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

XIV International AIDS Conference

Abstracts ThPeA7090-ThPeA7093 357

Presenting author: Antonio Pires, Dept Immunology, Chelsea & Westminster
Hospital, 368 Fulham Road, London, United Kingdom, Tel.: [phone], Fax:
++442087465997, E-mail: [email protected]
ThPeA7090 Growth hormone therapy induces HIV-1-specific
CD4 and CD8 T cell responses in HAART treated
patients
N. Imami, A. Pires, G. Moyle, A. Spentzou, B. Gazzard, F. Gotch. Imperial
College of Science Technology and Medicine, Immunology, ICSTM, Chelsea &
Westminster Hospital, 368 Fulham Road, London SW10 9NH, United Kingdom
Background: Immunotherapeutic strategies in chronic HIV-1 infection require induction of virus-specific CD4 and subsequent activation of CD8 T cells. Concomitant administration of recombinant human growth hormone (rhGH) with HAART
may boost immune reconstitution and specific T cell responses.
Methods: Twelve HIV-1 infected individuals with lipoatrophy on long-term successful HAART received rhGH. We evaluated HIV-1-specific and non-specific T
cell responses at baseline, after 12 weeks of rhGH therapy (4-mg/day), and at
24 weeks after randomisation into three groups: (i) placebo (ii) alternate-day dosing (iii) twice-per-week dosing for the second 12 weeks. CD4 HIV-1-specific responses were measured using the conventional lymphoproliferative assay, whilst
CD8 HIV-1-specific CTL responses were measured using pools of overlapping
peptides and vaccinia virus (rVV) constructs.
Results: At baseline lack of both CD4 and CD8 virus-specific responses were
noted in 11 of 12 individuals. In one patient significant virus-specific CD8 T
cell responses were observed in the absence of HIV-1 -specific CD4 T cell responses. Twelve weeks of subcutaneous administration of rhGH induced a significant (p<0.005) increase in both gag-specific and whole-HIV-1 antigen-specific
CD4 T cell responses in 9 of 12 patients. Whilst viral load, CD4 and CD8 T cell
counts remained unchanged, there was a significant increase in CD8 responses
evaluated with both rVV (p<0.05) and peptide pools (p<0.005) of gag or pol proteins in IFN-gamma ELISPOT assays. Improved CD4 T cell responses at week
12 were lost by week 24 even in patients who received alternate-day or twiceper-week dosing of rhGH, but CD8 responses were maintained even at week 24
regardless of which arm the patients were in.
Conclusions: Daily rhGH increases both CD4 and CD8 HIV-1 -specific T cell responses over a 12-week period in HAART treated chronic infection but complete
benefits may not be maintained with less frequent dosing.
Presenting author: Nesrina Imami, Immunology, ICSTM, Chelsea & Westminster Hospital, 368 Fulham Road, London SW10 9NH, United Kingdom, Tel.: +44
(0)20 8746 5987, Fax: [phone], E-mail: [email protected]
ThPeA7091 I Relationship between gag-specific T lymphocyte
responses during the early phase of human
immunodeficiency virus type-1 infection and
subsequent viral set point
R.C. Bollinger, D.S. Patke, L.M. Carruth, S.M. Keating, S.J. Langan,
B.R Sabundayo, T.C. Quinn, J.B. Margolick. Johns Hopkins University, Ross
1150, Division of Infectious Diseases, Johns Hopkins Medical School, 720
Rutland Ave, Baltimore, Maryland, United States
Background: The viral set point predicts the rate of HIV-1 disease progression.
A role for CD8-T lymphocyte mediated viral specific immunity has long been postulated, since such responses are more evident in individuals with long-term nonprogession and are temporally associated with clearance of viremia in primary
HIV-1 infection. However, little data is availableon the direct correlation between
early CD8+ T lymphocyte responses to HIV infection and the magnitude of the
viral set point.
Methods: T lymphocyte responses to HIV-1 gag peptides were measured by
interferon-y ELISPOT assay at three time points within the first 12 months of
infection, in 9 untreated individuals with recent onset of HIV infection.
Results: Subjects demonstrating early recognition of HIV-1 gag (n=7) had lower
subsequent HIV-1 viral load set points, measured during the first 2 years of infection, than did 2 subjects with undetectable gag-specific responses (median 4.27
vs 5.05 log10 RNA copies/ml, respectively; p = 0.028). There was an inverse
correlation between the magnitude of the gag-specific response and HIV-1 viral
load set point (r = -0.733; p = 0.025). Individuals with detectable gag-specific responses at all 3 time points had higher percentages of circulating naive CD8+
T lymphocytes, than did those with undetectable ELISPOT responses at one or
more time points.
Conclusion: Early sustained T lymphocyte responses to HIV-1 gag, associated
with a preservation of naive CD8+ T lymphocytes, appear to be important for
determining the magnitude of the viral set point.
Presenting author: Robert Bollinger, Ross 1150, Division of Infectious Diseases,
Johns Hopkins Medical School, 720 Rutland Ave, Baltimore, Maryland, United
States, Tel.: [phone], Fax: [phone], E-mail: [email protected]

ThPeA7092 Lymphocyte subsets in long-term non-progressors
(LTNP). Relevance of immune activation in
progression of HIV-1 infection
G. Mestre1, F. Garcia1, A. Soriano', M. Plana1, A. Cruceta1, J. Arostegui1,
M. Lejeune1, J. Joseph1, J.M. Miro, J. Del Romero2, A. Rodriguez2,
A. Barrasa2, J.1. Lorenzo3, J.M. Gatell1, T. Gallart1. 1Hospital Clinic, Infectious
Diseases Unit, Villarroel, 170, Spain; 2Centro Medico Sandoval, Madrid, Spain;
3Hospital La Fe, Valencia, Spain
Background: The factors involved in progression are not fully understood in HIV1 infection. The objective of this study was to assess the features of lymphocyte
T subsets in a cohort of LTNR
Methods: Cross-sectional study in 69 LTNP HIV-infected patients (median of
follow-up: 140 months, Median viral load: 2519 c/ml). A group of 39 chronic HIV-1
infected patients in very early stage (ES), matched for age, gender and degree of
immune-suppression (all had a CD4+ T cells above 500/mm3) (median of followup: 14 months, Median viral load: 26574 c/ml) and a group of 11 healthy individuals (HI) were included as control groups. The following lymphocyte T subsets
were assessed: CD4, CD8, naive and memory CD4+ and CD8+ T cells, CD8+28+
and CD28+38+ T cells, and expression of CXCR4 and CCR5 both in CD4+ and
CD8+ T cells.
Results: The group of LTNP had a similar value of CD4+ and CD8+ T cells than
ES group (p= 0.54) and a significantly lower value than HI (p=0,0001). There
were no differences in naive and memory CD4+ and CD8+ T cells between the 3
groups (p= 0.85). Concerning CD8+28+, LTNP had a similar value than ES group
(p= 0.53) and a significantly lower value than HI (p=0,0001). Conversely, LTNP
had significantly lower CD8+38+ levels than ES patients (p= 0.017) and similar
levels to HI group (p=0,97). The expression of co-receptors were similar between
the groups.
Conclusions: Markers of immune activation (as measured by CD8+CD38+ T
cells) are the main difference in lymphocyte subsets between LTNP and matchedchronic HIV-1 infected patients in very early stage. Levels of CD4+, CD8+ and
CD8+CD28+ T cells are abnormal even in LTNP when compared with healthy individuals. Conversely, markers of immune activation, naive and memory CD4+ and
CD8+ T cells, and expression of co-receptors were similar in LTNP and healthy
controls.
Presenting author: Felipe Garcia, Infectious Diseases Unit, Villarroel, 170,
Spain, Tel.: [phone], Fax: [phone], E-mail: [email protected].
es
I ThPeA7093 Correlation of HIV specific cellular immunity with
characteristics of exposing virus in highly exposed
persistently seronegative subjects (HEPS)
S. Fidler1, C. Nicholson1, R. Braganza1, S. Beddows 1, S. Pinheiro2, T. Dong2,
S. Rowland-Jones2, J. Weber1. 'ImperialCollege Faculty of Medicine, wright
fleming institute Dept GUM/HIV Faculty of Medicine, Imperial college St Marys
Hospital, London W2 1NY United Kingdom; 2Institute of Molecular Medicine,
Oxford, United Kingdom
Aims: This project aimed to identify whether HIV specific Cytotoxic lymphocytes
(CTL) responses quantified in HEPS individuals were a direct response to exposure to their HIV+ partners' virus.
Background: HIV specific immune responses have been identified in HEPS subjects to a broadspectrum of conserved regions of HIV. Whether these responses
are mediating protection from establishment of infection and are a direct response
to viral exposure is unclear. The regions of virus capable of inducing such a 'protective' immune response in HEPS individuals provide vital information relevant
for vaccine development.
Methods: 20 HIV serodiscordant couples in longterm monogamous relationships
with clear histories of sexual exposure to their partners virus were recruited. HIV
specific CD4+ and CD8+ cellular immune responses were demonstratedand compared from both the infected and HEPS partners over the course of 3 years using
ELISPOT technology. HIV was isolated and sequenced from the HIV+ partners
PBMC, and where possible genital tract samples around the regions of identified
CTL epitopes. At sequential time points quantifiable HIV specific CTL responses
in the HEPS were correlated with the sequence analysis of their partners virus at
the same time point.
Results: HIV specific CTL were demonstrated in all 20 HEPS studied at at least
one time point. Viral sequence data failed to identify any significant amino acid
substitutions around the conserved regions of previously identified HIV specific
CTL epitopes. There was no clear correlation between the measured HIV specific
immune resposnes and sexual exposure.
Conclusions: exposure to the same strain of HIV does correlate with the development of quantifiable HIV specific CTL that are not seen in unexposed individuals. We have been unable to show that these responses are specific to the
exposing viral strain. Similar work with more variable regions of virus maybe more
forthcoming to address this issue.

Presenting author: sarah fidler, wright fleming institute Dept GUM/HIV Faculty of
Medicine, Imperial college St Mary's Hospital, London W2 1NY, United Kingdom,
Tel.: [phone], Fax: [phone], E-mail: [email protected]