Gynecomastia associated with highly active antiretroviral therapy

OBJECTIVE: To report four cases of HIV-associated gynecomastia diagnosed during treatment with nucleoside analogs with or without protease inhibitors. CASE SUMMARY: Four HIV-infected patients developed gynecomastia while taking two nucleoside analogs (stavudine combined with lamivudine in 3 patients, stavudine with didanosine in 1 patient) and protease inhibitors (indinavir, nelfinavir, ritonavir-saquinavir in 3 patients) all patients had received prior treatment with single or associated nucleoside analogs for > or = 21 months. Gynecomastia occurred three to seven months after the start of a triple regimen in the first three patients, and 17 months after initiating the last dual nucleoside analog therapy in the remaining patient. Liver, kidney, and thyroid function were normal; a routine endocrinologic workup showed slight follicle-stimulating hormone and luteinizing hormone abnormalities in one patient only. Other possible causes of drug- or disease-induced gynecomastia were excluded. A concurrent fat redistribution syndrome was present in three patients (including the patient who received nucleoside analogs only), while serum lipid and/or glucose concentration abnormalities were present in all patients. Gynecomastia remained unchanged during the subsequent seven- to 16-month follow-up, even after modification of antiretroviral therapy. DISCUSSION: Gynecomastia has been recently associated with antiretroviral therapy, and all reported cases but one occurred two to 17 months after the start of a protease inhibitor-based regimen. Our experience underlines the possible occurrence of gynecomastia in the absence of protease inhibitor administration, its persistence despite changes of antiretroviral regimen (thus resembling some signs related to lipodystrophy syndrome), and the apparently constant association with prolonged nucleoside analog administration (especially stavudine). CONCLUSIONS: Gynecomastia should be included among emerging adverse effects of antiretroviral therapy, although its etiopathogenesis deserves further investigation.