Risk Factors and Impact of Patterns of Co-Occurring Comorbidities in People Living With HIV

Davide De Francesco; Jonathan Underwood; Emmanouil Bagkeris; Jane Anderson; Ian Williams; Jaime H. Vera; Frank A. Post; Marta Boffito; Margaret Johnson; Patrick W.G. Mallon; Alan Winston; Caroline A. Sabin; on behalf of the Pharmacokinetic and Clinical Observations in PeoPle Over fiftY (POPPY) study


AIDS. 2019;33(12):1871-1880. 

In This Article


Common patterns of comorbidities seen in PLWH appear to have different HIV-related and non-HIV-related risk factors and demonstrate different associations with quality of life, functional status and healthcare resource use.

As we previously reported,[5] disease patterns identified are consistent with those reported by other studies in PLWH[10] and in the general population[23–25] with the addition of the pattern of STDs, reflecting the high exposure to risk-taking sexual behaviours that is prevalent in PLWH.[26] Associations with risk factors varied from pattern to pattern with several associations reflecting previously known risk factors, for example BMI and age for both CVD and metabolic disorders. STDs were more prevalent in MSM and PLWH with a history of injection drug use, consistent with reports of high-risk sexual behaviours in both groups.[26,27] Injection drug use was also associated with mental health pattern severity. Although it is not possible to determine the direction of associations seen, evidence suggests that mental health problems can both lead to, and be a consequence of, injection drug use.[28] Age and BMI were associated with both the cancers and the chest/other infections pattern severity scores, however strong links with these patterns were also observed for HIV-specific factors such as the time since HIV diagnosis and prior clinical AIDS. AIDS-defining malignancies were considered separately from the three cancers that form the pattern (i.e. skin cancer, haematological and solid organ cancers). Therefore, this could reflect a genuine association where prolonged immune activation and inflammation and/or severe immunosuppression may have contributed to an increased burden of non-AIDS-defining cancers, as also suggested by a previous study.[29] Moreover, the time since HIV diagnosis and a prior AIDS diagnosis were associated with other patterns (CVD, mental health and metabolic), independently of age, suggesting a link between persistent immune activation and inflammation with CVDs and metabolic disorders as well as with mental health problems.

In contrast to what would be expected, neither tobacco smoking nor alcohol consumption were identified as potential risk factors for any pattern. This could reflect the generally moderate frequency of smoking and alcohol consumption in POPPY PLWH [the median (IQR) self-reported number of cigarettes smoked per day and units of alcohol consumed per week were 10 (5, 20) and 7 (2, 18), respectively]. Alternatively the lack of association could reflect reverse causation due to most comorbidities preceding the time when smoking and alcohol consumption were assessed (i.e. at baseline study visit). Current alcohol abstinence and/or nonsmoking status may reflect previous hazardous over consumption which may have led to disorders which, in turn, may have caused people to stop smoking and/or consuming alcohol.

Patterns were also significantly associated with health outcomes with differential effects from pattern to pattern. Of the six patterns identified, chest/other infections demonstrated the strongest associations with patient-reported physical health, functional impairment and hospitalization. Several of the infections included in this pattern, cytomegalovirus in particular, have been reported to act as proinflammatory agents, also involved in the process of chronic inflammation.[30,31] Given its association with age, time since HIV diagnosis and prior AIDS, this pattern is likely to be accompanied by prolonged immune activation and inflammation which, in turn, may have led to poorer physical health and functional limitations as also shown in different settings.[32,33] The mental health pattern showed strong associations with all health outcomes considered, independently from the associations between mental health and other patterns. Beside the expected link with patient-reported mental health, these results seem to support a strong link with physical functioning and healthcare resource use. Significantly, the STDs pattern appeared to be associated with better physical health and a lower number of GP visits, once accounting for the severity of the other patterns. Although results seem to suggest a positive effect, they should be read with caution as they are relative to the severity of other patterns and also to the average outcomes seen in the cohort. Nevertheless, this apparently positive effect may reflect the fact that treated STDs may no longer pose a serious health danger and/or PLWH with multiple STDs may be healthier overall than their counterparts with other patterns of comorbidities, such as CVDs or mental health disorders.

There are some limitations to our study that need to be considered. First, since there is not a uniform list of comorbidities and medical conditions to define multimorbidity, the list of comorbidities considered here can be debated. Some comorbidities may have been missed; some of those considered require a medical diagnosis, while others consist more of symptoms and were therefore less objectively defined. Second, although the self-reported nature of data collection may have led to under or over reporting of some comorbidities, our approach consisted in a structured interview conducted by trained staff to ensure consistency across study participants and that allowed to capture all the comorbidities with the same standardized procedure. Third, the cross-sectional nature of the analysis does not permit an assessment of causality or the direction of the associations seen (and whether they are bidirectional); longitudinal studies are on plan and would allow to shed light on the direction of associations. Finally, our cohort was designed to be representative of the population of PLWH seen in care in United Kingdom and Ireland, predominantly characterized by white MSM; therefore, results could be less generalizable to populations of PLWH within different HIV epidemic settings.

With an increasingly ageing population of PLWH[34] and the consequent increase in the prevalence of multimorbidity,[35] these findings highlight the need for targeted interventions and guidelines for the prevention, diagnosis, treatment and prognosis of multimorbidity in PLWH. The identification of risk factors for specific patterns of comorbidities could help the development of targeted interventions towards modifiable risk factors in PLWH presenting with one or more of the comorbidities in the pattern to prevent the onset of new comorbidities that are likely to co-occur with the existing ones. Similarly, treatment of comorbidities in patterns with the highest impact on quality of life and healthcare resource use could lead to potential benefits for both the patient and the healthcare system. Further longitudinal studies are justified to assess the change over time in patterns' severity and to elucidate the causal link with health outcomes.