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

HIV Med. 2008 Oct;9(9):731-7. doi: 10.1111/j.1468-1293.2008.00615.x. Epub 2008 Jul 21.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Anti-HIV Agents / adverse effects*
  • Anti-HIV Agents / economics
  • Antiretroviral Therapy, Highly Active / adverse effects
  • Antiretroviral Therapy, Highly Active / economics
  • CD4 Lymphocyte Count
  • Cohort Studies
  • Developing Countries
  • Dideoxynucleosides / adverse effects*
  • Dideoxynucleosides / economics
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / economics
  • HIV-1*
  • Humans
  • Male
  • Paresthesia / chemically induced*
  • Polyneuropathies / chemically induced
  • Prospective Studies
  • Risk Assessment
  • Viral Load

Substances

  • Anti-HIV Agents
  • Dideoxynucleosides