Incidence of and Risk Factors for Non-AIDS Comorbidities Following SARS-CoV-2 Infection in People Living with HIV in Atlanta, Georgia Restricted; Files Only

Abstract

Since the start of 2020, coronavirus disease 2019 (COVID-19), a clinical syndrome caused by infection with the novel coronavirus, SARS-CoV-2, has been at the forefront of the minds of researchers and citizens of the world alike. This virus has disproportionately affected persons with underlying health conditions and those living at a lower socioeconomic status. People living with HIV (PLWH) are infected with SARS-CoV-2 at a higher rate than their seronegative counterparts. Recent research has indicated that persons who acquire COVID-19 are at risk for developing incident comorbidities after acute infection. Risk factors for and incidence of post-COVID-19 non-AIDS comorbidities (NACM) in PLWH specifically remain unknown. Among PLWH co-infected with SARS-CoV-2 cared for at the Ponce de Leon Center in Atlanta, GA between March 1, 2020, and September 30, 2022, we 1) investigated the incidence of post-COVID-19 NACM and 2) identified risk factors among PLWH associated with post- COVID-19 NACM. Among 3540 PLWH included, 261 had documented COVID-19 and 3279 did not have documented COVID-19, with similar median age, race, CD4+ cell count, and HIV viral load (VL) between the groups. We assessed 8 categories of non-AIDS comorbidities, including cardiometabolic disease, cardiovascular disease, chronic kidney disease, diabetes mellitus, hypertension, lung disease, neurologic disease, and psychiatric disease both as the overall burden (e.g, presence of any NACM) and separately (e.g., incidence of each individual NACM). COVID+ participants had a longer time to development of any NACM, with a shorter time to development of cardiometabolic disease, compared with the COVID- group. The COVID+ group also had a lower risk of developing any incident NACM. A subgroup analysis revealed that participants with more prevalent NACM are at greater risk for developing incident NACM compared to those with fewer pre-existing NACM. Across COVID groups, female PLWH had a greater annual risk of developing any NACM, compared to males in both COVID groups. Our study among PLWH at a single center highlights that the subset of women with both HIV and COVID-19 are at particularly high risk for incident NACM and also underscores the negative effects that the pandemic had even on persons uninfected with COVID-19. 

Table of Contents

Table of Contents

Introduction ...................................................................................................................................1

Background and Study Inspiration

Non-AIDS Comorbidities (NACM) in Persons Living with HIV (PLWH) Chronic Post-COVID-19 Complications

COVID-19 in Persons Living with HIV

Study Aims

Methods ..........................................................................................................................................5

Study Design

Sample Size

Study Population and Enrollment Criteria Exposure Variable

Non-AIDS Comorbidity Incidence Covariate Selection

Data Analysis Plan

Results...........................................................................................................................................12

Baseline Participant Demographics

Prevalent and Incident Non-AIDS Comorbidities

Time to and Risk of Developing non-AIDS Comorbidities

Effect of Date of COVID-19 Diagnosis

Effect of Non-AIDS Comorbidities Burden

Incident non-AIDS Comorbidities within COVID+ Group Only

Risk Factors Associated with Annual Incidence of Non-AIDS Comorbidities All-Cause Mortality in People Living with HIV During the COVID-19 Pandemic

Discussion .....................................................................................................................................29

Participant Differences by COVID-19 Status

Sex Differences in and the Effect of Age and Detectable HIV VL on Incident Post-COVID-19 Incident Comorbidities

Time-Dependent Effects on Annual Incidence of Non-AIDS Comorbidity

Year of COVID-19 Diagnosis

Effect of Burden of Pre-Existing non-AIDS Comorbidities on incident non-AIDS Comorbidities Pandemic Effects on COVID- People Living with HIV

Limitations and Future Directions

Appendix ......................................................................................................................................37

Tables & Figures

Tables

Table 1. Definitions of Selected Classes of Non-AIDS Comorbidities

Table 2. Bivariate Analyses for Potential Confounders with Exposure and Outcome of Interest Table 3. Participant Demographic Data at Index Date

Table 4. Hazard Ratio for Risk of incident NACM by year of COVID Pandemic

Table 5. NACM Burden by COVID-19 Status

Table 6a. Sub-Group Analysis for incident NACM, grouped by NACM Burden

Table 6b. Sensitivity Analysis for incident NACM, comparing different NACM Burden

Table 7. Adjusted Risk for any Incident NACM in participants with NACM Burden = 0

Table 8. Hazard Ratio for Covariates associated with Annual Incident Risk of Any NACM

Table 9. Hazard Ratio for Covariates associated with Annual Incident Risk of Any NACM, separated by

COVID-19 Status

Table 10. Risk of Incident NACM in Females versus Males Living with HIV (both COVID+ and

COVID-)

Table 11. All-Cause Mortality at 365 Days from Index Date

Figures

Figure 1. Study Timeline, enrollment, and follow-up periods.

Figure 2. Directed Acyclic Graph evaluating Potentially Confounding Clinical Characteristics on the

Effect of COVID-19 on development of NACM

Figure 3. Flowchart of CFAR registry participants with eligibly criteria for this study

Figure 4. Annual Incidence of NACM in COVID+ and COVID- PLWH

Figure 5. Annual Prevalence and Incidence of NACM for COVID+ and COVID- PLWH

Figure 6. Median Time to development of NACM in COVID+ and COVID- PLWH

Figure 7. Adjusted Hazard Ratios for Development of Incident NACM in COVID+ versus COVID-

PLWH

Figure 8. Adjusted Survival Probability Curves for Incident NACM in COVID+ and COVID- PLWH Figure 9. Probability Curves for development of any incident NACM based on index year

Figure 10. Survival Probability for Incident NACM stratified by pre-existing NACM Burden

Figure 11. Time to Incident NACM within the COVID+ group

References ....................................................................................................................................44 

About this Master's Thesis

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School	Laney Graduate School
Department	Clinical Research
Degree	M.S.
Submission	Master's Thesis
Language	English
Research Field	Health Sciences, Medicine and Surgery Health Sciences, General Health Sciences, Public Health
Keyword	HIV COVID-19 non-AIDS comorbidities
Committee Chair / Thesis Advisor	Amita Manatunga, Emory University Jordan Kemper, Emory University
Committee Members	Cecile Lahiri, Emory University Minh Nguyen, Emory University Caitlin Moran, Emory University Lauren Collins, Emory University

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