Introduction

Social determinants of health (SDH) (comprising a range of social, economic, and environmental factors) are “the conditions in which people are born, grow, live, work and age” which influence health outcomes [1]. They play a central role in driving health inequalities; in the UK, despite free-at-the-point-of-contact healthcare, health outcomes demonstrate a marked social gradient, with the most socio-economically disadvantaged groups having the lowest life expectancy and disability-free life expectancy [2]. Low income and employment, low levels of education, poor quality housing and overcrowding, loneliness and social isolation, ethnicity, and sex have all been demonstrated to contribute to the development of long-term conditions and poor health outcomes [3]. SDH are also associated with multimorbidity, where an individual lives with more than one long-term condition [4]. Multimorbidity [5,6] affects almost one-third of adults in the UK, with a significant impact on healthcare resources, accounting for more than half of primary care appointments and admissions to hospital [7].

People with HIV experience a disproportionate level of intersecting social disadvantages including lower socioeconomic status [8], poor mental health [9], substance misuse [10], structural racism [11], sex-based violence [12], and in particular, HIV-related stigma including self-stigma [13]. The impact of SDH on engagement with HIV care and virological suppression is well recognized; nonwhite ethnicity, low education level, low health literacy, poverty, food insecurity, homelessness, criminal justice involvement, and intimate partner violence have all been associated with suboptimal engagement with care, poor adherence to antiretroviral therapy (ART) and/or viral rebound [14–18].

People with HIV already live with one chronic health condition, and compared with age-matched adults without HIV, are more likely to accumulate additional comorbidities and live fewer disability-free years, despite effective treatment with ART [19]. Age-related comorbidities such as atherosclerotic cardiovascular disease, diabetes, and chronic kidney disease are more prevalent in this population [20,21], may manifest at a younger age and/or follow a more accelerated course than in the general population [22,23], and contribute to an estimated three-fold increase in mortality per additional comorbidity acquired [24]. Poor mental health is also commonly reported by people with HIV [8,25–29].

The drivers of multimorbidity in people with HIV are many and complex. Apart from traditional risk factors (such as smoking, dyslipidemia, obesity, and hypertension), immune dysregulation, chronic inflammation, HIV viraemia, and exposure to (especially older) antiretroviral agents play an important role in pathogenesis of comorbidities in HIV [22,30–33].

Despite the well evidenced links between SDH and multimorbidity, and HIV and multimorbidity, there are limited data on the intersecting relationship between SDH and multimorbidity in people with HIV. Studies often focus on single exposures, such as the association between homelessness or housing insecurity and poor physical or mental health, or the association between low socioeconomic status and frailty [34]. Such approaches fail to attend to the complexity and intersectionality of people's lives and may limit our ability to provide optimal care and support for people experiencing social marginalization.

Drawing upon quantitative cross-sectional data from the Cardiovascular disease, Kidney disease, and Diabetes in people of African ancestry with HIV (CKD-AFRICA) study, we investigated associations between SDH and comorbidity and multimorbidity in people of black ethnicities living with HIV in South London, UK, an area with high socioeconomic deprivation, multimorbidity and HIV prevalence [35,36].

Materials and methods

This is an analysis of data from the CKD-AFRICA study, conducted to identify clinical and sociodemographic risk factors for cardiovascular disease, diabetes, and kidney disease. People were eligible to participate in the study if they were living with HIV, aged between 30 and 65 years, of self-reported black African, black Caribbean and/or other black ethnicities, and had previously participated in the Genetic Determinants of Kidney Disease in People of African Ancestry with HIV (GEN-AFRICA) study (NCT05685810) at one of three participating study sites across South London. Participation in GEN-AFRICA was open to all adults of black ethnicities with HIV, who attended for HIV follow-up care at one of nine recruiting sites across the UK, and who were able and willing to provide informed consent, demographic and clinical data, and a blood and urine sample for research [37]. All consecutive clinic attendees meeting these criteria were approached at routine clinic visits over a 21-month period and invited to participate.

Between September 2020 and January 2022, attendees were approached at routine clinic visits and invited and consented to participate in a single study visit. Participants were reimbursed £25 for time and travel after all study procedures had been completed. The study was approved by a National Health Service Research Ethics Committee (20/LO/0946) and the Health Research Authority (IRAS 278244) and all participants provided written informed consent.

Exposure variables

The following parameters were obtained at the study visit; sex at birth, age, anthropometric data (height, weight, and waist circumference) and three standardized blood pressure measurements. HIV parameters (time since HIV diagnosis, being on and time since starting ART, nadir and recent CD4+ cell count, HIV RNA, and hepatitis B surface antigen and antihepatitis C status) and other clinical parameters (use of antihypertensive medication, alcohol consumption, smoking status, CRP, HbA1c, and APOL1 status [0/1/2 variant alleles) were obtained from clinical notes, self-reported medical history, and fasted urine and blood samples.

Data on socioeconomic status and quality of life were measured by self-completion of paper questionnaires (with support when required), using validated tools; Questionnaire for Verifying Stroke-Free Status [38], St George's Respiratory Questionnaire [39], Hospital Anxiety and Depression Scale [40], the Short Discrimination and Stigma Scale [41], Social Functioning Questionnaire [42] and EQ-5D-5L [43]. Data on employment status, highest completed education level, housing status, income, food security, immigration status, caring responsibilities, and social support were obtained [44]. SDH were defined using composite or simple parameters and included financial insecurity, food insecurity, housing insecurity, migration status insecurity, job insecurity, low education status, social isolation, and discrimination (Table 1). Heath care access was not considered as a variable of interest as all UK-based clinics provide high-quality, free at the point of access healthcare and medication for HIV, regardless of migration status.

Table 1 - Definitions of the social determinants of health. Variable Type Definition Financial insecurity Composite Being behind with some or most bills, or
Not having enough money to meet basic needs or having enough money to meet basic needs only some of the time, or
Having needed financial support in the last year Food insecurity Simple Having needed food support in the last year Housing insecurity Simple Living in temporary accommodation, living with friends or family (lacking own accommodation), or being homeless Migration status insecurity Composite Having temporary or limited leave to remain, or having no legal status in the UK, or
Having needed immigration support in the last year Job insecurity Composite Being unemployed, sick, or disabled, or
Having needed employment support in the last year Low educational status Simple The equivalent of O levels (age 16) or less Social isolation Composite Being alone or isolated, defined as feeling often:
  - a lack of companionship, or
  - left out or isolated from others, or
  - lonely, or
Having no one to turn to for emotional support, or
Having needed support with loneliness/isolation in the last year Discrimination Composite Feeling little or not at all fairly treated
  - by friends, in dating situations, in starting a family or in their social life in general, or
  - with regards to housing, education or job opportunities, or
  - with regards to respect to their privacy or personal security and safety, or
Feeling avoided because of the HIV status
Outcome variables

A full self-reported medical history including previously diagnosed cardiovascular disease, diabetes, kidney, lung, liver disease and cancer as well as any other long-term conditions was obtained. Definitions of individual comorbidities of interest (diabetes, kidney disease, cardiovascular disease, lung disease, poor mental health, and chronic pain) are described in Table 2. These were chosen as prevalent conditions of clinical significance among people of black ethnicities and those living with HIV [45,46].

Table 2 - Definitions of risk factors, comorbidities, and multimorbidity. Variable Type Definition Risk factors  Obesity Simple BMI ≥30 kg/m2  Systemic hypertension Composite Mean of the second and third readings of SBP ≥140 mmHg and/or
 Mean of the second and third readings of DBP ≥90 mmHg and/or
 Being on antihypertensive medication Comorbidities  Diabetes mellitus Composite HbA1c ≥6.5% and/or
 Being on hypoglycemic medication  Kidney disease Composite eGFR <60 ml/min/1.73 m2 and/or
 albumin/creatinine ratio >3 mg/mmol  Cardiovascular disease Composite Arterial disease, defined as
 - Diagnosis of cardiovascular or cerebrovascular accident according to medical history or the stroke questionnaire; or
 - Diagnosis of congestive cardiac failure, or
 Venous disease, defined as having been diagnosed with deep venous thrombosis or pulmonary embolism  Lung disease Composite Having a diagnosis of asthma, chronic obstructive pulmonary disease, or interstitial lung disease; or
 Having symptomatic lung disease, i.e.: cough, phlegm, shortness of breath and/or wheezing on several or most days  Chronic pain Composite Pain present for >1 year, or
 Attending pain clinic, or
 Having moderate, severe, extreme pain resulting in time off work, seeing GP, or requiring analgesia  Poor mental health Composite HADS score for anxiety and/or depression >11; or
 Self-reported moderate, severe, or extreme anxiety and/or depression; or
 On medication for anxiety, depression, or other psychiatric illnesses Multimorbidity  Main definition Simple ≥2 of diabetes mellitus, kidney disease, cardiovascular disease, lung disease, and a composite of poor mental health and/or chronic pain  Restricted definition Simple ≥2 of diabetes mellitus, kidney disease, cardiovascular disease, and lung disease  Expanded definition Simple ≥2 of diabetes mellitus, kidney disease, cardiovascular disease, lung disease, other significant comorbidity (Table S2), excluding poor mental health and chronic pain  Sensitivity definition Simple ≥2 of diabetes mellitus, kidney disease, cardiovascular disease, lung disease, poor mental health, and chronic pain, each counted as separate comorbidities

BP, blood pressure; eGFR, estimated glomerular filtration rate; HADS, Hospital Anxiety and Depression Score.

Multimorbidity was defined as a simple count of the presence of two or more of the comorbidities of interest (in which poor mental health and chronic pain were a composite comorbidity). An expanded definition of multimorbidity included any other self-reported condition as described in Table 2.

No formal sample size calculation was performed. A pragmatic sample size based on the total number of participants in the GEN-AFRICA study, with the aim of recruiting 75 individuals each with diabetes and kidney disease, and 50 with cardiovascular disease, along with 200 people without any reported or measured comorbidity, was obtained; the total sample size was 400, enriched for some of the outcomes of interest as within the GEN-AFRICA study, the majority of participants did not report multiple comorbidities.

Statistical analysis

Participant characteristics were described, according to distribution of variables, and multiple correspondence analysis was performed to determine clustering of comorbidities. Logistic regression models were used to describe associations between SDH (financial insecurity, food insecurity, housing insecurity, migration status insecurity, job insecurity, low education status, social isolation, and discrimination) and the individual comorbidities of interest and multimorbidity.

All multivariate models were a priori adjusted for age and sex at birth [47]. Additional covariates considered for inclusion included those that were deemed to be clinically relevant, not on the causal pathway and P value less than 0.1 in univariable analysis. Where a comorbidity was associated with more than one SDH, separate multivariate models were generated for each SDH to account for collinearity among various SDH.

As poor mental health and chronic pain were noted to be strongly associated with SDH in multiple correspondence analysis (Fig S1, https://links.lww.com/QAD/D114), several posthoc sensitivity analyses were performed to examine this relationship. For associations with individual comorbidities, participants with poor mental health and/or chronic pain were excluded. For the multimorbidity analyses, participants with poor mental health and/or chronic pain were excluded and poor mental health and chronic pain were each included as individual comorbidities. Of note, obesity and hypertension were considered risk factors for diabetes and kidney/cardiovascular disease, respectively, and not analyzed as comorbidities or as constituents of multimorbidity.

The approach to the analysis was informed by the syndemics framework, which explicitly recognizes that HIV may cluster with other conditions, interact through social, psychological or biological pathways, and is driven by harmful social conditions [48]. We placed an emphasis on the co-occurrence with various SDH associates with both comorbidity and multimorbidity, rather than looking at only one determinant in isolation. Data were complete for clinical data and near complete for questionnaire data and complete case analysis was applied for missing data. All statistical analyses were performed using R (R Foundation, Vienna, Austria; version 4.2.1).

Results

A total of 398 participants were enrolled in the study. Of these, 112 (28%) were free of comorbidities; 19% had diabetes, 28% kidney disease, 8% cardiovascular disease, 16% lung disease, 30% poor mental health, 26% chronic pain, and 11% other comorbidities (Table 3, and Table S1, https://links.lww.com/QAD/D114); 131 participants (33%) had a single comorbidity and 155 (39%) had two or more comorbidities. Overall, median age was 52 (interquartile range [IQR] 45–57) years, 55% were women and most had longstanding and well controlled HIV on ART (Table 3, and Tables S2–S4, https://links.lww.com/QAD/D114). Hypertension and obesity were common (present in 53 and 50%, respectively) and 9·4% were current smokers. Several expected associations between demographic/clinical parameters and comorbidities were noted, including male sex, hepatitis C virus co-infection, BMI, systemic hypertension, and CRP with diabetes; systemic hypertension and diabetes with kidney disease; and smoking status with lung disease (Table S5, https://links.lww.com/QAD/D114).

Table 3 - Demographic, clinical, and social characteristics of the study participants. Overall Female Male n 398 218 180 P a Demographics/ HIV parameters  Age 52 [45,57] 51 [45, 56] 54 [45, 58] 0.026 Region of birth <0.001  Sub-Saharan Africa 288 (72.4) 174 (79.8) 114 (63.3)  Caribbean 37 (9.3) 10 (4.6) 27 (15.0)  UK/Other 73 (18.3) 34 (15.6) 39 (21.7) HIV acquisition mechanism 0.64  Sex between men and women 336 (87.7) 186 (88.6) 150 (86.7)  Sex between men 1 (0.3) 0 (0) 1 (0.6)  Vertical transmission 40 (10.4) 20 (9.5) 20 (1.6)  Blood products 1 (0.3) 1 (0.5) 0 (0)  Unknown 5 (1.3) 3 (1.4) 2 (1.2)  Time since HIV infection diagnosis (years) 14 [10, 18] 14 [10, 18] 14 [9, 18] 0.96  On ART 395 (99.2) 215 (98.6) 180 (100.0) 0.32  Time since starting ART (years) 10 [7, 15] 10 [7, 15] 11 [6, 15] 0.89  HIV RNA ≥200 copies/ml 23 (5.8) 11 (5.0) 12 (6.7) 0.64  Nadir CD4+ cell count 161 [70, 276] 138 [52, 266] 180 [81, 283] 0.11  Recent CD4+ cell count 548 [372, 749] 544 [362, 750] 562 [384, 746] 0.72  HCV Ab positive 5 (1.3) 3 (1.5) 2 (1.2) 1.00  HBsAg positive 27 (7.2) 17 (8.2) 10 (5.9) 0.50 Risk factors  Current smoker 36 (9.4) 17 (8.1) 19 (11.0) 0.43  Systemic hypertension 212 (53.3) 111 (50.9) 101 (56.1) 0.35  BMI (kg/m2) 30.0 [26.5, 34.2] 32.2 [27.6, 36.8] 28.2 [25.7, 31.3] <0.001  Waist (cm) 98 [90, 105] 98 [89, 107] 97 [90, 104] 0.29  CRP (mg/l) 2 [1, 5] 3 [1, 5] 2 [1, 3] <0.001 APOL1 gene - number of G1/G2 variant alleles 0.61  0 156 (41.5) 90 (43.7) 66 (38.8)  1 148 (39.4) 79 (38.3) 69 (40.6)  2 72 (19.1) 37 (18.0) 35 (20.6) Comorbidities  Diabetes mellitus 74 (18.6) 34 (15.6) 40 (22.2) 0.12  Kidney disease 111 (27.9) 60 (27.5) 51 (28.3) 0.95  Cardiovascular disease 33 (8.3) 18 (8.3) 15 (8.3) 1.00  Lung disease 64 (16.1) 34 (15.6) 30 (16.7) 0.88  Poor mental health 120 (30.2) 70 (32.1) 50 (27.8) 0.41  Chronic pain 105 (26.4) 74 (33.9) 31 (17.2) <0.001  Other comorbidities 45 (11.3) 27 (12.4) 18 (10.1) 0.56 Number of comorbidities 0.79  None 112 (28.1) 59 (27.1) 53 (29.4)  Single comorbidity 131 (32.9) 71 (32.6) 60 (33.3)  Multimorbidityb 155 (38.9) 88 (40.4) 67 (37.2) Socioeconomic factors  Financial insecurity 207 (52.3) 118 (54.4) 89 (49.7) 0.41  Food insecurity 83 (22.3) 54 (26.6) 29 (17.2) 0.040  Housing insecurity 44 (11.1) 27 (12.5) 17 (9.5) 0.43  Migration status insecurity 48 (12.3) 27 (12.6) 21 (11.9) 0.96  Job insecurity 113 (28.4) 65 (29.8) 48 (26.7) 0.56  Low educational status 124 (32.0) 74 (35.2) 50 (28.2) 0.17  Loneliness and isolation 129 (32.5) 74 (34.1) 55 (30.6) 0.52  Discrimination and unfair treatment 124 (33.3) 68 (33.7) 56 (32.9) 0.97 Number of SDH reported 0.62  None 68 (14.7) 35 (13.7) 33 (16.0)  One or more 330 (85.3) 183 (86.3) 147 (84.0)  HIV status not disclosed to family or friends 88 (22.2) 51 (23.5) 37 (20.6) 0.56

APOL1, Apolipoprotein L1; ART, antiretroviral treatment; CRP, C-reactive protein; HBsAg, hepatitis B virus surface antigen; HCV Ab, hepatitis C cirus antibody.aCategorical data are described with absolute (n) and relative (%) frequencies and compared with the Chi-squared test (with continuity correction), except HCV Ab frequencies which are compared by Fisher's exact test.Continuous data are described with the median and interquartile range and compared with the Kruskal–Wallis test.

bDefined as two or more comorbidities.Data in bold indicate statistically significant differences between female and male participants.

Social determinants of health were highly prevalent in the study population, with 330 (85%) reporting at least one SDH. Financial insecurity was reported by 52%, and loneliness and social isolation, discrimination, or unfair treatment by one-third; 22% had not disclosed their HIV status to anyone beyond their immediate healthcare providers (Table 3).

The associations between SDH and the comorbidities of interest are presented in Table 4. There were no associations between any SDH, and either diabetes or kidney disease. Job insecurity was associated with cardiovascular disease (adjusted odds ratio [aOR] 3.27, 95% confidence interval [CI] [1.44–7.56]); job insecurity (aOR 2.38 [1.30–4.31]), and food insecurity (aOR 2.38 [1.30–4.31]) were associated with lung disease. In sensitivity analyses restricted to participants without poor mental health or chronic pain, associations remained for both job insecurity and cardiovascular disease (aOR 3.53 [1.00–12.2]) and lung disease (aOR 2.69 [1.02–6.82]) but not for food insecurity and lung disease (aOR 2.07 [0. 67–5.80]).

Table 4 - Associations between social determinants of health and comorbidities. Diabetes mellitus (N = 74) Kidney disease (N = 111) Cardiovascular disease (N = 33) Univariate model Multivariate modela Univariate model Univariate model Multivariate modelb Social determinants of health OR 95%CI P aOR 95%CI P OR 95%CI P OR 95%CI P aOR 95%CI P Financial insecurity 1.09 0.66, 1.82 0.73 – – – 0.93 0.60, 1.44 0.74 1.37 0.66, 2.91 0.40 – – – Food insecurity 1.66 0.91, 2.94 0.09 1.91 0.96, 3.71 0.06 1.17 0.67, 1.98 0.57 1.48 0.62, 3.25 0.35 – – – Housing insecurity 0.96 0.40, 2.06 0.92 – – – 1.54 0.78, 2.94 0.20 0.23 0.01, 1.12 0.16 – – – Migration status insecurity 1.19 0.54, 2.43 0.65 – – – 1.10 0.55, 2.11 0.77 1.02 0.29, 2.75 0.97 – – – Job insecurity 1.27 0.73, 2.17 0.39 – – – 1.39 0.86, 2.22 0.18 2.60 1.25, 5.37 0.009 3.27 1.44, 7.56 0.005 Low educational level 0.64 0.35, 1.13 0.14 – – – 0.89 0.55, 1.43 0