Although few reports have discussed the development of cervical neck masses in HIV-infected patients receiving only nucleoside analogues (1, 2), it was not until the recent addition of protease inhibitors to the antiretroviral regimen that "buffalo humps" and atypical fat redistribution became more evident to the clinician (3). It has been suggested, but not proven, that there is a relation between the use of these agents in combination with nucleoside and non-nucleoside analogues and the development of these body habitus changes.

Stricker and Goldberg point out that there is probably a spectrum of body fat accumulation in HIV-infected patients receiving highly active antiretroviral therapy. This observation is probably true, but the reason why a significant percentage of patients receiving protease inhibitors develop abdominal fat accumulation without the development of cervicodorasal enlargements remains unclear. Additional investigators have reported the unexplained development of "buffalo humps" in patients receiving regimens containing protease inhibitor (2, 4).

We agree that our unexpected finding of dense fibrous collagen deposition in all of our patients may represent an unusual autoimmune abnormality that may represent a remodeling of tissue or an unusual manifestation of weight gain. Our patients were receiving protease inhibitors with dual nucleoside analogue therapy, and one was taking trimethoprim-sulfamethoxazole. No patients were receiving steroids or megestrol. Of the other reported cases of protease inhibitor-associated "buffalo humps," only a few reports described the histopathologic characteristics of these masses. Computed tomography of the neck of one our patients did seem consistent with a lipomatous lesion, but biopsy findings did not support this. One author commented on the intraoperative findings of a mass not characteristic of a lipoma: It adhered to surrounding tissues and was difficult to remove (2). One investigator reported that the masses consist of highly dense fibrous scar-like tissue that is difficult to liposuction. Their occurrence seems more common in the older HIV-infected patients who have longer exposure to antiretroviral agents (Abrams H. Personal communication). Two of our patients with cervical enlargements have significantly regressed without discontinuation of protease inhibitor therapy or changes in antiretroviral agents.

Many factors probably contribute to the abnormal fat distributions and body changes seen with highly active antiretroviral therapy. Stricker and Goldberg offer interesting theories of the interactions of HIV protease inhibitor with cellular aspartic proteases to increase metabolic hormones. Others implicate the protease inhibitors of cytochrome P-450 steroid metabolism⁵, which may directly affect glucocorticoid concentrations in fat cells.

As treatment with highly active antiretroviral therapy continues, other unusual side effects will probably be noted. The use of protease inhibitors for wasting in patients with cancer, although intriguing, may be fraught with other complications.