[Final Program, International Conference on AIDS (4th: 1988: Stockholm, Sweden), Book 2]

3609 ACTIVITY AND TOLERANCE OF AZT
Collaborative AZT Study Group
D6partement de Pharmacologie Clinique
Hopital Claude Bernard. Paris. France
Objective To evaluate the activity and toxicity of AZT, 3.5
mg/kg/4h. whenever possible or 3.5 mg/kg/8h. otherwhise.
Methods. 235 patients (pts.) with ARC (29) or AIDS (206)
diagnosed since 0.5 to 36 months (median 3) were enrolled in the
study. The mean follow-up is 19.5 wks. (median: 20.5: range:
8-33). 89% of the pts. were males (79% homosexuals). Of the 206
AIDS pts.. 9 had KS alone. 52 KS and OI, 145 OI only: 132 pts. had
had a single OI (PCP: 80. brain toxoplasmosis: 19).
Results. 27 (11.5%) pts. died. 14 (51.9%) within 8 wks. of
treatment. Of the 64 OI which appeared after the beginning of
AZT therapy, 39 (60.9%) occurred within 8 wks. of therapy.
Surviving pts. were evaluated with the following mean monthly
parameters:

3610 MAJOR OPPORTUNISTIC INFECTIONS IN AIDS PATIENTS
AFTER EIGHT TO ONE HUNDRED WEEKS OF ZIDOVUDINE
(ZDV) THERAPY
Dennis M. Causey, J.M. Leedom, and Hannah Melancon.
Univ. of Southern California, Los Angeles, CA USA.
Objective. To describe the incidence and types and
outcomes of AIDS-defining opportunistic infections (0I's)
in patients treated with ZDV for 8-100 weeks.
Methods. Twenty-two patients with previous Pneumocystis
carinii pneumonia (PCP) were enrolled. Nineteen of the 22
completed more than 8 weeks of ZDV therapy. Eleven
received ZDV 250 mg every 4 hours for 10-12 weeks and then
200 mg every 4 hours thereafter. The other 8 patients
received ZDV 200 mg every 4 hours. ZDV was reduced to 100
mg every four hours for granulocytopenia (PMN's <750) or
discontinued (PMN's < 500). ZDV was resumed when the
toxicity reversed.
Results. Fifteen of the 19 patients (79%) developed
recurrences of PCP between weeks 10 and 100. Most of these
recurrences were mild. However, fatal complications
developed in 3. Three patients developed cryptococcal
meningitis between weeks 12-60. Two were ultimately fatal.
Three developed cytomegaloviral (CMV) retinitis, another
CMV viremia with wasting syndrome, and another CMV colitis.
Three developed disseminated Mycobacterium avium. Two
developed central nervous system toxoplasmosis. One
developed cryptosporidial diarrhea. One developed chronic
peri-rectal herpes simplex. Adverse reactions to ZDV were
minimal except for bone marrow toxicity. Dosage
interruptions were required in all patients but seldom
lasted over 7 days.
Conclusion. 18 out of 19 patients (95%) developed major
01's during long-term ZDV therapy. Nine of these OI's were
fatal. While ZDV therapy may decrease the incidence of
OI's initially, such OI's continue to occur and can result
in fatality. Patients tolerate well long-term ZDV therapy
with occasional dosage modification if significant
granulocytopenia occurs.

Baseline
Evaluable pts. 235
Body weight (kg) 60 (36-127)
Karnofsky score (%): 90 (20-100)
Ly-mphocytes (/mm3): 792 (72-3015)
CD4 (/nmi3) 39 ( 0-490)
% pts treated full dose: 72.3

2 Mo.
175
+1.7
+3.4
+197
+45
36.2

3 Mo.
138
+2.3
+4.2
+199
+41
29.6

4 Mo.
95
+2.9
+4.7
-8
+10
18.2

5 Mo.
71
+2.3
+3.2
-160
+3
14.6

6 Mo
44
+1.2
-1.6
-85
-15
12.1

AZT had to be stopped (>6 d.) 170 times in 127 (54%) pts. for
leucopenia (70% of the stops), severe anemia (5.9%). other side
effects (10.6%) and need for other toxic drugs (13.5%).
Conclusion: Biological and clinical parameters transiently
ameliorated. Frequent interruptions of the treatment, linked to
the toxicity of the drug, mav explain in part the return to
baseline levels. Hence. it mav be worthwhile to evaluate lower
regimens of AZT.

Notes:

3611

ZIDOVUDINE TREATMENT OF AIDS AND ARC IN
DENMARK 1987.

L.S.Teglbjarg*, L.R.Mathiesen*, B.Seeberg**, L.Nielsen**,
B.Thorsen***, M.Buhl****, Depts. of Infectious Diseases,
*Hvidovre Hospital, **Rigshospitalet, ***Marselisborg
Hospital, ****Odense Hospital, Denmark.
In 1987, a total of 138 ptt. (94 AIDS and 44 ARC) have
received treatment with Zidovudine (ZID), 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 PCP, 1 Kaposi). Among the AIDS ptt. 38 new opportunistic infections (OI) were reported. 5 ptt. developed
primary PCP, 7 had recurrent episodes of PCP, 11 of the
DI were mycobacterial infections and 14 were others, including suspected opportunistic brain infections. 16 of
the OI occured within 6 weeks after treatment initiation.
79 patients have been observed for more than 3 months, 25
of these had their daily dose of ZID reduced, usually
from 1200 mg to 600 mg, 9 others were temporarily off
drug.
54 HIV-antigen positive and 39 HIV-antigen negative ptt.
had sufficient follow up data. Of these, 20 antigen positive became antigen negative, 7 of the antigen negative
became antigen positive within the first 8 weeks of ZID
treatment. In 47 ptt. the total count of CD4+ cells have
been evaluated. 28 of these had an increase and 19 had a
decrease in total CD4+ cells.
In nearly all patients an increase in MCV and a decrease
in neutrophile count was observed. 44 of the patients received a total of 307 blood transfusions on 94 occasions.

3612 FIRST EXPERIENCES WITH AZT IN FRANKFURT.
W. Stille, S. Staszewski, J. Luxem, C.Friebe,
W.D. Hofmeister, R. Brodt, L. Bergmann, E.B.
Helm (Center of Internal Medicine), H.W. Doerr (Center of
Hygiene), Frankfurt University Clinics.
From Jan. to Dec., 1987, a total of 101 patients were
treated with AZT in the course of an open, prospective
study at Frankfurt University Clinics. We report on the
clinical course of 97 patients (=p).
At the beginning of treatment, 63p had AIDS (CD4 82),and
34p had ARC (CD4 109). At the time of evaluation,
50% of p had been treated for 150-200 days, and 37% of p
for 200-300 days, respectively.
Dosage of AZT was 1000-1800mg/die according to body
weight. Under AZT, an average weight gain of 10% was observed. 66% of p mentioned an increase of physical health,
and 59% an increase of concentration powers.
30% of p developed an opportunistic infection (01) under
therapy, 6% developed Kaposi's sarcoma or malign, lymphoma.
The most common OI was PCP (17p), followed by mycobacterial infections (9p), and CMV choreoretinitis (4p).
2p died under AZT.
Out of 34p with ARC, 5 developed AIDS.
As severe complications, 29% of p developed anemia, and
8% developed significant leukopenia ((2000).
CD4 lymphocyte count showed an increase from 94/ml to
144/ml (average) during the first 28 days, and afterwards
a decrease to a minimum of 70/ml at treatment day 140.
Conclusion. AZT can increase life quality of AIDS
patients.
AIDS cannot be cured by AZT.

169