HIV-related neuropathy
•
4 likes•1,183 views
Presentation on HIV-associated sensory neuropathy that was delivered at the XXII World Congress of Neurology, Santiago, Chile, 2015, in a session on the management of difficult neuropathic pain conditions.
Recommended
More Related Content
What's hot
What's hot (20)
Similar to HIV-related neuropathy
Similar to HIV-related neuropathy (20)
More from University of the Witwatersrand
More from University of the Witwatersrand (9)
Recently uploaded
Recently uploaded (20)
HIV-related neuropathy
- 1. HIV-related neuropathy Peter Kamerman XXII World Congress of Neurology, Santiago, Chile, 2015 PAIN MT 30.1 - Management of difficult neuropathic pain conditions
- 2. Disclosures I have no actual or potential conflicts of interest related to the material being presented. Nor do I discuss off-label indications for any medications.
- 3. Overview
- 4. Characteristics SIGNS Reduced: Pin-prick sensitivity Vibration sense Reflexes Temperature sense SYMPTOMS Pain Numbness Paraesthesias Typical clinical characteristics Bouhassira et al., 1999; Tagliati et al., 1999; Martin et al., 2003; Wadley et al., 2011; Freeman et al., 2014; Phillips et al., 2014
- 5. Australia: Smyth et al., 2007; Malawi: Beadles et al., 2009; van Oosterhout et al., 2005; South Africa: Maritz et al., 2010; Wadley et al., 2011; SE Asia: Affandi et al., 2008; Wright et al., 2008 ; Uganda: Nakasujja et al., 2005; USA: Simpson et al., 2006; Ellis et al., 2010 Global prevalence: 30-60% Prevalence
- 6. For review: Kamerman et al., 2012a, 2012b Dorsal root ganglion Axon and peripheral terminalSpinal cord Pathogenesis
- 7. Risk factors For review: Kamerman et al., 2012b
- 8. HIV-SN is down, but not out Newer, less toxic treatments Ellis et al., 2010; Kamerman, 2015
- 9. Hung et al., 2005 HIV-SN is down, but not out Newer, less toxic treatments Neurotoxic drug regimen Other drug regimens Proportionwith worseningsigns Proportionwith worseningsymptoms
- 10. • HIV-SN is common • Expected to remain a problem Summary
- 11. Painful HIV-SN
- 12. Painful HIV-SN Pain is a common feature Veves et al., 2007; Sadosky et al., 2008; Haanpaa et al., 2009; van Hecke et al., 2014
- 13. Common causes of chronic pain in HIV Painful peripheral neuropathy 45-48% Low back pain 22-28% Arthralgia 6-13% Koeppe et al., 2010 Major cause of chronic pain in HIV Painful HIV-SN
- 14. Ellis et al., 2010; Hung et al., 2008; Malvar et al., 2015; Pillay et al., 2015 Risk of pain ↑ risk Previous neurotoxic drug use Past or current cART ↑ nadir CD4 T-cell count Current major depressive disorder Number of other pain sites ↑ age Female sex ↓ risk Current neurotoxic drug use ↑ time since HIV diagnosis Risk factors for having pain Painful HIV-SN
- 15. Keltner et al., 2014 Proportionwithpainful HIV-SN 0.6 0.4 0.3 0.2 0.1 0.0 0.5 Q1 Q2 Q3 Q4 Quartiles of adjusted log cortical volume loss Pain is associated with reduced cortical volumes Painful HIV-SN
- 16. Pain intensity ↑ intensity ↑ viral load ↓ intra-epidermal nerve fibre density ↑ pain catastrophizing ↑ depressive symptoms ↑ number of pain sites Genetic polymorphisms in KCNS1/TNFA/MHCIII Simpson et al., 2002; Polydefkis et al., 2002; Zhou et al., 2007; Lucey et al., 2011; Hendry et al., 2013; Hendry et al., 2015; Pillay et al., 2015 The pain typically is moderate-to-severe Painful HIV-SN
- 17. Having painful HIV-SN is associated with Being unemployed ↑ depression and anxiety ↑ severity of depressive symptoms ↑ sleep disturbance ↓ independence ↓ social functioning Ellis et al., 2010; Phillips et al., 2014 Impact of the pain Painful HIV-SN
- 18. • Pain is common • Typically is moderate-to-severe • Causes a significant decrease in QoL Summary
- 19. Treatment
- 20. Can we treat the pain? Phillips et al., 2010; Clifford et al., 2012* Treatment Pain relief superior to placebo Yes No Topical lidocaine gel (5%) Capsaicin patch (8%) ?* Amitriptyline Lamotrigine Mexilitine Gabapentin / Pregabalin
- 21. Can we treat the pain? Finnerup et al., 2015 “Pain due to HIV-related painful polyneuropathy…seems more refractory [to treatment] than other types of pain in our meta-analysis.” “This difference might be due to large placebo responses in HIV-related neuropathy trials”
- 22. Confounding by the placebo response Cepeda et al., 2012 HIV-SN trials show larger placebo response
- 23. Confounded by the placebo response ...and more placebo responders Cepeda et al., 2012
- 24. Failed drug or failed study? Simpson et al., 2010
- 25. Failed drug or failed study? Tuttle et al., doi: 10.1097/j.pain.0000000000000333 Increasing placebo response is a general phenomenon
- 26. Failed drug or failed study? Simpson et al., 2014 “Methodological refinements...to minimize the potential placebo response, which was quite large in the previous study”
- 27. Failed drug or failed study? “Methodological refinements...to minimize the potential placebo response, which was quite large in the previous study” ● High baseline pain scores ● Low baseline pain variability ● Long baseline period + single-blind placebo lead-in ● Restricted use of concomitant medications for pain ● Improved phenotyping Simpson et al., 2014
- 28. Failed drug or failed study? Simpson et al., 2014
- 29. Failed drug or failed study? “Methodological refinements...to minimize the potential placebo response, which was quite large in the previous study” ● High baseline pain scores ● Low baseline pain variability ● Long baseline period + single-blind placebo lead-in ● Restricted use of concomitant medications for pain ● Improved phenotyping Simpson et al., 2014
- 30. Failed drug or failed study? Simpson et al., 2010
- 31. “HIV-associated DSP was confirmed by the clinician at screening, ensuring that the patient had at least two of the three following neurological signs...reduced superficial sensation in the distal lower extremities bilaterally (using the pin-prick test)” Simpson et al., 2014 Failed drug or failed study?
- 32. Summary • HIV-SN is common • Is expected to remain a problem • Pain is common • Typically is moderate-to-severe • Causes a significant decrease in QoL • The evidence-base to guide treatment is poor
- 33. University of the Witwatersrand Antonia Wadley Zané Lombard Prinisha Pillay Liesl Hendry Burnet Institute, Melbourne Kate Cherry University of Western Australia, Perth Patricia Price Hayley Goullée Constance Chew Funding • National Research Foundation, South Africa • South African Medical Research Council • International Association for the Study of Pain • University of the Witwatersrand Acknowledgements