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50% Have Pain, Neuropathy in HIV+: its implications & psychological affects- distress opioid abuse, depression, adherence
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As we advance into the era of progressive & increasing aging among HIV+ this issue of pain will become increasingly more important, as neuropathy prevalence increases for which we have no treatment, and pain in general due to arthritis, and other causes will become increasing occurring in aging HIV+.
" 54 to 83% of people with HIV may experience clinically-meaningful persistent pain, and these estimates appear stable from the pre- to current cART era.....Approximately 42 to 66% of people with HIV have peripheral sensory neuropathy (HIV-SN), and around 54-78% of these experience neuropathic pain [84,88,129]. Importantly, pain in people with HIV is associated with increased disability and reduced quality of life [27].
this is the first systematic review to explore psychosocial variables associated with persistent pain in HIV......This review including over 13000 participants found 'some' or 'moderate' evidence supporting an association between pain outcomes and depression, psychological distress, post-traumatic stress, drug abuse, sleep disturbance, healthcare use, missed HIV clinic visits, ART adherence, unemployment, and protective psychological factors in people with HIV.
Chronic pain is a common symptom in people with HIV. Data from one systematic review indicate that 54 to 83% of people with HIV may experience clinically-meaningful persistent pain, and these estimates appear stable from the pre- to current cART era [80].
Neuropathic pain is a frequent complication of HIV and/or antiretroviral therapy. Approximately 42 to 66% of people with HIV have peripheral sensory neuropathy (HIV-SN), and around 54-78% of these experience neuropathic pain [84,88,129]. Importantly, pain in people with HIV is associated with increased disability and reduced quality of life [27].....depression was more severe in participants who developed symptomatic neuropathy....stigma, mental health problems, and substance abuse may influence pain and treatment engagement in people with HIV....depression was more likely in participants with versus without pain....participants with pain were more likely to have psychological distress than those without pain: OR=2.56.....post-traumatic stress symptoms (PTSS) were associated with significantly higher pain severity and interference over time in a sample with HIV and persistent pain.....The pooled odds ratio indicated that participants with pain at baseline were more likely at follow-up to be using heroin: OR=1.70.....a significant correlation between pain severity and sleep disturbance, and a non-significant correlation between sleep and functioning.....study(n=42) found significant positive correlations between pain severity and adherence forgetfulness and fears.....baseline pain predicted significantly higher odds (OR=1.6, 95%CI 1.2-2.0) of urgent care visits....those with pain at baseline had higher odds of a missed HIV clinic visit OR=1.42.....study found lower mean self-reported optimism in participants with (n=50) versus without pain.....pain predicted "negative social support" (i.e., overly intrusive or insensitive responses from others and a lack of support) ........ Chronic pain was associated with significantly poorer ratings of patient-provider engagement......moderate positive correlation between stigma and pain severity [122]. One low quality cross-sectional study (n=201) found that participants with 'Pain Disorder' reported higher stigma
Surprisingly few studies have examined protective psychological factors or social processes. There is a lack of high quality research on psychosocial factors related to chronic pain in people with HIV. These findings can inform future research and treatment development in this area.....Socioeconomic factors, such as poverty and gender, may thus alter the relationships between pain, functioning, and mental health [88,121]......From this review it is recommended that researchers (a) focus greater attention on protective psychological factors and social processes, such as stigma and processes to undermine stigma; (b) use higher quality assessment tools; and (c) develop and test treatments to target key psychosocial factors to improve pain outcomes in HIV. Improving quality of life is a priority as people with HIV live longer. Adequate, whole-person pain management is vital to achieve this goal."
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Psychosocial Factors Associated with Persistent Pain in People with HIV: A Systematic Review with Meta-Analysis
Scott, Whitney1; Arkuter, Chinar1; Kioskli, Kitty1; Kemp, Harriet2; McCracken, Lance M1,3; Rice, Andrew SC2; de C Williams, Amanda C4
Open Access
PAIN: August 16, 2018 - Volume Articles in Press - Issue - p
doi: 10.1097/j.pain.0000000000001369
Systematic Reviews and Meta-Analyses: PDF Only
Abstract
Chronic pain remains a prevalent and disabling problem for people living with the human immunodeficiency virus (HIV) in the current antiretroviral (ART) treatment era.
Psychosocial treatments may have promise for managing the impact of this pain. However, research is needed to identify psychosocial processes to target through such treatments.
The current systematic review and meta-analysis examined the evidence for psychosocial factors associated with pain, disability, and quality of life in people living with HIV and persistent pain.
Observational and experimental studies reporting on the association between one or more psychosocial factor and one or more pain-related variable in an adult sample of people living with HIV and pain were eligible.
Two reviewers independently conducted eligibility screening, data extraction, and quality assessment.
Forty-six studies were included in the review and 37 of these provided data for meta-analyses (12493 participants).
'Some' or 'moderate' evidence supported an association between pain outcomes in people with HIV and the following psychosocial factors: depression, psychological distress, post-traumatic stress, drug abuse, sleep disturbance, reduced ART adherence, healthcare use, missed HIV clinic visits, unemployment, and protective psychological factors.
Surprisingly few studies examined protective psychological factors or social processes, such as stigma.
There were few high quality studies. These findings can inform future research and psychosocial treatment development in this area. Greater theoretical and empirical focus is needed to examine the role of protective factors and social processes on pain outcomes in this context. The review protocol was registered with PROSPERO (CRD42016036329).
Introduction
The human immunodeficiency virus (HIV) remains a significant global health concern with 36.7 million people living with HIV worldwide [130]. The availability of combined antiretroviral therapies (cART) has drastically improved life expectancy [9,93,120]. In well-resourced countries, and increasingly in less well-resourced regions, the shift in HIV from a terminal illness to a chronic condition has led to a focus on disease and symptom management [59].
Chronic pain is a common symptom in people with HIV. Data from one systematic review indicate that 54 to 83% of people with HIV may experience clinically-meaningful persistent pain, and these estimates appear stable from the pre- to current cART era [80].
Neuropathic pain is a frequent complication of HIV and/or antiretroviral therapy.
Approximately 42 to 66% of people with HIV have peripheral sensory neuropathy (HIV-SN), and around 54-78% of these experience neuropathic pain [84,88,129]. Importantly, pain in people with HIV is associated with increased disability and reduced quality of life [27].
There are few pharmacological options for managing chronic HIV-related pain. A systematic review of 19 randomized controlled trials (RCTs) of pharmacotherapy for painful HIV-SN found efficacy only for topical capsaicin, smoked cannabis, and subcutaneous nerve growth factor [85]. However, nerve growth factor is not clinically available, capsaicin is not feasible in lower-resourced settings, and a subsequent review of cannabis showed no effect on neuropathic pain and concerns about long-term side-effects [32]. Additional negative RCTs of pregabalin, capsaicin, and amitriptyline have been published [17,24,103].
In the wider literature, psychological approaches are common in chronic pain management [34]. Psychological treatments, including cognitive-behavioural therapy (CBT), are associated with improved functioning and mood for chronic pain that is primarily musculoskeletal [124]. However, research on psychological treatments for pain in HIV is less well developed. Only two RCTs have examined CBT for people with HIV and chronic pain, but interpretation of these trials is hampered by small samples [118] and high drop-out rates [29]. An observational study of CBT for HIV-related pain showed similarly poor treatment completion [21,113]. There is a clear need for improving psychological treatments for people with HIV-related pain.
Improving psychological approaches for chronic pain in HIV will require consideration of the psychosocial complexities associated with HIV. For example, stigma, mental health problems, and substance abuse may influence pain and treatment engagement in people with HIV [36,69,71,111,123,132]. However, research has not systematically examined psychosocial factors associated with pain in this context. The systematic review by Parker et al. (2014) which estimated the prevalence of pain in HIV described five studies reporting psychosocial factors. However, that review did not specifically include assessment of psychosocial factors in the eligibility criteria. Furthermore, 33 potentially eligible studies were excluded due to low quality ratings [80], which limits our understanding of the range of psychosocial factors examined in this context. Therefore, we conducted a systematic review and meta-analyses to examine the associations between psychosocial factors and persistent pain in HIV. As the aims of the review were exploratory, we did not formulate specific hypotheses about the associations between these variables.
Depression
Depression was the most frequently assessed psychological variable, investigated in 29 studies. Two prospective studies reported hazard ratios for baseline depression predicting time to onset of symptomatic neuropathy. The pooled hazard ratio was significant and indicated that baseline depression was more severe in participants who developed symptomatic neuropathy at follow-up than those who did not: HR=1.04 (95% CI 1.02-1.07), z=3.23, p=0.001 (Supplemental Figure 1, available at http://links.lww.com/PAIN/A643). Heterogeneity was 0.0%. Two further prospective studies reported odds ratios. The pooled odds ratio was significant and indicted that higher baseline depression symptoms were associated with greater likelihood of follow-up pain: OR=2.26 (95% CI 1.47-3.47), z=3.72, p<0.001 (Supplemental Figure 2, available at http://links.lww.com/PAIN/A643).
Heterogeneity was medium (40.1%). Nine cross-sectional studies provided events data or odds ratios. The pooled odds ratio was significant such that depression was more likely in participants with versus without pain: OR=2.65 (95% CI 1.62- 4.34), z=3.90, p<0.001 (Figure 2). Heterogeneity was high (83.0%). Twelve cross-sectional studies provided data to compute SMDs (Figure 3). The overall effect was significant and showed moderately greater depression in participants with versus without pain: SMD=0.68 (95%CI 0.42-0.93), z = 5.22, p<0.001. Heterogeneity was high (I2=89.2%). Another cross-sectional study which reported the median and interquartile range found no difference in depression between groups with (n=125) and without pain (n=72) [88].
Psychological Distress
Eighteen studies examined variables representing psychological distress, including anxiety-related constructs and the presence of 'mental illness', which generally described a combination of anxiety and depression. Five cross-sectional studies provided events data (Figure 4). The pooled odds ratio was significant and indicated that participants with pain were more likely to have psychological distress than those without pain: OR=2.56 (95% CI 1.67-3.90), z=4.34, p<0.001. Heterogeneity was high (I2=68.3%). One prospective study (n=127) found that baseline mental illness did not predict presence of pain over follow-up [54]. Seven cross-sectional studies provided means and standard deviations (Figure 5). The pooled SMD showed a large and statistically significant difference between groups such that distress was worse in participants with versus without pain (SMD=0.85, 95% CI 0.35-1.35); z = 3.33, p = 0.001). Heterogeneity was very high (I2=95.4%). One further study which reported the median and interquartile range found no difference between groups [88].
Post-Traumatic Stress
Three studies investigated post-traumatic stress. These studies are reported separate from studies measuring psychological distress, given the specificity of post traumatic stress as a variable. Different study designs and analyses precluded meta-analysis.
One prospective study (n=143) found that post-traumatic stress symptoms (PTSS) were associated with significantly higher pain severity and interference over time in a sample with HIV and persistent pain [107]. One high quality cross-sectional study found that participants with pain (n=170) had significantly higher PTSS than those without pain (n=59) [79]. Within the pain group in this study, there was a non-significant correlation between PTSSs and pain severity, and small but significant correlations between PTSSs and pain interference (positive correlation) and quality of life (negative correlation) [79]. Posttraumatic stress disorder did not differ between groups with (n=150) and without (n=128) neuropathy in another cross-sectional study [31].
Drug Abuse
Fourteen studies examined drug abuse. We prioritised extracting opioid abuse data when multiple drug abuse categories were reported given the relevance of opioid use in chronic pain. Two prospective studies reported odds ratios for pain predicting heroin use at the time of follow-up. The pooled odds ratio indicated that participants with pain at baseline were more likely at follow-up to be using heroin: OR=1.70 (95%CI 1.22-2.38), z=3.13, p=0.002 (Supplemental Figure 10, available at http://links.lww.com/PAIN/A643).
Heterogeneity was low (I2= 14.0%). Conversely, another prospective study (n=493) reported that baseline opioid use disorder history predicted new onset of neuropathic pain, OR=2.87 (1.31-6.28), p<0.01 [60]. One low quality prospective study (n=127) found that baseline drug abuse history did not predict the presence of pain at follow-up, 0.55 (0.25-1.21) [54]. These two studies could not be combined due to different coding of the dependent variable.
Alcohol Abuse
Eleven studies investigated alcohol abuse. Two prospective studies reported odds ratios for baseline pain predicting subsequent alcohol abuse. The pooled odds ratio was not significant: OR=0.94 (95% CI 0.39-2.26), z=0.13, p=0.90 (Supplemental Figure 11, available at
http://links.lww.com/PAIN/A643). Heterogeneity was high (84.1%). Two additional prospective studies examined baseline alcohol abuse as a predictor of developing pain/neuropathy but could not be combined due to different analyses. Both studies reported a non-significant association between these variables [60,77]. Seven cross-sectional studies provided events data or odds ratios. The pooled odds ratio was not significant: OR=1.22 (95%CI 0.92 to 1.62), z=1.36, p=0.17 (Supplemental Figure 12, available at http://links.lww.com/PAIN/A643). Heterogeneity was medium (I2=39.0%).
SLEEP DISTURBANCES
.......pooled effect was significant and showed moderately greater sleep problems in participants with versus without pain: SMD=0.66 (95% CI 0.45- 0.87), z=6.12, p<0.001. Heterogeneity was 0.0% (Supplemental Figure 13, available at
http://links.lww.com/PAIN/A643). Another cross-sectional (n=45) study reported a significant correlation between pain severity and sleep disturbance, and a non-significant correlation between sleep and functioning [94].
ART Non-Adherence
Seven studies investigated the association between pain and suboptimal ART adherence. Data were analysed separately according to whether the adherence variable was coded in the direction of non-adherence or adherence. One prospective study (n=258) reported that severe pain at baseline predicted higher odds (OR=1.37, 95%CI 1.02 to 1.85) of follow-up ART non-adherence [46]. One cross-sectional study provided events data while another provided an odds ratio. The pooled odds ratio was significant and indicated that participants with pain were more likely to report non-adherence: OR=1.40 (95% CI 1.07 to 1.82), z=2.50, p=0.01 (Supplemental Figure 14, available at http://links.lww.com/PAIN/A643). Heterogeneity was 0.00%. One cross-sectional study(n=42) found significant positive correlations between pain severity and adherence forgetfulness and fears [57].
Healthcare Use
Six studies examined healthcare use. One prospective study (n=1521) found that baseline pain predicted significantly higher odds (OR=1.6, 95%CI 1.2-2.0) of urgent care visits [68].
Missed HIV Clinic Visits
The pooled odds ratio was significant, such that those with pain at baseline had higher odds of a missed HIV clinic visit OR=1.42.
Unemployment
The pooled odds ratio was significant, and indicated that participants with pain had higher odds of being unemployed than those without pain:
OR=2.09 (95% CI 1.59-2.76)
Protective Factors
Five studies examined protective psychological factors. One prospective study (n=62) found significant small and medium correlations between change in self-reported pain acceptance during CBT and post-treatment pain severity and interference, respectively [86]. One cross-sectional case-control study observed lower resilience in participants with (n=99) versus without pain (n=98; medium effect); however, this study found non-significant correlations between resilience and pain severity and interference in the pain group [121].
One high quality cross-sectional study found that participants with pain (n=170) reported lower disease management self-efficacy than did those without pain (n=59) (small effect) [79]. Within the pain group in this study, there were non-significant correlations between self-efficacy and pain severity and interference, and a small positive correlation between self-efficacy and quality of life [79]. One low quality cross-sectional study found that those with greater adherence self-efficacy were less likely to report pain (n=70) [8].
Lastly, one low quality cross-sectional study found lower mean self-reported optimism in participants with (n=50) versus without pain (n=46) (small effect) [101].
Social Factors
Baseline chronic pain predicted "negative social support" (i.e., overly intrusive or insensitive responses from others and a lack of support) at 12 months, controlling for baseline social support [73]. Another prospective analysis showed that no chronic pain at baseline predicted greater support reciprocity at follow-up [74]. Chronic pain was associated with significantly poorer ratings of patient-provider engagement in cross-sectional analyses [72].
Two studies examined self-reported stigma, but could not be combined. One
medium quality cross-sectional study (n=50) found a moderate positive correlation between stigma and pain severity [122]. One low quality cross-sectional study (n=201) found that participants with 'Pain Disorder' reported higher stigma scores than those without 'Pain Disorder'[98]. One medium quality cross-sectional study found no difference in mean number or quality of self-reported social supports between participants with (n=274) and without pain (n=164) [91].
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