Sarcopenia and Frailty in Persons Living with HIV on Integrase Strand Transfer Inhibitors (INSTIs): A Retrospective Observational Cohort Study Open Access

Buckley, Kahsavyah (Spring 2026)

Permanent URL: https://etd.library.emory.edu/concern/etds/ms35tb45r?locale=en
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Abstract

With increasing life expectancy among persons living with HIV (PLWH), age-related conditions such as sarcopenia and frailty have emerged as important contributors to morbidity and mortality. Integrase strand transfer inhibitors (INSTIs), now recommended as first-line antiretroviral therapy (ART), have been associated with weight gain and changes in body composition, raising concern for potential contributions to these conditions. This study aimed to evaluate the association between INSTI use and the prevalence of sarcopenia and frailty over time compared with non-INSTI ART regimens and persons without HIV (PWOH).

We conducted a retrospective longitudinal cohort analysis using data from the MACS/WIHS Combined Cohort Study (MWCCS), including 2,804 participants (567 INSTI, 754 non-INSTI, 1,483 PWOH). Sarcopenia was defined using grip strength adjusted for body mass index (BMI), and frailty was defined using the Fried frailty phenotype. Generalized linear mixed-effects logistic regression models were used to estimate adjusted odds ratios (ORs) over time relative to the pre-switch period, accounting for repeated measures and adjusting for key covariates. Sex-stratified analyses were also performed.

At baseline, the prevalence of sarcopenia and frailty was similar across groups. Over time, INSTI use was not associated with a statistically significant increase in the odds of sarcopenia or frailty compared with pre-switch levels or other groups. A transient increase in sarcopenia was observed among participants receiving non-INSTI ART at 1–2 years post-switch (OR 1.62, 95% CI 1.07–2.43), but this was not sustained. Across all models, confidence intervals frequently crossed unity, and no consistent or clinically meaningful trends were observed. Sex-stratified analyses yielded similar findings, with no statistically significant associations.

Despite the absence of significant differences between groups, the overall prevalence of sarcopenia and frailty remained relatively high, underscoring their clinical relevance in an aging HIV population. These findings suggest that INSTI-based ART may not independently increase the risk of sarcopenia or frailty over the observed follow-up period. Future studies incorporating more precise measures of body composition and longer follow-up are needed to further elucidate these relationships.

Table of Contents

TABLE OF CONTENTS

Introduction ……………………………………… 1

Aims and Hypotheses …………………… 3

Methods ………………………………………… 4

Results ………………………………………… 11

Discussion ……………………………………… 29

Conclusion ……………………………………… 34

References ……………………………………… 35

LIST OF TABLES

Table 1. Baseline Demographic and Clinical Characteristics of Study Participants by Study Group ………………… 13

Table 2. Baseline Distribution of Sarcopenia and Frailty by Study Group ………………………………………………… 16

Table 3. Distribution of Grip Strength and Gait Speed Components by Study Group ……………………………………… 16

Table 4. Adjusted and Sex Stratified Odds Ratios for Sarcopenia and Frailty Over Time by Study Group (95% Confidence Intervals and P Values) ……………………………………… 24

LIST OF FIGURES

Figure 1. Study Schema of Time Points Assessed Pre and Post Switch …………………………………………………… 4

Figure 2. Study Cohort Selection Diagram ………………… 6

Figure 3. Predicted Prevalence of Sarcopenia Over Time by Study Group ………………………………………………… 17

Figure 4. Predicted Prevalence of Frailty Over Time by Study Group …………………………………………………… 18

Figure 5. Forest Plot of Adjusted Odds of Sarcopenia Over Time by Study Group ……………………………………… 20

Figure 6. Forest Plot of Sex Stratified Adjusted Odds of Sarcopenia Over Time (Females) ……………………………… 20

Figure 7. Forest Plot of Sex Stratified Adjusted Odds of Sarcopenia Over Time (Males) ………………………………… 21

Figure 8. Forest Plot of Adjusted Odds of Frailty Over Time by Study Group …………………………………………… 22

Figure 9. Forest Plot of Sex Stratified Adjusted Odds of Frailty Over Time (Females) …………………………………… 23

Figure 10. Forest Plot of Sex Stratified Adjusted Odds of Frailty Over Time (Males) …………………………………… 23

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