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

376 Abstracts ThPeA7172-ThPeA7175

XIV International AIDS Conference

ThPeA7172 IBaseline thymic volume is a predictor for CD4+
T-cell repopulation in adult HIV-infected patients
under highly active antiretroviral therapy
R. de la Rosa', M. Leal', A. Rubio', M. Martinez-Moya2, J. Delgado 1,
E. Ruiz-Mateos', E. Merchante2, A. Sdnchez-Quijano1, E. Lissen'. '1Viral
Hepatitis and AIDS Study Group. Hospital U. Virgen del Rocfo, Grupo Estudio
Hepatitis vfrica y SIDA, Hospital Universitario Virgen del Rocio, Avda. Manuel
Siurot s/n, 41013 Seville, Spain; 2Department of Radiology Hospital U. Virgen
del Rocfo, Seville, Spain
Background: Several host and virological factors which seem to influence on
CD4+ cell repopulation in adult HIV-infected patients under HAART, such as, a
low rate of CD4+ impairment before HAART, a low HIV viral load levels at baseline and a progressive decrease in HIV-1 viremia levels during the first few weeks
under potent therapy had been previously reported. The role of the thymus in this
immunolological recovery in adult patients is still unclear. Objective: To assess
the impact of baseline thymic volume on the CD4+ cell repopulation induced by
HAART in HIV-infected adults.
Methods: Thirty-seven previously untreated HIV-1 infected adults were prospectively followed from August 1998 to September 2001. Clinical, biochemical, immunological (including CD4+ cell count) and virological examinations were performed at starting HAART (baseline), week 4, week 12 and every 12 weeks thereafter. CD4+ cell repopulation was considered as an increase > 200 cells/mm3
above baseline count. A thorax CT scan at starting HAA
RT was performed in all the patients to measure thymic volume.
Results: The median follow-up time was 189 [87.5-498.5] days. Twenty-one
(57%) patients achieved this CD4+ repopulation. Baseline thymic volume was
the main independent factor associated with CD4+ repopulation (p=0.016); this
factor was a positive predictor (adjusted hazard ratio [HR]: 1.25 [95% Confidence
Interval (CI), 1.1 to 1.4]). Although, CD4+ cell count and non-AIDS diagnosis at
baseline were associated with CD4+ cell repopulation on the univariate analysis
(p=0.03, and p=0.02, respectively), no statistical signification was found on the
multivariate test.
Conclusion: Baseline thymic volume is a predictor of CD4+ cell repopulation in
adult HIV-1 infected patients under HAART
Presenting author: Rafael de la Rosa, Grupo Estudio Hepatitis virica y SIDA,
Hospital Universitario Virgen del Rocio, Avda. Manuel Siurot s/n, 41013 Seville,
Spain, Tel.: [phone], E-mail: [email protected]
ThPeA7173 Lymphoproliferative (LP) responses to HIV-gag
antigen are not associated with improved immune
phenotype or functional responses to non HIV-1
antigens
C.G. Lange', P. Shankar2, B. Harnish2, Z. XU2, H. Valdez', S.J. Lee3,
J. Lieberman2, M.M. Lederman'. 'Center for AIDS Research, University
Hospitals, Case Western Reserve University, Medical Clinic, Research Center
Borstel, Parkallee 35, 23845 Borstel, United States; 2 The Center for Blood
Research, Harvard Medical School, Boston, United States; 3Dana Farber
Cancer Institute, Harvard Medical School, Boston, United States
Background: Preservation of CD4+ T-cell function has been proposed to underlie cytotoxic T-lymphocyte (CTL) mediated control of viremia in patients with acute
HIV-1 infection treated with HAART and in long-term asymptomatic (LTA) therapy
nalve patients. However, whether HIV-1 specific helper cell responses alter- immune phenotype and function in chronically HIV-1 infected patients treated with
HAART is unknown.
Methods: Markers of cytolytic activity on HIV tetramer+ CD8+ T-cells and CD4+
and CD8+ lymphocyte phenotype were examined by flow cytometry. LP responses to recall antigens were measured by thymidine incorporation and delayed type hypersensitivity skin tests (DTH) were performed in 39 HIV-infected
patients with HIV-RNA <400 copies/mL for >12 months and -strong (group A:
stimulation index (SI) >10, n=21) or absent (group B: SI<3, n=18) LP to HIVp24
antigen. Group comparisons were analyzed by non-parametric Mann-Whitney
tests.
Results: Median HIVp24 SIs were 21.9 and 1.5 (p<0.001), median current CD4+
T-cell counts were 744 and 731 cells/l L, median CD4+ T-cell nadirs were 266 and
299 cells/l.L, and duration of HIV-RNA <400 copies/mL on therapy was 38 and
35 months in groups A and B, respectively. Numbers of naive and memory CD4+
T-cells, CD8+ T-cells, LP and DTH responses to non-HIV antigens and the expression of granzyme A and perforin in HIV-1 specific CD8+ T-cells were comparable
in the two patient groups. Granzyme A was expressed in 49 and 58% and perforin
was expressed in 10 and 2% - of HIV tetramer+ CD8+ T cells in group A and B
patients, respectively (p>0.05).
Conclusion: After HAART-induced suppression of HIV-1 replication, the presence of HIV-1 specific T-helper cell responses is not associated with other indices
of improved immune phenotype or function on CD4+ or CD8+ T-lymphocytes.
Markers of cytotoxic function in HIV-1 specific CD8+ T-cells remain severely impaired in chronic infection despite HIV-1 specific lymphoproliferation.

Presenting author: Christoph Lange, Medical Clinic, Research Center Borstel,
Parkallee 35, 23845 Borstel, Germany, Tel.: [phone], Fax: [phone]
313, E-mail: [email protected]

ThPeA7174 ICorrelation between CD4 response and cost of
hospital treatment in anti-retroviral nalive HIV
infected patients started on triple HAART
S. Mandalia', D. Parmar', M. Fisher2, A. Pozniak3, A. Tang4, M. Youle5,
B. Gazzard'1, E.J. Beck6. 'Chelsea & Westminster Hospital, Imperial College
Department of Medicine, St Stephen's Centre, Chelsea and Westminster
Hospital, 369 Fulham Road, London SW10 9NH, United Kingdom; 2Royal
County Sussex Hospital, Brighton, United Kingdom; 3Chelsea & Westminster
Hospital, London, United Kingdom; 4Royal Berkshire Hospital, Reading, United
Kingdom; 5Royal Free and University College Hospital Medical School, London,
United Kingdom; 6Mc Gill University, Montreal, Canada
Background: to investigate the correlation of CD4 response to triple antiretroviral therapy (HAART) and costs of HIV service provision in England January
1998-December 1999. Methods: Data from 3 hospital clinics part of the National
Prospective Monitoring System on the use, cost and outcome of HIV service
provision in UK hospitals - HIV Health-economics Collaboration (NPMS-HHC).
Two-monthly mean CD4 count, mean inpatient days, outpatient and dayward visits were calculated. Activity data were multiplied by standard unit costs, which
included costs of non-anti-retroviral drugs, tests and procedures (1999/2000
prices). Average costs for 2NRTIs +1NNRTI and 2NRTIs + 1PI were added. Analyses were stratified by CDC stage of HIV infection for 24 month follow up period from start triple HAART Pearson correlations were calculated for mean CD4
count and costs within each of the three CDC stages and mean CD4 count and
average costs across CDC stages of HIV infection
Results: 585 patients were treated with 2NRTIs +1N NRTI or 2NRTIs+ 1PI. Of
all scenarios analyzed, the correlation between mean CD4 count and average
costs across all three CDC stages was strongest: r = -0.85, p<0.001. Annual
cost of treating patients with triple HAART and CD4 < 50 cells/ mm3, ranged
from UK~19,086 to ~18,390 (US$27,352 to US$26,354); for CD4 count 50 to
199 cells/mm3, cost ranged UK ~18,390 tol6,298 (US$26,354 to US$23,356);
for CD4 count 200 to 500 cells/mm3, cost ranged UK ~16,298 to ~12,117 (US$
23,356 to $17,365); for patients with CD4 >500 cells/mm3, cost was UK ~12,117
(US$17,365) or less per annum.
Conclusion: A linear relationship was observed between CD4 count and cost
of hospital treatment across all CDC stages: longer follow up may result in relationship changing into a non-linear one. Information can be used to assess costefficacy of drugs in RCTs and resource requirements for maintaining existing or
developing new services.
Presenting author: Sundhiya Mandalia, St Stephen's Centre, Chelsea and Westminster Hospital, 369 Fulham Road, London SW10 9NH, United Kingdom, Tel.:
[phone], Fax: [phone], E-mail: [email protected]
ThPeA7175 Higher CD4 and CD8 T-cell activation is associated
with lower CD4 T-cell gains in antiretroviral-treated
patients with sustained viral suppression
RP.W. Hunt, E. Sinclair, B. Bredt, E. Hagos, J.N. Martin, S.G. Deeks. University of
California, San Francisco, general internal medicine section (111A 1), va medical
center, 4150 clement street, san francisco, ca 94121, United States
Background: There is significant heterogeneity in the CD4 T-cell gains experienced by patients who achieve and maintain viral suppression on HAART Given
the association between T-cell activation and disease progression in untreated
patients, we postulated that T-cell activation might affect the CD4 T-cell gains associated with treatment-induced viral suppression.
Methods: HIV-infected participants in the Study of the Consequences of the
Protease Inhibitor Era (SCOPE) who had achieved and maintained plasma HIV
RNA <500 copies/ml on HAART were examined. The percentages of CD4 and
CD8 cells that were activated, as evidenced by CD38+HLA-DR+ phenotype, were
measured by flow cytometry. Change in CD4 count (ACD4) was calculated as the
CD4 count at the time of flow cytometry minus the pre-therapy nadir CD4 count.
Results: Of the 95 subjects evaluated, median values (25th-75th percentile
range) were: age, 44 (39-50); time since initial viral suppression, 19 months
(8.9-31.5), and nadir CD4 count, 103 cells/mm3(50-212). The median % activated CD4 and CD8 T-cells were 4.1% (2.1-6) and 10.2% (6.9-17.7) respectively,
both significantly greater than the medians in uninfected controls (1.4%, p<0.001;
and 1.3%, p<0.001 respectively). The median ACD4 was +323 cells/mm3 (211 -462). Higher levels of CD4 and CD8 T-cell activation were associated with lower
ACD4 after adjustment for time since viral suppression, nadir CD4 count, and
age. The adjusted treatment-mediated ACD4 was 15.3 cells/mm3 (p=0.01) and
7.2 cells/mm3(p=0.01) lower for every 1% increase in CD4 and CD8 activation
markers, respectively.
Conclusions: Among patients with durable viral suppression on HAART, elevated
levels of CD4 and CD8 T-cell activation are associated with decreased CD4 T-cell
gains. This supports the hypothesis that T-cell activation results in T-cell depletion
independent of the level of viremia.
Presenting author: peter hunt, general internal medicine section (111A1), va

medical center, 4150 clement street, san francisco, ca 94121, United States, Tel.:
[phone] x3392, Fax: [phone], E-mail: huntpw@medicine.
ucsf.edu