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

Tu.B.2346 - Tu.B.2350

Tuesday July 9, 1996

Objective: Surrogate rnarkers of HIV disease progression are needed fo, pror, i ur
poses and to decide on interventions such as initiation or change of aritiretrovisal theiapy
and prophylactic therapy Markers such as CD4(+) cell count (CD4s), have established vall
but more sensitive markers are needed. Several investigators have suggested meas urements
of viral replication (viral burden) and of activated CD 8(+) cells (CD8s) as such rnirkers.
We proposed to correlate the percentage of activated CD8s with disease statu to test its
usefulness.
Methods: HIIV infected individuals (diagnosed with two consecutive EL.ISAs and ac orfirmatory assay) visiting the JUniversity clinic of CAMC, were tested consecutively with dual color
flow cytometry of peripheral blood, using CD8 PE/CD38-FITC monroctonal antibodies for
the absolute number and percentage of CD8s and activated CD8s. Mean percentages were
calculated after stratifying all patients into four categories of CD4s. All measures were made
by the same technician using an EPICS XL Coulter flow cytonmeter In addition, patients
were divided into stable" and "progressing" groups based on four clinical criter ia: general
well being, weight stability presence of associated diseases (thrush, diarrhea, etc.) or AIDS
defining conditions.We used medical and laboratory personnel and HIV negative patients
with miscellaneous conditions as controls.
Results: The mean percentage of activated CD8s for the controls (27 reas irements) was:
3.2.The mean for HIV infected individuals with more than 500 CD4s (4 measurements):
was 17.6 The mean for individuals with 200 to 500 CD4s (18 measurements) was: 23.9.The
mean for individuals with 50 to 200 (six measurements) was: 39.2 and for individuals with
less than 50 CD4s (I 8 measurements) was 39.5. Patients classified clinically as stable had a
mean percentage of activated CD8s of 25%, while those classified as progressing had a
mean of 42%.
Conclusion: The percentage of activated CD8(+) cells measured by flow cytometr; corre
lates with HIV disease status and CD4 counts and percentages.Whether it is a more sensi
tive marker of disease progression or a better prognostic indicator deserves further study.
Jaime E. Hernandez, '1.D.,WestVirginia University School of Med. 3110 MacCorkle Avenue,
S.E., Charleston, West Virginia 25304 USA Phone: [phone] FAX: [phone]
Tu.B.2346
LOGARITHM OF CD-4 COUNTS:A GUIDE TO THE MANAGEMENT OF HIV
INFECTION
Sakamoto, Artsur, *Collins Do, *Guizado, RA, *Anthony D.*. East Valley Community Health
Center Pomona, California, USA
Objective:To demonstrate that following the lIogarithm of CD 4 counts (log CD 4) of
HIV-infected patients presents a rational guide to their managenment.
Methods: CD-4 counts of HIV-infected patients who enrolled in our cornnunity clinic dur
ing the first 21 months of inception and who had at least 3 CD-4 counts were plotted on
sernilog graphs with respect to timne.Various patterns of CD-4 count in response to HIV
infection and to therapy were noted. We also recorded the various medications administered as well as significant changes in the patients' life that we felt might be significant. Our
patients were treated with conventional reverse transcriptase inhibitors and other medications, such as prophylactic and other indicated anti infective agents and others.
Results: The rate of decline, or slope, of Log CD-4 of most of our HIV-infected patients
appeared to be remarkably linear Also, they were extremely variable with T I/2's ranging
firom 2 months to an estimated 10 to 15 years. A small nurmber of patients' CD 1 counts
remained above 550 with Log CD-4 slopes which were non--linear and quile variable, possi
bly being a characteristic of the group of "long term, nonprogressive survivors".
Characteristic responses to anti-retrovirals were noted, with a rapid elevation of the CD)-4
counts, followed by a level slope ("plateau"), and then a drop of Log CD-4 with the same
slope as that prior to therapy.
Conclusions: As we followed our patients' Log CD-4, it became evident that we had found
a powerful tool and a practical guide for the management of HFIV-infected patients.
Arthur Sakamoto, 4239 Via Arbolada. #310, Los Angeles, CA 90042-Telephone: [phone] Fax [phone] I1
Tu.B.2347
PROPOSED USE OF BIOELECTRICAL IMPEDANCE ANALYSIS (BIA) IN MEDICAL
MONITORING OF DISEASE PROCESS AND THERAPY EFFICACY:A CASE SERIES
Fields --Gardner Cade*, Bergec DS*", Bucher, G*, Cohan, G *,Weisman, J '*.The Cutting
Edge, Cary, IL; **Center for Special Irmmunology Chicago, IL; **Pacific Oaks Medical Group.,
Beverly Hills, CA, USA
Issue: Depletion of body cell mass (BCM) is strongly correlated with morbidity and mortality in HIV disease.Therapy efficacy in infectious disease is currently reliant upon prompt
diagnosis. BCM decline may precede clinically apparent symptoms and diagnosis. BIA measurerments have been validated for body composition estimates in HIV/AIDS patients using
RJL FNA 3.1.
Project: A program of serial BIA measurements for rmonitoring patients was instituted in
two HIV clinic settings. Data were centrally processed for rmore than 250 patients and
observed for trends anrid changes. Observations included changes in expected levels of calculated BCM, extracellular tissue (ECT), intracellular (ICW) and extracellular water (ECW).
and fat. Patient profiles were compared to expected profiles according to sex, but indepen
dent of other demographic data.
Results: Initial standards were set according to literature review. Fluid shifts between body
compartments and BCM decline were compared to optimal profiles as a means of identifying subclinical inflammatory processes and therapy efficacy (see table).
EVEN1 change in BCM:ECT change rin ICW:ECW change in FAT
optimal baseline > I > 15 0 20%"
irfectior/linflairiration dcraease erase sare, icreise
e tive therapy net results stabilization/increase stabhlization increase stabilizati oninrease
ntrion support responder stablvasin i se 'ablization/increas e stablization/increase
trition support: non i esponder stabnlization/dec rease stabilization/decrease incr ease
anabolic therapy increase increase deease

xere stabilization/slight increase stabilization/slight increase stabilized/decrease

Lessons Learned BI/,, iray be a useful tool to monitor medical events and therapy or rehabilitation efficacy B A nw al'Iso be a useful independent and objective tool in the early identification of,dvers medical events characterized by fluid shifts.
C. Fields,rdnirT Cie, utring Edge, PO. Box 922, Cary IL 60013 USA
-elephon.: 1-81 I 6-24.,'5 Fax [phone] e-mail: 74534.1061 coranpuserve.comi
Tu.B.2348
DISCORDANCE BETWEEN ABSOLUTE CD4 (ABSCD4) COUNTS AND CD4
PERCENTAGE (%CD4)AND THEIR RELATIONSHIP TO THE RATE OF CD4 CELL
DECLINE
Skowron, Gait1'2, Fisher A2, Fisher A1,3, Cole BF,2. Brown University, Roger Williams
Hospital and Stratogen Health, Providence, Rhode Island, United States
Objective: I) To describe the discordance between absCD4 and %CD4 in a group of
patients fiom a single clinical practice and 2) to describe rates of CD4 cell decline as mea
sured by CD4 absolute counts and percentage.
Methods: A group of 149 HIV-seropositive patients (pts) who had 2 3 C.D4 measuremrents
performed over 6 months were evaluated for concordance between absCD4 and %CD4
results at the initial visit. Rates of CD4 cell decline were calculated over the entire period of
followup using inear regression analysis; discordance between declines of CD4 absolute
counts and CD4 percentage were evaluated.
Results: On initial evaluation,"low" absCD4 (<200) agreed with "low %CD4( (' I %) n 33
pts; only one "low" absCD4 pt had "high" %CD4 (>31%) and one "low" %CD4t pt had
"high" absCD4 (>500). However, 8 of 21 pts (38%) with %CD4 between 16 and 20 had
absCD4 counts over 400. During followup, 28 pts had > 25 cell increase per year; of these.
4 had a %CD4 loss of > I percentage point per year (range -1.7 to -8.9% per year). 27 pts
had >1% per year gain in %CD4; of these, 4 had > at least a 25 cell loss per year in
absCD4 (range 177 to -363).
Conclusions: At %CD4 between 16 and 20, absCD4 counts suggest a less 'c 'ere state of
immunodeficiency than does ~%CD4 in more than a third of pts. Falls or rises in absC) I
and %CD4 over timre are sharply discordant in some pts.These discordances between
absCD4 counts and %CD4 during the course of HI-V infection may impair the clinician's
ability to interpret the true state of immunodeficiency or response to therapy in a given
patient. Clinical outcome and immunologic data in patients with marked discordance with
be presented.
Gail Skowron, M.D., Brown LUniversity, Roger Williams Hospital, 825 Ch-alkLtone Ave,
Providence, Rhode Islandc,lelt [phone], Fax [phone]
Tu.B.2349
VIROCO: EVALUATION OF MONITORING OF VIROLOGICAL AND IMMUNOLOGICAL PARAMETERS DURING TREATMENT OF HIV I INFECTED PATIENTS.
Tubiana R.*, Carcelin G.**-, Calvez V.***, Ktorza N.*, Mengual X.*, Autran B.**, Agut H.'*,
Katlama C.*. * Maladies Infectieuses, ** Immunologie. **Virologie, HOpital Pitie
Salpitriere, Paris, FRANCE.
Objectives: To determine HIV viral burden and immunological markers using different procedures and to analyse their modifications and correlations in a cothot of patients eceiving
antiretroviral treatment.
Methods: 40 patients with 50 to 500 CD4+ cells/mn3 were enrolled 21 naive patiernts
starting AZT (group A) and 19 previously treated (group B) receiving their first course of
D4T (n=9) or 3TC (n= 10).Virological and immunological evaluation including quanrtitative
cell virernmia and plasnma viremia by culture, HIV I plasma RNA with NASBA, p2.1 antigenemia,
CD4+ and CD8+ and CD4 activation markers CD4+CD25 - count was performed at day
0, M I, M4, and every four months after initiation of therapy
Results: These 40 patients were mainly male (82%) and homosexuals (53%). tMedian duration of prior antiviral therapy was 49 months in group B.The median follow up at the 31I
december 1995 is I 1.7 months (4-19). Mean baseline CD4 count, cellular anrid plasma
viremia were respectively: 255/mm3, 1.5 log, 0.22 log in group A and I 69/mm3, 0.46 log.
0. 13 log in group B. Naive patients had a significantly higher CD4 count (p==0.02) and cellular viremia (p-0.016) compared to pretreated. No difference was found for plasma viremia
and p24ag. Starting AZT induced a decrease of cellular viremia at M I (p=-0.048), M4
(p=0.017) and M8 (p=0.04) and of plasma viremia at M I (p=0.02), M4 (p=- 0.037). M8
(p=0.008). Contrasting with this beneficial effect on viremia no significant change was
observed in absolute CD4 count. However CD4+CD25+ increased between baseline and
M I (p<0.05) then decreased from M I to M4 (p- 0.01). In group B, 3TC or D4T
monotherapy did not induce any significant change in immunological parameters, the only
significant variation was an increase of cellular viremia at M4 (p- 0.047). AIDS related
events occured in 5 patients (12.5%) all belonging to group B. No modification neither of
immunological nor virological parameters was found to be predictive of the clinical worsen
ing. 32 patients (80%) switched from mono to combo therapy (18 AZT-3TC, 6 AZT-DDI. 5
AZT DDC, 3 D4T-3TC) after a median time of 7 (2-17) months. In 13 patients the mean
reduction in cellular viremia I to 3 months after starting the combination was 0.7 tog (p0.0037). Concomitantly plasma virenia and CD4+ count were not significantly modfied.
Looking at individual parameters such as variation of 20% CD4 cells or 0.5 log in cellular
virermia no correlation was demonstrated.
Conclusion: Monitoring of HIV viremia and new markers such as CD4+CD25+ in individual management of HIV infected patients requires further investigations in the light of more
effective antiretrovira! therapy to value their role and correlations.
R.Tubiana, Service des Maladies Infectieuses, Groupe Hospitalier Pitie-Salpitriere
47, Bd de I'H6pital 75013 PARIS.Tel: 42.I6.01.7I; Fax: 42.I6.0I.26
Tu.B.2350
THE CANADIAN RANDOMIZED OPEN-LABEL TRIAL OF COMBINATION THERAPY
FOR MAC BACTEREMIA: QUALITY OF LIFE OUTCOMES.
Singer- eIThorne A, Raboud JM. Fanning M,Toma ETurgeon F Duperval R. Schlech WVF.
Cameron DW, Smaill FM, Lemieux C, Senay H. Mackie ID, Mcfadden DK, Williams KE.
Thompson GW Walmsley SL, Shafran S,The Canadian MAC Study Group. Canadian HIV
I-nato Networ kVanrouver, Canada
Objective: A randomized open-label trial compared the efficacy and safety of ciprofloxacin
750 mg BID, ethambutol 15 mg/kg QD, rifampin 600 mg QD and clofszimine 100 mg QD

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