Psychological Distress and Associated Factors among Patients with Hemophilia Living with HIV: The Japan Cohort Study of HIV-Infected Patients through Blood Products

1. INTRODUCTION

Remarkable progress has been made in the treatment of people infected with HIV, and the mortality rate has decreased [1-5]. However, long-term medical treatment and mental and psychological conditions are becoming increasingly important issues.

Several studies have reported on the severity of psychological distress and its associated factors among people living with HIV. In Ethiopia, Tesfaye et al. (2020) found that generalized psychological distress was independently associated with moderate stress, low social support, multiple negative life events, non-disclosure of HIV status, and low CD4 cell count [6]. In a much earlier study, Blomkvist et al. (1994) showed that psychosocial self-prognosis, measured by a Coping Wheel psychosocial tool, was related to mortality and morbidity in patients with hemophilia and HIV infection [7]. In Canada, Choi et al. (2015) validated three screening instruments, including the Kessler Psychological Distress Scale, for identifying depression in HIV specialty care settings [8]. Across studies, between 5% and 39% of participants with HIV infection have been classified as experiencing mild to severe anxiety or depression [9-14]. Moreover, a recent meta-analysis reported that nearly one quarter of younger people living with HIV experience depression, with substantial proportions also reporting anxiety and suicidal ideation (Zhan et al., 2024) [15].

In Japan, there have been 1,432 cases of HIV infection through blood products (AIDS Surveillance Committee, & Ministry of Health, Labour and Welfare of Japan 2001) [16]. A research program for people with HIV infection has been carried out since fiscal year 1993, with support from the Ministry of Health and Welfare (currently the Ministry of Health, Labour and Welfare) [17] and the Japan Cohort Study of HIV Patients Infected through Blood Products. The Japan cohort study, based on this program, was started at the same time. In Japan, Kawado et al. (2023) recently reported that after the introduction of combination anti-HIV therapy over 24 years in patients with hemophilia living with HIV, HIV RNA levels decreased, resulting in decreased mortality, and HCV RNA levels decreased, resulting in decreased mortality [4]. These findings indicate that clinical outcomes in this population have markedly improved. However, despite these advances in survival and virological control, less is known about their psychological well-being, which is the focus of the present study. Limited studies have focused on the psychological status of patients with hemophilia living with HIV. Drotar et al. (1997) reported that total mood disturbance was observed in 39% of patients with hemophilia living with HIV, but aged 8-17 [18]. Brown et al. (1995) investigated how adolescents with hemophilia living with HIV cope with reminders of their HIV status, and about one-third of these reported experiencing intense nervousness and sadness [19]. However, there are few recent reports on psychological distress or its associated factors in patients with hemophilia living with HIV. The available studies have generally been based on small sample sizes, often limited to single-center experiences or qualitative case reports, and therefore provide only fragmentary evidence [20-23]. As a result, the psychological burden and related factors in this population remain insufficiently characterized, underscoring the need for large-scale, quantitative analyses such as the present study.

Thus, this study aimed to investigate the status of severe psychological distress in patients with hemophilia living with HIV and examine the associated factors, including worries and stress.

2. METHODS

3. RESULTS

Table 1 shows the participant characteristics and prevalence of severe psychological distress. Of 437 participants, 68 (15.6%) experienced severe psychological distress. The proportions of severe psychological distress among respondents with a subjective health status of “Bad” and “Moderate” to “Fair” were 31.9% and 6.5%, respectively, which is a significant difference. In the same way, the proportions of severe psychological distress among worries and stress of “Yes” and “No” were 19.8% and 1.0%, respectively, which was a significant difference. Only one person who answered “No” for “worries and stress” was classified as having severe psychological distress, but his K6 score was 13 points, which was the threshold value. There were no significant differences in the proportion of patients with severe psychological distress according to age group, CD4 cell count, HIV RNA level, anti-HIV regimen use, or living arrangements.

Table 2 shows the association between the causes of worries and stress and severe psychological distress among participants with worries and stress. The odds ratios for each of the eight causes of worry and stress for severe psychological distress were adjusted for subjective health status. The adjusted odds ratios of five items (“Relationships with family,” “Relationships with people other than family,” “Purpose in life,” “Income, household finances, and debt etc.,” and “Housing and living environment (including pollution, safety, and traffic conditions)”) ranged from 1.84 to 2.67, all of which were significant.

Table 3 shows the association between consultations on worries and stress and severe psychological distress. The odds ratio of each of the nine items of consultation about worries and stress for severe psychological distress was adjusted for subjective health status. The adjusted odds ratio of one item (“Cannot consult anyone”) was 2.32, which was significant. To further illustrate these findings, we created a forest plot of the significant factors identified in Tables 2 and 3, depicting odds ratios with 95% confidence intervals (Fig. S1).

The Hosmer–Lemeshow goodness-of-fit test showed p > 0.05 for all logistic regression models, suggesting that the models adequately fit the data. All pairwise correlations between explanatory variables were within ±0.3, indicating no serious multicollinearity.

4. DISCUSSION

This study investigated psychological distress and its related factors among patients with hemophilia living with HIV in Japan. Of 437 participants, 68 (15.6%) experienced severe psychological distress. In the general Japanese population, previous studies showed that the prevalence of a K6 score of 13 points or higher was 2% to 6% [34-36], which suggests a considerably higher prevalence of severe psychological distress among the participants in this study. For hemophilia patients, not limited to HIV-infected, Kempton et al. (2021) reported that 8% of the study participants showed severe psychological distress (K6 score of 13 points or higher) [37, 38]. Thus, our study participants were more likely to have severe psychological distress than those with hemophilia alone. The prevalence of severe psychological distress in this study was approximately twice that of the hemophilia population. Given the high capture rate of this study population, we concluded that a high proportion of patients with hemophilia living with HIV had severe psychological distress.

A highly significant association between severe psychological distress and subjective health status was found in all participants. Health conditions are considered primary and underlying causes of psychological distress. These results are consistent with previous research showing that poor self-rated health increases psychological distress [13]. CD4 cell count, HIV RNA level, and use of anti-HIV regimens, which are objective indicators of health status, were not related to the presence of severe psychological distress. This may reflect the characteristics of our stabilized cohort, in which all participants were HIV-infected but pre-AIDS and most were receiving effective antiretroviral therapy, resulting in relatively limited variability in these clinical parameters. In addition, neither age nor living arrangements were associated with severe psychological distress. This may be because the age distribution in this study was relatively narrow, ranging from 37 to 71 years, and there were only a few young or elderly individuals. Regarding the living arrangements, Garriga et al. (2020) reported that the prevalence of severe psychological distress was higher among men with HIV infection when they lived alone, but there was no difference at all among women with HIV infection [11]. In this study, no significant differences were found, and the details are unclear.

The overall prevalence of worries and stress was 76% (334/437), and worries and stress were strongly associated with severe psychological distress. Almost all individuals experiencing severe psychological distress experience worries and stress. This suggests that in this population, worries and stress appear to be a key correlate of psychological distress rather than a necessary condition. A previous study also showed a similar tendency regarding these relationships, in which depression symptoms and anxiety symptoms are strong indicators of psychological distress [39]. Due to the cross-sectional design of this study, causal relationships cannot be inferred. It is also possible that psychological distress itself may heighten the perception of worries and stress, suggesting a potential bidirectional relationship between these factors.

Among those with worries and stress, various factors, such as relationships with family, relationships with people other than family, purpose in life, income, and the environment, were found to be associated with psychological distress. Health conditions (e.g., “One’s own illness or nursing care”) were not found to be related to severe psychological distress. In a study of a general Japanese male population, there was also a strong tendency to have psychological distress when “purpose in life”, “relationships with family,” or “relationships with people other than family” were the causes of stress, while there was also no difference in psychological distress with respect to one’s own health [40]. Thus, it is clear that a variety of factors cause worry and stress, and that a support system tailored to each individual's situation is needed after clarifying the causes of each person's worries and stress.

Regarding the association of consultation about worries and stress with severe psychological distress, only one item (“Cannot consult anyone”) was significantly associated. The prevalence of severe psychological distress did not significantly differ according to the type of consultants listed in the survey questionnaire: family, friends, acquaintances, consultation desks, physicians, nurses, medical social workers, clinical psychologists, or counselors. It was confirmed that the lack of consultation is an important issue for countermeasures against psychological distress in this population. A previous study using the 2016 Comprehensive Survey of Living Conditions data to examine help-seeking behavior and psychological distress among healthy employees in Japan also reported a strong association between this item and severe psychological distress (K6 score 13 or more), with the largest effect size of all items related to consultation about worries and stress [36]. Although the previous study involved healthy participants, it suggested a specifically strong association between not being able to consult anyone about worries and stress and severe psychological distress, which is consistent with the results of our study. To cope with severe psychological distress, it is necessary to improve the situation so that individuals have someone to consult.

These findings have potential clinical implications. Brief instruments such as the K6 scale may be considered for screening psychological distress in clinics providing care for patients with HIV infection and hemophilia. Clinicians should also remain attentive to interpersonal, economic, and environmental stressors that may contribute to psychological distress. In addition, referral pathways should be strengthened so that patients consistently have someone available for consultation, including healthcare professionals, family members, or support organizations. Recent studies have also emphasized the importance of integrating mental health screening and referral into HIV care. For example, brief tools such as the PHQ-2 for depression or simple suicide risk questions have been shown to be feasible in HIV clinic settings [41], and qualitative research highlights both acceptability and barriers to help-seeking among people living with HIV [42].

This study had several limitations. First, we used data from the Japan Cohort Study of HIV Patients Infected through Blood Products, which was based on a research project supported by the Ministry of Health, Labor, and Welfare of Japan [4, 26]. The data used in this study were limited to those collected during this research project. It would be desirable to compare these findings with a non-infected control group.

Furthermore, given the purpose of this study, we wanted to include all patients with hemophilia living with HIV. However, the study population excluded those who had developed AIDS. However, this survey covered almost all patients with hemophilia living with HIV in Japan [4]. The capture rate of non-AIDS cases is quite high and is not likely to be sufficiently problematic to affect interpretation. Second, psychological distress, worries, and stress were assessed using a self-administered questionnaire, not by professional psychologists or medical doctors. Although the appropriateness of the method for measuring worries and stress is unknown, the survey questionnaire items are identical to those of the National Survey of Living Conditions, one of Japan's core statistics, and the Japanese version of the K6 has sufficient validity and reliability [32]. Data were reported by participants and included missing values owing to unreported data, which, as shown in the results, were scarce. Third, the factors addressed as causes of psychological distress were limited to survey questionnaire items. A previous study indicated that sleeping less than five hours per day was also an associated factor [36]. Although we adjusted for subjective health status, residual confounding cannot be excluded. In particular, factors such as sleep quality, substance use, comorbid pain, and experiences of stigma, which were not assessed in this survey, may also contribute to psychological distress.

Furthermore, the domains of worries and stress, and consultation sources were assessed with single-item questions, which may not fully capture their complexity. These measurement limitations should be considered when interpreting the findings. Nevertheless, we believe that we were able to address and examine the most likely associated factors. Finally, this was a cross-sectional study at one point, making it difficult to discuss causality or longitudinal trends. Therefore, it is meaningful to observe these changes over time. Moreover, further insight into the support is required.

CONCLUSION

Patients with hemophilia living with HIV have a high prevalence of severe psychological distress. It was suggested that their psychological distress was associated with worries and stress caused by interpersonal problems, economic circumstances, purpose in life, living environment, as well as not having anyone to consult.

REFERENCES