Symptoms and Comorbidities Differ Based on Race and Weight Status in Persons Living With HIV in the Northern United States: a Cross Sectional Study.

Background: Persons living with HIV (PLWHIV) on highly active antiretroviral treatments (HAART) may require specialized care based on health and demographic indicators. This study investigated the association of co-morbidities, race, weight status, gastrointestinal (GI), and cardiovascular symptoms (CV) and among PLWHIV. Methods: The Symptom Checklist, Co-Morbidity, and Sociodemographic Questionnaires were used to assessed weight status, GI, and CV symptoms among 283 PLWHIV. Data were analyzed using Latent Class Analysis on John's Macintosh Project 13 Platform. Results: Participants were majority Black (50%), 69% male, and 35% AIDS diagnosed. Ages were 25 to 66. Clusters included least symptomatic status, weight gain, and weight loss by Black and non-Black participants. The non-Black weight gain cluster reported a higher incidence of AIDS (70.6% vs 38.2%), nausea (70.6% vs 17.6%), diarrhea (70.6% vs 26.5%), and shortness of breath (58.8% vs 20.6%) compared to the Black weight gain cluster. The Black weight loss cluster reported a higher incidence of CV symptoms such as chest palpitations (42.2% vs 2.7%), chest pain (44.4% vs 8.1%), and shortness of breath (73.3% vs 35.1%), and a higher incidence of all GI symptoms with the most prominent being diarrhea (71.1% vs 48.6%) compared to the non-Black weight loss cluster. Conclusions: The existing racial disparities in health-related quality of life for PLWHIV may be improved through precision health and nutrition modications. Continued research is needed investigating differential health outcomes among PLWHIV on HAART.


Background
Human Immunode ciency Virus (HIV), a viral infection previously known as the wasting disease, has become a chronic yet manageable disease due to the advent of Highly Active Antiretroviral Treatments Although HAART has prolonged life, studies suggest that it may also be associated with weight gain, (7)(8)(9) CV disease, and GI symptoms. (4,7) Weight gain after initiating HAART occurs frequently and is associated with lower mortality, thus it is looked upon as a favorable outcome. (9) However, excessive weight gain may lead to an increased risk of chronic conditions such as hypertension, Diabetes Mellitus, and CV disease. (7) In fact, CV disease is the leading cause of death among PLWHIV.(8) Current literature has shown that weight changes in PLWHIV on HAART have signi cant implications for health outcomes. CV disease and PLWHIV on HAART must have ongoing investigations to identify factors that will guide care over the lifespan. Gastrointestinal symptoms such as nausea, vomiting, diarrhea, and loss of appetite affect health outcomes for PLWHIV on HAART. Increases in body mass index are common in HIV positive minorities and women. Symptoms were found to vary with patient race, age, and disease progression.(9, 10) Racial differences in conjunction with symptom presentation in uence treatment options. The clinician selects the proper treatment based on weight status (e.g., weight gain, weight loss), race, and symptoms (especially loss of appetite, acquired immunode ciency syndrome [AIDS] classi cation, diarrhea, vomiting, and overeating). The selection of a speci ed treatment option is of paramount importance because the grid of care options varies, care options even oppose one another for certain groups. The care for Black/African American PLWHIV on HAART that lose weight and have a loss of appetite is quite different than the care for Black/African American PLWHIV on HAART who gain weight and overeat. The proper choice of treatment option improves patients' outcomes and accuracy of care provided by practitioners.
Limited clinical research exists on the topics of changes in weight status, race classi cation, gastrointestinal health, and CV health among PLWHIV on HAART. Clinicians bene t from knowledge regarding this population that will guide personalized care that targets each speci c demographic group based on the needs based on their weight status, their demographics, and presenting symptoms. The health disparities for patients classi ed as Black/African American in terms of CV disease and HIV disease are well documented in nursing science. There is a higher burden of CV risk factors and CV disease in patients Black/Africa American.(11) Additionally, it is 13 times more likely that a Black/African American over the age of 50 will receive an HIV diagnosis than a White/Caucasian over 50. To address these disparities, providers must provide ongoing and personalized care for this population. (12) As such, monitoring for PLWHIV on HAART may require strati cation and personalization based on demographics and symptoms. The differences found may be attributable to patients' race, sex, weight status, comorbidities, and presenting symptoms. Moreover, as PLWHIV on HAART age, comorbidities require closer examination especially in terms of racial differences. (13) Current literature associated with weight status and multiple morbidities in PLWHIV either examine the change in weight status/body mass index [BMI] related to race after HAART initiation, (14) changes in BMI across a life span,(15) multiple morbidities and obesity without examining the effects of race(16) or multiple morbidities and aging, (17) with some attention to weight/obesity.(8) Although research has been conducted on this topic, there is limited clinical research investigating these variables in a clinical population. Most research included epidemiological large, cross-sectional studies and literature reviews.
The present study is a secondary data analysis of a clinical population. Therefore, the aim of this study was to investigate the association of race (Black and non-Black [Asian, Mixed-race and Whites]), weight status (weight gain and weight loss), and gastrointestinal and cardiovascular symptoms (nausea, vomiting, shortness of breath, chest pain) and co-morbidities (Hypertension, Coronary artery disease, heart failure) among persons living with HIV/AIDS. The ndings of this study will contribute to the growing body of research addressing adverse effects experienced by PLWHIV on HAART and provide important information related to personalized treatment, especially related to race.

Methods
A secondary analysis was performed on data from the parent study, Improving Adherence to Antiretroviral Therapy (R01 NR04749, PI, J. A. Erlen, University of Pittsburgh), in which the aim of the study was to improve adherence to antiretroviral therapy in PLWHIV through a nurse delivered, telephone-based intervention. The parent study recruited 356 PLWHIV on HAART from the Northern United States, speci cally, western Pennsylvania and eastern Ohio community hospitals, university-based clinics, comprehensive HIV care centers, and through self-referral.(18) Inclusion criteria for the parent study included a positive HIV diagnosis by a health care provider being treated with antiretroviral medication, access to a telephone, and consent to participate in the study.
In this cross-sectional secondary analysis, inclusion criteria included participants who submitted responses to all CV and GI symptoms and comorbidity questions on the Symptom Checklist, Co-Morbidity Questionnaire, and Sociodemographic questionnaire (Center for Research in Chronic Disorders, University of Pittsburgh School of Nursing, 1999). Applying these inclusionary criteria to the parent study sample resulted in 283 participants for the current study.
To analyze data from the 283 participants, Latent Class Analysis (LCA) was implemented with John's Macintosh Project [JMP] 13 to perform an analysis of self-reported data on the three aforementioned questionnaires. LCA is an unsupervised, multivariate grouping method that ts a model and determines the most likely 'latent class' of each participant, in a pre-selected number of discreet classes (Statistical Aanalysis System [SAS] Institute Inc., 2016). In this analysis, three groups were selected a-priori.

Results
Of the participants, approximately 50% self-identi ed as Black, 69% as male, and 35% as having AIDS.
Participants' ages ranged from 25 to 66 years (mean age = 43.70 years) as shown in Table 1. The participants were grouped into clusters by race, Black and non-Black. Within the Black and non-Black groups, a pattern developed among the three clusters. Each racial group had a cluster of PLWHIV who reported the lowest incidence of symptoms (weight loss, weight gain, vomiting, etc.) and comorbidities, a cluster characterized with a high incidence of weight gain and weight loss. Thus, each cluster was labelled based on the most prevalent symptom. Within each racial group (Black and non-Black), the clusters were: least symptomatic cluster, weight gain cluster, and weight loss cluster. Afterwards, descriptive statistics were calculated using International Business Machines Corporation Statistical Package for the Social Science (IBM SPSS) Version 25) to ascertain the overall and average number of self-reported symptoms and co-morbidities for each cluster within the Black and non-Black groups. A chart of the percentage of all GI and CV symptoms and comorbidities reported can be found in Table 2.

Weight Gain Clusters
Results revealed a high incidence of weight gain and overeating among participants in the weight gain clusters. Compared to the Black weight gain cluster, the non-Black weight gain cluster reported the highest incidence of AIDS (70.6% vs 38.2%), nausea (70.6% vs 17.6%), diarrhea (70.6% vs 26.5%), and shortness of breath (58.8% vs 20.6%). The Black weight gain cluster reported low incidence of GI symptoms (i.e., vomiting, abdominal pain), but a higher incidence of CV co-morbidities than the any other cluster (14.7%).

Discussion
The aim of this study was to investigate the association among race (Black, non-Black), weight status, (weight gain and weight loss) and symptoms/co-morbidities

Multiple Morbidities and Microbial Translocation/Disease Progression
Antiretroviral treatments aid in replenishing the CD4 T-cell count and decreasing the viral load, which reduces in ammation in the gut associated lymphoid tissue and promotes immune reconstitution.
Through the administered surveys, it appeared as though Black and non-Black participants in the least symptomatic clusters were able to manage their HIV. Of the participants in the Black and non-Black least symptomatic cluster, 23% vs 29.4%, respectively reported an AIDS diagnosis. The lower incidence of AIDS had an association with fewer reports of GI and CV symptoms and comorbidity compared to the weight gain and weight loss clusters. This nding may indicate a reduced occurrence of the translocation of microbes and/or restored or improved CD4 + T-cell count due to an early initiation of HAART. (21) It is also possible that the absence of an AIDS diagnosis is indicative of the e cacy and tolerability of HAART in participants in the least symptomatic cluster, which in turn suppresses the progression of HIV.

Race/Ethnicity and Weight Status
In this study, PLWHIV differed by race, weight status, and types of chronic disease conditions. Race included Black and non-Black individuals. Several studies (14,22) have likewise found these differences by race/ethnicity, co-morbidities, and weight status among PLWHIV. Additionally, among the participants diagnosed with AIDS in this study, non-Black men had the highest prevalence of the disease. However, according to the Centers for Disease Control and Prevention, Black men have the highest prevalence of AIDS diagnoses. (23) This atypical burden of a higher number of reported AIDS diagnoses in non-Black males may be attributed to more non-Black males with AIDS enrolled in the study compared to their Black male counterparts (52% vs 47%). The higher prevalence of non-Black men with AIDS enrolled in this study could also be indicative of factors such as later diagnosis and treatment, (24) or a lower tolerability of HAART.

HAART and Weight
Initiating HAART has been associated with increasing BMI, and long-term use can lead to obesity. (25) The Black Weight Gain cluster had a higher BMI than the non-Black weight gain cluster (29.8% vs 27.9%). The higher BMI and self-reported weight gain could be attributed to a "return to health," depression), or other factors such as unemployment (22) or metabolic syndrome.(26) According to several studies (14,22) race attributed to the differences between weight gain and BMI. Participants who identi ed as Black were found more likely to have higher BMI and weight gain than their counterparts. These differences may be due to higher CD4 T-cell count, a longer duration of HAART,(7) and/ or a higher pretreatment CD4 T-cell count. (14) The non-Black weight gain group reported a higher incidence of GI symptoms (loss of appetite, diarrhea, vomiting) compared to their counterparts in the Black weight gain group. Such symptoms typically are associated with weight loss.(27) A lower BMI has been shown to be associated with a higher mortality risk for patients on HAART. (25) Gastrointestinal symptoms such as nausea, vomiting, weight loss, and diarrhea are common in PLWHIV.
(4, 28) Although such symptoms were reported in both the weight loss and weight gain clusters, these symptoms were reported more frequently in the weight loss clusters. The GI symptoms could be attributable to the disease itself or a side effect of HAART medication.(29) A possible explanation for the higher incidence of weight loss and loss of appetite in the non-Black weight loss cluster could be a combination of multiple factors such as early vs late HAART initiation, antiretroviral e cacy and tolerability, disease progression, and race.

Strengths
This study adds to the growing body of literature investigating health status among PLWHIV. Our ndings contribute new knowledge to the limited research examining the role of weight and its effects on GI symptoms and cardiovascular risks among PLWHIV. Insights into the relationships among this tetrad (race, weight, GI symptoms, and cardiovascular risks) suggests a call for primary prevention to address and promote healthy weight status to improve health-related quality of life for PLWHIV.

Limitations
The research design included a secondary data analysis that utilized a sample size of approximately 283 individuals with complete information on three questionnaires. As such the sample size prevents (or limits) generalizability of the results as the secondary data analysis was not purposefully prospectively powered. Limited data points prevented in-depth statistical analysis.

Conclusions
Weight changes affect both GI and cardiovascular symptoms for PLWHIV. As such, nutritional interventions may be bene cial for managing weight and reducing adverse effects for PLWHIV. (30) Moreover, although the use of HAART medication is bene cial for treating and managing HIV infection, the long-term use of HAART medications may be problematic for healthy weight maintenance. Therefore, monitoring of weight status is important for PLWHIV for reducing chronic disease conditions such as cardiovascular disease, hypertension, and diabetes; co-morbid conditions that adversely affect healthrelated quality of life. Precision health initiatives hold promise for health-care treatments for PLWHIV; such advances may indeed continue to prolong years of healthy living.