Highly active antiretroviral therapy leading to resolution of porphyria cutanea tarda in a patient with AIDS and hepatitis C.

The association between HIV infection and porphyria cutanea tarda (PCT) is not well established. Since almost all HIV-infected patients with PCT previously described in the literature had additional risk factors for PCT, it is still unclear if HIV infection and not a cofactor such as hepatitis C virus is the trigger for PCT in this population. We describe a patient with AIDS and hepatitis C who developed bullous lesions due to PCT. The cutaneous lesions persisted for 18 months and resolved after he was placed on highly active antiretroviral therapy for HIV. No other therapeutic interventions were undertaken, while exposure to other known precipitants remained unchanged. During follow-up, skin lesions reappeared when the patient discontinued antiretroviral therapy, but PCT lesions again resolved after he restarted highly active antiretroviral therapy and HIV infection was controlled. This case supports the hypothesis that a direct causative relationship exists between HIV and the development of PCT.

Effect of acidic pH on radiosensitization of FSaIIC cells in vitro by misonidazole, etanidazole, or cis-diamminedichloroplatinum (II).

Because acidic regions may coexist with hypoxic regions in solid tumors, we have studied the effect of acidic extracellular pH on the abilities of misonidazole, etanidazole, and cis-diaminedichloroplatinum(II) (CDDP) to radiosensitize hypoxic FSaIIC cells in vitro. For 1-h exposures to misonidazole prior to and during irradiation, the sensitizer enhancement ratios (SERs) were 2.10 +/- 0.18 at 1 mM drug and 2.50 +/- 0.16 at 5 mM drug at pH 7.40 but only 1.90 +/- 0.14 and 2.30 +/- 0.14, respectively, at pH 6.45. For etanidazole the SERs at pH 7.40 at 1 and 5 mM drug were 1.90 +/- 0.13 and 2.40 +/- 0.18, respectively, but only 1.25 +/- 0.13 and 1.70 +/- 0.17, respectively, at pH 6.45. The decrease in the SERs for both 2-nitroimidazole compounds was statistically significant (P less than 0.01). When CDDP at concentrations of 1 and 5 microM was tested, SERs of 1.30 +/- 0.15 and 1.60 +/- 0.18, respectively, were observed at pH 7.40, and the increase was not significant at pH 6.45 (1.35 +/- 0.15 and 1.80 +/- 0.19, respectively). The cellular levels of misonidazole, etanidazole, and CDDP did not vary significantly at the environmental conditions tested. These results demonstrate that pH is a potentially important variable in the action of hypoxic cell radiosensitizing drugs and suggest that future evaluations of such agents should test the effects of pH.