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HIV-associated Peripheral Neuropathy in the HAART Era: Results from AIDS Clinical Trials Group Longitudinal Linked Randomized Trials Protocol A5001
Scott Evans*1, D Clifford2, H Chen1, G Schifitto3, T-M Yeh1, K Wu1, R Bosch1, J McArthur4, D Simpson5, and R Ellis6
1Harvard Sch of Publ Hlth, Boston, MA, US; 2Washington Univ, St Louis, MO, US; 3Univ of Rochester, NY, US; 4Johns Hopkins Univ, Baltimore, MD, US; 5Mt Sinai Sch of Med, New York, NY, US; and 6Univ of California, San Diego, US
Background:
Peripheral neuropathy (PN) is the most frequent neurological complication in
HIV infection. Symptoms including pain, numbness, and “pins and needles”
sensation, affect quality of life, often require analgesic therapy, and may
influence the choice of antiretroviral (ARV) drugs. No FDA-approved therapy
exists. While pre-HAART risk factors for PN included high HIV-1 RNA, low CD4,
and neurotoxic ARV (n-ARV) use, risk factors in the HAART era are not well
delineated. Objectives of this study include estimating the prevalence of
neuropathic signs and symptoms with ARV initiation in ARV-naïve patients and investigating
prognostic factors in the HAART era.
Methods:
Participants from the AIDS Clinical Trials Group (ACTG) A5001 cohort that
initiated HAART in randomized trials for ARV-naïve patients were annually
administered a brief PN screen by trained site personnel, evaluating symptoms and
signs of PN between January 2000 and June 2007. HIV-1 RNA, CD4, n-ARV and PI
use were concurrently collected longitudinally. PN was defined as at least mild
loss of vibration sensation in both great toes bilaterally or absent or
hypoactive ankle reflexes bilaterally relative to knees. Symptomatic PN (SPN)
was defined as PN plus bilateral symptoms. Multivariable logistic generalized
estimating equation regression models were used to estimate associations with PN
and SPN while controlling for potential confounders.
Results: We
analyzed 2135 naïve participants (81% male, 44% white, 32% black, median age 39,
median log HIV-1 RNA at HAART initiation 4.9). n-ARV use peaked at week 144 (25%)
dropping to 10.9% at week 384. The increasing prevalence of PN and SPN after
HAART initiation are summarized below:
|
Weeks
after
HAART Initiation
|
When CD4 >350
|
When HIV-1 RNA ≤400
|
|
n
|
PN (%)
|
SPN (%)
|
n
|
PN (%)
|
SPN (%)
|
|
48
|
768
|
25.7
|
8.2
|
1253
|
29.5
|
10.1
|
|
96
|
1042
|
29.9
|
7.9
|
1389
|
32.1
|
8.7
|
|
192
|
889
|
33.1
|
8.8
|
1053
|
33.5
|
9.6
|
|
288
|
494
|
37.9
|
11.7
|
556
|
41.5
|
14.0
|
|
384
|
287
|
41.5
|
13.6
|
331
|
44.4
|
14.2
|
Notable factors
associated with PN include: years since ARV-initiation (p <0.01, OR 1.09
for each additional year, 95%CI 1.06, 1.12), age (p <0.01, OR = 1.89
for a 10-year increase, 95%CI 1.73, 2.07), and n-ARV use (p = <0.01,
OR = 1.50, [1.29, 1.75]).
Conclusions:
The prevalence of PN and SPN increases with time after ARV initiation in
ARV-naïve patients despite increased virologic control and immune function, and
the decline of n-ARV use. Age and n-ARV use are notable risk factors for N and
SPN.
|
