Impact of long-term treatment with neurotoxic dideoxynucleoside antiretrovirals: Implications for clinical care in resource-limited settings

Abstract

Objectives: A minority of HIV-infected patients taking an antiretroviral (ARV) regimen containing dideoxynucleosides (d-drugs) such as stavudine (d4T) and didanosine (DDI) experiences dose-limiting neuropathic pain and paraesthesias, usually within weeks of starting these drugs. Because d-drugs are among the few affordable options available in developing countries, continuing d-drug therapy would be a desirable strategy for many HIV-infected individuals. Therefore, we evaluated the safety of continuing d-drug therapy. Methods: In a US cohort, we compared the rates of worsening neuropathic symptoms and signs in HIV-infected individuals on stable ARV regimens that did (n = 252) or did not (n = 250) include d-drugs. Rates of worsening were compared using proportional hazards model and the log-rank test. Results: The risk ratios (RR) were not significantly larger for worsening neuropathy signs [0.94; 95% confidence interval (CI) 0.84-1.07] or symptoms (0.99; 95% CI 0.88-1.14) in patients taking d-drugs continuously compared to those not taking d-drugs. Conclusions: Continued d-drug exposure among patients tolerating an initial trial did not increase the risk of worsening neuropathy compared to non-d-drug-containing regimens. If applicable in developing countries, these findings suggest that in most patients d-drugs can be continued safely in the long term without increasing the risk of worsening neuropathy. © 2008 British HIV Association.