Incidence of neuropathy in HIV-infected patients on monotherapy versus those on combination therapy with didanosine, stavudine and hydroxyurea

Background: Sensory neuropathy is a common adverse effect of the nucleoside analogue anti-retroviral drugs didanosine (ddl) and stauvudine (d4T). Thes e drugs are increasingly being used in combination, and it is not currently known whether the incidence of neuropathy is higher with combination compa red to individual drug use. It is also not known if hydroxyurea, used to po tentiate the antiviral efficacy of these drugs, may also increase the risk of neuropathy The purpose of this analysis is to investigate if the combina tion of ddl and d4T, with or without hydroxyurea, has a higher incidence of neuropathy than a single drug regimen. Methods: Data were obtained from patients followed longitudinally by the Jo hns Hopkins AIDS Services. Incidence rates of development of neuropathy wer e calculated for each of five regimens: ddl (+/- hydroxyurea), ddl + d4T (/- hydroxyurea), and d4T. Cox proportional hazard regression was used to co mpare the relative risk of neuropathy for each regimen adjusting for CD4 ce ll count, other drugs received, and time on therapy. Results: A total of 1116 patients received at least one of the five regimen s. There were 117 cases of neuropathy. The crude incidence rate of neuropat hy ranged from 6.8 cases per 100 person-years for ddl to 28.6 cases per 100 person-years for ddl + d4T + hydroxyurea. Compared with ddl alone, and adj usting for CD4 cell counts and other variables, the relative risk of neurop athy was 1.39 [95% confidence interval (CI): 0.84-2.32] for d4T alone, 2.35 (95% Cl: 0.69-8.07) for ddl + hydroxurea, 3.50 (95% Cl: 1.81-6.77) for ddl + d4T, and 7.80 (95% Cl: 3.92-15.5) for ddl + d4T + hydroxyurea. Conclusions: Based on the data, the risk of neuropathy is additive or even synergistic for ddl + d4T + hydroxyurea compared with ddl or d4T alone. The combination of ddl + d4T also increases the risk of neuropathy but less th an when hydroxyurea is included. (C) 2000 Lippincott Williams & Wilkins.