|Progressive Multifocal Leukoencephalopathy (PML)
Jun 11, 2000
I have a problem. I am very interested in being involved in a study of the treatment with Interleukin - 2 (IL2) to boost my T-cell count. The first time that I have contracted this virus (PML). Was in Sept. 1994. I was admitted to the Hospital, and they put me through various blood tests including numerous (MRIs). They found two large legions on the left side, and numerous others scattered throughout my brain, than a nursing home for about 9 months. I made a full recovery in about 2 years by monitoring the (MRI). No sign of legions. In Sept. 1998 I came down with it again. I assume that you are aware of the resurgence of the PML. My problem is; that my doctor and I seem to disagree on some basic treatment issues. My doctor seems to believe that if I try the Interleukin - 2 (IL2) to raise my immune system ie...T-cell count, it may cause a relapse of the PML. I on the other hand I seem to believe that if I am allowed to try the Interleukin - 2 (IL2) to boost my T-cell count it will decrease the chances of a flair up of the PML. My doctor refuses to even let me try. Im asking you for some help. I surf the NET every day, for hours looking for answers. I am HIV+, and I have Progressive Multifocal Leukoencephalopathy (PML). I contracted the HIV from intravenous drug use, educated guess: 1985, give or take a few years. Because of my Low T-cell count, for prolonged years, I developed the Progressive Multifocal Leukoencephalopathy (PML). Please keep me informed, because as you know time is not something that I have a-lot of . Thank you.
HIV+ with Progressive Multifocal Leukoencephalopathy (PML) ( NO MEDICATION) HCT. %. HGB. (n=42-52) (n=14-18) Bridgeport Hospital A: 09-22-94. 38.8 CD4 - 270 13.3 D: 10-21-94 Walnut Hill Convalescent Home A:10-22-94 D: 04-01-95 Walnut Hill Convalescent Home U-Conn. Health Center Doctor: 01-11-96 STARTED. AZT & 3TC Doctor: 01-11-96 46.3 CD4-70 15.8 Doctor: 03-21 96 39.8 CD4-140 14.0 Doctor: 04-18-96 39.5 13.9 Doctor: 05-30-96 39.6 CD4-240 14.1 Doctor: 07-01-96 43.6 CD4-190 15.2 Doctor: 07-01-96 MEDICATION: CRIXIVAN + AZT & 3TC Doctor: 07-29-96 38.9 CD4-150 13.6 Doctor: 09-19-96 43.9 CD4-140 15.1 Doctor: 12-23-96 44.5 CD4-163 15.5 Doctor: 03-12-97 CD4-206 Doctor: 06-12-97 CD4-184 Doctor: 09-04-97 CD4-317 Doctor: 12-04-97 CD4-300 Doctor: 02-11-98 CD4-301 Doctor: 04-23-98 CD4-298 Doctor: 07-16-98 47.1 CD4-340 16.3 Doctor: 10-12-98 CD4-358 Doctor: 10-22-98 43.5 15.4 Doctor: 10-29-98 43.2 15.5 2nd time .. Progressive Multifocal Leukoencephalopathy (PML) Added: 10-30-98 --- 10,000,000 units of Alpha Interferon 3 times a week to treat Progressive multifocal Leukoencephlopathy the ( J.C. virus ) + current medication. Doctor: 11-11-98 42.8 CD4-224 15.1 Doctor: 12-03-98 36.3 12.7 Doctor: 12-28-98 30.1 CD4-111 10.7 Doctor: 01-21-99 26.3 9.6 Nurse: 01-28-99 25.7 9.1 Nurse: 02-03-99 26.1 9.2 Nurse: 02-10-99 27.5 9.5 Nurse: 02-17-99 27.6 9.7 Nurse: 02-24-99. 28.7 10.0 Doctor: 02-25-99. 25.7 9.6 Nurse: 03-03-99. 30.8 10.8 Nurse: 03-10-99. 30.1 10.6 Nurse: 03-17-99. 30.3 10.4 Nurse: 03-24-99. 28.8 10.3 Nurse: 03-31-99. 26.9 9.7 Nurse: 04-07-99 26.7 9.5 Doctor04-08-99 CD4 -183 Nurse:04-14-99 28.5 10.0 Nurse: 21-99 Doctor05 -13-99 27.6 CD4-221 9 .9 07-01-99 Admitted Hospital ( J D H ) U - Conn. 07-01-99 13.9 CD4-320 5.2 07-02-99 After two unitss of whole blood 07-02-99 23.0 8.4 one more unit of whole blood 07-03-99 25.9 9.3 one more unit of whole blood 07-03-99 31.6 11.1 07-03-99 Discharged Hospital ( J D H ) U - Conn. Nurse: 07-06-99 30.0 10.0 Reticulocytes (n=0.5-1.5) Nurse: 07-12-99 28.3 10.2 0.2 Nurse: 07-19-99 27.0 9.9 0.2 Medication change: 07-23-99 CRIXIVAN + VIRAMUNE + VIDEX ( DDI ) + PREVACID Nurse: 07-27-99 27.6 10.0 1.9 Nurse: 08-03-99 34.2 11.0 5.2 Nurse: 08-10-99 41.6 13.5 Nurse: 08-17-99 42.4 14.0 3.8 Doctor:08-19-99 Viral Load: < 400 CD4: 245 Doctor:10-14-99 CD4: 337 Doctor:12-09-99 CD4: 349 Doctor:04-13-2000 Viral Load: < 50 CD4: 292 Doctor:05-25-2000 ?????????????????????
PI Perspective 27April 1999 Interleukin-2 (IL-2, Proleukin®)Several studies of IL-2 were reported at the recent conference. Together, they confirm the ability of IL-2, when added to anti-HIV therapy, to produce dramatic CD4+ cell count increases above what is observed when anti-HIV therapy is used alone. Moreover, study results confirm the safety of IL-2 with regard to its impact on HIV replication. In laboratory experiments, in which IL-2 acts alone independent of other processes of the immune system, IL-2 can dramatically increase HIV replication. It does this by activating T-cells, including those which are infected with HIV, causing them to produce more HIV and to replicate themselves, leading to even more HIV production. In human studies, however, the use of IL-2 has been shown to only temporarily increase HIV replication. Overtime, people receiving IL-2 in addition to standard anti-HIV therapy appear to have control of HIV replication comparable to those receiving only anti-HIV therapy. An important new finding from one study is that people receiving IL-2 with anti-HIV therapy may have even greater suppression of HIV replication compared to what is observed in people receiving anti-HIV therapy alone. What is the Optimal Starting Dose of IL-2?An IL-2 study in Argentina included 73 volunteers with CD4+ cell counts greater than 350 who received one of three doses of IL-2 in combination with anti-HIV therapy or anti-HIV therapy alone. Thirty-six volunteers received 1.5, 4.5 or 7.5 million international units (MIU) of IL-2, twice daily, delivered through injection under the skin (subcutaneous injection) for five consecutive days every eight weeks. The remaining 37 volunteers received only anti-HIV therapy. At the end of 6 months, the 4.5 and 7.5 MIU, twice daily IL-2 doses produced the most dramatic CD4+ cell increases. Those receiving the 1.5 MIU twice daily dose experienced a mean CD4+ cell count increase of 81 cells, whereas those receiving the 4.5 and 7.5 MIU twice daily doses had increases of 359 and 520 cells over their pre-therapy counts, respectively. Those receiving only anti-HIV therapy experienced an increase of about 100 after 6 months. These results are similar to those of other dose ranging studies of IL-2. When looked at together, studies seem to suggest that the most immediate and pronounced CD4+ cell increases are seen among people who start IL-2 at the higher (4.5 or 7.5 MIU twice daily) doses. However, even in these studies, most people who start at this highest dose (7.5 MIU, twice daily) experience side effects that necessitate IL-2 dose reductions. A number of different studies appear to show, in general, that after 1 year of IL-2 therapy the 4.5 MIU twice daily dose is the most commonly used dose to maintain CD4+ cell increases. What is the Effect of IL-2 Therapy on HIV?Another recent study (known as CS-L2002), examined the impact of IL-2 with anti-HIV ther-apy on CD4+ cell counts and HIV replication. This study concluded that IL-2 might also lead to enhanced control of HIV replication. CS-L2002 included people with pre-study CD4+ cell counts ranging from 200 to 500. Forty-one volunteers received anti-HIV therapy alone and 37 received IL-2 with anti-HIV therapy. Most studies of IL-2 reported to date were initiated in the pre-protease inhibitor era. This study is among the first initiated after 3-drug regimens had become the standard of care. Therefore, most of the people in the study were on at least a 3-drug combination, typically including a protease inhibitor. Note that a significant percentage of people in all groups started the study with viral load already under control due to their on-going use of anti-HIV therapy. The primary interest of the study was to measure the effect on CD4+ cell counts and to see whether adding IL-2 had any further positive or negative impact on viral load. The following are the results after 1 year: Results of IL-2 Therapy in Combination with Anti-HIV TherapyViral Load Count At Study Entry Results @ 1 Year Mean CD4+ cell count (AT alone) 341 405 (18% increase) Mean CD4+ cell Count (AT + IL-2) 355 739 (112% increase) % with viral load below 500 (AT alone) 44% 46% % with viral load below 500 (AT + IL-2) 59% 68% % with viral load below 50 (AT alone) 31% 36% % with viral load below
Response from Dr. Feinberg
There is no clearcut answer to your question-- you may experience a flare of the PML if your CD4 cells increase significantly (the "immune reconstitution syndrome"), or your T cells may increase without this happening. Flares seen with increases in T cells are probably less common than nothing adverse happening.
Il-2 appears to yield the best results when used by people who have only moderately impaired T cell counts to begin with. If you are determined to try IL-2, then perhaps your doctor will support you despite his misgivings. If not, and if you feel strongly enough about it to pursue IL-2 treatment, you may need to seek another physician. Good luck!
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