Impact of long-term treatment with neurotoxic dideoxynucleoside antiretrovirals: implications for clinical care in resource-limited settings.
OBJECTIVE
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.
Hung
C F
CF
University of California, San Diego, CA, USA.
Gibson
S A
SA
Letendre
S L
SL
Lonergan
J T
JT
Marquie-Beck
J A
JA
Vaida
F
F
Ellis
R J
RJ
D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000191:economics; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects / Q000191:economics; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D003906:Developing Countries; D015224:Dideoxynucleosides / Q000009:adverse effects* / Q000191:economics; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000191:economics; D015497:HIV-1; D006801:Humans; D008297:Male; D010292:Paresthesia / Q000139:chemically induced*; D011115:Polyneuropathies / Q000139:chemically induced; D011446:Prospective Studies; D018570:Risk Assessment; D019562:Viral Load
D019380:Anti-HIV Agents; D015224:Dideoxynucleosides