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Clinical Trial
. 2022 Sep 30;75(7):1154-1163.
doi: 10.1093/cid/ciac098.

Geographical Differences in the Self-Reported Functional Impairment of People With Human Immunodeficiency Virus (HIV) and Associations With Cardiometabolic Risk

Kristine M Erlandson  1 , Kathleen V Fitch  2 , Sara A McCallum  2 , Heather J Ribaudo  3 , Edgar T Overton  4 , Markella V Zanni  2 , Gerald S Bloomfield  5 , Todd T Brown  6 , Carl J Fichtenbaum  7 , Sara Bares  8 , Judith A Aberg  9 , Pamela S Douglas  10 , Evelynne S Fulda  2 , Jorge L Santana-Bagur  11 , Jose G Castro  12 , Laura E Moran  13 , Vidya Mave  14 , Khuanchai Supparatpinyo  15 , Ponego L Ponatshego  16 , Mauro Schechter  17 , Steven K Grinspoon  2
Affiliations
Clinical Trial

Geographical Differences in the Self-Reported Functional Impairment of People With Human Immunodeficiency Virus (HIV) and Associations With Cardiometabolic Risk

Kristine M Erlandson et al. Clin Infect Dis. .

Abstract

Background: We sought to explore multinational differences in functional status by global burden of disease (GBD) regions in the REPRIEVE cohort.

Methods: REPRIEVE is a prospective, double-blind, randomized, placebo-controlled, multicenter, phase III primary cardiovascular prevention study of pitavastatin calcium vs placebo among people with human immunodeficiency virus (HIV, PWH) ages 40-75 on antiretroviral therapy (ART). GBD super regions were defined using World Health Organization classifications. Participants were categorized by impairment on the Duke Activity Status Instrument (DASI: none, some, moderate, severe). Logistic regression models examined risk factors and GBD regions associated with functional impairment. The association between functional impairment and cardiometabolic risk was also explored.

Results: Of 7736 participants, the majority were from high-income countries (n = 4065), were male (65%), and had received ART for ≥ 10 years. The median DASI score was 58.2 (interquartile range [IQR] 50.2, 58.2); 36% reported at least some impairment. In adjusted analyses, functional impairment was significantly more frequent among participants from Southeast/East Asia. Other factors associated with greater impairment included female sex, Black race, older age, current/former smoking, higher body mass index, use of ART for ≥ 10 years, and select ART regimens; differences were seen in risks across GBD regions. Functional impairment was associated with increased cardiometabolic risk.

Conclusions: Over 1/3 of middle-aged and older PWH in a global cohort across diverse GBD regions demonstrate functional impairments. The associations between DASI and cardiometabolic risk suggest that a measure of functional status may improve risk prediction; these longitudinal associations will be further investigated over REPRIEVE trial follow-up.

Keywords: aging; cardiovascular disease; frailty; functional status; physical function.

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Conflict of interest statement

Potential conflicts of interest. K. V. F. declares funding from Gilead Sciences (educational grant) outside the submitted work. M. S. reports grants and personal fees from Gilead, ViiV, GSK, Janssen, and Merck outside the submitted work (all paid to the institution). K. M. E. reports grants and personal fees from Gilead, personal fees from ViiV, Jannsen, Theratechnologies outside the submitted work (all paid to the institution). T. B. reports personal fees from ViiV, Janssen, Merck, Gilead Sciences, and Theratechnologies outside the submitted work. T. O. reports personal fees and other from GSK/ViiV (support for Research Studies through the institution; personal fees for consultant role) outside the submitted work. C. F. reports grants from Gilead Sciences, ViiV Healthcare, and Merck outside the submitted work. H. R. reports grants from KOWA Pharmaceuticals, during the conduct of the study and grants from NIH/NHLBI, NIH/NIAID, NIH/NIDDK, and NIH/NIA outside the submitted work. M. Z. reports serving as PI of an investigator-initiated research grant from Gilead to institution outside the submitted work. S. B. reports grants and personal fees from Gilead Sciences, grants from Janssen, ViiV Healthcare, outside the submitted work. J. A. reports grants from Massachusetts General Hospital (NIH subaward) during the conduct of the study; grants from Atea (Multicenter Trial- Antiviral Treatment for COVID), Emergent Biosolutions (Single Site Trial of SARS_CoV-2 hyperimmune globulin pk study in healthy volunteers), Frontier Technologies (Multicenter Trial for HIV Treatment), Gilead Sciences (Multicenter Trials for antiviral treatment for COVID and HIV), Janssen (Multicenter Trials for Prevention of COVID (vaccine) and Treatment of HIV), Regeneron (Multicenter Trials for both Prevention and Treatment of COVID), ViiV Healthcare (Multicenter Trials of Antiretroviral Therapy for HIV), Pfizer (Multicenter Vaccine Trials for Prevention of COVID), GSK (Scientific Ad Board for VZV vaccine, Multicenter Trials for HIV Treatment), and Merck (Scientific Ad Board Review of HIV Therapy Protocol Development; Multicenter Trials of Antivirals for HIV) outside of the submitted work; personal fees from GSK and Merck outside the submitted work. S. K. G. reports grants from KOWA (for REPRIEVE), grants from Gilead (for REPRIEVE), grants and personal fees from ViiV (for REPRIEVE and consulting), grants and personal fees from Theratechnologies (for REPRIEVE and consulting), during the conduct of the study. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Figures

Figure 1.
Figure 1.
Univariate (left) and multivariate (right) estimates of the associations between demographic and HIV-related characteristics on the DASI score. Multivariate estimates were adjusted for all listed covariates. Estimates represent the difference in DASI score and the associated 95%CI. Parameter estimates not shown for covariate levels with sample size < 10. In the adjusted analysis, race effect estimated within high-income region only due to limited racial variability in other regions; the GBD region effects thus reflect differences compared to white race within the high-income region. Estimate and CI exceeds the plottable area. Abbreviations: ART, antiretroviral therapy; BMI, body mass index; CI, confidence interval; CIS, cisgender persons; DASI, Duke Activity Status Instrument; GBD, global burden of disease; HIV, human immunodeficiency virus; INSTI, integrase-strand transfer inhibitor; NNRTI, non-nucleoside reverse transcriptase inhibitor; NRTI, nucleoside/nucleotide reverse transcriptase inhibitor; PATS-F, persons identifying across transgender spectrum among natal females; PATS-M, persons identifying across the transgender spectrum among natal males; PI, protease inhibitor; .
Figure 2.
Figure 2.
Percent of participants reporting no impairment on each question type of the DASI. 100% indicates that all participants were able to complete. The color of each bar indicates the weighting in the calculated DASI score, with darker colors carrying more weight in the score (eg, question 4 and 8 with the most weight). The question is indicated along the X-axis, with specific questions provided in Supplementary Table. Abbreviation: DASI, Duke Activity Status Instrument.
Figure 3.
Figure 3.
In the left panel, functional status categories are grouped along the X-axis. Categories of ASCVD risk scores are shown with darker colors indicating higher risk within each functional status category and overall. In the right panel, functional status categories are grouped along the X-axis. Proportion of participants meeting metabolic syndrome criteria are shown within each functional status category and overall. Abbreviations: ASCVD, atherosclerotic cardiovascular disease; PCE, Pooled Cohort Equation.
Figure 4.
Figure 4.
Association between baseline functional status (no impairment, some impairment, or moderate/severe impairment) on the difference in BMI by kg/m2. ASCVD risk score or WC are in cm. Associations were estimated using linear regression adjusted for GBD region. Abbreviations: ASCVD, atherosclerotic cardiovascular disease; BMI, body mass index; CI, confidence interval; GBD, global burden of disease; WC, waist circumference.
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