Abstract Book Vol. 2 [International Conference on AIDS (14th: 2002: Barcelona, Spain)]

138 Abstracts WePeC6232-WePeC6235

XIV International AIDS Conference

changes are associated with a change in the rate of tryptophan degradation (expressed as the kynurenine to tryptophan ratio; kyn/trp) as an estimate for the activity indoleamine (2,3)-dioxygenase (IDO). IDO is induced during immune stimulation particularly by interferon-gamma and potentially diminishes T-cell responsiveness.
Methods: Plasma levels of tryptophan, kynurenine and neopterin were collected
pre-therapy and 6 months post-initiation of therapy in patients with HIV-1 RNA
levels of less than 1000 copies/ml 6 months after initiation of ART
Results: Before ART, the 45 patients had decreased tryptophan and increased
kynurenine concentrations compared to healthy controls. During ART, average
tryptophan levels increased, in the same time kynurenine and kyn/trp decreased
(p<0.001), however, not to normal levels. Pre-therapy tryptophan concentrations
correlated inversely with neopterin, kynurenine correlated with viral load and
neopterin but not with the CD4 cell count. The kyn/trp ratio positively correlated
with neopterin (rs = 0.60), with virus load (rs = 0.37) and very weakly with CD4+
cell counts (rs = 0.30). The change of the kyn/trp ratio during ART correlated more
strongly with the change of neopterin levels (rs = 0.49, p = 0.001) than with the
change of HIV RNA levels and only weakly with the change of the CD4 cell count.
Conclusion: Tryptophan degradation is increased in HIV infection and partially
reversed under ART The data indicate that HIV production eliciting T-cell activation represents the main stimulus for activating IDO. Hyperactivation of IDO may
be a critical link between immune activation and loss of T-cell functional responsiveness in patients.
Presenting author: Robert Zangerle, HIV Unit, University Hospital, Anichstrasse
35, A6020 Innsbruck, Austria, Tel.: [phone], Fax: [phone],
E-mail: [email protected]
WePeC6232I Factors associated with normal CD4:CD8 ratios in
HIV infected persons
P. Menezes1, S. Napravnik2, W.C. Miller1, J.J. Eron Jr.1. 1Schoolof Medicine,
University of North Carolina, University of North Carolina, CB# 7030, 547
Burnett Womack, Chapel HI//, NC27599, United States; 2Department of
Epidemiology, University of North Carolina, Chapel Hill, United States
Background: HIV infected persons uncommonly achieve normal CD4:CD8 ratios, even with antiretroviral therapy. We retrospectively examined potential factors
associated with normal CD4:CD8 ratios in HIV infected persons.
Methods: Cases (N=102) with 3 or more normal CD4:CD8 ratios (0.9 to 4.8)
were identified from -1300 HIV-infected patients seen between 6/00-8/01. Controls (N=30) were selected from patients with CD4:CD8 ratios <0.9 on 6 or more
occasions seen in the same period. Date of first normal/abnormal ratio was used
as date of comparative analysis (DCA). Data from the time of diagnosis (or earliest pre-antiretroviral therapy (ART) time point) were also collected.
Results: Age, race, gender, months from diagnosis to first ART and months to
DCA were not significantly different in cases and controls. HIV RNA at diagnosis/pretreatment and percentage of patients on therapy at the time of analysis
(88%controls, 91%cases) were similar. At diagnosis, CD4 counts were significantly higher in cases than controls (mean461 (S.D.238) vs. mean211 (S.D.176)
p<0.001) though CD8 counts were similar (mean628 (S.D.239) vs. mean484
(S.D.425) p=0.6). As expected, at DCA, CD4 counts were significantly higher in
cases (mean850 (S.D.361) vs. mean313 (S.D.141) p<0.001). In contrast, CD8
counts in controls were substantially higher than cases (mean1044 (S.D.433)
vs. mean680 (S.D.271) p<0.001) and higher than their corresponding baseline value (p=0.012). Cases achieved HIV RNA <400copies/ml more commonly
(75%vs.47%, p=0.022) and experienced fewer unique ART regimens (3.5 vs. 5,
p=0.008).
Conclusions: In our study patients with normal ratios had higher CD4 counts at
diagnosis and were more likely to have viral suppression on therapy. CD8 counts
were substantially higher in controls despite similar levels at diagnosis and similar
proportions treated in the two groups potentially representing immune activation
in the setting of on-going viral replication.
Presenting author: Prema Menezes, University of North Carolina, CB# 7030,
547 Burnett Womack, Chapel Hill, NC27599, United States, Tel.: [phone], Fax: [phone], E-mail: menez001 @ med.unc.edu
WePeC6233 Humoral response to hepatitis B vaccination and
its relationship with T CD4+ cell subsets in HIV-1
infected subjects
A.P.R. Veiga, S. Komninakis, N. Orii, R. Stellin, J. Casseb, A.J.S. Duarte. School
of Medicine of Sao Paulo University, Av. dr. Arnaldo 455 room 2345, 01246-903,
Brazil
Background: HIV/Hepatitis B co-infected subjects are at higher risk for chronic
hepatic disease and hepatocarcinoma. Thus, hepatitis B immunization is a formal
indication in HIV-infected individuals.
Methods: In order to determine the immunological status of the patients that may

result in best vaccine efficacy, TCD4+ cells subset and the anti-hepatitis B antibody levels were measured.
Results: 38 individuals were immunized (Euvax, LG Chemical, Korea), with
with 40mcg/dose at days 0, 30 180 days. All HIV-infected subjects were on
HAART, mean of 284 days. These patients were subdivided in 3 groups (T CD4
cells/mm3): Group 1: CD4+> 500, Group 2: CD4 200-499, Group 3: CD4 <200.
We also tested 28 volunteers HIV and hepatitis B seronegative controls. Statisti
cal analysis used the Mann-Whitney test (* when p value <0.05 was considered
statistically significant). Antibody levels were measured by commercial kit (EIA,
DiaSorin, Italy). Table 1 shows the pre-vaccination TCD4 cells counts and antiHBs levels.
Pre-vaccination >500 (n=6) 200-499 (n=25) <200 (n=7) Controls (n=28)
HIV + HIV+ HIV+
T CD4+ cells n. (%) 724 (32.5) 355 (20) 131 (11) 964 (43.5)
T CD4+ naive cells n. (%) 386 (17)* 149 (8.4)* 32 (3) * 441 (21)
T CD4+ memory cells n (%) 339 (15.6)* 198 (10.6)* 128 (11)* 505 (23.3)
RNA HIV load (log 10) 3.15 3.15 3.8 -
Anti-HBS> 1OUI/L (%) 5/6 (83) 12/25(57) 2/7 (28.5) 95%
Conclusions: 1. The seroconversion rate as defined by anti-HBS titers > 10 UI/L
in the HIV-infected individuals ranged from 28.5% to 83% and the control group
was 95%, suggesting a certain correlation with the pre-vaccinal TCD4+ cell status; 2. Pre-vaccinal HIV RNA viral load was similar in the 3 HIV groups, having
no predicitive value for the evaluation of the anti-hepatitis B response. 4. There
was a direct correlation between seroconversion rate and the pool of naive TCD4
cells, underscoring the importance of this subset to the generation of immune response to new antigens; 5. Therefore, vaccination against hepatitis B virus should
be preferentially offered to HIV+ individuals with either TCD4+ cells above 200
cells/mm3 or with more than 150 naive T CD4 cells.
Presenting author: Ana Paula Veiga, Av. dr. Arnaldo 455 room 2345, 01246 -903, Brazil, Tel.: [phone], Fax: [phone], E-mail: gppierre
@ uol.com.br
WePeC6234 Characterization of HIV-1 genome from a patient
who is western blot weak positive and HIV
genome undetectable by PCR for 18 months
M.K. Kondol, T.S. Shimal, K.S. Sudo1, M.N. Nishizawa1, S.I. Iwamuro2,
TO. Okabe2, M.I. Imai1. 'Department of Virology, Kanagawa Prefectural Public
Health Laboratory, 1-1-1 Nakao Asahiku, Yokohama,241-0815, Japan;
2Kanagawa Prefectural Atsugi Hospital, Atsugi, Japan
Background: When the western blot (WB) gives an indeterminate result or very
weak positive results, serial testing of additional serum samples will usually clarify
the situation. But in one case (GM43), serial testing give the same weak positive
results for long period and HIV-1 genome (HIV-1 proviral DNA in peripheral blood
mononuclear cells (PBMC) was detected 18 months later and the viral RNA was
detected 53 months later. To investigate the slow course of infection, we characterized HIV-1 genome from the patient GM43.
Methods: Serum samples were tested for HIV-1 antibodies by an enzyme immuno assay, gelatin particle agglutination assay, and WB. HIV-1 proviral DNA
was detected by nested PCR and HIV-1 RNA in plasma was detected by Amplicor HIV-1 Monitor kit (Roche) by ultra sensitive methods.
The full-length HIV-1 proviral DNA in PBMC (GM43) was amplified by nested
polymerase chain reaction (PCR) in overlapping fragments and fully sequenced.
Nef/LTR region of HIV-1 from the patient (GM43) serial PBMC and plasma samples were amplified by PCR and sequenced.
Results: and discussions: The full-length sequence of HIV-1 proviral DNA from
GM43-18 (18 month since 1 st bleed) revealed 84 nucleotides deletions in nefLTR overlap region, and no other significant deletions were detected as compared
with reference HIV-1 (AE.TH.CM240) sequence. HIV-1 progenome from GM43 -23 (57 month since 1 st bleed) had 391 nucleotides deletions in nef alone region
and nef-LTR overlap region, and HIV-1 RNA in plasma had the same deletions.
The Sydney Blood Bank Cohort study indicates the reduced pathogenic potential
of Nef defective HIV-1 (subtype B). Follow up studies on the patient GM43 (subtype A/E) will provide additional information regarding the contribution of Nef to
HIV-1 (subtype A/E) pathogenesis.
Presenting author: Makiko Kondo, 1-1-1 Nakao Asahiku, Yokohama,241 -0815, Japan, Tel.: [phone], Fax: [phone], E-mail: macoco
@ bekkoame.ne.jp
WePeC6235 A synergistic effect of human immunodeficiency
virus and cytomegalovirus infection/reactivation
on response to HAART and plasma CD8/CD38 but
not CD4 cell populations in patients with primary
human immunodeficiency virus Infection
L. Goh1, M. Bernard2, F Lampe3, G. Janossy3, D. Cooper4, P. Cunningham4,
J. Andersson5, S. Kinloch3, H. Mcdade1, L. Perrin2, A. Capt6.
SGlaxoSmithKline, GlaxoSmithKline Research and Development, Greenford,
Middlesex, United Kingdom; 2eHpital Cantonals Genve, Switzerland; 3Royal
Free and University College Medical School London, United Kingdom;
4 nvest of New South Wales, Sydney Australia; 5Karolinska Institutet,
Huddinge, Sweden; 6Roche Molecular Systems, New Jersey United States

Background: A synergistic effect between HIV and CMV infection on more rapid
HIV disease progression has been proposed. We studied the effect of CMV on
indices of HIV disease before initiation of treatment and after 28 Wks of HAART
in PHI patients.
Methods: This was a multi-centre study in treatment-naive PHI pts. Blood samples were taken at baseline (BL) and regular intervals from the start of treatment