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.

Context counts: Investigating pain management interventions in HIV-positive men living in a rural area.

BACKGROUND: Pain remains a prevalent and burdensome complaint for people living with human immunodeficiency virus and/or aquired immunodeficiency syndrome (LWHA). Positive Living (PL), a multimodal pain intervention, reduced pain in female South Africans LWHA. We investigated the efficacy of the PL programme in South African males living with human immunodeficiency virus and/or acquired immunodeficiency syndrome (MLWA) in a rural community. AIM: To determine the effects of a multimodal pain intervention in MLWHA. SETTING: Various primary care clinics in Manguzi, Kwa-Zulu Natal, South Africa. METHODOLOGY: Therapeutic relationship (TR) intervention alone or in combination with the PL programme were allocated to HIV-positive men between the ages of 18-40. Pain intensity and interference were the primary outcome measures. Secondary outcome measures included physical function, health-related quality of life, depressive symptoms and self-efficacy. RESULTS: Forty-seven men (mean age 35 ± 3 years) were recruited with baseline mean pain severity of 5.02 (± 3.01) and pain interference of 4.6 (± 3.18). Nineteen men were allocated to the TR intervention alone, 28 were allocated to the TR intervention and PL programme. Attendance at the intervention sessions varied from 10% to 36%. No changes in any outcomes were recorded. CONCLUSION: Poor attendance at the intervention and follow-up sessions make these results an unreliable reflection of the intervention. Contextual factors including internal migration and issues around employment were identified. These may influence healthcare utilisation for MLWHA living in rural settings.Contribution: Unmet healthcare needs of MLWHA in a rural community have been identified. If we are to 'leave no one behind', healthcare interventions should account for context and be 'rural-proofed'.

Slow and Steady But Not Related to HIV Stigma: Physical Activity in South Africans Living with HIV and Chronic Pain.

HIV stigma may influence physical activity in people living with HIV (PLWH) and chronic pain. We prospectively examined the relationship between stigma, activity and chronic pain in a convenience sample of PLWH initiating antiretroviral therapy in an inner-city clinic in Johannesburg, South Africa. Participants wore accelerometers to measure daily duration and intensity of activity for 2 weeks. Stigma was assessed with the Revised HIV Stigma Scale. Participants [n = 81, 89% female, age mean (SD) 42 (8)] were active for a median of 7 h daily (IQR 5.2, 9.2), but at very low intensity, equivalent to a slow walk [median (IQR): 0.39 m s-1 (0.33, 0.50)]. Duration and intensity of activity was not associated with stigma, even after controlling for age, self-assessed wealth, pain intensity and willingness to engage in physical activity (p-values > 0.05). As stigma did not associate with greater activity, drivers of sustained activity in South African PLWH remain unclear.

RESUMEN: El estigma del VIH puede influir en la actividad física de las personas que viven con el VIH (PVVS) y el dolor crónico. Se examinó prospectivamente la relación entre el estigma, la actividad y el dolor crónico en una muestra de conveniencia de PVVS que iniciaba la terapia antirretroviral en una clínica del centro de la ciudad en Johannesburgo, Sudáfrica. Los participantes usaron acelerómetros para medir la duración diaria y la intensidad de la actividad durante dos semanas. El estigma se evaluó con la escala revisada de estigma del VIH. Los participantes [n = 81, 89% mujeres, media de edad (SD) 42 (8)] tenían una actividad de intensidad muy baja, para una mediana de siete horas diarias (IQR 5.2, 9.2), pero, equivalente a una marcha lenta [mediana (IQR): 0.39 m s−1 (0.33, 0.50)]. La duración y la intensidad de la actividad no se asociaron con los niveles de estigma, incluso después de controlar la edad, la riqueza autoevaluada, la intensidad del dolor y la voluntad de participar en la actividad física (valores de p > 0.05). Como el estigma no se asoció con una mayor actividad, los impulsores de la actividad sostenida en las PVVS sudafricanas siguen sin estar claros.

South African men and women living with HIV have similar distributions of pain sites.

BACKGROUND: No studies have investigated sex differences in the location and number of pain sites in people living with human immunodeficiency virus (HIV) (PLWH), despite evidence that women, in general, bear a greater burden of pain than men. AIM: To determine sex differences in the location and number of pain sites, and whether there were demographic or disease-related differences in the number of pain sites. SETTING: South African tertiary hospital HIV clinics and a community healthcare centreMethods: We conducted a retrospective analysis of records from South African PLWH who had pain. RESULTS: Of the 596 participant records, 19% were male (115/596) and the median number of pain sites for both sexes was 2 (interquartile range [IQR]: 1 to 3). Pain was most frequently experienced in the head (men: 12%, women: 38%), feet and ankles (men: 42%, women: 28%), abdomen (men = 19%, women = 28%) and chest (men = 20%, women = 20%). After correcting for multiple comparisons, males were less likely to experience headache than females (Fisher's exact text, odds ratio [OR] = 0.23, 95% confidence interval [CI]: 0.12 - 0.42, p = 0.000). Pain at other body sites was experienced similarly between the sexes. There was no meaningful variation in the number of pain sites between the sexes (logistic regression, p = 0.157). CONCLUSION: A similar location and number of pain sites were experienced by male and female South African PLWH. The locations of pain sites were different from previous reports, however, suggesting that research into pain in PLWH cannot necessarily be generalised across cultures.

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 .

High individual pain variability in people living with HIV: A graphical analysis.

BACKGROUND: People living with HIV (PLWH) frequently experience pain. Following calls to analyse individual-level data in addition to group-level data in pain studies, we compared individual and group-level changes in pain prevalence, intensity and number of pain sites over 48 weeks in a large cohort of PLWH. This is the largest ever cohort study of pain in PLWH, and is the first to report pain at the level of the individual. METHODS: Participants included all participants with complete pain records from a randomized clinical trial (RCT) for the treatment of HIV (n = 787/1053). At weeks 0, 12, 24, 36 and 48 we assessed participants' pain in the last week; presence of pain, and if present, the intensity and locations of the pain. We used standard averaging methods to describe data at the group level, and unique graphical reporting methods to analyse data at the level of the individual. RESULTS: Group-level data demonstrated a trend for pain prevalence to decline over time (19% week 0, 12% week 48). Worst pain intensity remained stable (median between 4/10 and 5/10), as did the number (median = 1) and common sites of pain across the 48 weeks. In contrast, individual-level data demonstrated high intra-individual variability with regards to the presence of pain, and the intensity and location of the pain. CONCLUSIONS: While our group-level data were similar to previous longitudinal studies, an apparent reduction in pain over 48 weeks, the individual-level data showed large variability within individuals in that same time frame. SIGNIFICANCE: This graphical analysis highlights the high variability in pain (pain prevalence, intensity and body sites) across time in people living with HIV, and how presenting averaged data hides this important variability. Our data support the reporting of individual-level data in human experimental and observational studies.

Working nights and lower leisure-time physical activity associate with chronic pain in Southern African long-distance truck drivers: A cross-sectional study.

BACKGROUND: In South Africa, the trucking industry employs over 70,000 people and the prevalence of chronic pain in this occupational group was reported at 10%. We investigated factors associated with chronic pain in truck drivers including mental health, physical activity, and sleep, as no study has done so. METHODS: Southern African male, long-distance truck drivers were recruited at truck stops in Gauteng and Free State Provinces, South Africa (n = 614). Chronic pain was defined as pain present for at least the last three months. Depressive symptoms were assessed with the Patient Health Questionnaire-9, post-traumatic stress disorder with the Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5), exposure to traumatic events with the Life Events Checklist-5 (LEC-5) and daytime sleepiness with the Epworth Sleepiness Scale. Sleep quality was measured on a four-point Likert scale. Leisure-time physical activity was measured using the Godin-Shephard leisure-time physical activity questionnaire. Associations between these factors, demographic factors and chronic pain were investigated. RESULTS: Multivariate analysis showed that working ≥ 2 nights/week (OR = 2.68, 95% CI = 1.55-4.68) was associated with chronic pain and physical activity was protective (OR = 0.97, 95% CI 0.95-0.98). In an exploratory analysis, greater depressive symptoms (p = 0.004), daytime sleepiness (p = 0.01) and worse sleep quality (p = 0.001) was associated with working ≥ 2 nights/week. Lower leisure-time physical activity was associated with worse sleep quality (p = 0.006), but not daytime sleepiness or depressive symptoms (p>0.05). CONCLUSIONS: There is a clear relationship between working nights and activity levels, and chronic pain, sleep quality, and depression in truck drivers.

Pain in Clients Attending a South African Voluntary Counseling and Testing Center Was Frequent and Extensive But Did Not Depend on HIV Status.

BACKGROUND: The frequency of pain is reported to be high in people living with HIV, but valid comparisons between people living with HIV and HIV-negative cohorts are rare. We investigated whether HIV infection influenced frequency and characteristics of pain in adults undergoing voluntary testing for HIV. SETTING: Participants were recruited from an HIV voluntary counseling and testing center at the Chris Hani Baragwanath Academic Hospital, Soweto, South Africa. METHODS: Pain was assessed using the Wisconsin Brief Pain Questionnaire. Depressive and anxiety symptomatology was determined using the Hopkins Symptom checklist-25. We then stratified by HIV status. RESULTS: Data from 535 black South Africans were analyzed: HIV-infected n = 70, HIV-uninfected n = 465. Overall, frequency of any current pain was high with 59% [95% confidence interval (CI): 55 to 63, n: 316/535] of participants reporting pain, with no difference related to HIV status: HIV-infected 50% (95% CI: 37 to 61, n: 35/70), HIV-uninfected 60% (95% CI: 56 to 65, n: 281/465). Pain intensity and number of pain sites were similar between the groups as were symptoms of anxiety and depression: mean Hopkins Symptom Checklist-25 1.72 (95% CI: 1.57 to 1.87) HIV-infected participants and 1.68 (95% CI: 1.63 to 1.73) HIV-uninfected participants. Univariate analysis showed female sex and greater depressive and anxiety symptomatology associated with pain. In a multivariable modeling, only depressive and anxiety symptomatology was retained in the model. CONCLUSION: The high frequency of pain found in both HIV-infected and HIV-uninfected individuals presenting at a voluntary counseling and testing center was more likely to be associated with depression and anxiety, than with the presence or absence of HIV.

Clinical diagnosis of sensory neuropathy in HIV patients treated with tenofovir: A 6-month follow-up study.

BACKGROUND: Sensory neuropathy (SN) is a common and often painful neurological condition associated with HIV-infection and its treatment. However, data on the incidence of SN in neuropathy-free individuals initiating combination antiretroviral therapies (cART) that do not contain the neurotoxic agent stavudine are lacking. AIMS: We investigated the 6-month incidence of SN in ART naïve individuals initiating tenofovir (TDF)-based cART, and the clinical factors associated with the development of SN. METHODS: 120 neuropathy-free and ART naïve individuals initiating cART at a single center in Johannesburg, South Africa were enrolled. Participants were screened for SN using clinical signs and symptoms at study enrolment and approximately every 2-months for a period of ~6-months. Diagnostic criteria for symptomatic SN was defined by the presence of at least one symptom (pain/burning, numbness, paraesthesias) and at least two clinical signs (reduced vibration sense, absent ankle reflexes or pin-prick hypoaesthesia). Diagnostic criteria for asymptomatic SN required at least two clinical signs only (as above). RESULTS: A total of 88% of the cohort completed three visits within the 6-month period. The 6-month cumulative incidence of neuropathy was 140 cases per 1000 patients (95% CI: 80-210) at an incidence rate of 0.37 (95% CI: 0.2-0.5) per person year. Height and active tuberculosis (TB) disease were independently associated with the risk of developing SN (P < .05). INTERPRETATION: We found that within the first 6 months of starting cART, incident SN persists in the post-stavudine era, with 11 (9%) of individuals developing asymptomatic SN, and 9 (8%) developing symptomatic SN.

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 > 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.

Barriers to implementing clinical trials on nonpharmacological treatments in developing countries: lessons learnt from addressing pain in HIV.

Pain affects over half of the people living with HIV/AIDS (LWHA), and pharmacological treatment has limited efficacy. Preliminary evidence supports nonpharmacological interventions. We previously piloted a multimodal intervention in amaXhosa women LWHA and chronic pain in South Africa with improvements seen in all outcomes, in both intervention and control groups. A multicentre, single-blind randomised controlled trial with 160 participants recruited was conducted to determine whether the multimodal peer-led intervention reduced pain in different populations of both male and female South Africans LWHA. Participants were followed up at weeks 4, 8, 12, 24, and 48 to evaluate effects on the primary outcome of pain, and on depression, self-efficacy, and health-related quality of life. We were unable to assess the efficacy of the intervention due to a 58% loss to follow-up (LTFU). Secondary analysis of the LTFU found that sociocultural factors were not predictive of LTFU. Depression, however, did associate with LTFU, with greater severity of depressive symptoms predicting LTFU at week 8 (P = 0.01). We were unable to evaluate the effectiveness of the intervention due to the high LTFU and the risk of retention bias. The different sociocultural context in South Africa may warrant a different approach to interventions for pain in HIV compared with resource-rich countries, including a concurrent strategy to address barriers to health care service delivery. We suggest that assessment of pain and depression need to occur simultaneously in those with pain in HIV. We suggest investigation of the effect of social inclusion on pain and depression.

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 > 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

Pharmacogenetic variation influences sensory neuropathy occurrence in Southern Africans treated with stavudine-containing antiretroviral therapy.

BACKGROUND: The use of the HIV antiretroviral drug stavudine (d4T), a thymidine analogue, is associated with the development of mitochondrial toxicities such as sensory neuropathy (SN). Genetic variation in genes relating to d4T transport and metabolism, as well as genetic variation in the thymidine synthesis pathway, could influence occurrence of d4T-related toxicity. METHODS: We examined this hypothesis in a cohort of HIV-positive South African adults exposed to d4T, including 143 cases with SN and 120 controls without SN. Ten SNPs in four genes associated with stavudine transport, and 16 SNPs in seven genes of the thymidine synthesis / phosphorylation pathway were genotyped using Agena mass spectrometry methods. Associations between sensory neuropathy and genetic variants were evaluated using PLINK by univariate and multivariable analyses. RESULTS: Age and height were significantly associated with SN occurrence. Using logistic regression with age and height as covariates, and uncorrected empirical p-values, genetic variation in SLC28A1, SAMHD1, MTHFR and RRM2B was associated with SN in South Africans using d4T. CONCLUSION: Variation in genes relating to d4T transport and metabolism, as well as genetic variation in the thymidine synthesis pathway may influence occurrence of d4T-related SN. These data contribute to the characterisation of African pharmacogenetic variation and its role in adverse response to antiretroviral therapy.

Psychological Factors Associated With Painful Versus Non-Painful HIV-Associated Sensory Neuropathy.

HIV-associated sensory neuropathy (HIV-SN) is a common, and frequently painful complication of HIV, but factors that determine the presence of pain are unresolved. We investigated: (i) if psychological factors associated with painful (n = 125) versus non-painful HIV-SN (n = 72), and (ii) if pain and psychological factors affected quality of life (QoL). We assessed anxiety and depression using the Hopkins Symptoms Checklist-25. Pain catastrophizing and QoL were assessed using the Pain Catastrophizing Scale and Euroqol-5D, respectively. Presence of neuropathy was detected using the Brief Neuropathy Screening Tool, and pain was characterised using the Wisconsin Brief Pain Questionnaire. Overall, there was a high burden of pain, depression and anxiety in the cohort. None of the psychological variables associated with having painful HIV-SN. Greater depressive symptoms and presence of pain were independently associated with lower QoL. In those participants with painful HIV-SN, greater depressive symptom scores were associated with increased pain intensity. In conclusion, in a cohort with high background levels of psychological dysfunction, psychological factors do not predict the presence of pain, but both depression and presence of pain are associated with poor quality of life.

Genetics of HIV-associated sensory neuropathy and related pain in Africans.

Despite the use of safer antiretroviral medications, the rate of HIV-associated sensory neuropathy (HIV-SN), the most common neurological complication of HIV, remains high. This condition is often painful and has a negative effect on quality of life. Up to 90% of those with HIV-SN experience pain for which there is no effective analgesic treatment. Genetic factors are implicated, but there is a lack of a comprehensive body of research for African populations. This knowledge gap is even more pertinent as Africans are most affected by HIV. However, recent studies performed in Southern African populations have identified genes displaying potential as genetic markers for HIV-SN and HIV-SN-associated pain in Africans. Here, we review the published studies to describe current knowledge of genetic risk factors for this disease in Africa.

Predictors of Cold and Pressure Pain Tolerance in Healthy South African Adults.

BACKGROUND: Studies on relationships between sex, ethnicity, and pain have largely emanated from the United States and Europe. We compared cold (CPT) and pressure pain tolerance (PPT) in male and female South Africans of African and European ancestry and assessed whether psychosocial factors (including pain beliefs) predicted differences in pain tolerance. METHODS: We recruited 106 (62 female) students of African ancestry and 106 (55 female) of European ancestry and subjected them to a cold-pressor test and pressure algometry. Socioeconomic status (SES), pain catastrophizing, depression, anxiety, and pain beliefs were assessed as predictors of pain tolerance. RESULTS: CPT was lower in students of African compared with European ancestry (for both sexes), and PPT was lower in female than male students (for both ethnicities). Females were very accepting of men expressing pain and males less so. Males of African ancestry were least accepting but still tolerant. Multivariate analysis identified African ancestry, and particularly being a female of African ancestry, as strong predictors of lower CPT. Anxiety was a weak predict or of CPT. Sex was the only strong predictor of PPT on multivariate analysis (PPT females < males), and catastrophizing was a weak predictor. Female sex and African ancestry were strong predictors of acceptance of expression of pain in males. SES was a weak predictor of the Appropriate Pain Behavior Questionnaire-Malescore. CONCLUSIONS: Despite different cultural and social backgrounds from US and European cohorts, we saw similar patterns of sex and ethnic differences in CPT and PPT in an African cohort. Traditional psychosocial predictors of pain sensitivity predicted variation in the outcome variables but were not strong predictors.

Resilience does not explain the dissociation between chronic pain and physical activity in South Africans living with HIV.

Pain burden is high in people living with HIV (PLWH), but the effect of this pain on functionality is equivocal. Resilience, the ability to cope with adversity, may promote adaptation to pain, so we hypothesised that higher resilience would correlate with less pain-related impairment of activity. We recruited 197 black South African PLWH, 99 with chronic pain (CP) and 98 patients without. We measured pain intensity and interference using the Brief Pain Inventory, and resilience using the Resilience Scale. Participants were generally highly resilient. Greater resilience correlated with better health-related quality of life, but not with pain intensity or interference. We also measured physical activity objectively, by actigraphy, in a subset of patients (37 with chronic pain and 31 without chronic pain), who wore accelerometers for two weeks. There was no difference in duration or intensity of activity between those with and without pain, and activity was not associated with resilience. In this sample, pain was not associated with altered physical activity. Resilience did not explain differences in pain intensity or pain interference but was associated with improved quality of life. Financial stresses and the fear of HIV stigma may have driven patients to conceal pain and to suppress its expected impairment of activity.

Diagnosing and treating HIV-associated sensory neuropathy: a global perspective.

HIV-associated sensory neuropathy (HIV-SN) is a common complication of HIV and remains highly prevalent even with modern HIV management strategies, causing debilitating pain in millions globally. We review HIV-SN diagnosis and management. We suggest most HIV-SN cases are easily recognized using clinical screening tools, with physician assessment and/or specialized testing prioritized for atypical cases. Management aims to prevent further nerve damage and optimize symptom control. Symptom relief is difficult and rarely complete, with a lack of proven pharmacological strategies. Work is needed to clarify optimal use of available medications. This includes understanding the marked placebo effect in HIV-SN analgesic trials and exploring 'responder phenotypes'. Limited data support nondrug strategies including hypnosis, meditation, psychology, physical activity and a positive therapeutic relationship.

Polymorphisms in CAMKK2 may predict sensory neuropathy in African HIV patients.

HIV-associated sensory neuropathy (HIV-SN) is the most common neurological condition associated with HIV. HIV-SN has characteristics of an inflammatory pathology caused by the virus itself and/or by antiretroviral treatment (ART). Here, we assess the impact of single-nucleotide polymorphisms (SNPs) in a cluster of three genes that affect inflammation and neuronal repair: P2X7R, P2X4R and CAMKK2. HIV-SN status was assessed using the Brief Peripheral Neuropathy Screening tool, with SN defined by bilateral symptoms and signs. Forty-five SNPs in P2X7R, P2X4R and CAMKK2 were genotyped using TaqMan fluorescent probes, in DNA samples from 153 HIV(+) black Southern African patients exposed to stavudine. Haplotypes were derived using the fastPHASE algorithm, and SNP genotypes and haplotypes associated with HIV-SN were identified. Optimal logistic regression models included demographics (age and height), with SNPs (model p < 0.0001; R (2) = 0.19) or haplotypes (model p < 0.0001; R (2) = 0.18, n = 137 excluding patients carrying CAMKK2 haplotypes perfectly associated with SN). Overall, CAMKK2 exhibited the strongest associations with HIV-SN, with two SNPs and six haplotypes predicting SN status in black Southern Africans. This gene warrants further study.

TNF Block Gene Variants Associate With Pain Intensity in Black Southern Africans With HIV-associated Sensory Neuropathy.

OBJECTIVES: HIV-associated sensory neuropathy (HIV-SN) is a common neurological complication of HIV infection, and it is often painful. Tumor necrosis factor (TNF)-α is implicated in neuropathic pain, but associations between neuropathic pain and polymorphisms in the TNFA gene have not been identified. The "TNF block" is a region of high linkage disequilibrium within the central major histocompatability complex that contains several genes involved in the regulation of inflammation, including TNFA. Polymorphisms in the block have been associated with an altered risk of HIV-SN, but no investigations into whether this region is associated with the painful symptoms of neuropathy have been undertaken. Therefore, we investigated whether polymorphisms in the TNF block are associated with pain intensity in black Southern Africans with HIV-SN. METHODS: Single-nucleotide polymorphisms (SNPs) defining TNF block haplotypes and African-specific tagSNPs were genotyped in samples from 150 black Southern Africans with HIV-SN. RESULTS: One SNP allele, rs28445017*A, was significantly associated with an increased pain intensity after correction for age, sex, and the CD4 T-cell count. A common 3-SNP haplotype containing rs28445017*G remained associated with a reduced pain intensity after correction for covariates and multiple comparisons. DISCUSSION: We identified a novel genetic association between polymorphisms in the TNF block and the pain intensity in black Southern Africans with HIV-SN. Our study implicates rs28445017 in painful HIV-SN, although its precise role and whether it may be causative is unclear. rs28445017 was not associated with the risk for HIV-SN as such, highlighting potential differences between the pathophysiology of the neuropathy and the painful features of the neuropathy.