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

538 Abstracts 31213-31217

12th World AIDS Conference

mocystis carinii pneumonia is limited because of serious adverse effects. We
hypothesize that the multiple pharmacological actions of the drug may be due
to its conformational flexibility which allows the drug to bind to both target and
non-target macromolecules.
Methods: In order to study the effect of restricting the conformational flexibility of pentamidine congeners on anti-P. carinii activity, a series of pentamidine
congeners with rigid linkers (X) separating the benzamidine or benzimidazoline
groups were synthesized (I). These linkers (X) are of different ring sizes and
geometry. The in vitro anti-P. carinii activity of these compounds have been evaluated in a cell culture model at 0.1 i/M and 1.0 /M. The DNA binding affinity of
these compounds were also evaluated by measuring DNA melt temperatures.

(I) R- --X- --R

R = Amidine or Inidazoline
X = Linker

Results: A total of 10 compounds have been synthesized and tested for in vitro
anti-P. carinii activity. Three of the compounds were significantly more potent than
pentamidine at 0.1 1/M. All the compounds showed greater affinity for poly(dA-dT)
than for calf thymus DNA. The most potent compounds also showed greater
binding to DNA and poly(dA-dT) than the less potent compounds.
Conclusion: A series of conformationally constrained congeners of pentamidine have been synthesized and tested for in vitro anti-P. carinii activity in a cell
cuture model. Several compounds were found to be more potent than pentamidine at 0.1 pM. The most active compounds also showed enhanced binding to
DNA.
S31213 The susceptibility of 23 strains of Cryptococcus
neoformans isolated from CNS Fluid of AIDS patients to
seven antifungal drugs in Brazil
Francisco H. Aoki1, J. Uno2, K. Yarita2, M. Miyaji2, K. Yamamoto1, H. Taguchi2,
N.F. Nishimura1. 'State University of Campinas, Rua Iracema Salani Palazo NP
186 CEP-13086-000; 2Chiba University, Chiba, Japan
Objectives: The Minimal Inhibitory Concentration (MIC) and the Minimal Fungicidal Concentration (MFC) of 23 strains of Cryptococcus neoformans isolated from
CNSF of 16 AIDS patients with meningitis or encephalitis at the State University
of Campinas, Brazil were measured based in a method designated by National
Committee for Clinical Laboratory Standards (NCCLS). As controls, 9 strains of
C. neoformans isolated from HIV negative patients were used.
Materials and Methods: The following 7 antifungal drugs were used in this
experiment: amphotericin B (AMB), nystatin (NYS), 5-fluorocytosine (5-FC), itraconazole (ICZ), fluconazole (FCZ), miconazole (MCZ) and ketoconazole (KCZ).
RPMI 1640 was used for 7 drugs and Sabouraud dextrose broth (SDB) was
used for those except 5-FC in this experiment. Yeast nitrogen base and glucose (YNB-G) was used only to 5-FC. Each strain was diluted and yeast cell
suspensions of 1 x 103/ml and 1 x 104/ml of Colony Forming Unit (CFU) were
prepared.
Results: MIC values of each antifungal drug were as follows. When RPMI was
used, MIC values of AMB ranged from 0.5 to 2.0 /g/ml and those of NYS, 5-FC,
ICZ, FCZ, MCZ, and KCZ, from 1.0 to 8.0 pg/ml, from 5.0 to 8.0 Lg/ml, from 0.13
to 0.5 pg/ml, from 2.0 to 8.0 /lg/ml, from 0.03 to 0.25 /cg/ml and from 0.06 to 0.25
pg/ml, respectively. When SDB was used, MIC values of 6 antifungal drugs were
similar to those mentioned above.
Conclusions: There is no difference in the susceptibility between strains isolated from AIDS patients and control ones, in this experiment. Even though there
is no resistant strain, some strains grew slowly compared to the other strains
isolated at the State University of Campinas.
31214 Fever of unknown origin in 69 HIV-infected persons
Powel H. Kazanjian1, W. Armstrong, J. Katz2. 1University of Michigan/3120
Taubman Ctr, Ann Arbor, Michigan; 2Brigham & Women's Hospital, Boston, MA,
USA
Objective: To define the clinical features of FUO in HIV-infected patients at two
large US medical centers.
Design: Retrospective, descriptive study.
Methods: The 1991 Durack and Street criteria for HIV-associated FUO (unexplained fever >101" F persisting >4 weeks in outpatients or >3 days in hospitalized
patients) was used to identify patients at the University of Michigan Hospital (Ann
Arbor, MI) and the Brigham and Women's Hospital (Boston, MA) between 1989
and 1997.
Results: 69 HIV-infected persons had FUO; the mean age was 36 ~ 7 yrs
(range 21-51), 84% were male, and the mean CD4 count was 58 ~ 78 (range
0-457). The mean duration of fever was 44 ~ 52 days (range 4-365). An etiology
was identified 81 times for an individual episode of FUO in 56 patients; 36 patients
had one etiology determined (51% of patients) and 20 patients (29%) had multiple
etiologies established. The etiologies of FUO identified in these patients are in
Table 1.
Table 1. Etiologies of FUO established in 69 HIV-infected persons
Etiology No. Patients (%) Etiology No. Patients (%)
Mycobacteria 27 (39) CMV 8 (12)
MAC 22 (32) Neoplasm 6 (9)
MTB 4 (6) Histoplasmosis 5 (7)
PCP 11 (16) Other 14 (20)
Pyogenic 10 (14) No Diagnosis 13 (19)

Conclusions: Multiple etiologies are established in a significant number of
HIV-infected patients who have FUO. FUO occurs most often in the late stage of
HIV infection and MAC is the single most common etiology.
31215 1 Prevalence of fungal infections and the response to
treatment among AIDS patients treated at Colombo, Sri
Lanka
Anura Piyadigamage. 22/29 Dealwisroad Mountlavinia, Colombo, Sri Lanka
Objective: To determine the prevalence of common fungal infections in AIDS
patients and response to current treatment modalities
Background: Specific anti-retroviral drugs are either not available widely or
too expensive to use in HIV infected patients in Sri Lanka. Comprehensive knowledge of diagnosis and treatment of opportunistic infection remain the main line of
therapy for these patients.
Methods: A retrospective analysis done using the data recorded in the bed
head tickets of all AIDS patients treated at the Infectious Diseases Hospital at
Colombo, Sri Lanka from January 94 to August 97.
Results: Twenty-one in-ward patients were studied, with a mean age of 39.9
years (SD = 8.69) and a male: female ratio of 3.2:1. Oral or esophageal candidiasis was seen in 95.2% (20/21) of them and 52.3% (11/21) had only severe
oral involvement and 42.8% had oral and esophageal candidiasis. Tinea coporis
infection was seen in 33.3% (7/21) and dematophyte infection in 9.5% of patients.
Cryptococcal meningitis was seen among 14.2% (3/21) of patients. Histoplasmosis and Penicilliosis were not encountered. Eighty-five percent of candidiasis
responded to oral Ketoconazole. Cryptococcal meningitis patents were treated
with combination of Amphoteracin B and Fluconazole and the response rate was
66% during the first episode.
Conclusion: Severe Candidiasis infection is a common AIDS defining illness
in the study group and the response to oral Ketoconazole was satisfactory. Ketoconazole can be consider as the first line anti fungal in esophageal candidiasis
as it is available and cost effective.
31216 Emergence of fluconazole resistance among vaginal
candida albicans isolates from an HIV+ woman
Beth Arthington-Skaggs', D. Warren1, R.S. Klein2, J.D. Sobel3, C.J. Morrison1.
SCenters for Disease Control, 16000 Clifton Road, Atlanta, GA; 2Montefiore
Medical Center, Bronx, NY; 3Wayne State University, Detroit, MI, USA
Currently, little is known about the emergence of azole antifungal drug resistance
in vaginal Candida albicans (CA) isolates and how infection with HIV affects
the risk for the development of drug-resistant vaginitis. Fluconazole (FLU) is
routinely used prophylactically to suppress recurrent disease; however, breakthrough infections are becoming more common, and isolation of FLU-resistant
vaginal isolates has been documented in our laboratory. We have identified a
participant in the HIV Epidemiology Research Study (HERS) from whom positive
vaginal CA cultures were obtained over a 3-yr period. Antifungal susceptibility
testing identified a progressive increase in FLU minimum inhibitory concentration
(MIC) from 1.0 pg/ml to 64 pg/ml over the 3-yr period. Strain typing of the isolate recovered at each visit, by both karyotype and Ca3 fingerprinting, indicated
replacement of the FLU-sensitive strain (MIC = 1 /lg/ml) recovered at visit 1 and
visit 2 with a dose-dependent FLU-resistant strain (MIC = 16 /tg/ml) recovered
at visit 3. This strain was maintained at visit 4, but, the FLU MIC increased
to 64 pg/ml, demonstrating evolution of FLU-resistance within the same strain.
Sensitivity of ergosterol biosynthesis to FLU was determined for each consecutive
isolate, and results indicated that increased resistance to inhibition of ergosterol
biosynthesis, by FLU, corresponded with a rising MIC for FLU, suggesting either
over-expression of the lanosterol demethylase enzyme or decreased intracellular
accumulation of fluconazole. A review of this participant's medical history revealed
that the progression towards FLU resistance correlated with FLU use.
These results demonstrate the emergence of antifungal drug resistance in
vaginal CA isolates by strain replacement and by evolution of drug resistance.
This suggests that prolonged antifungal use correlates with the development of
resistance.
[ 31217 | The impact of highly aggressive antiretroviral therapy
(HAAT) on the incidence of oral candidosis
Evelina Tacconelli1, M. Tumbarello1, A. Torosantucci2, R. Caudal, A. Cassone2,
L. Ortona1. 1Malattie Infettive Universita Cattolica, Largo Gemelli, Roma;
2Batteriologia E Micologia ISS, Roma, Italy
Objectives: To evaluate the influence of HAAT with a protease inhibitor (PI) plus
two reverse transcriptase inhibitors (RTI) on the incidence of oral candidosis (OC)
in HIV+ patients (pts).
Methods: A one year prospective matched case-control study was perfomed,
considering 93 HIV+ pts with an history of recurrent OC. All pts were sub-grouped
into PI- (group 1; n = 30) and non-PI-treated (groups 2, 3, 4; n = 63). The

matching criteria were: sex; age; stage of HIV infection; number of CD4+ cells;
absence of antifungal prophylaxis. Control group 2 (n = 21) included HIV+ pts
under antiretroviral therapy with two RTI drugs. The control group 3 (n = 14)
included HIV+ pts who refused antiretroviral therapy. The third control (group 4;
n = 28) had the same inclusion criteria of group 2, but it was matched after 6
months from the beginning of HAAT in group 1. Time-to-event analysis was done
using Kaplan-Meier curves and the Cox proportional hazard model.