Re: Norm..belated THANKS

[Guest guest]

In 1994 I started using Interleukin-2 and brought my viral load down from 116,217 to undetectable (which at the time was under 500). That's more than a two log reduction.

This was without antivirals, as my virus had become resistant to the existing antivirals I could use at the time, ddI and ddC. Both had also become problematic anyway due to neuropathy with developed within days of use.

I was sold on Interleukin-2 after that, as you can imagine. Since using Interleukin-2 I have never developed viral resistance to any drug, with the possible exception of a recent interesting experience with Norvir boosted Reyataz.

After using Reyataz with Viread and Emtriva for three years, with an undetectable viral load, my new Doctor in March 2006 was very excited about adding 50 mg Norvir to this combo, as its one of the latest and useless fads among HIV Doctors.

After using the Norvir boost for for a few months, I discontinued it in June and discovered I now had an HIV viral load of 713. I had been lax about using Interleukin-2 every other month, so I began using it again and reduced my viral load back to undetetctable.

There is some evidence that some protease inhibitors like Norvir interfere with the normal immune control of HIV. This experience led me to experiment discontinuing my antivirals for Days 2 and 3 of my 3 day Interleukin-2 therapy. The results both times I have done this were quite better than Interleukin-2 with antivirals.

Several weeks before the second time I used this, I dropped the Viread and Emtriva, using just Reyataz. Since Reyataz alone has a much shorter half-life (12 hours) than Viread and Emtriva (10 in plasma and 60 hours in cells), I discontinued the Reyataz for only one day, on my second day of Interleukin-2. Still no viral load.

Next, I'm tempted to switch out the Reyataz monotherapy for either Viread and Emtriva monotherapy, or Sustiva monotherapy to see if Reyataz is interfering in any way with lipids or immune function.

Obviously, I now realize that I'm better off health-wise with a modest antiviral regimen with Interleukin-2, as opposed to "antiviral stacking" which seems very much in vogue. Taking many antivirals appears necessary if you're not using Interleukin-2, but with Interleukin-2 I think its counter-productive. With a T4 count of 1,366 and 34%, my goal is to minimize my use of antivirals and their potential long-term negative health effects.

In retrospect, I would have discontinued my use of Crixivan sooner than I did after eight years, and used Sustiva until Reyataz was available. I am very hopeful that long-term use of an Integrase inhibitor as monotherapy with Interleukin-2 will be the healthiest way to go. There's no evidence Integrase inhibitors interfere with normal anti-HIV immune function and our bodies don't use Integrase. But time will tell.

> >> ...And since your post is anecdotal, is there anything out there > that shows IL-2 in the absence of meds decreases viral load?> ...> > > > > Not in the absence of meds, but il-2 decreases viral load more than > when just the antivirals are used. See abstracts below. Il-2 is > intended as an immune booster, not a direct hiv fighter. So while > the antivirals target hiv, decrease the viral load and increase t4s > usually modestly, il-2 targets and normalizes the immune system. Il-> 2's boosting of t4s is just the tip of the iceberg. It effects many > of the other markers of the immune system, like the il-2 receptors, > nk cells, and mechanisms that fight off other pathogens. Abstracts > below double dashed lines for examples.> > PS Thanks Norm for so tenaciously and articulately explaining and > defending il-2. If smartly used, it would have saved many people > and kept them much healthier.> > > > 1: AIDS Res Hum Retroviruses. 1999 Jan 20;15(2):97-103. Links > Dynamics of provirus load and lymphocyte subsets after interleukin 2 > treatment in HIV-infected patients.Zanussi S, Simonelli C, Bortolin > MT, D' M, Comar M, Tirelli U, Giacca M, De Paoli P. > Department of Microbiology-Immunology and Virology, Centro di > Riferimento Oncologico, IRCCS, Aviano, Italy.> > The association of antiretroviral agents plus interleukin 2 (IL-2) > represents an efficient approach to the treatment of HIV+ subjects. > While the effects of IL-2 on the immune system have been > investigated, little is known concerning its impact on HIV dynamics. > Two antiretroviral drugs control HIV viremia, but have minimal > effects on the proviral load, a predictor of disease progression and > response to therapy. The aim of this study was to define the effect > of rIL-2 on HIV proviral copy numbers and its relationship to > changes in CD4+ and CD8+ subsets. Twelve HIV+ patients with CD4 cell > counts between 200 and 500 cells/mm3 were treated with six cycles of > subcutaneous rIL-2, in combination with zidovudine and didanosine. > This regimen resulted in a rapid and durable decrease in proviral > load in the peripheral blood, in an increase in CD8+ lymphocytes, > and in the emergence of a CD4+CD45RA+ T subset. These results > demonstrate that the rationale for IL-2 administration to HIV+ > patients may depend not only on its effects on the immune system, > but also on the reduction of the number of infected cells, > reinforcing the notion that IL-2 can have a favorable impact on the > natural history of HIV infection.> ----------------------------------------------------------------> J Infect Dis. 2000 Aug;182(2):428-34. Epub 2000 Jul 28. Links > Comment in: > J Infect Dis. 2001 Feb 15;183(4):679-80. > Pooled analysis of 3 randomized, controlled trials of interleukin-2 > therapy in adult human immunodeficiency virus type 1 disease.Emery > S, Capra WB, DA, Mitsuyasu RT, Kovacs JA, Vig P, Smolskis M, > Saravolatz LD, Lane HC, Fyfe GA, Curtin PT. > National Centre in HIV Epidemiology and Clinical Research, Sydney, > NSW 2010, Australia. semery@...> > We collected human immunodeficiency virus (HIV) disease progression, > survival, most recent CD4 cell count, and plasma HIV RNA levels from > patients (n=157) who participated in randomized clinical trials of > interleukin (IL)-2 that commenced before 1995. Data were available > for 155 (99%) patients. Statistical analyses were based on the > intention-to-treat principle. Median follow-up was 28 months and 30 > months for control and IL-2 patients, respectively. Twenty-five > (16%) patients developed AIDS or died during follow-up (16 control > patients vs. 9 IL-2 patients; R2=0.57; P=.22). Mean change from > baseline CD4 cell count was significantly higher in patients > randomized to receive IL-2 (368 vs. 153 cells/microL; P=.003). Mean > change from baseline plasma HIV RNA was significantly lower in > patients randomized to receive IL-2 (-0.98 vs. -0.63 log copies/mL; > P=.004). Significant improvements in CD4 cell count and plasma HIV > RNA in recipients of IL-2 relative to control patients were > associated with a nonsignificant trend toward improved clinical > outcome.> -------------------------------------------------------------------> JAMA. 2000 Jul 12;284(2):183-9. Links > Comment in: > JAMA. 2000 Oct 25;284(16):2055-6. > Immunologic and virologic effects of subcutaneous interleukin 2 in > combination with antiretroviral therapy: A randomized controlled > trial.Davey RT Jr, RL, Graziano FM, Boswell SL, Pavia AT, > Cancio M, Nadler JP, Chaitt DG, Dewar RL, Sahner DK, Duliege AM, > Capra WB, Leong WP, Giedlin MA, Lane HC, Kahn JO. > National Institutes of Health, Bethesda, MD 20892-1880, USA. > rdavey@...> > CONTEXT: While interleukin 2 (IL-2) is capable of inducing a marked > expansion of the CD4 T-lymphocyte pool, limited data exist on > whether IL-2 treatment can add significantly to the immunologic and > virologic effects of potent antiretroviral therapy (ART). OBJECTIVE: > To determine the rate and magnitude of CD4 cell recovery and viral > suppression when using a combination therapy of IL-2 and ART > compared with ART alone. DESIGN AND SETTING: Randomized, controlled > multicenter trial conducted from April 1996 through April 1998 at 8 > clinical sites in the United States. PATIENTS: Eighty-two adult > outpatients who were infected with human immunodeficiency virus > (HIV) and had baseline CD4 cell counts of 200 x 10(6)/L to 500 x 10> (6)/L and baseline RNA levels of fewer than 10,000 copies/mL were > randomized; 78 completed the study. INTERVENTIONS: Thirty-nine > patients were randomly assigned to receive a combination therapy of > subcutaneous IL-2 (administered in 5-day courses every 8 weeks at a > starting dosage of 7.5 mIU twice per day) and ART; 43 were to > receive ART therapy alone. MAIN OUTCOME MEASURES: Interleukin 2 > safety and differential effects on CD4 cell counts, CD4 cell > percentages, and plasma HIV RNA levels. RESULTS: The mean (SD) > percentage increase in CD4 cell counts at 1 year for patients who > received IL-2 was 112% (113%) compared with 18% (35%) in recipients > of ART alone (P<.001). Both groups had mean (SD) increases in CD4 > cell percentage: from 20.4% (6.3%) to 32.3% (12.4%) for the > combination therapy group compared with 20.4% (5.1%) to 23.0% (7.2%) > for recipients of ART alone (P<.001). Using a sensitive viral RNA > assay, mean viral load changes were -0.28 and 0.09 log(10) copies > for IL-2 recipients and control patients, respectively (P=.03). > Twenty (67%) of 30 evaluable patients receiving IL-2 achieved final > viral loads of fewer than 50 copies/mL compared with 13 (36%) of 36 > control patients (P=.02). Toxic effects were common among patients > who received IL-2 and were managed with antipyretics, hydration, > rest, and dosage reduction as needed. CONCLUSIONS: Intermittent > therapy with IL-2 and ART produced a substantially greater increase > in CD4 cells and was associated with a larger decrease in viral load > than ART alone. Clinical end-point trials will be necessary to > determine whether the enhanced viral suppression and CD4 cell > increases associated with IL-2 therapy will translate into improved > clinical outcomes. JAMA. 2000;284:183-189> ---------------------------------------------------------------------> ---------------------------------------------------------------------> AIDS. 1999 Jan 14;13(1):140-1. Links > Recombinant interleukin-2 for treatment of HIV reduces hepatitis C > viral load in coinfected patients.Uberti-Foppa C, De Bona A, Morsica > G, Guffanti M, Gianotti N, Boeri E, Lazzarin A. > ---------------------------------------------------------------> Clin Exp Immunol. 1998 Jul;113(1):85-91. Links > Effects of IL-2 therapy in asymptomatic HIV-infected individuals on > proliferative responses to mitogens, recall antigens and HIV-related > antigens.Kelleher AD, Roggensack M, Emery S, Carr A, French MA, > DA. > Centre for Immunology, St 's Hospital, Sydney, Australia.> > The effects of IL-2 therapy on lymphoproliferative responses to > mitogens, recall antigens and HIV epitopes were studied in > asymptomatic HIV-infected patients enrolled in a phase II study of > intermittent continuous intravenous (Ci.v.) IL-2 and subcutaneous > infusions of polyethylene glycol-modified (PEG) IL-2. Sixteen > consecutive patients randomized to receive Ci.v. IL-2 (n = 5), PEG > IL-2 (n = 7) or anti-viral therapy alone (n = 4) were studied. All > patients were vaccinated with tetanus toxoid (TT) before receiving > therapy. Proliferative responses to phytohaemagglutinin (PHA), > soluble anti-CD3, TT, streptokinase/streptodornase (SK/SD) and 11 > previously described HIV-specific T-helper epitopes from gag and env > were studied at weeks 0, 16, 30 and 48. Median CD4+ lymphocyte > increases of 272 and 255CD4+ cells/microl were observed in the Ci.v. > IL-2 and PEG IL-2 groups at week 48, while decreasing by 104 > cells/microl in the anti-retroviral therapy alone group. At each > time point proliferative responses to PHA, anti-CD3, TT and SK/SD > were not different between treatment arms. Similarly, no differences > in responses to HIV epitopes were found between the groups and no > new responses to HIV epitopes were detected. IL-2 therapy results in > a significant increase in peripheral blood CD4+ lymphocyte count, > but this increase is not associated with quantifiable improvements > in lymphoproliferative responses to mitogens, recall or HIV antigens.> --------------------------------------------------------------------> AIDS. 2003 Feb 14;17(3):343-51. Links > Effects of interleukin-2 therapy combined with highly active > antiretroviral therapy on immune restoration in HIV-1 infection: a > randomized controlled trial.Levy Y, Durier C, Krzysiek R, Rabian C, > Capitant C, Lascaux AS, Michon C, Oksenhendler E, Weiss L, Gastaut > JA, Goujard C, Rouzioux C, Maral J, Delfraissy JF, Emilie D, > Aboulker JP; ANRS 079 Study Group. > Unit of Clinical Immunology, Hospital Henri Mondor, 51 avenue du > Marechal de Lattre de Tassigny, 94010 Creteil Cedex, France.> > BACKGROUND: Intermittent interleukin-2 (IL-2) therapy leads to a > sustained increase of CD4 T cells in HIV-1-infected patients. > METHODS: Symptom-free HIV-1-infected patients who were naive to all > antiretroviral drugs (n = 68) and/or to protease inhibitors (n = 50) > and had a CD4 cell count of 200-550 x 10(6) cells/l were randomly > assigned to start lamivudine/stavudine/indinavir alone (controls) or > combined from week 4 with subcutaneous IL-2 (5 x 10(6) IU twice > daily for 5 days: every 4 weeks for three cycles, then every 8 weeks > for seven cycles). Immunological and virological results were > monitored until week 74. RESULTS: CD4 T cell counts increased more > in the IL-2 group than in the controls (median increases 865 and 262 > x 10(6) cells/l, respectively; P < 0.0001); an 80% increase in CD4 T > cells was achieving by 89% of the IL-2 group and by 47% of the > controls (P < 0.0001). Decrease of plasma viral loads was similar in > both groups. Compared with controls, IL-2 induced a greater increase > of naive and memory CD4 T cells, lymphocyte expression of CD28 and > CD25 (P < 0.0001) and natural killer cells (P < 0.001). In a > logistic regression analysis, odds of being responders to recall > antigens was 8.5-fold higher in IL-2 recipients (P = 0.002) than in > controls. The former experienced a higher level of antibody response > to tetanus vaccination at week 64 than controls (32 and 8 > haemagglutinating units/ml, respectively; P = 0.01). CONCLUSIONS: > The combination of antiviral drugs and IL-2 induced a greater > expansion and function of CD4 T cells than antiretroviral drugs > alone.>