Pathogenesis of HIV-associated sensory neuropathy: evidence from in vivo and in vitro experimental models

HIV-associated sensory neuropathy (HIV-SN) is a frequent neurological complication of HIV infection and its treatment with some antiretroviral drugs. We review the pathogenesis of the viral- and drug-induced causes of the neuropathy, and its primary symptom, pain, based on evidence from in vivo and in vitro models of HIV-SN. Viral coat proteins mediate nerve fibre damage and hypernociception through direct and indirect mechanisms. Direct interactions between viral proteins and nerve fibres dominate axonal pathology, while somal pathology is dominated by indirect mechanisms that occur secondary to virus-mediated activation of glia and macrophage infiltration into the dorsal root ganglia. The treatment-induced neuropathy and resulting hypernociception arise primarily from drug-induced mitochondrial dysfunction, but the sequence of events initiated by the mitochondrial dysfunction that leads to the nerve fibre damage and dysfunction are still unclear. Overall, the models that have been developed to study the pathogenesis of HIV-SN, and hypernociception associated with the neuropathy, are reasonable models and have provided useful insights into the pathogenesis of HIV-SN. As new models are developed they may ultimately lead to identification of therapeutic targets for the prevention or treatment of this common neurological complication of HIV infection

Symptomatology of peripheral neuropathy in an African language.

The terminology used to describe neuropathic pain appears to be conserved across languages, which facilitates the translation of validated neuropathic pain screening tools into other languages. However, this assumption has not been assessed in an African language. Therefore we investigated the terminology used by 54 patients whose native language was isiZulu, a major Bantu language of Africa, when describing their symptomatic HIV-associated sensory neuropathy. Also, because English is a commonly spoken second-language in the region, we assessed these patients' knowledge and understanding of 21 English terms commonly used to describe neuropathic pain. English translations of the most commonly used isiZulu symptom descriptors included: "hot/burning" (50%), "cramping" (35%), "painful/sore/aching" (32%), "itching" (22%), "numb" (22%), "cold/freezing" (17%), and "stabbing/pricking/pins-and-needles" (13%). Thus, the isiZulu terminology to describe neuropathic pain was very similar to that used in non-African languages. However, knowledge and understanding of English neuropathic pain descriptors by these non-native English speakers was highly variable. For example, knowledge of English terms ranged from >98% ("hot", "cold/freezing", "cramping") to <25% ("pricking", "radiating", "throbbing"), and true understanding of English terms ranged from >90% ("hot", "burning", "cramping") to <35% ("tingling", "jumping", "shooting", "radiating"). In conclusion, we show significant similarity in the terms used to describe neuropathic pain in isiZulu compared to non-African languages, thus indicating that translation of existing neuropathic pain screening tools into this, and possibly other Bantu languages, is a viable option. However, the usefulness of English-language screening tools in this non-native English speaking population may be limited

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

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.

Concordance between spontaneously used isiZulu terms and English terms chosen from a list of neuropathic symptom descriptors.

*<p>Only participants who had used the word in their spontaneous descriptions were included in this analysis.</p

Demographic and disease-related characteristics of participants.

<p>a: Sample <54 because data missing from medical records.</p><p>b: Four participants would not divulge their educational level.</p