Abstracts Vol. 1 [International Conference on AIDS (11th: 1996: Vancouver, Canada)]

Tuesday, July 9, 1996

Tu.B.181 - Tu.B.184

Results: Incidence of SBI's/ 10,000 days at risk (I-SBI) by ANC strata were:
ANC: 30 300 499 500 749 750 999 1000-1500 1500 2300 2300-3549 3500-5000 >5000
I SBI: /3.6 36.0 65 9.9 5.8 3.6 3.0 3.3 5.6
95% CI: 54 101 26 49 12 23 9.5- 14 4.2 8 2.6-5 2.2-4.1 2.4-4.5 4.1-7.7
In a multivariate analysis that included absolute CD4 count, age, gender, and race, only
severity and duration of neutropenia were highly significant predictors of SBI risk (p<.00 I).
Conclusion Among 2047 patients with HIV disease, ANC's < 1000 cells/uL (especially
<500) were associated with increased risk of being hospitalized for SBI's compared to
milder or no neutropenia.This observation has important clinical implications for HIV
patient care management.
Mark A. Jacobson, San Francisco General Hospital 995 Potrero Ave
Bldg 80 Wd 84 San Francisco CA 94110, [phone]
Tu.B.181
INCIDENCE OF BACTERIAL INFECTIONS IN A COHORT OF HIV POSITIVE
PATIENTS RECEIVING PCP/TOXO PROPHYLAXIS.
Murri Rita, Pallavicini F., Scoppettuolo G., *Pezzotti P, #SpanuT., Linzalone A., Cingolani A.,
Ammassari A., Antinori A. Department of Infectious Diseases and of #Microbiology, Catholic
University, and *Centro Operativo AIDS, Istituto Superiore di SanitS, Rome, Italy.
Objective: To evaluate the effect of cotrimoxazole versus dapsone-pyrimethamine prophylaxis on the incidence of all bacterial infections and in particular serious infections such as
sinusitis, pneumonia and sepsis in a trial of PCP/Toxo prophylaxis performed in HIV-positive
patients (pts) with CD4 less than 200/pl.
Methods: Data collected from a randomized open-label prospective study on PCP/Toxo
prophylaxis (UCMI-PCP-03). Pts were randomly assigned to receive a) cotrimoxazole
(CTX) I DS tablet daily, or b) dapsone 50 mg daily + pyrimethamine 50 mg weekly + folinic acid 25 mg weekly (DP). Pneumonia was diagnosed if there were clinically compatible
findings, focal radiographic consolidation and eventually the isolation of a likely pathogen
that responded to therapy Sinusitis was diagnosed if clinical findings, radiological signs and
response to therapy was present. Sepsis was defined by presence of two or more positive
blood cultures with systemic symptoms. Statistics: Crude incidence rates were calculated
and cumulative probability of remaining free of different diseases was estimated by the
Kaplan.-Meier method and a Cox model was fitted after adjustment for baseline and ontreatment covariates.
Results: 200 pts were enrolled in the trial (CTX= I0 I; DP=99).The two groups were
homogeneous for all baseline characteristics. After a mean of 372 days of follow-up, 114
episodes of bacterial infections (52 in CTX; 62 in DP arm) were registered; of these, 85
were observed during drugs administration (on trerrment) (46 in CTX; 39 in DP).
Considering only oni treotrent analysis, rate of overall bacterial infections was 55.4 for CTX
and 62.0/ 100 p-y for DP with a 2-year probability of remaining free of a first serious bacterial episode of 0.52 and 0.58 respectively Incidence of on-treatment pneumonia was 24. I for
CTX and I I.5/100 p-y for DR with a 2-year probability of remaining free of a first episode
of pneumonia of 0.67 and 0.9I respectively (P at log-rank-0.2 I). Adjusted risk of having a
first serious bacterial infection and pneumonia for DP group was 1.04 (95% CI 0.57-1.89)
and 0.66 (95%CI 0.24-1.82), respectively. Only a WHO 3/4 neutropenia (R.R. 3.5; 95%CI
I.2-9.9) or a CD4 count less than SO/pI (R.R. 2. I: 95%CI I.0-4. I) were independently related to respectively an augmented risk of pneumonia and of serious bacterial infections.
Conclusions: At a preliminary evaluation no significant advantages were observed and a
theoretical higher efficacy of CTX as antibacterial prophylaxis was not confirmed. Possible
explanations may be related to an antibacterial activity of dapsone, or to a selection of
drug-resistant strains by CTX in prolonged administration. A further evaluation in long-term
follow-up including organism cultures analysis and susceptibility tests are ongoing.
R. Murri, L-.Go A. Gemelli, 8 - Unversita Cattolica S. Cuore - 00168 Roma, Italy
Tel: [phone] Fax: [phone]
Tu.B. 182
HIGH PREVALENCE OF TRIMETHOPRIM-SULFAMETHOXAZOLE [TMP-SMX]
RESISTANT STREPTOCOCCUS PNEUMONIAE IN HIV-INFECTED PATIENTS ON
TMP-SMX FOR PNEUMOCYSTIS PROPHYLAXIS:THERAPEUTIC IMPLICATIONS
Kadree, Margaret A. Morehouse School of Medicine, Atlanta, Georgia, United States of America.
Objective: To determine whether the use ofTrimethoprim-Sulfamethoxazole [TMP-SMX]
for the prophylaxis of Pneumocystis carinii pneumonia [PCP] predisposes patients to the
development ofTMP-SMX pneumococcal disease.
Methods: Reports of Pneumococcal isolates recovered from blood cultures of 535 patients
at an inner city hospital during the period, November 1992 and June 1995, were reviewed.
Charts of those patients whose HIV serostatus was known were examined and data collected pertaining to CD4 cell counts at time of diagnosis, length of time on PCP prophylaxis, previous patterns of antibiotic use and TMP-SMX and penicillin sensitivity.
Results: Of the 535 patients, 179 were documented to be HIV(+) and 98 HIV(-).The
mean age of the HIV(+) patients was 35 [range 1-68] while that of the HIV(-) patients was
40 [range 1-86]. Of the HIV(+) patients - 29% were female and 7 I% male and the HIV(-) -
36% female and 64% male. Forty two [42] percent of isolates from HIV(+) patients were
resistant to penicillin [PCN] but only I2% of isolates from the HIV(-) group.Thirty-four of
the 45 PCN-resistant isolates from the study group were tested againstTMP-SMX of which
44% were found to be resistant. Sixty [60] percent of the TMP-SMX resistant isolates were
recovered fiom the HIV(+) patients.TMP-SMX resistance correlated better with mean
length of time on PCP prophylaxis with TMP-SMX [45 months in HIV(+) group versus 20
months in HIV(-) group; P=.05,95% confidence limits; CI 18.25-31.75] than with absolute
CD4 counts [I 2I in HIV(+) versus 66 in HIV(-)] group.
Conclusions: TMP-SMX resistant isolates were more commonly retrieved fbom DIV
seroprasitive patients than those who were seronegative, with mean length of time on PCP
prophylarxis of 45 months being a more sensitive predictor of resistance than a low absolute
CD4 count.These findings suggest that in HIV-infected patients who have been on TMPSMX prophylaxis and who may have: pneumococcal sinusitis, otitis media, early pyogenic

pneumonitis with features indistinguishable clinically f-om PCP as well as meningitis in the
PCN-allergic patient - situations in which TMP-SMX might be used empirically - careful consideration must be given as to the appropriateness of usingTMP-SMX.
Margaret Kadree, Morehouse School of Medicine, 720 Westview Drive, SW Atlanta,
Georgia, USA.Tel: [phone] Fax: [phone]
Tu.B. 183
A CONTROLLED TRIAL OF INTRAVENOUS IMMUNE GLOBULIN FOR THE
PREVENTION OF SERIOUS INFECTIONS IN ADULTS WITH ADVANCED HUMAN
IMMUNODEFICIENCY VIRUS INFECTION
Michael Kiehl MD, Reinhard Stoll, MD, Martin Broder Christoph Heese, MD, Carsten
Mueller, MD, Eva Baecker, MD, Ernst-Ch. Foerster, MD,PhD, Wolfram Domschke, MD. Dept.
of Internal Medicine, University of Muenster, Muenster, Germany
Objective: To determine the efficacy of intravenous immune globulin (IVIG) in preventing
infections and reducing days with fever and duration of hospitalisation in human immunodeficiency virus (HIV) infected adults.
Design: Prospective, randomised, open outpatient clinical trial. According to the Centres for
Disease Control and Prevention (CDC) classification adults CDC B and C were randomised to be treated with (n=70) or without (n=57) IVIG. Interventionr: Patients assigned
to treatment with IVIG received 400 mg IVIG per kilogram (kg) initially and 200 mg IVIG
per kg every 21I days thereafter. Main outcome meosures: Primary endpoints were occurrence of laboratory proved or clinically diagnosed infections or death due to infection.
Results: In comparison to patients of the control group, IVIG treatment significantly increases the time free from serious infections (p=0.000 I) in patients CDC B and C.
Furthermore, mortality due to infection was significantly reduced (p=0.01I) in IVIG treated
patients CDC C. In addition, IVIG treatment was associated with an overall reduction in the
number and duration of hospitalisation for acute care (p=0.0019) in patients CDC C. On
account of these results the study was stopped by the local ethics review board.
Conclusion: These findings indicate that prophylactic IVIG therapy reduces the occurrence
of serious infections in patients CDC B and C as well as mortality due to infection in
patients CDC C. Furthermore, the time of inpatient treatment was abridged in HIV infected patients CDC C by IVIG treatment.Therefore, prophylactic IVIG treatment may be helpful in the therapy of advanced HIV infection and may increase quality of life in these critical
ill patients.
M. Kiehl, Albert-Schweitzer-Str 33, 48 129 MOnster GermanyTel.: +49 (25 I) 83-76I10
Fax +49 (25 I) 83-7680 email: kiehl@uni-muenste:de
Tu.B. 184
A RANDOMIZED, DOUBLE-BLINDED, PLACEBO-CONTROLLED STUDY OF
CIDOFOVIR TOPICAL GEL FOR ACYCLOVIR-RESISTANT HERPES SIMPLEX VIRUS
INFECTIONS IN PATIENTS WITH AIDS
Sc F h 5 m S 6 I 70Ce A;
Lalezari Jacob, SchackerT2, Feinber J3, Lee 5'4, Gathe J5, Kramer F6, Kessler H7, Cheung
T8, Drew WL1, McGuire B9, Jaffe HS, Safrin 5.10.1 Mt. Zion/UCSF, San Francisco CA USA;
2U. Washington, Seattle WA USA; 3Johns Hopkins, Baltimore MD USA; 4UNC, Chapel Hill
NC USA; 5Houston Clinical Research Network, Houston TX USA; 6LAC-USC Medical
Center, Los Angeles CA USA; 7Rush Medical College, Chicago IL USA; 8Mt. Sinai, New York
NY USA; 9Gilead Sciences, Foster City CA USA; IuSFGH/UCSF, San Francisco CA USA.
Objective: To determine the safety and clinical efficacy of cidofovir topical gel for the treatment of mucocutaneous Herpes simplex lesionslnially unrespons ccrive to acyclovir (ACV) in
patients with AIDS.
Methods: Patients with AIDS and clinical evidence of mucocutaneous HSV infection unresponsive to ACV were randomized to receive either placebo gel or cidofovir topical gel at
0.3% or I% applied once daily for 5 days followed by observation. After the initial doubleblinded cycle, additional 5-day open-label cycles of I% gel were permitted.Two marker
lesions were designated to be followed for response according to the following criteria:
Complete = complete healing, Good - >50% decrease in sum of lesion area, Partial = 25 -50% decrease, Poor = <25% decrease or increase. Primary endpoints included complete +
good healing rate and conversion to culture negativity Additional endpoints included complete healing rate, pain score changes (using a 0- I 0 scale), and safety Viral drug susceptibility
and pharmacokinetic studies were also performed.
Results: Thirty patients received study drug: 24 males and 6 females. Baseline characteristics
were comparable between groups. Median CD4 count was 9/mm3 (range: 0- I 19), median
Karnofsky was 80 (range: 50-100), and median marker lesion surface area 1675 mm2
(range: 25-50,000). Incidence rates of adverse events were similar between treatment
groups; there was no evidence of significant drug-related local or systemic toxicity. Efficacy
results were as follows by group:

\O
ON'
0
C
V)
O
0
0
(1)
U
Ca
C
c
0
O
V
0
rd
C
c
)

All Cidofovir
vs.Placebo

Placebo 0.3% Cidofovir I% Cidofovir All Cidofovir
(n= 10) (n=I I) (n=-9) (n=20)

Complete +
Good Healing 0% 55% 44%
Complete
Healin.... 0% 27% 33%
Conversion to.
CultureNeg 0% __ 78% 100%
Median Days to
CultureNeg - 7 _ 2
Mean Pain
AUC Change -0.34 _ -2.29 _ -1.34
* stratified analysis using baseline lesion surface area as covariate

50% p=0.008*
30% p=0.047*
87% p=0.00004
2 _ p>0.0001
-I.86 p-0.039

Conclusions: Cidofovir topical gel was well tolerated and provided effective therapy for
healing herpes lesions unresponsive to ACV in patients with AIDS.Treatment also reduced
viral shedding and lesion-associated pain.
Jacob Lalezari, M.D. Mt. Zion Medical Center of UCSF 2300 Sutter Street, Suite 202 San
Francisco, CA 94 I 15 (4 15) 476-3622 (tel) (4 15-476-3622 (fax)

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