Patterns of Co-occurring Comorbidities in People Living With HIV

Davide De Francesco, Sebastiaan O Verboeket, Jonathan Underwood, Emmanouil Bagkeris, Ferdinand W Wit, Patrick W G Mallon, Alan Winston, Peter Reiss, Caroline A Sabin, Pharmacokinetic and Clinical Observations in PeoPle Over fiftY (POPPY) study and the AGEhIV Cohort Study, Daphne Babalis, Marta Boffito, Laura Burgess, Paddy Mallon, Frank Post, Caroline A Sabin, Memory Sachikonye, Alan Winston, Jane Anderson, David Asboe, Marta Boffito, Lucy Garvey, Paddy Mallon, Frank Post, Anton Pozniak, Caroline A Sabin, Memory Sachikonye, Jaime Vera, Ian Williams, Alan Winston, Amanda Clarke, Jaime Vera, Andrew Bexley, Celia Richardson, Sarah Kirk, Rebecca Gleig, Marta Boffito, David Asboe, Anton Pozniak, Margherita Bracchi, Nicole Pagani, Maddalena Cerrone, Daniel Bradshaw, Francesca Ferretti, Chris Higgs, Elisha Seah, Stephen Fletcher, Michelle Anthonipillai, Ashley Moyes, Katie Deats, Irtiza Syed, Clive Matthews, Peter Fernando, Chido Chiwome, Shane Hardwick, Jane Anderson, Sifiso Mguni, Rebecca Clark, Rhiannon Nevin-Dolan, Sambasivarao Pelluri, Frank Post, Lucy Campbell, Selin Yurdakul, Sara Okumu, Louise Pollard, Beatriz Santana-Suarez, Paddy Mallon, Alan Macken, Bijan Ghavani-Kia, Joanne Maher, Maria Byrne, Ailbhe Flaherty, Sumesh Babu, Ian Williams, Damilola Otiko, Laura Phillips, Rosanna Laverick, Michelle Beynon, Anna-Lena Salz, Abigail Severn, Alan Winston, Lucy Garvey, Jonathan Underwood, Lavender Tembo, Matthew Stott, Linda McDonald, Felix Dransfield, Andrew Whitehouse, Laura Burgess, Daphne Babalis, Margaret Johnson, Nnenna Ngwu, Nargis Hemat, Martin Jones, Anne Carroll, Sabine Kinloch, Mike Youle, Sara Madge, Caroline A Sabin, Davide De Francesco, Emmanouil Bagkeris, P Reiss, F W N M Wit, M van der Valk, J Schouten, K W Kooij, R A van Zoest, E Verheij, S O Verboeket, B C Elsenga, M Prins, M F Schim van der Loeff, L Del Grande, V Olthof, M Dijkstra, S Zaheri, M M J Hillebregt, Y M C Ruijs, D P Benschop, A El Berkaoui, N A Kootstra, A M Harskamp-Holwerda, I Maurer, M M Mangas Ruiz, A F Girigorie, B Boeser-Nunnink, W Zikkenheiner, F R Janssen, S E Geerlings, A Goorhuis, J W R Hovius, F J B Nellen, T van der Poll, J M Prins, P Reiss, M van der Valk, W J Wiersinga, M van Vugt, G de Bree, F W N M Wit, J van Eden, A M H van Hes, F J J Pijnappel, A Weijsenfeld, S Smalhout, M van Duinen, A Hazenberg, P G Postema, P H L T Bisschop, M J M Serlie, P Lips, E Dekker, N van der Velde, J M R Willemsen, L Vogt, J Schouten, P Portegies, B A Schmand, G J Geurtsen, F D Verbraak, N Demirkaya, I Visser, A Schadé, P T Nieuwkerk, N Langebeek, R P van Steenwijk, E Dijkers, C B L M Majoie, M W A Caan, H W van Lunsen, M A F Nievaard, B J H van den Born, E S G Stroes, W M C Mulder, S van Oorspronk, Davide De Francesco, Sebastiaan O Verboeket, Jonathan Underwood, Emmanouil Bagkeris, Ferdinand W Wit, Patrick W G Mallon, Alan Winston, Peter Reiss, Caroline A Sabin, Pharmacokinetic and Clinical Observations in PeoPle Over fiftY (POPPY) study and the AGEhIV Cohort Study, Daphne Babalis, Marta Boffito, Laura Burgess, Paddy Mallon, Frank Post, Caroline A Sabin, Memory Sachikonye, Alan Winston, Jane Anderson, David Asboe, Marta Boffito, Lucy Garvey, Paddy Mallon, Frank Post, Anton Pozniak, Caroline A Sabin, Memory Sachikonye, Jaime Vera, Ian Williams, Alan Winston, Amanda Clarke, Jaime Vera, Andrew Bexley, Celia Richardson, Sarah Kirk, Rebecca Gleig, Marta Boffito, David Asboe, Anton Pozniak, Margherita Bracchi, Nicole Pagani, Maddalena Cerrone, Daniel Bradshaw, Francesca Ferretti, Chris Higgs, Elisha Seah, Stephen Fletcher, Michelle Anthonipillai, Ashley Moyes, Katie Deats, Irtiza Syed, Clive Matthews, Peter Fernando, Chido Chiwome, Shane Hardwick, Jane Anderson, Sifiso Mguni, Rebecca Clark, Rhiannon Nevin-Dolan, Sambasivarao Pelluri, Frank Post, Lucy Campbell, Selin Yurdakul, Sara Okumu, Louise Pollard, Beatriz Santana-Suarez, Paddy Mallon, Alan Macken, Bijan Ghavani-Kia, Joanne Maher, Maria Byrne, Ailbhe Flaherty, Sumesh Babu, Ian Williams, Damilola Otiko, Laura Phillips, Rosanna Laverick, Michelle Beynon, Anna-Lena Salz, Abigail Severn, Alan Winston, Lucy Garvey, Jonathan Underwood, Lavender Tembo, Matthew Stott, Linda McDonald, Felix Dransfield, Andrew Whitehouse, Laura Burgess, Daphne Babalis, Margaret Johnson, Nnenna Ngwu, Nargis Hemat, Martin Jones, Anne Carroll, Sabine Kinloch, Mike Youle, Sara Madge, Caroline A Sabin, Davide De Francesco, Emmanouil Bagkeris, P Reiss, F W N M Wit, M van der Valk, J Schouten, K W Kooij, R A van Zoest, E Verheij, S O Verboeket, B C Elsenga, M Prins, M F Schim van der Loeff, L Del Grande, V Olthof, M Dijkstra, S Zaheri, M M J Hillebregt, Y M C Ruijs, D P Benschop, A El Berkaoui, N A Kootstra, A M Harskamp-Holwerda, I Maurer, M M Mangas Ruiz, A F Girigorie, B Boeser-Nunnink, W Zikkenheiner, F R Janssen, S E Geerlings, A Goorhuis, J W R Hovius, F J B Nellen, T van der Poll, J M Prins, P Reiss, M van der Valk, W J Wiersinga, M van Vugt, G de Bree, F W N M Wit, J van Eden, A M H van Hes, F J J Pijnappel, A Weijsenfeld, S Smalhout, M van Duinen, A Hazenberg, P G Postema, P H L T Bisschop, M J M Serlie, P Lips, E Dekker, N van der Velde, J M R Willemsen, L Vogt, J Schouten, P Portegies, B A Schmand, G J Geurtsen, F D Verbraak, N Demirkaya, I Visser, A Schadé, P T Nieuwkerk, N Langebeek, R P van Steenwijk, E Dijkers, C B L M Majoie, M W A Caan, H W van Lunsen, M A F Nievaard, B J H van den Born, E S G Stroes, W M C Mulder, S van Oorspronk

Abstract

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.

Keywords: HIV; comorbidities; multimorbidity; patterns of comorbidities.

Figures

Figure 1.
Figure 1.
Significant nonrandom associations between comorbidities (as indicated by a significant Somers’ D at the 0.1% significance level) in all POPPY PLWH (n = 1073). The thickness of the line is directly proportional to the absolute value of the Somers’ D. Abbreviations: CABG, coronary artery bypass graft; CMV, cytomegalovirus; GERD, gastro-esophageal reflux disease; IBS, irritable bowel syndrome; LGV, lymphogranuloma venereum; MI, myocardial infarction; PLWH, people living with HIV; PVD, peripheral vascular disease; TB, tuberculosis; TIA, transient ischemic attack.
Figure 2.
Figure 2.
Significant nonrandom associations between comorbidities (significant Somers’ D at the 0.1% significance level) in all older POPPY PLWH (A) and AGEhIV PLWH (B). The thickness of the line is directly proportional to the absolute value of the Somers’ D. Abbreviations: CABG, coronary artery bypass graft; CMV, cytomegalovirus; COPD, chronic obstructive pulmonary disease; IBS, irritable bowel syndrome; LGV, lymphogranuloma venereum; MI, myocardial infarction; PLWH, people living with HIV; PVD, peripheral vascular disease; TIA, transient ischemic attack.

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