Clusters of co-morbidities in those with HIV show major non-HIV medical needs

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Most health problems in people living with HIV in two large cohorts can be classified in six clusters, with cardiovascular disease, metabolic problems, sexually transmitted infections and mental health conditions being the most common in Britain, Ireland and the Netherlands, according to researchers at University College London, Amsterdam Institute for Global Health and Development, Imperial College London, and University College Dublin.

The clusters identified in the study reveal the major non-HIV medical needs of people living with HIV, especially older adults, and the needs for prevention of ill health. Findings from the study were also presented at the Conference on Retroviruses and Opportunistic Infections (CROI 2019).

Two cohorts were analysed in the study, which was designed to detect patterns in potentially preventable co-morbidities in people living with HIV and to provide information to help better targeting of interventions and a better understanding of shared patho-physiology of co-morbidities.

The POPPY cohort consisted of 699 people with HIV aged 50 or over and 374 younger people with HIV, receiving care in the UK and Ireland – 85% of the cohort was male, the median age was 52, 15.9% were black African, and 76% were men who have sex with men. Participants had been living with HIV for a median of 13.2 years, 97.5% were on antiretroviral treatment and 89.9% had a viral load below 50 copies/ml.

The median age in the over-50 segment of the cohort was 57 years and duration of HIV infection was slightly longer (15.8 years) but in other respects the older segment was demographically similar to the overall cohort.

The AGEhIV cohort consisted of 598 people living with HIV aged 45 and over receiving care in the Netherlands. Demographic characteristics and HIV history were very similar to the overall POPPY cohort.

Co-morbidities were captured through a structured interview cross-checked against medical records. There were a few differences in the list of co-morbidities asked about in the two cohorts.

The most common single co-morbidities in POPPY were gonorrhoea (42.6%), syphilis (30.4%), depression (32.4%) and dyslipidaemia (27.3%). In AGEhIV the most common co-morbidities were hypertension (43.1%), osteopenia/osteoporosis (42.6%), lipodystrophy/lipoatrophy (32.1%) and candidiasis (31.9%). In both cohorts, people reported a median of five co-morbidities.

The researchers analysed the relationship between co-morbidities to identify conditions that are more likely to occur together in the same person than would be expected by chance alone. In the POPPY cohort, they identified six clusters: cardiovascular (angina, coronary bypass surgery, heart attack, heart failure, high blood pressure, peripheral vascular disease, end stage kidney disease); sexually transmitted diseases (gonorrhoea, lymphogranuloma venereum [LGV], chlamydia, hepatitis C); mental health (depression, anxiety, panic attacks); cancers (blood cancers, skin cancer, solid organ cancer);
metabolic (abnormal lipids, lipodystrophy, high blood pressure); and chest and other infections (cytomegalovirus [CMV], pneumonia, dizziness/vertigo, asthma/bronchitis/chronic obstructive pulmonary disease [COPD], chest infection).

Similar clusters were seen in AGEhIV.

Moreover, in the POPPY study: people with a higher burden of cardiovascular disease tended to have a lower burden of sexually transmitted infections, and vice versa; and depression was associated with sleeping problems and irritable bowel syndrome. Greater severity of mental health problems was strongly associated with severity of all other health patterns, but especially cancers and chest and other infections.

In the older people in the POPPY cohort, greater cardiovascular disease severity was associated with greater severity of mental health, metabolic and asthma scores. In older individuals, panic attacks were associated with asthma/bronchitis/COPD.

In the AGEhIV study: cardiovascular disease was most strongly associated with a past history of Aids-defining conditions; depression was associated with neurological problems such as dizziness/vertigo; and more severe general health problems were strongly associated with greater severity of cardiovascular disease, chest or liver disorders, and mental health or neurological problems.

The investigators say that their findings demonstrate that “comorbidities do not co-occur at random, and in general, are likely to cluster in specific patterns, some which are consistent across different cohorts.”

Although some of the clusters – such as cardiovascular disease and metabolic problems – are well recognised and have common pathologies, other patterns are less well established, they say. The strong association between mental health and neurological problems deserves more investigation, as do the associations between mental health disorders and cardiovascular disease, metabolic problems and sexually transmitted infections.

Looking at the POPPY cohort alone, the researchers also found that different co-morbidity clusters were associated with different risk factors. For example, prior Aids was associated with cardiovascular disease, mental health problems, cancers and chest or other infections, but not with metabolic problems. People with a history of injecting drug use, who formed about 10% of the cohort, were less likely to have co-morbidities except for mental health problems or sexually transmitted infections.

Surprisingly, current or former smoking was not associated with any co-morbidity cluster, and nor was nadir CD4 cell count.

Abstract 1
Background: The aims of this study were to identify common patterns of comorbidities observed in people living with HIV (PLWH), using a data-driven approach, and evaluate associations between patterns identified.
Methods: A wide range of comorbidities were assessed in PLWH participating in 2 independent cohorts (POPPY: UK/Ireland; AGEhIV: Netherlands). The presence/absence of each comorbidity was determined using a mix of self-reported medical history, concomitant medications, health care resource use, and laboratory parameters. Principal component analysis (PCA) based on Somers’ D statistic was applied to identify patterns of comorbidities.
Results: PCA identified 6 patterns among the 1073 POPPY PLWH (85.2% male; median age [interquartile range {IQR}], 52 [47–59] years): cardiovascular diseases (CVDs), sexually transmitted diseases (STDs), mental health problems, cancers, metabolic disorders, chest/other infections. The CVDs pattern was positively associated with cancer (r = .32), metabolic disorder (r = .38), mental health (r = .16), and chest/other infection (r = .17) patterns (all P < .001). The mental health pattern was correlated with all the other patterns (in particular cancers: r = .20; chest/other infections: r = .27; both P < .001). In the 598 AGEhIV PLWH (87.6% male; median age [IQR], 53 [48–59] years), 6 patterns were identified: CVDs, chest/liver, HIV/AIDS events, mental health/neurological problems, STDs, and general health. The general health pattern was correlated with all the other patterns (in particular CVDs: r = .14; chest/liver: r = .15; HIV/AIDS events: r = .31; all P < .001), except STDs (r = –.02; P = .64).
Conclusions: Comorbidities in PLWH tend to occur in nonrandom patterns, reflecting known pathological mechanisms and shared risk factors, but also suggesting potential previously unknown mechanisms. Their identification may assist in adequately addressing the pathophysiology of increasingly prevalent multimorbidity in PLWH.

Davide De Francesco, Sebastiaan O Verboeket, Jonathan Underwood, Emmanouil Bagkeris, Ferdinand W Wit, Patrick WG Mallon, Alan Winston, Peter Reiss, Caroline A Sabin

Abstract 2
Comorbidities in people living with HIV (PLWH) may occur in clusters, potentially affecting quality of life and general health in different ways. We explored associations of risk factors and patient reported health outcomes with common clusters of co-occurring comorbidities.
We considered 65 comorbidities reported by PLWH via a structured interview with trained staff. Principal component analysis was used to identify non-random clusters of co-occurring comorbidities and obtain a score for each cluster proportional to the number of comorbidities included in the cluster and present in an individual. Cluster scores were standardised (mean=0, SD=1), with higher scores indicating a greater number of comorbidities characterising a cluster. Multivariable median regression was then used to investigate associations of sociodemographic, lifestyle and HIV-specific factors with each cluster score. Multivariable linear regression was used to evaluate associations of cluster scores (independently of each other) with physical and mental health summary scores (obtained from SF-36 questionnaire, range 0-100).
In 1073 PLWH (85% male, 84% white ethnicity, median (IQR) age 52 (47-59) years) we identified 6 comorbidity clusters (Table). ‘CVDs’, ‘metabolic’ and ‘chest/other infections’ scores were independently associated with older age and longer time since HIV diagnosis (all p’s<0.001). Higher body-mass index was associated with higher scores in the ‘CVDs’ (p=0.009), ‘cancers’ (p=0.03) and ‘metabolic’ clusters (p=0.006). PLWH with prior AIDS events had higher scores than PLWH without prior AIDS events for all clusters (p<0.05) except ‘STDs’. Associations with smoking and alcohol consumption were weak across all clusters (all p’s>0.05). Higher scores in the ‘mental health’ and ‘chest/other infections’ clusters were independently associated with poorer SF-36 physical (p’s<0.001) and mental health scores (p<0.001 and p=0.03, respectively – Table). ‘CVDs’ and ‘cancers’ scores were associated with poorer physical (p=0.02, p=0.03) but not mental health (p’s>0.05).
Comorbidity clusters in PLWH are associated with different demographic, lifestyle and HIV-related factors, and significantly impact on quality of life, particularly physical functioning. Identifying common comorbidity clusters in PLWH may help prioritise interventions for those at risk for poorer health outcomes and focus research to understand common pathophysiological pathways contributing to comorbidities in treated PLWH.

Davide De Francesco, Sebastiaan Verboeket, Jonathan Underwood, Ferdinand Wit, Emmanouil Bagkeris, Patrick W Mallon, Alan Winston, Peter Reiss, Caroline Sabin

Aidsmap material
Open Forum Infectious Diseases abstract
CROI 2019 abstract

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