative individuals,[10,11] and is increasing.[12] Hypertension in HIV-positive individuals has been linked to traditional CVD risk factors such as diabetes, renal impairment, older age, male gender, black African ethnicity, dyslipidaemia and high body mass index (BMI).[12–16] Furthermore, factors related to HIV infection, such as immunosuppression, inflammation, increased arterial stiffness, fat redistribution and lipodystrophy, may also contribute to an increased risk of hypertension.[17–20]

Controversy remains as to whether exposure to antiretroviral (ARV) drugs poses an additional risk for the development of hypertension. While some studies have reported an increased risk of hypertension in those exposed to cART overall,[21–25] others have not observed any such association.[12,13,26–29] A previous analysis from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study in 2005 showed no clear association between exposure to ARV drugs and the risk of hypertension, although traditional CVD risk factors were significant predictors of hypertension.[13]

Given the increased life expectancy of people living with HIV, it is important to continuously improve our understanding of CVD risk factors so as to recommend appropriate preventative measures. Our aim was to capitalize on the additional follow-up that is now available in the D:A:D study to re-investigate the potential associations between exposure to individual ARV drugs and the risk of hypertension, as well as to identify non-ARV predictors of hypertension.

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