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

12th World AIDS Conference

Abstracts 31208-31211 537

Methods: We followed for a year 10 HIV-positive HCC (173 to 378 CD4+/mm3;
5 PPD-negative) and 20 HIV-negative HCC (800 to 950 CD4+/mm3; 10 PPDnegative), matched by age, time of exposure to the tuberculous patients, and all
BCG vaccinated). T cell function was measured by lymphoproliferative response
(LPR) against Mtb (PPD, H37Ra-proteins and LAM)-antigens. PPD skin test was
determined every 4 months in PPD-negative subjects.
Results: The HIV-positive HCC group showed no response to Mtb-antigens,
even regarding their PPD skin test status or peripheral CD4* T cell count (PPD
2.1 ~ 0.4; H37Ra 1.8 ~ 0.4; LAM 1.3 ~ 0.2). All PPD-negative HCC individuals
were re-analyzed by LPR and clinical evaluation twice or thrice for 1 year period.
50% of the HIV-negative HCC converted the PPD skin test, enhancing the LPR at
least 5-fold. However, all HIV-positive HCC followed during this time did not show
conversion of PPD skin test and no changes regarding the LPR to Mtb-antigens.
Interestingly, 5 PPD non-convertors HCC showed an increased LPR, compatible
to the PPD convertors. With this observation a new clinical evaluation was requested and one of them had pulmonary tuberculosis (HIV-positive), and another
pleural tuberculosis (HIV-negative).
Conclusions: We conclude that HIV-positive patients with Tb have a reduced
enrichment and activation of immune cell, and the failure of CD4+ limits an effective immune response against M. tuberculosis leading to a decrease in Tb control
and patient survival. These results indicate that DTH positivity criteria and the
initial chemoprofilactic intervation should be re-evaluated in high risk HIV-positive
individuals to prevent tuberculosis disease. Previous BCG vaccination is not an
indicator of PPD skin test positivity in adults.
31208 Clinical evaluation of an algorithm for treatment of
respiratory conditions in HIV-1 seropositive adults in
Kenya
Ephantus Njagi1, J. Kimani1, A. Mwathal, J. Ambani1, N. Fraser2, J.J. Bwayo1,
F.A. Plummer2. 1Nairobi University, PO Box 19676, Nairobi, Kenya; 2Manitoba
University, Winipeg, Canada
Objective: To evaluate the clinical efficacy of an algorithm for treatment of respiratory conditions in HIV seropositive adults and to determine sensitivity, specificity
and positive predictive value of the algorithm.
Methods: HIV seropositive patients presenting with respiratory complains (persistent or worsening cough and or chest pain and or dyspnoea) were enrolled in a
prospective study at a commercial sex workers clinic in Nairobi, Kenya. Informed
consent was obtained from all participants. Severely ill patients were excluded
from the study. A detailed clinical history and a physical examination were done
using a questionnaire. All consenting patients were treated with 1 gm twice-daily
oral Ampicillin and clinical condition on day 3 and 7 was obtained according to the
algorithm. Sputum samples were obtained for smear and cultured for common
bacteria and mycobacterium. Chest radiographs were done on all patients.
Results: A total of 92 patients were recruited from 1995 to 1996. 84 and 83
were seen on the 3rd and 7th day respectively. 70/84 (83%) and 58/83 (70%) had
clinical improvement on day 3 and 7 respectively. 6/14 (43%) and 8/25 (32%) who
did not improve on day 3 and 7 respectively had TB. 5/14 (36%) and 5/25 (20%)
who did not improve on day 3 and 7 respectively had pneumonia compared to
17/70 (24%) and 16/58 (28%) who improved. The sensitivity of the algorithm was
determined as 55% on day 3 and 67% on day 7. The specificity was determined
to be 89% and 76% on days 3 and 7 respectively.
Conclusion: The respiratory algorithm was found to have a low sensitivity and
therefore should be used with caution. Results from this study suggest treatment
failures on the third day should be investigated for TB.
31209 Stability of cutaneous anergy in women with or at risk for
HIV infection
Timothy Flanigan1, R.S. Klein2, D. Smith3, J. Margolick4, J. Sobel5. The Miriam
Hospital 164 Summit Avenue Providence Rhode Island; 2Montefiore Medical
Center Bronx NY; 3Centers for Disease Control Atlanta GA; 4Johns Hopkins
Hygiene & Public Health Baltimore MD; 5 Wayne State School of Medicine
Detroit Ml, USA
Objective: To study the stability of cutaneous energy over time in women with or
at risk for HIV infection.
Design: Prospective, observational study.
Methods: 436 HIV+ and 252 HIV- women in the HER Study, a multi-centered
study of HIV infection in women, had interview on demographics and HIV risk
factors, CD4+ cell measurements, and intradermal (Mantoux) skin testing with
mumps, candida, and tetanus antigens on two occasions from 12 to 158 (median 74.5) weeks apart. Anergy was defined as induration <2 mm to all three
antigens.
Results: In HIV- women, 202/233 (86.7%) of those not anergic at baseline
were not anergic at retesting, compared with 10/19 (52.6%) anergic at baseline
(P <.001). In HIV+ women, 108/169 (63.9%) anergic at baseline were anergic
at retesting, compared with 77/267 (28.8%) not anergic at baseline (P <.001).
Among initially anergic HIV+ women, CD4+ cell counts at the time of initial DTH

testing for those who remained anergic (median 248/mm3, range 3-1077) were
significantly lower than for those who subsequently reacted (median 444/mm3,
range 57-1400) (P <.001). Similarly, the CD4+ cell counts at the time of retesting
were lower (median 192/mm3, range 0-1226) for those who remained anergic
compared with those who subsequently became reactive (median 353/mm3,
range 54-1035) (P <.001). Among HIV+ women, the odds ratios for anergy at
retesting among initially anergic women compared with initially reactive women

were 9.5 (95% CI 2.8-34.4) for those with CD4+ counts <200/mm3, 3.6 (95% Cl
1.9-6.8) for CD4+ 200-500/mm3, and 1.9 (95% Cl 0.7-4.8) for CD4+ > 500/mm3.
Conclusion: Although anergic HIV+ women may subsequently become reactive, cutaneous anergy predicts a higher likelihood of anergy at retesting and lower
CD4+ levels. Stability of anergy is greatest in HIV+ women with low CD4+ counts.
Despite limitations in assessment of individuals, anergy testing may remain useful
for assessment of immune status at a group level.
1312101 Infection by atypical mycobacteria (AM) in HIV-1+ patients
Gerardo Ortega1, OscarMarcelo Bases2, S.M. Oliva2, A. Maranzana2,
M. Ambroggi3, D.V. Pugliese2, J.A. Benetucci2. 1 Vidt 2069 20 A 1425 Buenos
Aires; 2Hospital Muhiz Ward 17 Fundai/Foundation, Buenos Aires; 3Hospital
Muhiz- Microbacterias Lab. Buenos Aires, Argentina
Objective: To analize the clinical and epidemiological characteristics of infections
by AM in HIV-1+ patients.
Method: Between 1987 and 1997, 2385 people who had AIDS were examinedand followed. 141 had AM infection and 64 turned out to be assessable: 60
males and 4 females. The average age was 32.6.
Heterosexuals: 12/64; homo/bisexuals: 18/64 and IVDU: 34/64.
Results: Mycobacterium avium-intracelullare (MAC) was isolated in 57 (89%);
M. scrofulaceum (MS): 4/64 (6.25%); M. kansassi (MK): 2/62 (3.1%) and M.
fortuitum (MF): 1/64 (1.5%). In 25/64 patients MA was the first opportunistic
infection and 33/64 (51.6%) had pulmonary involvement; 25 bilateral, 6 unilateral
and 2 cavity lesions. The 33 patients had positive sputum. Other clinical forms
were: bacteriemia in 26/64 (40.6%), cutaneous in 3/64 (4.7%), ganglionar in 2/64
(3.12%), articular 1/64 (1.5%) and abdominal 1/64 (1.5%). The blood culture
was positive in 38 patients, in 26 of them it was the only isolation, in 9 it was
accompanied by sputum isolation and in 3 by culture of ganglionar biopsies.
The germ found was MAC in 35 cases, MS in 2 and MK in 1. The CD4 cells
count were carried out in 57/64 cases, all of which were below 200 cells and
66.6% were below 50 cells. 76.5% of patients (49/64) had died, being the average
survival 4.2 months.
Conclusions: 1) Low incidence of infection by AM in our experience. 2) High
mortality. 3) Association to severe immunological deterioration. 4) High incidence
of bacteriemium and pulmonary forms. 5) High usefulness of blood culture as a
diagnosis method.
31211 1 HIV protease inhibitors have a direct anti-Candida effect
by inhibition of Candida aspartyl proteinase
Antonio Cassone1, D. Adriani2, E. Tacconelli3, R. Cauda3, F. De Bernardis2.
1Laboratorio Di Batteriologia, 2lstituto Superiore Di Sanita-Roma; 3Malattie
Infettive Universita Cattolica, Roma, Italy
Background and Objectives: The use of HIV protease inhibitors (PI) causes a
dramatic reduction in the incidence of mucosal candidosis, that is interpreted as
due to the improvement of immune function. Since: i) the target of HIV-PI is an
aspartyl proteinase; ii) a family of secretory aspartyl proteinases (SAP) is also
possessed by C. albicans and plays a role in mucosal candidosis, we examined
whether HIV-PI inhibited SAP and exerted a curative anti-candidal activity in a
mucosal experimental model.
Methods: SAP production during in vitro growth of C. albicans was assessed
both by antigen production with ELISA and enzimatically using BSA as substrate.
An estrogen dependent rat vaginitis was used as a model of mucosal candidosis.
HIV-PI were used in a concentration range of 1-100 p/M. Pepstatin A (PA), a
prototypic SAP inhibitor, and fluconazole (FZ), an effective anticandidal agent,
were used as positive controls. All drugs were administered intravaginally 2 hours
before and 1, 3, 5, days after Candida challenge. Drug vehicle was used as
negative control.
Results: Indinavir, ritonavir and PA, but not FZ, exerted a marked dose-dependent inhibition (>80% by both PI at 10 tAM) of SAP activity in vitro. In the rat
model, HIV-PI greatly accelerated the fungal clearance from the vagina. In a
typical experiment, on day 3 after challenge with 107 C. albicans cells, the vaginal
fungal cell counts were >100, 4.6 ~ 1, 4.1 ~ 1, 6.4 ~ 3 and 5.6 ~ 3 (x103/ml
of vaginal fluid; mean ~ SE, 5 rats per group) in controls (no PI, no PA, no
FZ), indinavir-, ritonavir-, PA- and FZ-treated rats, respectively. The differences
between PI-treated and untreated rats were as statistically significant (P < 001,
Student's ttest) as those between PA- and FZ-treated and untreated animals. On
day 21, all PI-treated rats had <100 whereas both controls and FZ-treated rats
had >103 cells/ml vaginal fluid.
Conclusion: In an experimental mucosal infection, HIV-PI have a therapeutic anticandidal effect which appears to be mediated by inhibition of Candida
SAP activity. This could add to the immunological improvement in explaining the
marked reduction in the episodes of mucosal candidiasis in HIV patient under PI
treatment regimens.
31212 Conformationally constrained pentamidine congeners as
anti-pneumocystis carinii agents

Tien L. Huang1, B. Tao1, Q. Zhang1, L. Jackson1, A.T. White1, S.F. Queener2,
1.0. Donkor3. 1Xavier University of Louisiana College of Pharmacy New Orleans,
LA; 2Indiana University Schoolf of Medicine, Indianapolis; 3 The University of
Tennessee,, USA
Background: The use of pentamidine in the treatment of AIDS-related Pneu