Bridging the Gap: Conference Record [Abstract book, International Conference on AIDS (12th: 1998: Geneva, Switzerland)]

12th World AIDS Conference

Abstracts 60796-60800 1147

being p24 antigen positive as compared to 55 1 9% under serum-conditions (p <
0.005). RT activity of M-MAC was always about 100-fold lower than of SER-MAC.
Accordingly, p24 in the supernatant was lower under serum-free conditions. We
also switched SER-MAC to serum-free conditions and found a sharp decrease
in RT activity. However, the RT level could always be rescued by the addition of
serum even after a long serum-free culture period. Furthermore HIV-1 replication
in MO/MAC was highly depending on the donor from whom the cells derived.
However, no significant difference in cellular phenotype and cytokine/chemokine
secretion between different donors was observed.
Conclusions: We show that serum has an important role for the replication
of HIV-1 in MAC. Our results suggests that beside the role of CD4 and CKR5
other microenvironmental factors which are not provided by the target cell itself
are involved in the regulation of MAC infection and replication by HIV-1.
(This project was supported by BMBF 01KI9411/3. The Georg-Speyer-Haus is
supported by the Bundesministerium fOr Gesundheit and the Hessische Ministerium fur Wissenschaft und Kunst.)
60796 T-cell renewal capacity in organ culture is diminished in
PBMC of HIV-1 infected individuals: Longitudinal
analyses from the Amsterdam cohort
Dawn R. Clark1, S. Repping1, J.M.A. Lange2, J. Prins2, R.A. Coutinho3,
F. Meidema1. 1Clinical Viro-lmmunology, CLB, Plesmanlaan 125, 1066 CX,
Amsterdam; 2NATEC, Academic Medical Centre, Amsterdam; 3Dept. Public
Health, Municipal Health SV, Amsterdam, Netherlands
Objectives: The cause of CD4+ T-cell depletion in HIV infection is still debated:
high turnover and exhaustion or limited renewal. T-cell progenitor capacity was
shown to be impaired in HIV-1 infection in a cross-sectional study. Longitudinal
analyses of T-cell renewal capacity in PBMC of individuals who progressed to
AIDS and long term survivors (LTS) were performed to determine when T-cell
progenitor capacity is impaired and whether all groups of infected individuals are
affected. An analysis was also conducted on PBMC from individuals enrolled
in therapy trials to determine whether the defect is reversible and what the
parameters of recovery of T-cell renewal capacity might be.
Methods: PBMC were used in a T-cell development assay, fetal thymus organ
culture, to determine functional T-cell progenitor capacity. Pre-seroconversion
and several timepoints post-seroconversion were analyzed for the progressors
and LTS ( -8 yrs AIDS-free and CD4 count -400 in the 8th year). For patients
enrolled in therapy trials, pre-treatment and multiple timepoints post-treatment
were analyzed.
Results: Patients who progressed to AIDS showed an average 8-fold drop in
T-cell renewal capacity, as assessed by CD4+ T-cell development, within 2 years
after seroconversion and this low level continued throughout the period analyzed.
Long term survivors however, maintained their pre-seroconversion level of T-cell
renewal capacity in organ culture throughout the entire period analyzed. Patients
responding (improved CD4 counts and T-cell function and reduced viral load) to a
rigorous therapy regimen of five medications showed some improvement in T-cell
renewal capacity compared to their pre-treatment levels at 6 months after start of
treatment.
Conclusion: The difference in T-cell development profiles between progressors and LTS suggests that the decline in T-cell progenitor capacity contributes to
CD4' T-cell depletion and progresssion. The T-cell renewal capacity improved in
individuals who responded by other parameters to an extreme treatment regimen
suggesting that the defect is not permanent and that there is the possiblity that
the immune system can be restored.
S60797 Failure of prophylaxis for Pneumocystis carinii
pneumonia (PCP) in HIV-infected individuals
Takashi Takahashi1, T. Nakamura1, K. Shimada2, A. Iwamoto1. 'Institute of
Medical Science, University of Tokyo, 4-6-1, Shirokanedai Minato-Ku, Tokyo 108;
2Tokyo Senbai Hospital, Tokyo, Japan
Objectives: To find clinical characteristics of prophylaxis failure and perform early
diagnosis and treatment for PCP in HIV-infected patients.
Design: Retrospective study.
Methods: We examined the clinical characteristics of unsuccessful primary
and secondary prophylaxis for PCP in HIV-infected individuals from 1986 to 1997.
Results: Primary prophylaxis was 121 episodes and had 7 failure events by
pentamidine. Secondary prophylaxis was 61 and had 6 failures by pentamidine.
No failures by cotrimoxazole were observed. Ten patients (76.9%) with failures
had CD4+ lymphocyte counts less than 50//I1. In failures of primary prophylaxis,
pentamidine was intravenously given at the dose of 3 mg/kg (intervals of 4 and 7
weeks) for 2 events (18.2%) and at 4 mg/kg (intervals of 4, 5, and 8 weeks) for
three (21.4%). Other 2 events (11.8%) had inhalation of pentamidine at 300 mg
(intervals of 4 and 5 weeks). In failures of secondary prophylaxis, pentamidine
was intravenously given at 3 mg/kg (interval of 4 weeks) for 2 events (14.3%)
and at 4 mg/kg (interval of 4 weeks) for two (20%). Other 2 events (22.2%) had
inhalation of pentamidine at 300 mg (interval of 2 weeks). Antiretroviral therapy

by nucleoside analogues or protease inhibitors was combined with prophylaxis
by pentamidine in 8 failure events. In 3 episodes, pentamidine prophylaxis was
combined with administration of ganciclovir.
Conclusion: Intensive observation for PCP in HIV-infected patients with CD4
counts less than 50/pl appears to be necessary when prophylaxis by pentamidine
is issued together with antiretroviral or ganciclovir treatment.

60798 1 Radioliological and clinical aspects of tuberculosis in HIV
infection
Miguel Lopez Dupla1, D.A. Delegido Antonio2, R.X. Raga Xavier3,
S.J.C. Soriano Juan Carlos2, B.J. Batista Joan3, P.J.A. Porras Jose Antonio2,
B.P. Perez Belen2. 'Rambla Vella 14, 43003 Tarragona; 2Internal Medicine,
Tarragona; 3Microbiology, Tarragona, Spain
There exist several reports that have remarked on the effect of HIV infection on
some aspects of tuberculosis (TB) presentation.
Objective: To assess the influence of HIV infection on the clinical and radiological patterns of TB.
Material and Methods: The presence or absence of cavities in chest radiographs, TB location and CD4+ lymphocyte count were examined in a series of HIV
infected patients between 1992 and 1997. TB diagnosis criteria were: 1. Positive
Lowenstein culture (LC) 2. Positive Ziehl-Neelsen staining (ZN) with suggestive
TB diagnosis in spite of negative LC. 3. Necrotizing granuloma in a pathological
examination with suggestive TB diagnosis despite negative LC and ZN. 4. Clinical signs (only in pulmonary TB) and a good response to tuberculostatic drugs
despite the absence of microbiological or histological confirmation.
Results: 40 TB patients with HIV infection (31 M, 9 F; mean age 35 i 9 y)
among 156 TB patients were studied. There was a higher incidence of extrapulmonary TB in HIV infected patients than in non-HIV infected patients (p - 0.001).
Otherwise, extrapulmonary TB was more frequently present in HIV infected patients with a lower CD4+ cell count. In HIV-related pulmonary TB the occurrence
of cavitation was more frequent when the CD4+ lymphocyte count was above
200/mm3 (p < 0.05). Likewise, CD4+ cell count was higher in PPD-positive HIV
patients (p < 0.05). TB was the first AIDS-defining illness in 27 patients.
Conclusion: A lower incidence of PPD-positive reactions, a preference for
extrapulmonary presentation, and a lower presence of cavitations in chest radiographs could be appreciated in the most immunodepressed HIV-related TB
patients.
60799 Temporal trends in the Israeli AIDS hospice, 1993-1997
Itzchak Levi1, D. Ben David1, E. Rubenstein1. Infectious Dis. Unit, Sheba
Medical Cen., Tel Ramat Gan, Israel
Objectives: The Israeli AIDS hospice was inaugurated 4 years ago with its main
goal to support palliatively terminal AIDS patients. The aim of this study is to
analyze the temporal trends in the approach, management and outcome of such
patients.
Methods: The medical records of all patients admitted to the AIDS hospice
from its opening on December 1993 until December 1997 were analyzed for
temporal trends in socio-demographic characteristics, main medical problems,
reasons for admission, mortality rates and interventions.
Results: The records of 100 patients were analyzed. There was no significant
change in sociodemographic characteristics (age, risk profile, socioeconomic
level) between the years 1993-1997. The main medical problems, reasons for
admission and hospitalization criteria have not changed over the years. A significant reduction (50%) in two years mortality rate between 1993 and 1997 was
observed. As HAART was introduced only on the second half of 1997, it can
not account for reduced mortality. A change in the attitude of the hospice staff,
from the traditional passive approach into a more active attitude led to intensive
diagnostic interventions coupled with antimicrobial therapy were started on 1995
and may explain this reduction in mortality rate-at least partially. Psychosocial
support was another major factor that seemed to determine individual patient's
prognosis.
Conclusion: The general approach of the AIDS hospice is continuously evolving. Although mortality and morbidity rates are changing over time, especially due
to the introduction of HAART, Aggressive management along with psychosocial
factors still play a major role in the prognosis of terminal AIDS patients. This
change in mortality should bear consequences on the patient, family, health care
provider and medical insurer.
| 60800 Bacteremia in Israeli AIDS patients
Itzchak Levi1, A. Barzilai1, B. Rubinowitz1, D. Ben David1, N. Keller2,
E. Rubenstein. 1 Infectious Dis. Unit, Sheba Medical Center, Tel Hashomern
Ramat-Gan; 2Microbiology Lab., Sheba Med. Center, Ramat Gan, Israel
Objectives: The prevalence and risk factors for bacteremias in AIDS patients
hospitalized between 1990 and 1997 at the Sheba Med. Ctr. were studied.
Methods: All patients with proven bacteremia were identified. Data on demographic factors, medical characteristics and bacteriological identification were
analyzed.
Results: A total of 35 bacteremias in 32 patients were identified, all in patients
with CD4 < 100/mm3 11 bacteremias were due to gram(+) organisms (3 - S.
aureus, 2 - S. coagulase negative, 2-enterococci, 3 - S. Pneumoniae and 1 - S.
Pyogenes).
13 bacteremias were caused by gram ( ) (5 - Salmonella spp., 3 - Pseu
domonas spp, 2 - X. maltophilia, 2 - E. coli and 1 - Shigella sp.). MOTT (MAC
and M. simiae) were isolated from 11 patients. G(+) bacteremias were nosocomially acquired, indwelling catheter being associated with staphylococci. G (-)
bacteremias, in particular salmonella, were especially prevalent among Ethiopian
immigrants. MOTT and S. Pneumonia were not prevalent among Ethiopian patients although Ethiopian immigrants represent more than a third of Israeli AIDS
patients.