Pain in People Living with HIV

Original Editor - Melissa Coetsee Top Contributors - Melissa Coetsee and Carina Therese Magtibay

Introduction[edit | edit source]

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Since the introduction of Anti-retroviral Therapy (ART), there has been a significant reduction in the mortality associated with Human Immunodeficiency Virus (HIV)[1]. As a result more people are living with HIV as a chronic condition, and this has necessitated an increased focus on factors affecting morbidity. Pain is one such a factor that has been shown to negatively affect the quality of life and function of people living with HIV (PLWH)[2][1].

The prevalence of pain among PLWH vary among populations. Parker et al. (2014)[2] found that pain (mostly moderate to severe) is reported in 54-67% of PLWH. In later studies, high variability in frequencies were found, but most reported a pain prevalence of more than 50%[1]. It is clear that pain is a prominent concern in PLWH, and it remains poorly controlled and undertreated in this population[2][3].

Impact of Pain[edit | edit source]

Untreated and poorly managed pain can be very debilitating. In PLWH it has been shown to have significant negative effects on the following:

  1. Sleep[2]
  2. Ability to work[2][4]
  3. Mood[2]
  4. Quality of life[4]
  5. ART adherence[4][5]

This clearly demonstrates the importance of addressing pain in PLWH in order to limit its impact on quality of life and function[2]. Although the current WHO HIV package of care guidelines recommend psychosocial counselling and support[6], there is a need to included screening and treatment of chronic pain in order to comprehensively manage PLWH.

Factors Contributing to Pain[edit | edit source]

The following factors have been found to increase the risk of pain in PLWH:

  • Depression and anxiety[2] - Depression has specifically been associated with greater intensity in pain in PLWH and is very common in PLWH[7][8][4]
  • Lack of social support[2]
  • Lower level of education, in both developing and developed contexts[2]
  • Poor sleep, especially associated with zidovudine and efavirenz[8][4]
  • Substance abuse[4]
  • Stigma - Although common in PLWH, there is a lack of evidence on the effect of stigma on pain[4]

The African Context[edit | edit source]

Studies measuring physical activity in PLWH in the US/EU have found that pain in the population results in significant physical impairment - this however is not the case in the African context, were little to no functional interference occurs[9]. A study conducted in SA concluded that stigma and family responsibilities may drive patients to push through despite pain[9].

Common Pain Conditions[edit | edit source]

Zhu et al. studied symptom clusters in PLWH, and found "numbness, muscle aches, and joint pain" to be the fourth most common symptom cluster[8]

  1. Peripheral Neuropathy: More than one-third of PLWH suffer from HIV-neuropathy, with some studies reporting incidence rates of up to 66%[7][4]. Of those with neuropathy, 38-78% experience painful neuropathy (neuropathic pain)[7][4]
  2. Spinal Pain: Low back pain or neck pain is present in 1% to 55% of PLWH[1]
  3. Lower extremity pain: present in 3-58% of PLWH, most commonly affecting the feet and legs[1]
  4. Joint Pain: Osteoarthritis is present in 2-50% of PLWH[1]
  5. Upper and extremity pain: present in 2-5% of PLWH, mostly involving the hands and shoulders[1]

Pain Mechanisms in HIV[edit | edit source]

PLWH can present with complex pain conditions as a result of the virus itself, or as a side-effect of ART. It can be useful to consider the possible pain mechanisms involved in order to provide targeted treatment.

Neuropathic pain[edit | edit source]

Causes of Neuropathic pain:

  • Neurotoxicity caused by the HIV-1 glycoprotein (infects Schwann cells and neurons)
  • Neurotoxicity caused by certain anti-retroviral drugs (causes mitochondrial dysfunction)[10][11]. Nucleoside analogue-transcriptase inhibitors (NRTIs) (Zidovudine, didanosine, stavudine, lamivudine and abacavir) have be closely linked with severe peripheral neuropathy[10] - Stavudine-based anti-retroviral drugs should be phased out for this reason[10]
  • Opportunistic infections affecting peripheral nerves[11]

Regardless of the cause, symptoms and clinical signs are similar and include distal polyneuropathy with paraesthesia and may involve hyperalgesia and allodynia[7]

Nociceptive pain[edit | edit source]
  • Tissue damage can occur with an injury. PLWH tend to have elevated inflammatory cytokines, which could result in an amplified pain response following tissue damage[12][11]
  • Elevated inflammatory cytokine are associated with increasing age[11]
Chronic Nociplastic pain[edit | edit source]

Chronic pain is influenced by a range of immunological and psychosocial factors[3]

  • Chronic inflammation caused by the virus can lead to central sensitisation[11]
  • The stigma associated with HIV, as well as the high prevalence of depression and anxiety, can negatively modify pain-pathways resulting in persistent pain[4]
  • Fear-avoidance could potentially influence pain in PLWH and required further research[4]

Pain Assessment Tools[edit | edit source]

  • Brief Pain Inventory
  • Pain, Enjoyment of Life and General Activity Scale (PEG)
  • Beck Depression Inventory
  • SF-36 - measure 8 domains, including pain

See also Pain Assessment

Interventions for Pain in PLWH[edit | edit source]

Pharmacologic[edit | edit source]

HIV medication.jpg

Various studies have failed to identify drugs that have proven effectiveness in reducing pain (especially neuropathic pain) in PLWH[10]. The South African Medical Research Council has reported that there is an "absence of empirical evidence supporting efficacy of pharmacological agents typically recommended for the management of neuropathic pain in this population group" [13]

ART[edit | edit source]

There is no correlation between ART and pain reduction, which indicates that treatment of the virus alone is not effective in managing pain in PLWH[2]

Neuropathic Pain Medication[edit | edit source]

Medications often used to treat neuropathic pain have not been effective in relieving HIV related neuropathic pain - these include anti-depressants, anticonvulsants, topical agents, opioids and non-steroidal anti-inflammatories (NSAIDs)[14][10][4].

Other[edit | edit source]
  • Cannabis: There is some evidence that smoking cannabis has a positive effect on neuropathic pain in PLWH, by activating the endocannabinoid system (ECS)[14][7]. It is however not recommended as a feasible option for pain management, as HIV is a chronic condition and the long-term use of smoked cannabis can have negative psycho-active effects. The research does however suggest that targeting cannabinoid receptors may be an effective approach in managing neuropathic pain in PLWH. Non-psychoactive cannabinoids administered via other routes would be more suitable and require further research[14].
  • Topical capsaicin: There is some evidence of a short term positive effect on pain in PLWH[7][10].

Non-Pharmacologic[edit | edit source]

Non-pharmacological interventions seem the hold the most promise in addressing HIV related pain. There is however still a great need for further, high-quality research to determine which interventions are superior and the most cost-effective and feasible in different contexts[7].

Exercise[edit | edit source]
  • Group aeobic exericse.jpg
    A recent systematic review on neuropathic pain concluded that both aerobic exercise and progressive resistance exercise is superior to usual care (including education) in treating neuropathic pain in PLWH in low- and middle income countries (LMICs)[15][16][17].
  • The frequency of exercise shown to be effective is 30-60min, 3 times per week for 12 weeks[15][16] [17].
  • One study conducted a follow-up 12 weeks after the intervention ended, and found that continued home exercises resulted in sustained reduction in pain[16].
  • Exercise seems to be less effective if it is initiated >7 years after diagnosis[16].
  • Exercise has various other proven benefits for PLWH - see Exercise for People Living with HIV
Psychological Interventions[edit | edit source]
  1. Relaxation: Yoga, relaxation strategies and mindfulness may provide benefits, especially when anxiety and depression are present
  2. Cognitive Behavioural Therapy (CBT): A recent systematic review found that CBT can result in significant reductions in neuropathic pain intensity[7].C CBT can be very useful to identify behaviours that could be making pain worse (e.g. avoiding activity) and to work on coping strategies[11]
  3. Supportive Psychotherapy: Effectiveness is comparable with CBT, for neuropathic pain[7]

Also see Mental Health Interventions for PLWH

Education and Self-management[edit | edit source]
  • A recent systematic review found that there is limited evidence to suggest that "self-management interventions (delivered either online, face-to-face or group-based with a booklet) are effective in improving pain, physical symptoms and quality of life in PLWH with chronic pain"[5].
  • The Positive Living Workbook is a 6-week peer-led exercise and education intervention that was developed by Romy Parker. It offers a multimodal intervention for pain by incorporating education, exercise, CBT and self-management strategies[18] [3]. Two studies that utilised this workbook demonstrated a significant reduction in pain interference and improvement in function in women living with HIV[3][19].
  • Turner et al utilised a similar programme, named Living Better Beyond Pain. Education sessions were offered monthly over 6 months. Pain was not measured, but the intervention resulted in significant improvements in physical function (note that this study also included people without HIV)[20].
  • A study conducted in Malawi, found that a single educational session with carers and late-stage HIV patients resulted in improvements in pain. These sessions focused on HIV related pain, myths about pain and management strategies[21].
Therapeutic Relationship[edit | edit source]
  • Jackson et al. found that a good therapeutic relationship (established by frequent communication in one's home-language with an caring research assistant) can have significant positive effects on pain levels in PLWH[3].
  • This finding supports the promotion of less fragmented care in managing PLWH. There is a need for consistent empathetic care in health systems[3].
  • Physiotherapists are well trained and positioned to provide such a relationship. In low-resource or rural settings, this role could be filled by training community healthcare workers (CHWs) [3].
Other[edit | edit source]
  • Massage: There is low to moderate evidence to support the use of massage in PLWH. It may improve quality of life, but it has not been shown to have any effect on pain on activity levels. Given the lack of evidence, it could be useful as a self-management/care-giver tool, but should not be the focus of pain management programmes/interventions[22].
  • Splinting: Night splinting for neuropathic pain has not been found to be effective[7]

The Role of Physiotherapy[edit | edit source]

Physiotherapists can play a very important role in the management of pain in PLWH

  • Biopsychosocial Approach to Pain Management in HIV[11]
    Exercise - Physiotherapists are experts in exercise prescription. They can assess patients' physical status, help design appropriate strengthening and aerobic exercise plans and monitor progress in physical function.
  • Biopsychosocial approach - chronic pain is complex and requires a holistic approach, especially with the added biological, psychological and social complications that PLWH face. Physiotherapists have the knowledge and communication skills to identify core contributing factors that influence pain[11].
  • Goal setting and motivation - Through motivational interviewing, encouragement and goal directed management plans, physiotherapists can assist patients in achieving their functional goals
  • Therapeutic relationship - Physiotherapists often have more time with a patient and typically see patients at regular intervals. This makes them ideally positioned to build a strong trust relationship with PLWH, which has therapeutic benefits.
  • Training of CHWs - In low resource/rural settings physiotherapists can play an important role in training mid-level community workers in implementing simple, yet effective, self-management programmes for PLWH in their community.
  • Education - Physiotherapists, especially those trained in chronic pain management, have an in-depth understanding of pain physiology and pain management strategies. They can act as facilitators in delivering group education interventions, or provide one-on-one information patients.

The Multi-Disciplinary Team (MDT)[edit | edit source]

Teamwork MDT.png

The complexity of chronic pain, especially in PLWH, ultimately requires an integrated team approach - with the patient at the centre.

  • Medical doctors - Ensure early initiation on ART, and adjust medication as needed. Prescription of medication for pain, based on underlying pain mechanisms, in conjunction with referral to pain and rehabilitation team members.
  • Nurses - Screening for chronic pain; Monitoring adherence and the effect of interventions
  • Public Health Practitioners - Continuous research into the most cost-effective and contextually appropriate interventions; promoting health and advocating for policies that ensure integrated care models are in place for PLWH - with particular focus on addressing stigma and mental health (contributors to pain)
  • Occupational therapists - Assist with functional goal setting and coping strategies, as well as mental health interventions
  • Psychologists - Counselling and facilitation of support groups

Health care workers need to collaborate and communicate to ensure PLWH are receiving the comprehensive care that their condition requires, and which they deserve.

Resources[edit | edit source]

References[edit | edit source]

  1. 1.0 1.1 1.2 1.3 1.4 1.5 1.6 Berg LS, Young JJ, Kopansky-Giles D, Eberspaecher S, Outerbridge G, Hurwitz EL, Hartvigsen J. Musculoskeletal Conditions in Persons Living with HIV/AIDS: A Scoping Review. Current Medical Science. 2022 Feb;42(1):17-25.
  2. 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 Parker R, Stein DJ, Jelsma J. Pain in people living with HIV/AIDS: a systematic review. Journal of the International AIDS Society. 2014 Jan;17(1):18719.
  3. 3.0 3.1 3.2 3.3 3.4 3.5 3.6 Jackson K, Wadley AL, Parker R. Managing pain in HIV/AIDS: a therapeutic relationship is as effective as an exercise and education intervention for rural amaXhosa women in South Africa. BMC Public Health. 2021 Dec;21:1-4.
  4. 4.00 4.01 4.02 4.03 4.04 4.05 4.06 4.07 4.08 4.09 4.10 4.11 Scott W, Arkuter C, Kioskli K, Kemp H, McCracken LM, Rice AS, Williams AC. Psychosocial factors associated with persistent pain in people with HIV: a systematic review with meta-analysis. Pain. 2018 Dec;159(12):2461.
  5. 5.0 5.1 Nkhoma K, Norton C, Sabin C, Winston A, Merlin J, Harding R. Self-management interventions for pain and physical symptoms among people living with HIV: a systematic review of the evidence. JAIDS Journal of Acquired Immune Deficiency Syndromes. 2018 Oct 1;79(2):206-25.
  6. World Health Organization. Consolidated guidelines on HIV prevention, testing, treatment, service delivery and monitoring: recommendations for a public health approach. World Health Organization; 2021 Jul 16.
  7. 7.0 7.1 7.2 7.3 7.4 7.5 7.6 7.7 7.8 7.9 Amaniti A, Sardeli C, Fyntanidou V, Papakonstantinou P, Dalakakis I, Mylonas A, Sapalidis K, Kosmidis C, Katsaounis A, Giannakidis D, Koulouris C. Pharmacologic and non-pharmacologic interventions for HIV-neuropathy pain. A systematic review and a meta-analysis. Medicina. 2019 Nov 28;55(12):762.
  8. 8.0 8.1 8.2 Zhu Z, Zhao R, Hu Y. Symptom clusters in people living with HIV: a systematic review. Journal of Pain and Symptom Management. 2019 Jul 1;58(1):115-33.
  9. 9.0 9.1 Wadley AL, Mitchell D, Kamerman PR. Resilience does not explain the dissociation between chronic pain and physical activity in South Africans living with HIV. PeerJ. 2016 Sep 13;4:e2464.
  10. 10.0 10.1 10.2 10.3 10.4 10.5 Winias S, Radithia D, Savitri Ernawati D. Neuropathy complication of antiretroviral therapy in HIV/AIDS patients. Oral Diseases. 2020 Sep;26:149-52.
  11. 11.0 11.1 11.2 11.3 11.4 11.5 11.6 11.7 Slawek DE. People living with HIV and the emerging field of chronic pain—what is known about epidemiology, etiology, and management. Current HIV/AIDS Reports. 2021 Oct;18(5):436-42.
  12. Merlin JS, Westfall AO, Heath SL, Goodin BR, Stewart JC, Sorge RE, Younger J. IL-1β levels are associated with chronic multisite pain in people living with HIV. Journal of acquired immune deficiency syndromes (1999). 2017 Aug 8;75(4):e99.
  13. Augustine TN, Cairns CJ, Chetty S, Dannatt LG, Gravett N, Grey G, Grobler G, Jafta Z, Kamerman P, Lopes J, Matsabisa MG. Priority areas for cannabis and cannabinoid product research in South Africa. African Journal of Primary Health Care & Family Medicine. 2018;10(1):1-3.
  14. 14.0 14.1 14.2 Aly E, Masocha W. Targeting the endocannabinoid system for management of HIV-associated neuropathic pain: a systematic review. IBRO Neuroscience Reports. 2021 Jun 1;10:109-18.
  15. 15.0 15.1 Zhang YH, Hu HY, Xiong YC, Peng C, Hu L, Kong YZ, Wang YL, Guo JB, Bi S, Li TS, Ao LJ. Exercise for neuropathic pain: a systematic review and expert consensus. Frontiers in Medicine. 2021:2239.
  16. 16.0 16.1 16.2 16.3 Tumusiime DK, Stewart A, Musenge E, Venter FW. The effects of a physiotherapist-led exercise intervention on peripheral neuropathy among people living with HIV on antiretroviral therapy in Kigali, Rwanda. South African Journal of Physiotherapy. 2019 Jan 1;75(1):1-9.
  17. 17.0 17.1 Maharaj SS, Yakasai AM. Does a rehabilitation program of aerobic and progressive resisted exercises influence HIV-induced distal neuropathic pain?. American Journal of Physical Medicine & Rehabilitation. 2018 May 1;97(5):364-9.
  18. 18.0 18.1 Parker, R. 2014. Positive Living Workbook. Lesson plan. University of Cape Town.
  19. Parker R, Jelsma J, Stein DJ. Managing pain in women living with HIV/AIDS: A randomized controlled trial testing the effect of a six-week peer-led exercise and education intervention. The Journal of Nervous and Mental Disease. 2016 Sep 1;204(9):665-72.
  20. 20.0 20.1 Turner BJ, Liang Y, Simmonds MJ, Rodriguez N, Bobadilla R, Yin Z. Randomized trial of chronic pain self-management program in the community or clinic for low-income primary care patients. Journal of General Internal Medicine. 2018 May;33:668-77.
  21. Nkhoma K, Seymour J, Arthur A. An educational intervention to reduce pain and improve pain management for Malawian people living with HIV/AIDS and their family carers: a randomized controlled trial. Journal of Pain and Symptom Management. 2015 Jul 1;50(1):80-90.
  22. Hillier SL, Louw Q, Morris L, Uwimana J, Statham S. Massage therapy for people with HIV/AIDS. Cochrane database of systematic reviews. 2010(1).
  23. Butler, D. & Moseley, L. Explain Pain. 2nd edition. Adelaide, South Australia: Noigroup Publications, 2013