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

Tu.B.2240 - Tu.B.2245

Tuesday July 9, 1996

Tu.B.2240
PROGNOSTIC FACTORS FOR DELAYED TYPE HYPERSENSITIVITY ANERGY IN HIVINFECTED PERSONS.
Kityo Cissy*, Opit C*, Loughlin A", George K**, Busingye J*, Oluput G*, Okiror J1,
Mugyenyi P*,Whalen C., Mugerwa RD* *, Ellner J**. *Joint Clinical Research Center;
Kampala, Uganda; Case Western Reserve University, Cleveland, OH, USA; ***Makerere
University, Kampala, Uganda.
Objectives:To determine the prevalence of delayed type hypersensitivity anergy in HIV- I
infected adults in Uganda and identify factors related to anergy which may be related to
risk ofTB infection, progression to AIDS and overall mortality
Methods: HIV- I infected Ugandan adults (n=3237) had a Mantoux test as enrollment criteria into a clinical trial of TB preventive therapy Prevalence of anergy is based on Mantoux
tests placed at enrollment. Baseline correlates for anergy and long-term follow-up (medical
history and physical exams, CD4 cell counts, complete blood cell counts, 132 microglobulins)
comparing the progression of disease, survival and incidence of opportunistic infection (01)
was done. Follow-up was completed on 332 Mantoux reactors and 331 anergic patients
enrolled into the placebo arms of the trial.
Results: Prevalence of anergy in this HIV- I infected cohort was 33.8%. At baseline, 57-59%
of anergics vs. 10-43% reactors had a history of genital sores or papular rash (p<.00 I). Also
at baseline, anergics were more immune-compromised compared to non-anergics: CD4
count 403 vs 557 cells/uL (p=0.0004); total lymphocyte count 1980 vs 2230 cells/uL
(p=0.002) and WBC count 5250 vs 5670 cells/uL (p=0.01 ). By I12 months, approximately
54 58% of the anergics vs. 42-46% of the non-anergics had presented with ora thrush or a
papular rash (p=0.03). At I 2 months, CD4 counts and WBC still remained significantly
lower in anergics. Incidence of thrush persisted in anergics by month 24, 56% vs 44%
among reactors (p=0.05). No other Ois were more frequent in anergics as compared to
reactors. The incidence of suspected TB for anergics and non-anergics was 2.5/ 100 personyears vs. 4.0/I 00py Overall, all cause mortality was in excess among anergics (6.8 I / 100 py)
vs non-anergics (4.88/100I OOpy RR= 139).
Conclusions: TB is a common complication of HIV infection, therefore screening and providing preventive therapy forTB seems warranted. Anergy is related with decreased immunity increased rates of opportunistic infections, and higherTB incidence and all cause mortality rates. With a high prevalence of anergy in HIV infected adults, the ability to detect TB
infection is limited:; therefore givingTB prophylaxis to such patients is indicated.
Cissy Kityo, Joint Clinical Kesearch Centre, PO Box 10005, Kampala, Uganda, phn: 256-41 -270-622, fax: [phone] E-mail: jcrc(@mukla.gn.apc.org
Tu.B.224 I
NATURAL HISTORY OF HIV DISEASE IN CHILDREN WITH VERY LOW CD4 LYMPHOCYTE COUNTS
Pelton, Stephen I.*, Hsu H**, Reddington C"*, Cohen J**, Caldwell B***. *Boston University
School of Medicine, Boston, MA; *MA Dept of Public Health, Boston, MA: **CDC,
Atlanta, GA; and the PSD Clinical Consortium
Objective: To describe the natural history of HIV infection in children with <100 CD4 lymphocytes/cu mm (CD4< 100).
Methods: Through the Pediatric Spectrum of Disease Project, medical records of perinatally
HIV exposed children are abstracted every 6 months in 8 regions. Perinatally infected children over age I year with CD4 counts < 100 were included in this analysis if the previous
count was > 100. We examined factors associated with short and long term survival, which
were defined as death <18 months and survival > 18 months after CD4< 100, respectively.
Results: Of 2,900 HIV-infected children, 330 had a CD4 count which fell below I100; 97
were I -2 years old, 92 were 3-4 years, and 14 I were 5 + years at the first CD4< 100. After
CD4< 100, MAI was the most common opportunistic infection (Ol), occurring in 39 (I 2%)
children with mean survival time of seven months after 01 diagnosis, followed by Candida
esophagitis occurring in 28 (8%) with survival of 9 months, PCP in 15 (5%) with I I months
survival and CMV in 10 (3%) with 5 months survival. Follow-up time after CD4< 100 averaged 14 months (range I1-79), with 71I children dying within 18 months. Of the remaining
259, 101 survived > 18 months, and 23 of these survived > 36 months. Factors associated
with short survival time included encephalopathy (Risk Ratio (RR) 2.6, 95% Confidence
Interval (CI) I.f-3.7), failure to thrive (RR 2.2, 95% ClI 1.4-3.4), and oral candidiasis (RR 2.4,
95% ClI 1.4-4. I;. Par otitis was associated with long survival (RR 1.4, 95% Cl I. I-1.8).
Conclusion: M ny children are surviving for one or more years with severe immunosuppression, highli1 sting the importance of research in the prevention of opportunistic infections for this group.
Stephen I. Pelton, M.D., Boston City Hospital/Boston University School of Medicine
Pediatrics, 8 I 8 Harrison Ave - Finland 5 I 2, Boston, MA 02 118; (Ph) 617-534-7408, (Fax)
617-534-5806, (email) [email protected]
Tu.B.2242
DESCRIPTIVE AND MOLECULAR EPIDEMIOLOGY OF HIV-I INFECTION AMONG
WOMEN IN HAWAII
Shikuma CM, NerurkarVR, Dashwood W-M, Hoffmann PR, Kindrick AV Heath-Chiozzi M,
Yanagihara R Hawaii AIDS Research Program, University of Hawaii at Manoa, Honolulu, Hawaii
Objective: To determine the natural history, clinical manifestations and virological correlates
among HIV- I -infected women in Hawaii.
Methods: Extensive clinical and epidemiological parameters, as well as laboratory results of
T-cell subsets, tests for HBV, HCV, HTLV, STD and TB, were analyzed for 17 HIV- I-infected
women. In addition, a 338-nucleotide region spanning the principal neutralizing domain (V3
loop) of the gp I 20-encoding en gene of HIV- I was amplified and sequenced from uncultured PBMC.
Results: Of the 17 women, I 4 were infected with HIV- I between 199 I -95, 2 between
1986-90 and I between 1981-85. 13/I 7 were classified as Caucasians and 4 as Asian/Pacific
Islanders.The women ranged in age from 24-45 years (mean, 35.2 years), and all but three
were born in the U.S.A. 9/I 7 (53%) were IVDU and the remainder admitted to having had
sex with an IVDU or bisexual partner All were asymptomatic, except one woman who had
wasting and lymphoma. 3/17 were PPD positive and one had tuberculosis. CD4 counts
were 250 cells/L in 6 (35.2%), 25-500 in 3 (I 7.6%), 50 -750 in 6 (35.2%) and > 75I in 2

(I 1.8%) women; and CD4:CD8 ratios were 0.5 in 9 (52.9%), 0.6-1.0 in 7 (41.2%) and
I. I in I (5.9%) women. 6/I17 and 5/I17 were seropositive for HBV and HCV, respectively
6/17 (35.2%) had an abnormal pap smear. None of the HIV- I-infected women had syphilis

or other STD at the Oime of enrollment. Sequence analysis revealed HIV- I subtype B in all
women. However GPGR motif of the V3 loop was altered to either GPGK, APGR, GPGS,
GPSK, GPGG or GQGR in 13/17 (76%) women, compared to 10/48 (20.8%) virus-infected
homosexual men in Haisaii. Phylogenetic analysis, employing the maximum parsimony and
neighbor-joining retlhd i Ivalidated the presence of HIV- I subtype B in our study population.
Conclusions: All I/ '^,,xen had HIV- I subtype B.These data conform to our earlier results
on 48 HIV I inife.ted honmosexual men in Hawaii.The significance of the change in the
GPGR motif in 76% of virus-infected women warrants further investigation.
[This work was supported by an institutional grant from the NCRR-RCMI Program, NIH
(G 12RR/AI -0306 I-10)].
C.M. Shikuma, M.D., Hawaii AIDS Research Program, Leahi Hospital, Young Building, 6th Fir.,
3675 Kilauea Ave., Honolulu, Hawaii 968 I 6, U.S.A.; Tel: [phone] I; Fax: [phone] email: nerurkar0hawaii.edu
Tu.B.2243
DIFFERENT SI PHENOTYPE OF HIV-I IN BLOOD AND SEMEN.
Rousseau Sylvette*,Tamalet C*, Duclos N*,Tivoli N*,Tourres C*, Lafeuillade A". *Virology
Department,Timone Hospital, **General Hospital Toulon, France
Objective:To compare biological phenotype of blood and semen HIV- I isolates.
Methods: Cross-sectional study of HIV- I isolates from blood and semen of 19 HIV- I infected individuals, 6<200 CD4+, II with 200-500 CD4+, 2>500 CD4+.Two blood fractions
(PBMC, plasma) and 2 semen fractions (white cells, cell-free fluid) were tested for virus
detection by quantitative (q) cultures, qDNA and qRNA PCR. SI phenotype was investigated using MT-2 cells.
Results: HIV coculture firom PBMC was positive in 16 subjects (84%) and from plasma in 6
subjects (32%): PBMC DNA PCR and plasma RNA PCR were positive in the 19 subjects
(100%). HIV- I was recovered from seminal cells in 7 subjects (37%) and from seminal cellfree fluid in I patient with less than 200 CD4+. 5 subjects (26%) had SI isolates in blood, 4
from PBMC and 2 from plasma isolates. None seminal cell isolate was SI.The only subject
harbouring a seminal cell-free fluid SI isolate also had a plasma SI isolate while PBMC and
seminal cell isolates of whom were NSI.
Conclusions: This patient's observation suggests that seminal cell-free fluid compartment is
not a separate one, independent from plasma compartment, and turnover of provirus in
PBMC and seminal cells is probably slower than that of free HIV- I in plasma and seminal fluid.
Dr Sylvette Rousseau,Virology Department, H6pital Timone, Bd Jean Moulin I 3385
Marseille Cedex 5 France.Tel:[phone]. Fax: [phone]
Tu.B.2244
CHANGES IN B CELL PHENOTYPE IN HIV POSITIVE INDIVIDUALS
Hammond GW Conway B,2 Patenaude R2 Janmohamed F, Montaner ISG.2
O'Shaughnessy MV,2 Dawood, Magdy R.2 I Cadham Provincial Laboratory Winnipeg, MB,
Canada; 2British Columbia Centre for Excellence in HIV/AIDS,Vancouver, BC, Canada
Objectives:To evaluate changes in B cell phenotypes as surrogate markers of HIV disease
progression.
Methods: Anticoagulated blood was obtained from 15 HIV-infected and 6 uninfected individuals. Plasma was removed and HIV viral load was measured in the infected individuals
using the Amplicor HIV- I Monitor assay (Roche Diagnostic Systems). CD4 cell counts were
also determined by conventional flow cytometry in these individuals. In all samples, B cells
were purified from isolated PBMCs using magnetic beads coated with anti-CD I 9. B cells
were stained with a mixture of anti-CD22 Tri-colour, anti-p FITC and anti-g PE. The presence of the double positive p/g phenotype (expressed as a percentage of total B cells) was
measured by flow cytometry
Results: Only I/6 uninfected individuals carried >5% double-positive B cells, as compared
with 9/ S15 infected patients. No clear association was noted with CD4 cell depletion (6/8
with CD4 >200 vs. 3/7 with CD4<200 cells/pi). Plasma viremia was measurable in 13 individuals. In 4 with <20,000 copies/ml, the mean double positive count was 4.4 (2.78 - 8.0)%.
In those with higher loads (median 79543), the double positive cell count was 63.65%
(range 2.4 - 98.6, median 71.2%).
Conclusions: In this small pilot evaluation, B cell phenotype seems to be somewhat correlated with plasma viremia, but less so with CD4 cell count.The precise nature and magnitude of the association awaits further study
M Dawood, 750 William Ave., Winnipeg, MB, R3C 3Y I Canada Fax: [phone]
Tu.B.2245
NATURAL HISTORY OF HIV-INFECTION IN THE FORMER USSR
Edward Karamov, N.G.Yaroslavtseva, VV Lukashov, P G. Rytik, A.P Kozlov, M.Yu. Shchelkanov.
D.V. Martovitskii,V.F. Eremin, S.A. Chaplinskas. Ivanovsky Institute of Virology Moscow, Russia
Objective:To investigate geno- and serotypes of HIV-I variants in Russia. Byelorussia and
Lithuania.
Methods: Sera from 100 HIV-I infected patients were tested in an ELISA with a set ofV3
synthetic peptides and serum HIVV3 RNA was amplified and sequenced.
Results: Sequence comparison of the envelope V3 region among specimens tested revealed
a 2-29% range of nucleotide divergence with an average of 19%. Phylogenetic analysis clustered the V3 sequences recovered with subtypes A.B.C.D.G and F. All sequences fr-om the
homosexual men were shown to belong to subtype B and most of the heterosexually
infected individuals were of subtypes A and C. Sequences from the parenterally infected
individuals were more heterogeneous. In the peptide ELISA three reactivity patterns were
found. Serum samples from most homosexual men showed reactivity to peptides pl 08 or
p Il 0 representing V3 amino acid sequences found in US/West European HIV-I isolates.
Most of serum samples from heterosexual patients were reactive to peptide pl 69.
Parenterally infected patients were peak reactive to pl 68.
Conclusions: Factor analysis allowing to visualize results ofV3 serotyping shows great heterogenicity of subtype B found in homosexual population. Genetically and antigenically distinct HIV-I variants were found in Russia. Byelorussia and Lithuania, introduced simultaneously in the mid-1980s.This diversity was shown to be associated with the route of transmission rather than with the geographical origin of the infected patients.
E.V. Karamov, 16 Gamaley Street, 123098. Moscow, Russia.Tel.: [phone]
Fax: [phone]

307