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Fatigue among HIV+ patients in the era of HAART
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HIV Medicine
Volume 6 Issue 5 Page 347 - September 2005
M Henderson1, F Safa1, P Easterbrook2 and M Hotopf1
1Department of Psychological Medicine, Institute of Psychiatry, King's College, London, and 2Department of HIV/GU Medicine, Guy's, King's and St Thomas' School of Medicine, King's College, London, UK
"....Using a well-validated measure, we found that 65% had significant fatigue.... is similar to levels found in other chronic illnesses such as heart failure, systemic lupus erythematosis and rheumatoid arthritis. A high proportion of patients (68%) were identified as psychologically distressed.... this was strongly associated with fatigue.... We did not demonstrate an association between the presence of fatigue and more advanced HIV disease as measured by CD4 count and viral load....results suggest that fatigued patients feel they have little control over their condition and its progression.... the fatigued HIV-positive population had a much poorer quality of life...(ED NOTE: this study did not evaluate the presence or affect of HCV/HBV, which can affect fatigue & depression).
..... The strong association between psychological distress and markers of quality of life has implications for the clinical management of fatigue in HIV-infected patients. Firstly, it suggests that the symptom of fatigue should elicit not only a search for physical mechanisms, but also detailed questioning about depression and anxiety. Secondly, the high rates of psychological distress described here suggest that a proportion of patients have significant depression or anxiety which may benefit from specific interventions, such as antidepressant medication, which may also improve fatigue. Thirdly, there is growing evidence that nonpharmacological treatments such as cognitive behaviour therapy and graded exercise therapy are effective in the treatment of medically unexplained fatigue occurring in chronic fatigue syndrome [50-52]. Such treatments aim to help improve functioning by giving patients strategies for managing fatigue. Given the high prevalence, and apparently serious consequences for functional capacity, of fatigue in individuals with HIV infection, there is a need for further evaluation of these interventions in the HIV-infected patient population.....'
ABSTRACT
Objective: To describe the prevalence of operationally defined fatigue in an ethnically diverse HIV-infected population in south London, and to examine the association of fatigue with demographic characteristics, stage of disease, antiretroviral therapy and psychological factors.
Methods: A descriptive comparative cross-sectional study of HIV-infected patients attending a London HIV clinic over a 5-month period in 2002 was performed. Demographic and clinical data were obtained from the local database. Participants completed four self-administered questionnaires-the Chalder Fatigue Scale (CFS), a measure of physical and mental fatigue; the General Health Questionnaire (GHQ-12) to detect anxiety and depression; the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) to measure functional status, and the Illness Perception Questionnaire (IPQ). Fatigue 'cases' were defined as those scoring at least 4 on the CFS. Multivariate logistic regression was used to identify factors associated with the presence of fatigue.
Results: Two hundred and five patients were approached and 148 (72%) agreed to participate. Overall, 65% of patients were defined as fatigued. Significant psychological distress on the GHQ-12, functional impairment on the SF-36 and a higher CD4 count were all independently associated with the presence of fatigue. There was no association with use of antiretroviral therapy or demographic characteristics.
Conclusions: The presence of fatigue in HIV-infected patients is most strongly associated with psychological factors and not with more advanced HIV disease or the use of highly active antiretroviral therapy. This highlights the importance of investigation and management of underlying depression and anxiety in patients presenting with fatigue.
RESULTS
Two hundred and five eligible HIV-infected clinic patients were approached, and 143 completed questionnaires, a response rate of 70%. Compared with our total clinic population, our study population was more likely to be male (78% vs. 63%; P<0.001), less likely to be black African or black Caribbean (35% vs 43%; P<0.001) and more likely to be homosexual or bisexual (60% vs 38%; P<0.001) or on HAART (81% vs 68%; P<0.001). The prevalence of fatigue was 65.1% (95% confidence interval 57.4-72.8%).
Table 1 describes the demographic, clinical and psychological factors in patients with and without fatigue. There were no statistically significant differences in gender or age between the two groups. Fatigued individuals were more likely to be white (63.1% vs 44%) and to be homosexual or bisexual (61.3% vs 46%), but these were not statistically significant associations. Fatigue cases had higher CD4 counts than noncases (474 vs 399 cells/muL), but this was not statistically significant. The viral load was similar in the two groups. The type of antiretroviral therapy at the time of evaluation was also similar between the two groups. The presence of psychological distress as measured on the GHQ-12 was strongly associated with fatigue (86% vs 34%; P<0.001). There was also a strong correlation between total fatigue score and total GHQ-12 score (r=0.71; P<0.001). Fatigue cases had significantly higher scores on the 'consequences' scale of the IPQ, indicating that they perceived their HIV as having more serious consequences. There was a strong association between fatigue and SF-36 variables of functional status. On every dimension of the SF-36, fatigued participants scored lower, indicating greater impairment.
Multivariate logistic regression analysis was used to identify independent associations of fatigue, shown in Table 2. The final model indicated that four variables were associated with fatigue: higher CD4 counts, significant psychological distress on the GHQ-12, and reporting impairments on the SF-36 physical function and general health perception dimensions. When we included use of HAART in this model as a single variable and as an interaction term with CD4 count, it did not alter the magnitude or direction of the association between fatigue and CD4 cell count (result not shown).
INTRODUCTION
Since the introduction of highly active antiretroviral therapy (HAART) in 1996, there has been a substantial reduction in HIV-related mortality and the incidence of opportunistic infections in developed nations [1]. The use of HAART may also impact on HIV-related symptoms, with resolution of diarrhoea, night sweats and weight loss. Fatigue is a common symptom in individuals with chronic disease including HIV infection. Studies in the pre-HAART era found fatigue was present in 9 to 86% [2-13] of HIV-positive patients, and its presence has been associated with a significant impact on employment [5,14,15], self-care [3], and quality of life [2,5,7,9,12,16-18]. Factors associated with fatigue include increasing age [19,20], female gender [2,7] and injection drug use [2], as well as malnutrition [3,21], HIV myopathy [22,23], pain [2,24] and anaemia [2,5,11,19,25]. There is contradictory evidence regarding the association between HIV-related fatigue and stage of disease, with some studies demonstrating an association [5,7,19,26], yet others failing to do so [2,12,27-31]. Those studies examining fatigue in association with psychological factors, such as depression, have concluded that fatigue is more strongly associated with such factors than with immune or viral parameters [2,19,29,30,32-36]. Finally, most studies have used nonvalidated measures to assess fatigue [37], and were conducted prior to the widespread availability of HAART [5,19,38].
Our aim was first to assess the frequency of fatigue in an ethnically diverse HIV-infected population in south London using a well-validated measure, and then to examine its association with use and type of antiretroviral therapy, stage of disease, demographic characteristics, and psychological factors, including psychological distress and illness perceptions. There is increasing evidence that the way a patient perceives and understands his symptoms has a significant impact not only on 'coping' but also on broader aspects such as medication adherence and illness-related disability.
DISCUSSION
This is one of the first studies to examine the prevalence of fatigue and the relative importance of psychological, biological and treatment factors, solely in the HAART era in an HIV-infected clinic population. Using a well-validated measure, we found that 65% had significant fatigue. This is at the higher end of the prevalence range reported previously in the literature [2,6,7] but is similar to levels found in other chronic illnesses such as heart failure [43], systemic lupus erythematosis [44,45] and rheumatoid arthritis [46]. A high proportion of patients (68%) were identified as psychologically distressed on the GHQ-12, and this was strongly associated with fatigue.
We did not demonstrate an association between the presence of fatigue and more advanced HIV disease as measured by CD4 count and viral load. Surprisingly, fatigued patients had higher CD4 cell counts than nonfatigued patients, which was not explained by the use of antiretroviral therapy. Similarly, fatigue was not associated with the use or nonuse of HAART or any particular antiretroviral regime, supporting the results of Phillips et al. [47]. However, because this was a cross-sectional study, we were unable to assess the impact of HAART on fatigue symptoms longitudinally.
Fatigued patients scored highly on the 'consequences' section of the IPQ, suggesting that they perceived their illness to have a large impact on their lives. However, this association was not maintained in the multivariate analysis, after adjustment for the SF-36 variables of functional status in the model. The modest association with low scores on the 'cure-control' section (suggesting that fatigued patients feel they have little control over their condition and its progression) and the 'timeline' section approached significance. These findings echo Petrie's finding that catastrophic responses to illness are associated with more profound fatigue and greater levels of disability [47].
Fatigued HIV-infected patients were significantly more disabled than their nonfatigued counterparts across the whole spectrum of the assessment, based on the SF-36 questionnaire. The questionnaire also indicated that even nonfatigued HIV-positive patients are more disabled than the general population [48]. Overall, in combination with the high levels of psychological distress demonstrated by the scores on the GHQ, the fatigued HIV-positive population had a much poorer quality of life.
Limitations of this study include the cross-sectional nature of the data and possible selection biases which might reduce generalizability. Certain groups were under-represented in our study sample relative to our overall clinic population, particularly black Africans and women. These two factors are likely to have opposing effects on the prevalence estimate-most studies find women to have higher rates of fatigue than men [49], but the present study found that black Africans had lower levels of fatigue than whites. We do not have information on those patients who declined to fill in the questionnaire, but it is possible that fatigued patients were more likely to participate, leading to an overestimate of the prevalence of fatigue. However, as a description of HIV-infected patients presenting in routine clinical practice, we believe our sample is representative. Finally, in this cross-sectional study we cannot draw any conclusions about the direction of causality, and whether the association between psychological distress is a cause or a consequence of the fatigue.
Participants
This was a cross-sectional study of all HIV-1-infected patients aged >17 years who had attended the HIV clinic at King's College Hospital on at least one Thursday (the busiest clinic day) over a 5-month period in 2002. Patients who did not speak or read English or who had evidence of cognitive impairment were excluded. At the time of the study, there were approximately 900 HIV-infected patients registered at the clinic, of whom 63% were male, 43% were black African, 38% were homosexual or bisexual, and 2% were injecting drug users. Sixty-eight per cent had received or were currently receiving antiretroviral medications.
Measures
All participants completed a self-administered questionnaire which comprised the following.
(1) The Chalder Fatigue Questionnaire (CFS) [39], which is a validated measure of mental and physical fatigue. Cases of fatigue were defined where the total score was >4 [39].
(2) The General Health Questionnaire 12 (GHQ-12) [40]. This is a 12-item validated questionnaire developed to detect anxiety and depression in clinical populations. We define cases of psychological distress as having a total score >2 [40].
(3) The Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) [41], which measures functional status on eight domains (physical functioning, social functioning, physical role limitation, emotional role limitation, vitality, pain, mental health and general health).
(4) The Illness Perception Questionnaire (IPQ) [42], which measures four domains of illness perception. 'Timeline' reflects the perception of the likely duration of the problem (acute, chronic or cyclical). 'Consequences' assesses beliefs about the severity of the problem and its impact on functioning. 'Cure-control' is about the perception that the symptom is amenable to intervention. 'Cause' reflects the patient's ideas about the cause of the symptoms (e.g. viral, psychological or genetic).
Demographic and clinical information (including recent CD4 cell counts, viral loads and antiretroviral treatments) were obtained from the local clinic database and the patients' medical records. We obtained approval from the King's College Hospital Local Research Ethics Committee.
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