Body Mass Index and the Risk of Serious Non-AIDS Events and all-cause Mortality in Treated HIV-Positive Individuals

D: A: D Cohort Analysis

Amit C. Achhra, MBBS, MPH, PhD; Caroline Sabin, PhD; Lene Ryom, MD, PhD; Camilla Hatleberg, MD, PhD; Monforte Antonella d'Aminio, MD, PhD; Stephane de Wit, MD; Andrew Phillips, PhD; Christian Pradier, MD; Rainer Weber, MD; Peter Reiss, MD, PhD; Wafaa El-Sadr, MD, PhD; Fabrice Bonnet, MD; Amanda Mocroft, PhD; Jens Lundgren, MD, PhD; Matthew G. Law, PhD

Disclosures

J Acquir Immune Defic Syndr. 2018;78(5):579-588. 

In This Article

Abstract and Introduction

Abstract

Background: The relationship between body mass index (BMI) [weight (kg)/height (m2)] and serious non-AIDS events is not well understood.

Methods: We followed D:A:D study participants on antiretroviral therapy from their first BMI measurement to the first occurrence of the endpoint or end of follow-up (N = 41,149 followed for 295,147 person-years). The endpoints were cardiovascular disease (CVD); diabetes; non–AIDS-defining cancers (NADCs) and BMI-NADCs (cancers known to be associated with BMI in general population); and all-cause mortality. Using Poisson regression models, we analyzed BMI as time-updated, lagged by 1 year, and categorized at: 18.5, 23, 25, 27.5, and 30 kg/m2.

Results: Participants were largely male (73%) with the mean age of 40 years (SD 9.7) and baseline median BMI of 23.3 (interquartile range: 21.2–25.7). Overall, BMI showed a statistically significant J-shaped relationship with the risk of all outcomes except diabetes. The relative risk (RR) for the BMI of <18.5 and >30 (95% confidence interval) compared with 23–25, respectively, was as follows: CVD: 1.46 (1.15–1.84) and 1.31 (1.03–1.67); NADCs: 1.78 (1.39–2.28) and 1.17 (0.88–1.54); and "BMI-NADCs": 1.29 (0.66–2.55) and 1.92 (1.10–3.36). For all-cause mortality, there was an interaction by sex (P < 0.001): RR in males: 2.47 (2.12–2.89) and 1.21 (0.97–1.50); and in females: 1.60 (1.30–1.98) and 1.02 (0.74–1.42). RR remained around 1 for intermediate categories of BMI. The risk of diabetes linearly increased with increasing BMI (P < 0.001).

Conclusions: Risk of CVD, a range of cancers, and all-cause mortality increased at low BMI (<18.5) and then tended to increase only at BMI > 30 with a relatively low risk at BMI of 23–25 and 25–30. High BMI was also associated with risk of diabetes.

Introduction

Excess weight is now increasingly prevalent in HIV-positive individuals receiving antiretroviral therapy (ART).[1,2] Although body mass index (BMI) [measured as weight (kg)/height (m2)] is an anthropometric measure and does not directly measure total body fat or biological markers of disease, it remains an easy and low-cost metric to screen for risk of certain conditions.[3] However, in HIV-positive individuals, the relationship between BMI and various serious non-AIDS events (SNAEs) is not well studied.

In the general population, increasing BMI is associated with increased risk of various clinical outcomes including cardiovascular disease (CVD),[3] diabetes mellitus (DM), several cancers such as those of gastrointestinal tract and endometrium,[4] and all-cause mortality.[5] Also, very low BMI has been associated with increased risk of mortality.[5]

HIV-positive individuals are unique in that they are exposed to ongoing inflammation/immune activation, ART toxicities, higher prevalence of lifestyle risk factors such as smoking, and a higher overall risk of various SNAEs than general population.[6] Furthermore, BMI in this group is itself associated with immunosuppression and certain antiretroviral drugs among other factors.[2] In one large cohort study, BMI correlated strongly with CD4 count response to ART regardless of baseline CD4 count, with a highest CD4 count response at BMI levels of 25–30 but worse at higher or lower levels.[7] However, weight gain after ART initiation has been shown to be harmful to cardiometabolic health, especially in those with "normal/overweight" weight at baseline.[8] It is therefore possible that being HIV-infected modifies the relationship between BMI and various outcomes in this population. However, limited, if any, studies have rigorously evaluated BMI as a risk factor for non-AIDS outcomes.[9] Better understanding of how BMI relates to SNAEs in HIV-positive individuals is therefore needed. This information will provide the key data to clinicians and the HIV community regarding the health implications of BMI—a well-known, easily and economically measured potential risk factor.

In this study, we analyzed the data from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study, a large heterogeneous cohort with well-validated outcomes and available data on a wide range of risk factors, to assess the relationship between latest BMI and the subsequent risk of various SNAEs and all-cause mortality.

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