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

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.