On Sun, 11 Oct 1998 15:14:35 GMT, gmc0 at ix.netcom.com (George M.
Carter) wrote:
>johnburgin at worldnet.att.net wrote:
>>>>In any event, speaking of dementia, it was your idiotic statement that
>>>people now were taking LESS than the former commonly prescribed dose.
>>>I gave you a study, I can give you others, ergo, it wasn't idiotic.
>>No. It was just dead cold wrong.
Well, have I moved off of the idiotic list, Mr Carter? I've been
upgraded to simply dead wrong? I gave you "A" study, I can give you
lots more with higher doses. Want to keep looking foolish?
AZT was approved in 1987. By the
>early 90's, it became apparent that the lower dose (600 mg/d or
>thereabouts) worked as well with less side effects.
No argument from me on less side effects with less AZT, just different
ones with the PI's added in.
>>*****
>Zidovudine treatment of AIDS and ARC in Denmark 1987. Scand J Infect
>Dis 1989;21(4):367-73
>Teglbjaerg LL, Mathiesen LR, Soeberg B, Nielsen L, Thorsen B, Buhl M,
>Pedersen C, Bonnevie O, Nielsen C, Vestergaard BF, et al
>Department of Infectious Diseases, Hvidovre Hospital, Copenhagen,
>Denmark.
>>In 1987, a total of 138 Danish patients (94 AIDS and 44 ARC) received
>treatment with zidovudine, a total observation period of 572 treatment
>months. 15 AIDS and 1 ARC patient died after a median of 70 days
>(range 2-295). In the ARC group 4 patients developed AIDS (3
>Pneumocystis carinii pneumonia, 1 Kaposi's sarcoma). Among the AIDS
>patients 38 new opportunistic infections were reported. 24 of these
>opportunistic infections occurred within 6 weeks after treatment
>initiation. 79 patients were observed for more than 3 months, 25 of
>these had their daily dose zidovudine reduced, usually from 1,200 mg
>to 600 mg, 9 others were temporarily off drug. HIV antigen was
>analyzed in serum samples from 93 patients. Of these, 28 (52%) of 54
>initially HIV antigen-positive became antigen-negative, 7 (18%) of 39
>initially HIV antigen-negative became antigen-positive within the
>first 8 weeks of zidovudine treatment. In 57 patients the total count
>of CD4+ cells were evaluated. A significant increase in the number of
>CD4+ cells was observed during treatment. In nearly all patients an
>increase in MCV and a decrease in neutrophil count was observed. 44 of
>the patients received a total of 307 blood transfusions on 94
>occasions and 19 (14%) patients required multiple transfusions. The
>mortality among the AIDS patients was significantly lower compared to
>historical controls. In our experience zidovudine treatment is
>reasonably well tolerated and the side effects are manageable.
>******
>>Ann Intern Med 1988 Feb;108(2):175-80
>Human immunodeficiency virus (HIV) antigenemia (p24) in the acquired
>immunodeficiency syndrome (AIDS) and the effect of treatment with
>zidovudine (AZT).
>Jackson GG, Paul DA, Falk LA, Rubenis M, Despotes JC, Mack D, Knigge
>M, Emeson EE
>Department of Medicine, University of Illinois College of Medicine,
>Chicago.
>>Infection with human immunodeficiency virus (HIV) may cause viral
>antigenemia, detected primarily as p24 viral core protein. Among 16
>patients with the acquired immunodeficiency syndrome (AIDS) or
>AIDS-related complex studied serially, 12 had or developed antigenemia
>ranging from 16 to 3006 pg/mL in plasma. The level could be
>categorized as high (greater than 100 pg/mL) or low (15 to 65 pg/mL).
>Three patients with anti-p24 antibody had no antigenemia. Zidovudine
>(AZT), 200 or 250 mg every 4 hours, reduced antigenemia by about 90%;
>other regimens were less effective. Leukocyte cultures were positive
>for HIV from patients with antigenemia, and in one third of samples in
>the absence of antigenemia. High levels of antigenemia correlated with
>symptoms, CD4 cell count, and prognosis. Drug toxicity requiring a
>lower dose was followed by increased antigenemia, recurrent symptoms,
>and decreased CD4 cells, suggesting lymphocyte toxicity. Monitoring
>antigenemia can be useful in evaluating patients with HIV infection
>and in evaluating the effect of antiviral chemotherapy.
>>*******
>Intern Med 1992 Jul;31(7):871-6
>A randomized trial of reduced doses of azidothymidine in Japanese
>patients with human immunodeficiency virus type 1 infection.
>Kimura S, Oka S, Toyoshima T, Hirabayashi Y, Kikuchi Y, Mitamura K,
>Shimada K
>Department of Infectious Diseases and Applied Immunology, University
>of Tokyo, Japan.
>>Adverse reactions to the standard dose (1,200 mg/day-1,500 mg/day) of
>azidothymidine (AZT) are serious. An in vitro pharmacokinetic study
>of intracellular AZT-5'-triphosphate suggested the feasibility of a
>clinical trial with reduced doses of AZT. A randomized trial with
>reduced doses of AZT (group A; 400 mg/day, n = 15, group B; 800
>mg/day, n = 13), was conducted enrolling 28 patients with human
>immunodeficiency virus infection. The effective rate of AZT on CD4+
>lymphocyte counts was similar for both groups, but the duration of the
>effect of AZT was significantly longer in group A (p less than 0.05).
>In group B, adverse reactions were more frequently observed (p less
>than 0.01), and AZT was withdrawn or the dose was reduced more
>frequently (p less than 0.05). These results suggest that AZT at a
>dose of 400 mg/day is less toxic, and is more beneficial for long-term
>treatment.
>>>You simply proved my point, that is, that higher amounts were given in
>>the past. Do you want to keep going with this or put it to rest?
>>I'll keep going.
>>You stated
no I didn't. I said higher doses were used than today. Don't mislead
our audience. Remember, they can read too.
that people were taking 1200 mg or some high dose until the
>protease inhibitors came along, then the dose dropped. To support the
>notion that people SUDDENLY started taking a lot less. This is just
>dead cold wrong.
I'm not trying to support anything except reevaluation of bad drug
usage for a disease caused by behavior. jb
>> George M. Carter
>>See also: Ann Intern Med 1992 Jun 15;116(12 Pt 1):961-6
>Quality-of-life evaluation in a clinical trial of zidovudine therapy
>in patients with mildly symptomatic HIV infection. The AIDS Clinical
>Trials Group. Gelber RD, Lenderking WR, Cotton DJ, Cole BF, Fischl
>MA, Goldhirsch A, Testa MA
>>Also:
>Ann Intern Med 1992 Sep 15;117(6):487-501
>Zidovudine: five years later.
>McLeod GX, Hammer SM
>New England Deaconess Hospital, Boston, Massachusetts.
>>Zidovudine, a nucleoside analog, was the first agent proved to be
>effective in the management of human immunodeficiency virus type 1
>(HIV-1) infection. After demonstration of zidovudine's in-vitro
>activity against HIV-1 in 1985, the drug was rapidly evaluated in
>phase I and phase II clinical trials and was found to be effective in
>decreasing both mortality and the incidence of opportunistic
>infections in patients with the acquired immunodeficiency syndrome
>(AIDS) and advanced AIDS-related complex; the drug was also found to
>have a substantial but tolerable toxicity profile. Since the licensure
>of zidovudine in 1987, an intensive clinical research effort has
>established the drug's efficacy in the prevention of disease
>progression in asymptomatic and mildly symptomatic HIV-infected
>persons and has established the success of lower-dose therapy in
>patients at all stages of disease. The current recommendation is to
>use zidovudine at a dose of 500 to 600 mg/d in both symptomatic and
>asymptomatic persons with CD4 counts of less than 500/mm3. The major
>toxicities of anemia and neutropenia are less frequent at the lower
>doses presently used and can be managed by dose reduction or by use of
>hematopoietic growth factors. The inexorable disease progression seen
>despite zidovudine therapy and the isolation of clinical strains of
>HIV-1 resistant to zidovudine in vitro highlight the limitations of
>prolonged monotherapy with this agent. Although alternative
>dideoxynucleoside agents (for example, didanosine [dideoxyinosine and
>zalcitabine dideoxycytidine]) are available for the management of
>HIV-infected persons, zidovudine remains the cornerstone of
>antiretroviral therapy. Current research efforts are directed at
>elucidating the clinical relevance of zidovudine resistance and
>studying regimens in which zidovudine is used in combination with
>other agents. This latter approach holds great promise for improving
>efficacy, limiting toxicity, and perhaps preventing the emergence of
>viral resistance. For the forseeable future, zidovudine will continue
>to play a role in the development and in our understanding of
>antiretroviral therapy.
>>>
