Peripheral neuropathy update
Paul Blanchard, HIV i-Base
Sensory neuropathy is the most common neurological complication of HIV-infection. In the pre-HAART era approximately 30% of inpatients with AIDS suffered some degree of this form of neuropathy.
The clinical features of HIV sensory neuropathy and neuropathy induced by nucleoside analogue toxicity overlap. Both present as a length-dependent sensory neuropathy (ie feet affected first) manifested by pain in the soles of the feet in over 60% of individuals and paresthesias in 40%. Weakness is almost never a presenting symptom. Neurological examination shows abnormal sensory thresholds in up to 85% of individuals and reduced or absent ankle reflexes in up to 96%. Motor findings are uncommon, with only a third of patients having distal weakness.
The prevalence of sensory neuropathy since the introduction of effective antiretroviral therapy has not been well described. Dr Catherine Cherry of Monash University, Melbourne, Australia presented data at the 9th CROI from a study of HIV-infected outpatients compared to an historical control. Prevalence and risk factors for sensory neuropathy were determined using a standardised screening and multivariate analysis performed over 4 months up to March 2001. Comparisons were made with an historical control of outpatients screened for sensory neuropathy in 1993.
There was found to be a significant increase in both the symptoms and signs of neuropathy in the 2001 cohort compared to the 1993 cohort (p<0.0001). In 1993 symptoms of neuropathy were present in 19% (18/94) of the out-patient population compared to 60% (84/140) in 2001. Clinical screening revealed at least one sign of sensory neuropathy in 14% of the 1993 cohort compared to 44% in the 2001 cohort. This represents a huge rise in the prevalence of both signs and symptoms of peripheral neuropathy since the introduction of HAART.
Cherry and colleagues went on to attempt to determine the risk factors for the development of sensory neuropathy in these cohorts and examined age, duration of HIV-infection, AIDS classification, CD4 count, nadir CD4, viral load, antiretroviral use and dideoxynucleoside (ddI, d4T, ddC) use in both univariate and multivariate analysis.
Univariate analysis revealed that those patients with sensory neuropathy tended to be older, to have been infected with HIV longer, to be more likely to have received both any antiretrovirals and dideoxynucleosides specifically and to have had lower CD4 nadirs (all p <0.05). AIDS diagnosis, median HIV viral load and median CD4 count were not found to be predictive of sensory neuropathy.
Multivariate analysis revealed only age (odds ratio 1.1) and dideoxynucleoside use (odds ratio 26) as significant predictors of the presence of neuropathy. Further analysis was performed to try and determine if either duration of dideoxynucleoside exposure increased risk or if any particular dideoxynucleosides were associated with increased risk.
Univariate analysis revealed significant risk factors for the presence of peripheral neuropathy to be:
- Longer duration of dideoxynucleoside use
- Longer duration of ddC use
- Longer duration of d4T use
- Longer duration of ddI use
- Longer duration of dual dideoxynucleoside use
Independent predictors from multivariate analysis were history of exposure to d4T ever (odds ratio 7.4) or ddI ever (odds ratio 3.2).
Cherry concluded that there had been an increased prevalence of clinical sensory neuropathy since the introduction of HAART and that increased age and having used a dideoxynucleoside were independent risk factors for sensory neuropathy. Moreover d4T and ddI use were independently associated with sensory neuropathy, but not cumulative exposure. Additionally use of dual dideoynucleosides (ie. d4T + ddI) was not independently associated with neuropathy in this cohort.
Cherry C, McArthur J, Costello K et al. Increasing Prevalence of Neuropathy in the Era of Highly Active Antiretroviral Therapy (HAART). 9th Conference on Retroviruses and Opportunistic Infections; February 24-28, 2002; Seattle, Washington. Abstract 69.