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Predicting Neuropathy Risk before Stavudine Prescription: An Algorithm for Minimizing Neurotoxicity in Resource-limited Settings
Catherine Cherry*1, J Affandi2, E Yunihastuti3, S Vanar4, D Imran3, A Kamarulzaman4, K Smyth5, A Wadley6, P Kamerman6, and P Price7
1Macfarlane Burnet Inst, Alfred Hosp, Monash Univ, Melbourne, Australia; 2Murdoch Univ, Perth, Australia; 3Pokdisus Clinic, Cipto Mangunkusumo Hosp, Univ of Indonesia, Jakarta; 4Univ of Malaya, Kuala Lumpur, Malaysia; 5Australian Natl Univ, Canberra; 6Univ of the Witwatersrand, Johannesburg, South Africa; and 7Royal Perth Hosp, Univ of Western Australia
Background: Sensory neuropathy (SN) is a common, disabling
complication of stavudine (d4T) therapy, with prevalence rates >40% reported
from d4T-treated cohorts of patients with HIV. Despite its toxicity, d4T is an
effective, relatively inexpensive HIV treatment and remains important in
resource-limited centers. Methods of predicting SN risk are needed to guide
antiretroviral prescribing in countries where some use of d4T remains an
economic necessity.
Methods: We undertook SN screening programs in Melbourne (low d4T use), Kuala Lumpur (intermediate d4T use), and Jakarta (routine d4T
use) in 2006 to describe SN risk factors among HIV patients in our region. SN
was defined by the presence of symptoms and signs on the AIDS Clinical Trials
Group Brief Peripheral Neuropathy Screen. Patients’ height, age, and weight
were recorded and demographic, laboratory, and treatment data obtained from the
medical file. Statistical analyses using Stata 9.2 defined factors associated
with SN. The role of patient demographics in predicting SN was then assessed in
patients who were free of neuropathy symptoms when prescribed d4T.
Results: We assessed 294 patients (100 Australians, 98
Malaysians, and 96 Indonesians). Prevalence rates of SN were 42%, 19%, and 34%,
respectively and 32% overall. In addition to treatment exposures, increasing
age (p = 0.002) and height (p = 0.001) were independently
associated with SN risk. Receiver operating characteristic analysis suggested
“cut offs” of ≥170 cm or ≥40 years for predicting patients at risk
of SN. These were applied to the 181 d4T-exposed patients who were asymptomatic
pre-d4T. This yielded an SN risk of 20% in younger, shorter patients, 33% in
younger but taller patients, 38% in older but shorter patients, and 66% in
those older than 40 years and taller than 170 cm prescribed d4T.
Conclusions: d4T is infrequently prescribed in Australia because of its high rates of toxicity, but remains an important HIV treatment in Jakarta and Kuala Lumpur. Rates of SN, a common d4T toxicity that impairs quality of life
and may reduce patients’ ability to work, vary with patients’ age and height. These
data support prioritizing patients taller than 170 cm or older than 40 years
(factors measurable at no extra cost) for access to antiretrovirals other than
d4T.
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