Priorities for HIV and chronic pain research results from a survey of individuals with lived experience

The Global Task Force on Chronic Pain in HIV published seven research priorities in the field of HIV-associated chronic pain in 2019: (1) causes; (2) management; (3) treatment individualization and integration with addiction treatment; (4) mental and social health factors; (5) prevalence; (6) treatment cost effectiveness; and (7) prevention. The current study used a web-based survey to determine whether the research topics were aligned with the priorities of adults with lived experiences of HIV and chronic pain. We also collected information about respondents' own pain and treatment experiences. We received 311 survey responses from mostly US-based respondents. Most respondents reported longstanding, moderate to severe, multisite pain, commonly accompanied by symptoms of anxiety and/or depression. The median number of pain treatments tried was 10 (IQR = 8, 13), with medications and exercise being the most common modalities, and opioids being viewed as the most helpful. Over 80% of respondents considered all research topics either "extremely important" or "very important". Research topic #2, which focused on optimizing management of pain in people with HIV, was accorded the greatest importance by respondents. These findings suggest good alignment between the priorities of researchers and US-based people with lived experience of HIV-associated chronic pain.</p

The Global Task Force for Chronic Pain in People with HIV (PWH):Developing a research agenda in an emerging field

Chronic pain is a common comorbidity in people with HIV (PWH), with prevalence estimates of 25-85%. Research in this area is growing, but significant gaps remain. A Global Task Force of HIV experts was organized to brainstorm a scientific agenda and identify measurement domains critical to advancing research in this field. Experts were identified through literature searches and snowball sampling. Two online questionnaires were developed by Task Force members. Questionnaire 1 asked participants to identify knowledge gaps in the field of HIV and chronic pain and identify measurement domains in studies of chronic pain in PWH. Responses were ranked in order of importance in Questionnaire 2, which was followed by a group discussion. 29 experts completed Questionnaire 1, 25 completed Questionnaire 2, and 21 participated in the group. Many important clinical and research priorities emerged, including the need to examine etiologies of chronic pain in PWH. Pain-related measurement domains were discussed, with a primary focus on domains that could be assessed in a standardized manner across various cohorts that include PWH in different countries. We collaboratively identified clinical and research priorities, as well as gaps in standardization of measurement domains, that can be used to move the field forward

Factors associated with developing symptomatic HIV-associated sensory neuropathy

HIV-associated sensory neuropathy (HIV-SN) is one of the most common neurological problems of HIV. It is frequently painful and reduces quality of life. HIV-SN can be caused both by HIV itself and by exposure to neurotoxic antiretrovirals such as stavudine. The South African Department of Health now recommends use of tenofovir in place of stavudine as first line treatment. However many people remain on stavudine and or live with the side effects. Stavudine is still prescribed in many other resource-poor countries. This thesis presents the first systematic study of clinical and genetic risk factors for the development of symptomatic HIV-SN in Black Southern Africans. I recruited 404 Black HIV-positive Africans from the Virology Clinic of the Charlotte Maxeke Academic Hospital, Johannesburg and assessed HIV-SN using the AIDS Clinical Trials Group (ACTG) Brief Peripheral Neuropathy Screen. HIV-SN was defined as present if the patient had both symptoms and signs of peripheral neuropathy. If present, the distribution and intensity of symptoms were recorded. Of those exposed to stavudine, 57% (226/395) had HIV-SN. Pain was the most common symptom and was experienced by 74% (172/226). Of these, 76% (128/172) reported their pain as moderate to severe. As in previous studies, increasing age and height were independently associated with risk of HIV-SN. However nadir and current CD4 T-cell counts and sex were not associated with SN. Patients donated blood for DNA extraction and single nucleotide polymorphisms (SNPs) were selected from the literature and genotyped using Illumina Golden GateTM technology. 342 individuals were assessed for genetic associations with HIV-SN and a subset of 159 positive for HIV-SN were assessed for associations with painful HIV-SN. I completed four genetic analyses: SNPs and haplotypes from TNF and adjacent genes from the major histocompatability complex on chromosome six were assessed for association with HIV-SN. I found no association with TNF-1031, even though this had associated with risk of HIV-SN in Caucasian, Chinese and Malay cohorts. Novel associations were identified between HIV-SN protection and 5 other SNPs (BAT1 rs3130059, rs2523504; ATP6V1G2 rs2071594; NFKBIL1 rs2071592, rs2071591). Associations were also found with haplotypes: FV15-23 weakly associated with risk and FV30-31 associated with protection against HIV-SN in this cohort. Analysis of 8 SNPs not previously assessed produced two novel associations with LTA SNPs (rs1041981, rs909253), where the minor alleles conferred protection against HIV-SN. Analysis of linkage disequilibrium (LD) suggests that there is linkage disequilibrium within the TNF block, that it differs between ethnicities and that TNF-1031 is unlikely to be a causative SNP for risk of HIV-SN. SNPs from other cytokines and chemokines implicated in the pathogenesis of HIVSN and the associated pain were assessed in Chapter 5. The major allele of the antiinflammatory gene IL4 (rs2243250) associated with risk of HIV-SN. This allele has been associated with higher CD4 T-cell counts, so I have proposed a role for high IL- 4 in early stage HIV-SN. A 3-SNP haplotype of IL10 associated with protection against HIV-SN whilst another IL10 haplotype showed a trend for risk of painful HIVSN. These data and the involvement of TNF haplotype (Chapter 4) suggest an inflammatory etiology for HIV-SN. Polymorphisms of UCP2 (rs659366) and UCP3 (rs1800849) have previously associated with risk of diabetic neuropathy. These SNPs encode uncoupling proteins 2 and 3 which regulate reactive oxygen species and may affect development of neuropathy via the effects of oxidative stress and mitochondrial dysfunction. Alleles of these SNPs did not associate with HIV-SN in this cohort. Patterns of linkage disequilibrium may differ between the two ethnicities or UCP2 and UCP3 may associate with a mechanism particular to diabetic neuropathy. I also assessed a ‘pain protective haplotype’ and SNPs of GCH1 which have been associated with decreased pain intensity in radicular pain following lumbar discectomy. Associations of the 3-SNP ‘pain protective’ haplotype (rs10483639*C, rs3783641*A and rs8007267*T) and a 6-SNP haplotype containing this motif with protection against pain were significant but dependent on age, sex and CD4 T-cell count. Association of another 3-SNP haplotype (rs10483639*G, rs3783641*T and rs8007267*C) with increased risk of pain in HIV-SN was also not independent of age, sex and CD4 T-cell count. The weaker associations here compared to Caucasian cohorts may be a result of differing LD between ethnicities or demonstrate different pain mechanisms between HIV-SN and radicular pain following lumbar discectomy. My results highlight the prevalence of HIV-SN and frequency of pain in this Southern African cohort. The genetic studies identify a likely inflammatory component and identify genes worthy of further investigation both in HIV-SN and the associated pain

A comparison of a pedometer-based walking program versus physiotherapy for patients suffering from nociceptive or neuropathic chronic, recurrent low back pain in Johannesburg.

Research Aim:To assess whether a pedometer based walking program assist standard physiotherapy treatment to decrease pain and improve function in patients who report chronic or recurrent LBP.Research Objectives:To assess whether a walking program will decrease lower back and/or leg pain*.To assess if a walking program will increase function*.To assess the duration, frequency and speed of walking necessary to change pain and dysfunction*.To assess which pain phenotype best matches treatment expectation to outcome.*objectives 1-4 relate to either or both of the CLBP phenotype

A preliminary analysis of the association between perceived stigma and HIV-related pain in South Africans living with HIV

Background: Stigma related to the human immunodeficiency virus (HIV) remains common and has been associated with severity of HIV-related symptoms. Associations between HIV stigma and HIV-related pain, one of the most common symptoms in HIV, have however not been investigated. Data from low back pain populations suggest that stigma is associated with worse pain intensity and so we hypothesised that the same would be the case in HIV.Aim: The goal of this study was to assess the association between HIV stigma and pain intensity in people living with HIV (PLWH) with chronic pain whilst controlling for depression, a well-established correlate of pain.Setting: The study took place at an HIV clinic in Johannesburg, South Africa.Methods: Mediation analysis was used to assess the effect of depression on the relationship between stigma and pain intensity in a cross-sectional cohort of 50 PLWH and chronic pain (pain most days of the week for &gt; 3 months). All participants were assessed using the HIV/AIDS Stigma Instrument – PLWA, an 11-point numerical pain rating scale and the Beck Depression Inventory II.Results: In all, 88% (44/50) of participants reported experiencing some form of HIV stigma (HIV stigma scale score ≥ 1). Worst pain intensity and depressive symptoms individually correlated with total stigma score (Spearman’s r = 0.33, p = 0.02 for both). The mediation analysis highlighted that mediation of the relationship by depression was equivocal (b = -0.002, bootstrapped confidence interval -0.02 to 0.00).Conclusion: Whilst these preliminary data are marginal, they do suggest that associations between HIV stigma and HIV-related pain warrant further investigation. Future study should also include potential mechanisms, which may include mediation through depression

A comparison of a pedometer-based walking program versus physiotherapy for patients suffering from nociceptive or neuropathic chronic, recurrent low back pain in Johannesburg.

Research Aim:To assess whether a pedometer based walking program assist standard physiotherapy treatment to decrease pain and improve function in patients who report chronic or recurrent LBP.Research Objectives:To assess whether a walking program will decrease lower back and/or leg pain*.To assess if a walking program will increase function*.To assess the duration, frequency and speed of walking necessary to change pain and dysfunction*.To assess which pain phenotype best matches treatment expectation to outcome.*objectives 1-4 relate to either or both of the CLBP phenotype

Managing pain in HIV/AIDS: a therapeutic relationship is as effective as an exercise and education intervention for rural amaXhosa women in South Africa

Background Pain is one of the most prevalent symptoms in people living with HIV/AIDS and is largely undermanaged. Both a peer-led exercise and education Positive Living programme (PL programme) and the PL programme workbook alone were previously found to be effective in reducing pain in urban amaXhosa Women Living With HIV/AIDS (WLWHA). A therapeutic relationship was hypothesised to have contributed to the efficacy of both interventions. The aim of the study was to determine the effectiveness of the PL programme and a therapeutic relationship, compared to a therapeutic relationship alone in managing pain amongst rural amaXhosa WLWHA on pain severity and pain interference, and secondary outcomes, symptoms of depression, health-related quality of life (HRQoL) and self-efficacy. Methods In this two-group, single-blind, pragmatic clinical trial with stratified convenience sampling, the PL programme and therapeutic relationship, was compared to a therapeutic relationship alone in rural amaXhosa WLWHA. The PL programme was a 6-week, peer-led intervention comprising education on living well with HIV, exercise and goal setting. The therapeutic relationship comprised follow-up appointments with a caring research assistant. Outcome measures included pain severity and interference (Brief Pain Inventory), depressive symptoms (Beck Depression Inventory), HRQoL (EuroQol 5-Dimensional outcome questionnaire) and self-efficacy (Self-efficacy for Managing Chronic Disease 6-Item Scale). Follow-up was conducted at 4, 8, 12, 24, and 48 weeks. Mixed model regression was used to test the effects of group, time, and group and time interactions of the interventions on outcome measures. Results Forty-nine rural amaXhosa WLWHA participated in the study: PL group n = 26; TR group n = 23. Both intervention groups were similarly effective in significantly reducing pain severity and interference and depressive symptoms, and increasing self-efficacy and HRQoL over the 48 weeks. A clinically important reduction in pain severity of 3.31 points occurred for the sample over the 48 weeks of the study. All of these clinical improvements were obtained despite low and suboptimal attendance for both interventions. Conclusions Providing a therapeutic relationship alone is sufficient for effective pain management amongst rural amaXhosa WLWHA. These findings support greater emphasis on demonstrating care and developing skills to enhance the therapeutic relationship in healthcare professionals working with rural amaXhosa WLWHA. Trial registration PACTR; PACTR201410000902600, 30th October 2014; https://pactr.samrc.ac.za

Resilience.HIVPain v0.1.1

v0.1.1 (pre-release): Minor edits to README text. This repository includes data, analysis scripts, and the associated markdown and figure outputs for the analysis of physical activity and resilience questionnaire factor structures from a study of resilience in HIV-positive patients with pain

Pharmacological treatment of painful HIV-associated sensory neuropathy

Background. HIV-associated sensory neuropathy (HIV-SN) is a common and frequently painful complication of HIV infection and its treatment. However, few data exist describing the frequency, type and dosage of pain medications patients are receiving in the clinic setting to manage the painful symptoms of HIV-SN.Objective. To report on analgesic prescription for painful HIV-SN and factors influencing that prescription in adults on combination antiretroviral therapy. Methods. Using validated case ascertainment criteria to identify patients with painful HIV-SN, we recruited 130 HIV-positive patients with painful HIV-SN at Chris Hani Baragwanath Hospital, Johannesburg, South Africa. Demographic and clinical data (including current analgesic use) were collected on direct questioning of the patients and review of the medical files.Results. We found significant associations, of moderate effect size, between higher pain intensity and lower CD4 T-cell counts with prescription of analgesic therapy. Factors previously identified as predicting analgesic treatment in HIV-positive individuals (age, gender, level of education) were not associated with analgesic use here. Consistent with national guidelines, amitriptyline was the most commonly used agent, either alone or in combination therapy. Importantly, we also found that despite the relatively high analgesic treatment rate in this setting, the majority of patients described their current level of HIV-SN pain as moderate or severe. Conclusion. Our findings highlight the urgent need for both better analgesic options for HIV-SN pain treatment and ongoing training and support of clinicians managing this common and debilitating condition.