Final Program and Oral Abstracts [International Conference on AIDS (8th: 1992: Amsterdam, Netherlands)]

WeB 1016-WeB 1021

TRACK B: CLINICAL SCIENCE AND CARE

WeB 1016 ORAL CORTICOSTEROIDS ACCELERATE RECOVERY OF MILD AIDSRELATED PNEUMOCYSTIS CARINII PNEUMONIA
Quieffin. Jean*; Montaner JSG; Guillemi SA; Lawson LM; Levit N; Le TN; Ruedy J;
Schechter, Martin T. St. Paul's Hospital/UBC; Canadian HIV Trials Network & BC Centre for
Excellence in HIV and Related Diseases, Vancouver, CANADA and *H6tel Dieu, Paris, FRANCE.
Obiectives: To evaluate the effect of the early introduction of oral corticosteroids (CS) in patients with mild AIDS-related
pneumocystis carinii pneumonia (PCP).
Methods: We conducted a subgroup analysis of a double blind, placebo controlled, randomized trial, restricted to patients
whose baseline oxygen saturation by pulse oximetry (02 SAT) was x 90% at rest. This subgroup analysis was based on a prespecified subgroup and was not data driven. All patients were having their first episode of PCP, had exercise desaturation and
had no other known active pulmonary pathology. Subjects received either prednisone, 60 mg/day for 7 days, followed by a
progressive tapering over 14 days or identical placebo (PCB). All patients had 02 SAT, exercise testing and LDH measured at
days 0,3,7,14 and 28. Early deterioration, the pre-defined end-point of the trial, was defined as a 10% decrease in baseline 02
SAT at rest after day 2. The full trial was terminated after the 37th patient based on a sequential analysis.
Results: At termination, there were 12 and 11 subjects in the PCB and CS groups respectively. Baseline characteristics were
similar in the groups. Early deterioration developed in 7 and 1 patients in the PCB and CS groups respectively (P0.027). By
day 3, a number of parameters were less favorable in the PCB group relative to the CS group including median 02 SAT (85 vs
97%; P=0.003), LDH (1514 vs 763 U/L; P=0.013), respiratory rate (30 vs 22 bpm; P=0.003), heart rate (100 vs 81 bpm;
P=0.002), and temperature (39 vs 37"C; P=0.024). Even though patients suffering early deterioration in the PCB group were
treated with CS on an open label basis, significant differences between the groups persisted to day 30 with regard to exercise
tolerance. On day 30, more than half of patients initially assigned to PCB could not exercise whereas the CS group exercised
for a median of 6.5 minutes (P=0.017).
Conclusion: It is known that corticosteroids are of benefit in patients with moderate to severe PCP. The present subgroup
analysis would suggest that early introduction of adjunctive corticosteroids prevent deterioration and increase exercise tolerance
even in patients with mild AIDS-related PCP. Early return of exercise capability has obvious implications for the functional
capacity and quality of life of persons with mild PCP.
Supported in part by NHRDP, Health & Welfare, Ottawa; and the BC Health Care Research Foundation. Vancouver.
Dr. Jean Quieffin, Canadian HIV Trials Network, Pacific Region, 210-1033 Davie Street;
Vancouver, BC, CANADA V6E IM7. Telephone [phone]; Facsimile (604)-631-5210;
eB 1018 EFFICACY OF AEROSOLIZED PENTAMIDINE AND LOW DOSE COTRIOXAZOLE
WeB 101 FOR PRIMARY PREVENTION OF PNEUMOCYSTIS CARINII PNEUMONIA.
Schneider MarAriet ME, Hoepelman In, Danner SA, Nielsen TH,
van der Graaf Y, Weigel HM, van der Ends ME, Kolsters AFP and
Borleffs JCC. Dutch AIDS treatment group, c/o University
Hospital Utrecht, The Netherlands.
Backoround. Primary prophylaxis against Pneumocystie carinil pneumonia (PCPlis
retommended for HIV-infected patients and a CD4-cell count lower than 200 per
mm. There are no studies reported assessing the efficacy of aerosolized
pentamidine versus low dose of co-trimoxazole in primary prevention of PCP. So
we conducted a prospective randomized multicentre trial comparing aerosolized
pentamidine and two low doses of co-trimoxazole.
Methods. 214 HiV-eeropositive, PCP-naive patients with a CD4-cell count lower
than 200 per mm were randomly assigned to either aerosolized pentamidine 300 mg
once per month, co-trimoxazole 960 mg or co-trimoxazole 480 mg once daily. The
incidence rate of PeP was analyzed with the Mantel log rank test as a function
of time spent in the trial. The analysis was performed on a intention-to-treat
basis.
Results. At interim analysis 6 of 71 patients in the pentamidine arm had a
confirmed first period of PCP compared with no cases of PCP in 71 patients in
each co-trimoxazole arm (P value = 0.009). There was a much higher incidence of
adverse events in the co-trimoxazole 480 mg and 960 mg group than in the
pentamidine group (17 and 18 patients versus 2 patients). The mean length of
time until adverse reactions occurred was significantly longer in the- cotrimoxazole 480 mg group than in the 960 mg group (57 versus 16 days, P value -
0.001).
Conclusions. After one year of follow-up low dose co-trimoxazole is 100 percent
effective versus 90 percent effectiveness of aerosolized pentamidine in primary
prophylaxis against PCP in HIV-infected patients. An equal beneficial effect of
co-trimoxazole 480 mg and co-trimoxazole 960 mg is suggested.
WeB 1020 CLINDAMYCIN/PRIMAQUINE VERSUS TRIMETHOWeB 1020 PRIM/SULFAMETHOXAZOLE AS PRIMARY THERAPY FOR PNEUMOCYSTIS CARINII
PNEUMONIA IN AIDS. Toma, Emil; Fournier, S.; Dumont, M.; Bolduc,
P.; Deschamps, H. Hotel-Dieu de Montraal, Montreal, Canada.
Objectives: To assess the safety and efficacy of clindamycin/primaquine (C/P) in
comparison with trimethoprim/sulfamethoxazole (TMP/SMX) as primary treatment of
AIDS-related Pneumocystis carinii pneumonia (PCP).
Methods: This was a randomized, double-blind trial conducted at one university hospital. Sixty-five individuals with a first episode of possible PCP were randomly
assigned to receive C/P (34) or TMP/SMX plus folinic acid (31). Diphenhydramine was
given to all patients from the 5th day of therapy. All but 5 subjects had a Pa 02
at entry higher than 50 torr. Intent-to-treat and analysis of only proven PCP were
done. The main measurements were: the positive response, survival and relapse rates
outcome of severity markers, incidence and severity of adverse reactions.
Results: The 2 groups of patients had similar baseline characteristics. PCP was
proven in 27 (C/P) and 22 (TMP/SMX) individuals respectively. The positive response
(89 vs 91%) and survival rate wiyhin 2 months (93 vs 95%) were similar. The relapse
rate was higher (30 vs 41%) but not significantly (p"0.6) with TMP/SMX. The seve -
rity markers improved in parallel with the 2 therapies but dyspnea was ameliorated
significantly (p 0.005) by day 3 only with C3P. The incidence and severity of adverse reactions were lower (p=0.07 and 0.08 respectively) with C/P.
Conclusions: Although the slight differences between the 2 regimens were not significant (probably because of the small patient population) this trial favors C/P as
primary therapy for AIDS-related PCP. Therefore, this study served to design a
larger multicentre, clinical trial.
Toma, Emil, H~tel-Dieu de Montrhal, 3840 St-Urbain, Montrhal,Qu6.
H2W 1T8 Canada; Telephone:[phone]; Fax: [phone]

WeB 1017 DAPSONE-PYRIMETHAMINE (D/P) VS
AEROSOUZED PENTAMIDINE (AP) FOR PRIMARY PROPHYLAXIS OF PNEUMOCYSTOSIS (PCP) AND NEUROTOXOPLASMOSIS.
GOrard Perme-Marle.Lanman R, Gaudebout C, Jelasko P. Gaudebout Ch, Certain A
Olvares R, Coulaud JP and the PRIO group. INSERM U13, 75019 Parto France
Oblecttes: To compare D/P vs AP for primary prophylaxis of PCP and to assess the value of D/P for
primary prophylaxis of neurotoxoplaxmosts.
Methods: From July 89 to December 90, a multicenter, randomized, controlled trial recruited 362
symptomatic HIV patients (pts) with CD4 lymphocytes count below 200/mm3 and without history of
PCP or neurotoxoplasmosis and/or contraindication to either regimen. Pts were randomized to
receive AP, 300 mg monthly via a Respirgard I nebulizer, or dapsone (50mg/day) + pyrlmethamine
(50mg/wk) and folinic acid (25mg/wk). At randomization, pts were stratified according to their
clinical status (AIDS/non AIDS) and to prior therapy with zidovudine. Analysis was done according
to the intention-to-treat rule in 349 patients having received at least one dose of treatment.
Results: The trial was discontinued in Dec. 91 (mean follow up of 476~137 d) on the basis of the
interim analysis disclosing a highly sgnificanctprotectve effect of D/P against toxoplasmosis: 29
cases In AP group vs 15 in D/P group, (Log rank, p = 0.016); 7 of these 15 toxoplasmosis cases
occurred after discontinuation of D/P. Toxoplasmosis occurred In sero-toxo positive pts only.
Seven and 9 cases of proved or presumptive PCP were diagnosed in D/P and AP group, respectively
(Log rank, p = 0.62). Interruption of prophylaxis for side effects was more frequent under DP (n =
40/173) than under AP (n = 3/176), p<103. The most frequent of these side effects were cutaneous
(n=15) and/or hematological (n=12).
Conclusions: (1) D/P and AP are equally effective for preventing first episode of PCP (2) D/P is an
effective prophylaxis of first episode of toxoplasmosIs (3) D/P is significantly less well tolerated
than AP.
GIRARD Pierre-Marie
190, bd Mac Donald 75018 PARIS 33140353644 Fax [phone]
WeB 1019 COMPARISON OF 566C80 & TRIMETHOPRIM-SULFAMETHOXAZOLE (TMP-SMZ) FOR
THE TREATMENT OF P. carinii PNEUMONITIS (PCP). Hughes, Walter;
Leoung, G; Kramer, F; Bozzette, S; Frame, P; Clumeck, N; Masur, H;
Lancaster, D; Hyland, R; Lavelle, J; Safrin, S; Sampson, J;
Weinberg, W; Falloon, J; Feinberg, J; LaFon, S; Rogers, M; Sattler,
F; and others. An International Multicenter, CCTG, & ACTG
Collaboration.
Objectives: Preliminary studies suggested that a hydroxynaphthoquinone, 566C80, was
effective and well tolerated in the treatment of PCP. We compared the efficacy and
safety of 566C80 and TMP-SMZ in the treatment of PCP in AIDS.
Methods: A randomized, double-blind study enrolled 322 AIDS patients with mild (Aa[D02]<35 mm Hg) and moderately severe (A-a[D02]-35-45 mm Hg) PCP. One hundred and
sixty patients received 750 mg 566C80 and 162 received 320 mg TMP-1600 mg SMZ orally
t.i.d. for 21 days.
Results: With mild PCP 63% of the 111 patients treated with 566C80 and 63% of the 115
treated with TMP-SMZ met the criteria for therapeutic success. Therapeutic failures
due to drug toxicity occurred in 6X and 19% (p-0.005) and due to inadequate response
in 18% and 7% (p-0.015) of the 566C80 and TMP-SMZ-treated groups, respectively.
Similar responses occurred in the moderately severe group (n-96) with therapeutic
success in 59% of 49 and 66% of 47 patients receiving 566C80 and TMP-SMZ, respectively
(p-0.532). As in the mild group, more therapeutic failures occurred due to toxicity
in the TMP-SMZ group (23 vs 8%) and due to nonresponse in the 566C80 group (16 vs 4%)-.
The overall survival rates 4 weeks post therapy were 93X for the 566C80 group (n-160)
and 99X for the TMP-SMZ group (n-162). Treatment-limiting adverse effects included
leukopenia (0 vs 3X); rash (3 vs 7%); fever (0.5 vs 5X); liver function abnormalities
(0.5 vs 7.5%) and vomiting (1 vs 6.5%) in the 566080 and TMP-SMZ groups, respectively.
By logistic regression analysis, therapeutic success was directly related to steady
state plasma concentration of 566080. Conclusions: Therapeutic response of PCP to
566C80 was less than to TMP-SMZ but treatment-limiting adverse effects were greater
with TMP-SMZ, resulting in a similar overall rate of therapeutic efficacy.
Hughes, Walter, St. Jude Children's Research Hospital, 332 N.
Lauderdale, Memphis, TN 38105, USA, Telephone: [phone], FAX:
[phone].
WeB 1021 MICROBIOLOGIC DIAGNOSIS OF PNEUMOCYSTIS
CARINII PNEUMONIA IN HIV POSITIVE PATIENTS IN ZIMBABWE.
Gwanzura Lovemore*, Mason,P.*, Winter,M.**, Katzenstein,D.**
*University of Zimbabwe Medical School, Harare,Zimbabwe.
**Stanford University Medical Center,California, USA.
Objective: There is conflicting data on the presence or absence of
P.carinii in patients with pnuemonitis in sub-Saharan Africa. This study was undertaken in order to demonstrate unequivocally the presence of P.carinii in specimens
from HIV positive patients and to determine which diagnostic procedure was most
appropriate under local conditions.
Methods: Pulmonary samples were obtained from 76 hospitalised HIV positive (ELISA)
patients who showed clinical and radiological evidence of pneumonia. Bronchoalveolar
lavage (BAL) specimens were obtained from 41 patients, induced sputum (IS) from 29
patients and both BAL and IS from 6 patients. Specimens were examined microscopically
following staining with "Diff Quick", Toluidine Blue 0 and Grocot silver-methanamine.
To confirm the presence of P.carinii, primers described by Wakefield (pAZ 102-E and
pAZ 102-H) were used to amplify DNA obtained by digestion of specimens with
Proteinase K.
Results: P.carinii cysts or trophozoites were detected in 6/47 (13%) BAL specimens
and 4/35 (11%) IS specimens, including a single case where both the BAL and IS were
positive. Organisms were detected by all three staining procedures in positive
specimens, though the Diff Quick stain was by far the easiest to complete and the
least expensive. DNA amplification was successful in two specimens only, and the
reason for failure in the other specimens is being investigated currently.
Conclusion: Pneumonia caused by P.carinii does occur in immunocompromised patients
in Zimbabwe. The examination of IS specimens using the Diff Quick stain is a simple
method for investigation of PCP, that can be completed without the need for bronchoscopy. In at least two cases, DNA from African P.carinii was amplified using primers
based on sequence from European strains, suggesting there is little variation in the
sequence detected by these primers.
Gwanzura Lovemore, University of Zimbabwe Medical School, Box A178,
Avondale, Harare, Zimbabwe.
Telephone: [phone] Ext. 286 Fax: [phone]

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