Hyperthermia is a process in which blood is taken out of the body and heated to 42 degrees C for one hour before raising the temperature to 49 degrees C. The blood is then allowed to cool before being returned into the body. It has been suggested that such heat treatment can kill HIV and stimulate cytokine responses which will combat the development of Kaposis sarcoma. Hyperthermia treatment has been used with some success to treat some forms of cancer, although not on a large scale.

Hyperthermia treatment for HIV-related conditions has been popularised by one doctor in the US, who reported that one patient who received the treatment lost all signs of KS lesions and underwent a CD4 cell count rise from 250 to 800, which was sustained for at least two years after treatment. Four other patients treated with hyperthermia were reported to have a complete remission of lesions which lasted at least one year. The best responders amongst those who have undergone treatment have been individuals with relatively high CD4 counts, and the poorest responders have been individuals with CD4 below 50 and high levels of interleukin 6, a cytokine believed by some to be associated with the development of Kaposis sarcoma.

The treatment has received substantial media coverage, yet there is no evidence from properly controlled trials that hyperthermia has any long-term benefits. The treatment has caused considerable controversy owing to the death of two patients within hours of undergoing heat treatment. Potential dangers include the possibility of damage to the brain from over-heating and the long time that recipients must spend with tubes in their veins, risking bacterial infections. Critics also point out that the majority of the HIV in the body is located outside the blood, such as in the lymph nodes, where this therapy presumably has no effect.

In December 1994 the US Food and Drug Administration (FDA) authorised IDT Inc. in conjunction with HemoCleanse Inc. to undertake trials of hyperthermia. Published results of a six person study suggested that the treatment did cause improvements in KS and reductions in viral load, but this lasted only one week after the procedure. However, a larger 30-person trial among people with an average CD4 count of 120 found that the procedure had no significant effect on recipients CD4 counts, and a brief drop in viral load among treated people lasted only a few days.

In February 1996 the FDA authorised the treatment of an additional 60 people, noting that the treatment had not caused some of the feared side-effects such as brain damage, but that it still had not been proven to benefit treated people.

Key research

Alonso reported the long-term results of a single session of low-flow (0.3 L/min) extracorporeal perfusion hyperthermia on 29 men and 2 women with disseminated Kaposi's sarcoma and profound immunologic impairment. Antiretroviral treatment was stopped 72 hours prior to treatment and withheld during the period of follow-up. Core temperature was raised to 42 degrees C and held for 1 hour with extracorporeal perfusion and ex vivo blood heating to 49 degrees C as the means of temperature control. Of 31 patients, 2 died of complications secondary to treatment (cardiac arrhythmia; CNS bleed). There were two cases of intravascular coagulopathy. At 30 days post-treatment complete or partial regressions were seen in 20/29 of those treated, with regressions persisting in 14/29 of those treated by 120 days posttreatment. At 360 days, 4/29 maintained tumour regressions with 1 in complete remission (at 26 months). The patient in complete remission remained culture-negative and PCR-negative for HIV and his CD4 count rose from around 250 to around 800. Selected healed lesions were biopsied to demonstrate tumor absence. Patients were selected for treatment if pre-treatment testing of the tumour showed regression in vitro with heat exposure. Analysis of the early and midterm failures showed little sustained rise of the CD4 cells if presenting total CD4 counts were below 50 and had been at such low levels for extended periods. Analysis of the tumors of the few men not responding demonstrated elevated levels of IL-6 as compared to responders (12 vs < 1 pg/ml). At 120 days 29/31 patients remained alive (expected, 20). At 360 days, 21/31 remained alive (expected, 11). In no patient was HIV activity stimulated with heat exposure.

Steinhart enrolled six men with CD4 counts below 200 and at least three KS lesions in the first FDA-approved trial of hyperthermia. Participants underwent one hour of whole-body hyperthermia at 40 or 42 degrees Centigrade. No adverse side-effects were observed during treatment. KS lesions partially regressed immediately following whole-body hyperthermia in all participants but returned to pretreatment status in five people after one week. Participants experienced a significant reduction in HIV RNA immediately after cool-down in the 42 degree Centigrade treatment group which returned to pretreatment levels after one week. A larger trial is continuing.

References

Alonso K et al. Systemic hyperthermia in the treatment of HIV-related disseminated Kaposi's sarcoma. Long-term follow-up of patients treated with low-flow extracorporeal perfusion hyperthermia. Am J Clin Oncol 17(4):353-359, 1994.

Steinhart CR et al. Effect of whole-body hyperthermia on AIDS patients with Kaposi's sarcoma: a pilot study. J Acquir Immune Defic Syndr Hum Retrovirol 11(3):271-281, 1996.