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

XIV International AIDS Conference

Abstracts ThPeA7158-ThPeA7161 373

ThPeA7158 Impaired CD4+ cell counts recovery and immune
deactivation following highly active antiretroviral
therapy (HAART) among drug-naive
HIV/HCV-coinfected patients
J.A. Pineda1, J. Macias1, F Lozano2, J.E. Corzo2, A. Ramos1, R. Cozar1,
J.A. Garcia-Garcia1, FJ. Fernandez-Rivera1, E. Leon2, J. Gomez-Mateos2.
1Servicio de Medicina Interna, Hospital Universitario de Valme, servicio de
medicina interna, hospital universitario de valme, ctra de cadiz s/n, 41013
seville, Spain; 2 Seccion Enfermedades Infecciosas, Hospital Universitario de
Valme, Seville, Spain
Background: and objective: HIV/HCV coinfection is highly prevalent in Southern Europe. However, data about the effect of HCV carriage on the response to
HAART are very scant. Because of this, we investigated the recovery of CD4+
T-cells and the decrease in the levels of a2-microglobulin (B2M) following HAART
among antiretroviral-naive patients seropositive for HIV with and without HCV
coinfection.
Patients and methods: Two hundred and one HIV-infected patients, without previous exposure to antiretroviral drugs, from a prospective cohort were included in
the study. CD4+ cell counts were performed at baseline and every three months,
after starting HAART The time to recover 50 and 200 CD4+ cells/ml, and the
mean CD4+ cell counts gain over the baseline values were analyzed. The mean
changes in the levels of B2M were assessed at baseline, 12 and 24 months of
HAART in 40 patients, 16 of them with HCV infection, with sustained undetectable
viremia. B2M levels were also measured in 40 healthy individuals.
Results: HCV coinfection was detected in 123 (61%) patients. The time to recover 200 CD4+ cells/ml was longer in the HCV-positive group (p < 0.001). In
a Cox model, HCV infection and lack of persistent HIV viremia < 200 copies/ml
were associated with the gain of 200 CD4+ cell counts [hazard ratio (95% confidence interval) 0.51 (0.33-0.79) and 0.62 (0.38-0.97), respectively]. Similar results were obtained for the time to recover 50 CD4+ cells/ml. The mean CD4+ cell
counts gain was lower in the HCV-positive group along the first year of therapy
(p = 0.02). The mean levels of B2M decreased significantly less among the HCVcoinfected patients (p < 0.001). None of the patients groups achieved normal
B2M levels.
Conclusions: HIV/HCV-coinfected patients, naive for antiretroviral therapy, show
a delayed CD4+ cell counts recovery after starting HAART This effect could be
due to a worse immune deactivation among HCV-coinfected patients in response
to HAART.
Presenting author: pineda juan antonio, servicio de medicina interna, hospital universitario de valme, ctra de cadiz s/n, 41013 seville, Spain, Tel.: +34
954015174, Fax: [phone], E-mail: [email protected]

ThPeA7160 Changes in cytokine profile in HIV/AIDS patients in
the course of HAART
V. Terzieva1, R. Markova1, Y Todorova1, H. Taskov1, K. Kostov2. 1National
Center of Infectious & Parasitic Diseases, National Center of Infectious &
Parasitic Diseases, Central Immunology Lab, 26 Yanko Sakazov Blvd., Sofia
1504, Bulgaria; 2Hospital for Infectious Diseases "Prof. I. Kirov", Sofia, Bulgaria
Background: Changes in T-cell function during HIV-1 infection are of interest for
their potential contribution to the monitoring and management of patients during
HAART. The aim of this prospective ongoing study is to evaluate the effect of
HAART on cytokine balance in patients in different stages of HIV-1 infection.
Methods: 52 HIV-1 - infected pts (30 men aged 22-58 and 22 women aged 18-54
years) were set up in two groups according to their baseline CD4+ count: 30 pts
with CD4+ <200 cells/iL and 22 pts with CD4+ >200 cells/iL. All patients received
2 NRTIs and one PI. Patients were followed-up at baseline, 2 and 6 months after
the start of HAART. Production of IL-2, IL-12, IL-10, and TNF-a was measured
in ELISA, in spnts of isolated and stimulated in vitro PBMCs with PHA and HIV-1
p24 Ag. CD4+ cell count was determined flowcytometrically. Statistical analysis
was done using Wicoxon's matched paired test and Spearman's rank test.
Results: At baseline high levels of Th2 cytokines and low levels of IL-2 and IL12 were found in all patients. On month 2 a diminution of IL-6, IL-10 and TNF-a
concentration together with elevated levels of IL-2 and IL-12 was found in pts with
CD4+ >200 cells/iL. This tendency persisted till the end of month 6 (p<0.05) and
correlated well (r=0.7) with the absolute number of CD4+ T cells. A weak recovery of Thl cytokine production was observed not until month 6 in pts with CD4+
<200 cells/iL.
Conclusions: The results obtained, even preliminary, demonstrate an impaired
T cell function in all patients regardless of the stage of HIV-1 disease. The recovery of Thl/Th2 balance started earlier, two months after the onset of therapy, in
asymptomatic pts and was less expressed in pts with CD4+ <200 cells/iL. Our
data suggest that the assessment of cytokine profile in HIV/AIDS patients is important for evaluation the degree of immune reconstitution during HAART and
have prognostic value for disease progression.
Presenting author: Velislava Terzieva, National Center of Infectious & Parasitic
Diseases, Central Immunology Lab, 26 Yanko Sakazov Blvd., Sofia 1504, Bulgaria, Tel.: [phone], Fax: [phone], E-mail: terzieva@ncipd.
netbg.com
ThPeA7161I Long term immune reconstitution in HIV-1 infected
subjects receiving potent antiretroviral therapy
K. Tsalimalma1, A. Dimitrakopoulou2, T. Kordossis3, U. Dafni4,
H. Choremi-Papadopoulou 1. 1lmmunology Department, General Hospital
"LAIKO" Athens, Immunology Dept., General Hospital Athen, GR- 11526
ATHENS, Greece; 2Immunology Department "Laiko "General Hospital, Athens,
Greece; 3Dept of Pathophysiology (AIDS Unit) Athens University School of
Medicine, Athens, Greece; 4Dept. of Public Health, School of Nursing, University
of Athens, Athens, Greece
Background: Although the benefits of highly active antiretroviral therapy
(HAART) are well documented, studies have shown that HAART does not result
in optimal suppression of viral replication in all patients and a significant number
experience viral rebound. Moreover immune reconstitution could be influenced by
the level of viral suppression and its extent as well as its long term duration are
still controversial topics.
Our aim was to determine the long term immune reconstitution in HIV-1 (+) subjects on HAART in relation to pVL suppression.
Methods: We measured by flow cytometry CD4+, CD8+ T lymphocyte subsets
and studied CD28 costimulation and PWM, PHA stimulation at baseline and up to
42 months every 6 months. Participants were divided into three groups according
to their pVL response: a) Full Responders (FR n=41) achieved and sustained a
pVL < 500 copies/ml, b) Partial Responders (PR n= 11) achieved a pVL < 500
copies/ml, followed by a rebound, c) Non Responders (NR n= 20) that exhibited
pVL > 500 copies/ml over the study period.
Results: Overall there was a median increase compared to baseline CD4+ cells
of 269 cells/l in FR and 273 cells/li and 107cells/ll in PR and NR respectively in the first year after HAART. CD4+CD45RA+/CD62L+ cells were 124/122
cells/li in FR, 124/120 cells/l in PR and 20/15 cells/l in NR. CD4 cells
were more increased after 24 months (380 cells/l) and after 42 months (400
cells/Rl) in the FR, (CD4+CD45RA+/CD62L+ 24m:207/190 cells/l, 42m:202
cells/Rl) while the increase in PR was at 24m:235 cells/Rl, at 42m: 295 cells/il,
(CD4+CD45RA+/CD62L+ 24m:151/147 cells/l, 42m:103 cells/Rl) and in NR
at 24m: 51cells/l, at 42m: 105 cells/li (CD4+CD45RA+/CD62L+ 24m: 28/11
cells/l, 42m: 36 cells/l).
The CD28 costimulation was at 42M among the normal range inl2/21 FR while
in 5/9 PR and 2/13 NR.
Conclusion: These results indicate that long term immune reconstitution is
stronger with continued pVL suppression.

Presenting author: Kalliroi Tsalimalma, Immunology Dept., General Hospital
Athen, GR-11526 ATHENS, Greece, Tel.: [phone], Fax: [phone],
E-mail: [email protected]

ThPeA71591

Effects of 6 months of highly active antiretroviral
therapy (HAART) on the CD8+ T-cell noncytotoxic
anti-HIV response (CNAR) in chronically
HIV-infected individuals at intermediate and late
stages of HIV disease

K.J. Torres, F Gutierrez, A.S. Reyes, J. Zuniga, G. Salgado, S. Ridha,
M.E. Mayar, M.E. Mackewicz, G. Reyes-Teran. Instituto Nacional de
Enfermedades Respiratorias, Calzada de Tlalpan 4502, Col. Seccidn XV,
Tlalpan 14080, Mexico, DF Mexico
Background: The sudden decline in viral load (VL) promoted by HAART during
primary infection induces a reduction in the level of CNAR. CTL responses also
diminish in the absence of detectable viremia. However, it is not known when
the HAART-associated loss of the cellular immune response occurs. Thus, we
evaluated the effect of HAART on CNAR in HIV -Infected individuals at intermediate and late stages of the disease. Methods: Twenty-four asymptomatic,
chronically HIV-infected individuals without previous use of anti HIV therapy
were enrolled prospectively Thirteen were classified as intermediate (CD4+Tc
>200<500) (group 1) and 11 as late stage (CD4+Tc <200 /RL) (group 2) of HIV
disease. Clinical status, plasma VL, CD4+ Tc counts and CNAR were evaluated
and monitored at baseline and at 4, 12 and 24 weeks after HAART initiation.
CNAR assay was done at CD8/CD4 ratios of 2:1, 1:1, 1:2, and 1:4. Non parametric statistics was used for this analysis.
Results: At baseline, the median
CD4+ Tc counts and pVL were 344/RL and 5.8 log respectively for group 1, and
92/RL and 5 log respectively for group 2 (p0.05). The difference in the baseline CNAR (CD8/CD4 ratio: 1:4) between both groups was statistically significant
(group 1= 83% and group 2= 36%) (p <0.05). Sixteen patients that reached undetectable levels of pVL (<50 copies/mL) after 6 months of HAART were considered
for analysis. Ten were in group 1 and 6 in group 2. From group 1, 22% had an
increase in CNAR by week 4 after HAART initiation. By week 12, 70% presented
an increased CNAR. By week 24, 80% had a decrease of CNAR and only 20%
had an increased CNAR when compared with the week 12. Conversely, 66% of
patients in group 2 consistently increased CNAR.
Conclusions: Patients at intermediate stage of HIV disease presented a temporary increase in CNAR followed by a significant decline over time. In contrast,
most of patients at late stage partially reconstitute CNAR.
Presenting author: Klintsy J. Torres, Calzada de Tlalpan 4502, Col. Secci6n XVI,
Tlalpan 14080, Mexico, DF, Mexico, Tel.: [phone], Fax: [phone],
E-mail: [email protected]