Improved uptake and retention of lipophilic prodrug to improve treatment of HIV.

Dideoxynucleosides currently in use for anti-HIV therapy have been found to be inefficient in passing through the blood-brain barrier to enter and maintain therapeutic drug levels in brain, a very significant reservoir of HIV. The low bioavailability of these drugs combined with the bone marrow toxicity of AZT (3'-azido, 3'-deoxythymidine, Zidovudine), resulting in anemia and leukopenia, pancreatitis with ddI (2',3'-dideoxyinosine, Didanosine) and painful peripheral neuropathy in case of ddC (2',3-dideoxycytosine, Zalcitabine) are the limiting factors in their use. In addition, the emergence of strains of HIV resistant to AZT, the most commonly used drug, further restricts its use.

Extracorporeal whole body hyperthermia treatments for HIV infection and AIDS.

Whole body hyperthermia therapy (WBHT) is the elevation of the core body temperature to 42 degrees C. In vitro studies have confirmed that 42 degrees C is cytocidal for virally infected lymphocytes, and even more effective when heating is repeated 4 days later. The safety and efficacy of two successive sessions of WBHT (4 days apart) was evaluated in 30 patients with AIDS (not on protease inhibitors), randomized to: 1) untreated controls, 2) low temperature WBHT for 1 hour at 40 degrees C and repeated 96 hours later, and 3) high temperature WBHT for 1 hour at 42 degrees C and repeated 96 hours later.

Effect of whole-body hyperthermia on AIDS patients with Kaposi's sarcoma: a pilot study.

The safety and possible efficacy of extracorporeal whole-body hyperthermia (WBHT) were evaluated in the first FDA-approved feasibility study of WBHT in persons with AIDS. Six gay men, aged 20-50 years, CDC class C-3, underwent 1 h of WBHT at either 40 degrees C or 42 degrees C, employing a system that minimizes the physiological and biochemical changes that occur during WBHT. All subjects had Kaposi's sarcoma (KS), were free of opportunistic infections, and had significant elevations of plasma HIV RNA.