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

XIV International AIDS Conference

Abstracts ThPeA7150-ThPeA7153 371

Methods: All cases of newly diagnosed AITD in 6 HIV treatment centres were
identified. Data was collected on the clinical spectrum, thyroid function, CD4 count
(cells/mi), plasma HIV RNA viral load (VL), thyroid antibody (Ab) and technetium
scans. Ab to microsomal, thyroglobulin and thyroid stimulating hormone receptor
(TSHR) were also assayed from paired archival samples by one laboratory.
Results:10 pts with thyrotoxicosis (9 female and 1 male) were identified. Median
age 37 (range 33-53). All pts were taking HAART The median CD4 count prior to
HAART commencement was 50 (range 1-215). The median time (months) from
first VL <50 to diagnosis of AITD was 14 (range 14-32) and mean increase in
CD4 count was 311 (44-680). Clinically, Graves' Disease (GD) was diagnosed in
9 pts (8 female, 1 male). One GD pt had a rarely seen association of profound
secondary hypoadrenalism (plasma ACTH < 20ng/1). 2 pts developed GD 8-12
months after childbirth. 1 pt developed autoimmune thyroiditis. She became profoundly hypothyroid 3 weeks after thyrotoxic phase, giving a Hashi-toxicosis picture. 8 pts showed sequential rise in Ab titres. Very high TSHR blocking Ab titres,
not previously recorded, were observed in 2 pts (73.5 and 48.5, range >1,<2
stimulation index).
Conclusions: Knowledge of prevalence data of AITD in HAART nalive patients
is needed. However, our observations of varied and rare AITD phenotypes, in a
credible temporal and epidemiological setting, appear unlikely to be chance observations and the overlap of their natural history with the main phase of naive
CD4+ lymphocyte release, makes IR-AITD a biologically plausible phenomenon.
Detecting autoreactive clones during IR may improve understanding of autoimmunity
Presenting author: fabian chen, 6 arran road, catford, london, se6 2nl, United
Kingdom, E-mail: [email protected]
ThPeA7150 The impact of HAART on HIV-specific CD8+ cell
responses in subjects with moderately advanced
HIV infection
E. Connick1, R. Schlichtemeier1, A. Mian1, R. Kim2, R. Bosch2, M. Lederman3,
A. Landay4. 1 University of Colorado Health Sciences Center, Division of
Infectious Disease, Denver, CO, United States; 2Harvard School of Public
Health, Boston, United States; 'Case Western Reserve University, Cleveland,
United States; 4Rush Medical College, Chicago, United States
Background: To assess the impact of HAART on HIV-specific CD8+ cells, 19
subjects enrolled in ACTG study 315/375 with 100-300 CD4+ cells were evaluated up to 3 years after initiation of HAART
Methods: ELISPOT assays for IFN-gamma were performed using PBMC stimulated by autologous B-cell lines infected with vaccinia recombinants that express
Env, Gag, Nef, Pol, Env-Gag-Pol, and control antigens.PBMC were stained with
11 HIV peptide/MHC tetrameric complexes; ELISPOT assays were performed for
the same peptides.
Results: ELISPOT responses to HIV antigens were not significantly correlated
with plasma HIV RNA (range -0.23 to 0.27) at baseline. ELISPOT responses to
all HIV antigens increased significantly at week 4 and then declined. ELISPOT
responses to HIV peptides paralleled those to HIV antigens. In 10 subjects evaluated at 1 year, there was no difference between ELISPOT responses to Env-GagPol (median=65 spot forming cells [SFC]/106 PBMC) compared to baseline (median=56 SFC/106 PBMC). In 6 subjects on therapy for 3 years with sustained HIV
suppression, there was no difference in ELISPOT responses at baseline, 1 and 3
years. CD8+ tetramer staining cells were detected in 3 of 17 subjects at baseline.
Tetramer staining rapidly declined in 2 subjects who achieved viral suppression;
ELISPOT responses to these peptides transiently increased or remained stable.
Conclusions: HAART had little long-term impact on HIV-specific CD8+ cell
ELISPOT responses. The early transient increase in ELISPOT responses on
HAART may be due to redistribution of HIV-specific cells with a short half-life
from lymphoid tissues. Subsequent stability in ELISPOT responses up to 3 years
may be due to exposure to low levels of virus or to a long half-life of responding
cells. The pattern of ELISPOT responses on HAART differs from the decline seen
in tetramer reactivity suggesting these assays are not equivalent.
Presenting author: Elizabeth Connick, 4200 E. 9th Avenue, UCHSC Box B168,
Division of Infectious Disease, Denver, CO 80262, United States, Tel.: [phone], Fax: [phone], E-mail: liz.connick@ uchsc.edu
ThPeA7151 Immunological and virological correlates of
intermittent interleukin-2 (IL-2) therapy
S. Ghezzi, F. Neri, C. Fortis, F. Pacciarini, G. Vallanti, L. Soldini, S. Nozza,
A. Lazzarin, G. Tambussi, G. Poli. San Raffaele Scientific Institute, San Raffaele
Scientific Institute, Italy
Background: Intermittent IL-2 administration plus antiretroviral therapy (ART) to
infected individuals stably restores the numbers of circulating CD4+ T lymphocytes and improves immune function.
Methods: 61 HIV individuals with 200-500 CD4+ T cell/p l were enrolled in a con
trolled study of 3 IL-2 plus ART regimens or ART alone. Twentyfive patients (12
receiving ART+IL-2, and 13 receiving only ART) have been investigated in detail
thus far after a year of IL-2 therapy. PBMC-associated sjTRECs and HIV-1 DNA
levels were measured by real-time PCR (TaqMan). Standard HIV isolation from
PBMC was performed. Viral phenotype (SI/NSI on MT-2 cells) and chemokine coreceptor usage on U87 cells coexpressing CD4 and CCR1 or CCR2b or CCR3 or
CCR5 or CXCR4 were defined.

Results: A sustained significant increase in circulating CD4+ T lymphocytes
was observed in patients receiving ART+IL-2 vs. those receiving ART alone (p=
0,0006 Student's T test). SjTREC levels were superimposable in the two groups
at entry and decreased after 12 months in patients receiving either ART+IL2
(p=0,00026) or ART alone (p=0,0003). CD4-associated HIV-1 DNA decreased
in individuals receiving ART+IL-2 but not in those treated with ART alone. The
frequency of HIV isolation in the first 20 patients examined thus far decreased
from 70% to 35% at entry and after 12 month, respectively. This pattern was not
observed in the ART-treated patients tested thus far. Four primary isolates obtained at entry in individuals treated with ART+IL-2 were SI and included 2 X4, 1
R5X4dualtropic and 1 R3R5X4 multitropic viruses. All primary isolates from patients receveing ART alone were NSI at entry
Conclusion: No increase of plasma viremia or cell associated HIV DNA levels were observed in individuals receiving ART+IL-2. A comparable decrease of
sjTREC was observed in ART-treated individuale receiving or not IL-2, suggesting that cytokine therapy may partially reconstitute the pool of peripheral naive T
cells.
Presenting author: Silvia Ghezzi, San Raffaele Scientific Institute, Italy, Tel.:
[phone], Fax: [phone], E-mail: [email protected]
ThPeA7152 ILongitudinal follow-up of patients with discordant
responses to pi-based HAART
S. Sufka1, G. Ferrari1, G. Tomaras1, T. Wrin2, S. Fiscus3, V. Gryszowka1,
V. Teaberry1, N. Hellmann2, K. Weinhold1, C. Hicks1. IDuke University Medical
Center, 727 glen hollow dr, durham nc, 27705, United States; 2 ViroLogic, Inc.,
So. San Francisco, CA, United States; 3University of North Carolina, Chapel Hill,
NC, United States
Background: We have previously shown that patients with discordant CD4N/VL
responses to HAART have decreased viral replicative capacity, predominance of
R5 phenotype, decreased cellular activation, and enhanced CD8 responses to
gag and tat.
Methods: 30 HIV+ patients on PI-based HAART were studied in 3 groups: Failure
(F): VL increasing, CD4 decreasing; Discordant (D): VL 500-5000, CD4 >200
and increasing over >2 yr; Success (S): VL <50, CD4' >200 and increasing over
>2 yr. Group D subjects returned 1 year after initial study visit to assess changes
over time in: CD8 responses to gag, rev, tat, vpr by IFN-y ELISpot; noncytolytic
CD8 activity by a quantitative CD8+ suppression assay; T-cell subsets and CD38
antibodies bound per cell quantitated by flow cytometry; R5/X4 phenotype; phenotypic and genotypic drug susceptibility testing; and replicative capacity testing.
Comparisons were by Wilcoxon Rank Sum or Fisher's Exact Test.
Results: 9/10 discordant subjects were available for follow-up. Despite high-level
drug resistance, CD4 cells continued to increase and viral load remained controlled. Diminished HIV replicative capacity persisted. A higher proportion of D
subjects had potent suppressive noncytolytic CD8 activity to X4 tropic virus than
F subjects. Evolution of viral and immunologic responses were observed during
the additional year of follow-up.
Conclusion: Despite ongoing detectable viremia and high-level resistance to current therapy, patients with discordant responses demonstrate improved immunologic responses to HIV and sustained CD4+ recovery in the setting of diminished
HIV replicative capacity
Presenting author: susan sufka, 727 glen hollow dr, durham nc, 27705, United
States, Tel.: [phone], Fax: [phone], E-mail: [email protected]
ThPeA7153 IL-7 production by bone marrow-derived stromal
cells in HIV-1 infected patients during HAART
A. lsgrb1,l1. Mezzaroma1, A.A. Aiuti2, E. Pinter1, A.M. Mazzone 1, F. Lebba1,
F. Aiuti 1. Division of Allergy and Clinical Immunology, Rome, Italy; 2S. Raffaele
Telethon Institute for Gene Therapy, Milan, Italy
Background: IL-7, mainly produced by bone marrow stromal cells, is well recognized as a crucial cytokine for the early development of lymphocyte subpopulations. It may be hypothesized that, following HAART, the control of viral replication
and the increase in CD4+ T cell number could determine a regulation in the production of IL-7 at stromal level. To verify that, we analysed stromal IL-7 production
in bone marrow cultures before and during HAART in HIV-1 infected subjects.
Methods: BM mononuclear cells, obtained from breastbone in 6 HIV+ subjects,
were plated in long-term BM culture until stromal confluence (3-4 weeks), to evaluate the stromal production of IL-7 by ELISA. A second breastbone was performed after 3 months of HAART. Three seronegative subjects were studied as
controls.
Results: Compared with uninfected controls, an altered cytokine production has
been observed, characterized by elevated IL-7 levels. This pattern was reverted
during HAART in association with a rise in peripheral CD4+ T cells and decreased
plasma HIV-1 RNA levels. An inverse relationship has been also observed between the levels of stromal IL-7 and peripheral CD4+ T cell number.

Conclusion: Before starting HAART, in response to CD4+ T-cell depletion, increased levels of stromal IL-7 have been observed. During HAART the control
of viral replication and the recovery of CD4+ T cell numbers revert the BM stromal IL-7 production, that reaches values comparable to those observed in control
subjects. In response to HIV-related CD4+ T cell depletion, some soluble factors
may be responsible for this feedback mechanism.