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

50 Abstracts WePeB5877-WePeB5880

XIV International AIDS Conference

Presenting author: Alain Lafeuillade, Unite infectiologie, Hospital Chalucet,
83056 Toulon, France, Tel.: [phone], Fax: [phone], E-mail:
[email protected]
WePeB5877 The development of HIV-1 DNA load during
structured therapy interruption (STI)
L.E. Eriksson', G.A. Bratt2, B. Wahren3, K.I. Falk3, A.C. Leandersson3,
T. Leitner3. 'Dept of Virology, Swedish Institute for Infectious Disease
Control/Microbiology and Tumor Biology Center, Karolinska Institutet, Dept of
Virology, Swedish Institute for Infectious Disease Control, SE-171 82 Solna,
Sweden; 2Gay Mens Health Clinic, Stockholm Sdder Hospital, Stockholm,
Sweden; 3Dept of Virology Swedish Institute for Infectious Disease Control,
Stockholm, Sweden
Background: Effective protease inhibitor based antiretroviral combination therapy (PI-ART), reduces the number of HIV-virions (HIV-RNA) in plasma to undetectable levels. There is, however, major short and long term adverse effects associated with PI-ART. Structured therapy interruption (STI) is an attempt to lower
the risk of negative treatment effects. In connection with therapy interruption, the
HIV-RNA levels will increase to approximately the same level as before the initiation of therapy. The purpose of this study was to quantify HIV-DNA genomes in
CD4+ cells in connection with STI by real-time PCR.
Methods: A real-time PCR, amplifying fragments of the HIV-1 po/ gene and the
human albumin gene simultaneously, was used to quantify the frequency of HIVDNA in CD4+ cells. Fifteen patients were investigated before and several times
during STI. CD4+ cells were isolated from frozen PBMC and DNA was extracted
from the isolated cells. Simple linear regression was used to obtain individual HI
V-DNA slopes (copies/cell X month) out of the frequencies of HIV-DNA obtained
by the real-time PCR analysis.
Results: The amount of HIV-DNA increased after therapy interruption in all the
investigated patients. Three patterns were observed: Slow increase (three patients), rapid increase (three patients) and rapid initial increase with subsequently
stabilising levels (nine patients). The individual HIV-DNA slopes correlated with
the individual HIV-RNA maxima, steady states and late and total slopes. Further,
there was an inverse correlation between HIV-DNA slope and duration of observation after therapy interruption.
Conclusions: HIV-DNA levels increase in connection with therapy interruption.
The extent of this increase seems to be positively related to late HIV-RNA development.
Presenting author: Lars E. Eriksson, Dept of Virology, Swedish Institute for Infectious Disease Control, SE-171 82 Solna, Sweden, Tel.: [phone], Fax:
[phone], E-mail: [email protected]
WePeB5878I Discontinuation of antiretroviral treatment in
patients with a high CD4 count: a possible
treatment strategy
C. Mussini1, R. Bugarini2, V. Borghi1, A. Bedinil, C.F Perno3, A. Antinori3,
A. Cossarizza4. ' Clinic Infectious Diseases, clinic of infectious diseases,
policlinico, via del pozzo 71, 41100 Modena, Italy; 2Chiron, Siena, Italy;
3National Institute Infectious Diseases, Rome, Italy; 4Dept of Biomedical
Sciences, Modena, Italy
Background: Aim of this study was to evaluate in patients who fail a current antiretroviral regimen with a high CD4 count and that discontinue therapy instead
of changing it, how long they would stay out of treatment before reaching a CD4
count below 350 cells/VL.
Methods: In patients treated with antiretroviral therapy who had an HIV plasma
viral load >3 loglo0copies/mL with a CD4 count >500 cells/pL instead of changing regimen it was discontinued antiretroviral therapy A mixed model with a random intercept and an autoregressive variance-covariance structure for patient
was used to detect changes in CD4 count and HIV RNA plasma level over time.
Results: Sixteen HIV positive patients (11 males, median age 37 years) discontinued antiretroviral therapy from June 1999 to July 2000. The median duration of
treatment before discontinuation was: 36 (range:18-50) months and all patients
reached an undetectable viral load before failure. During treatment patients experienced a mean CD4 count increase of 7.6 (95%C1: 4.27-10.83) cells/mL per
month and a mean HIV plasma viral load decrease of 0.018 (95%C: 0-0.03)
log10 per month.
At discontinuation median CD4 count was: 755 (range: 578-1125) cells/itL and
the median HIV plasma viral load was: 3.38 (range:1.7-4.2) log10. The median observation time was: 20.4 months (range: 15-29 months). During the
first six months after discontinuation, mean CD4 count showed a decrease of
46.2 (95%CI:28.6-72.1) cells/mL per month, and after then, a decrease of 10.2
(95%CI:-2.2-19.3) cells/kL per month. Concerning HIV plasma viral load, in the
first 6 months after discontinuation it showed a mean increase 0.22 (95%CI: 0.07 -0.38) log10 per month and after then a mean increase of 0.08 (95%CI: -0.01-0.19;
p=0.07) log10 per month. At present, 5 patients restarted treament and all of them

showed viro-immunological success.
Presenting author: cristina mussini, clinic of infectious diseases, policlinico,
via del pozzo 71, 41100 Modena, Italy, Tel.: [phone], Fax: +39 059
4222604, E-mail: [email protected]

WePeB5879 Interruption of Protease Inhibitor containing
antiretroviral treatment (PI-ART)
G.A. Bratt', K. Koppel', L. Eriksson2, E.L. Fredriksson', E. Sandstrom'.
'Venhalsan, Sodersjukhuset, Venhalsan, Sodersjukhuset, 118 83 Stockholm,
Sweden, Sweden; 2Dpt of Virology, Karolinska Inst, Stockholm, Sweden
Background: Protease inhibitor containing antiretroviral therapy (PI-ART) generates a continuous increase of CD4+ lymphocytes by approximately at least
100cells/mm3 per year in most patients. However, serious adverse effects, such
as hyperlipidemia, insulin resistance, diabetes and lipoatrophy have become a
major concern in the long-term clinical management. We have studied the effects
of long-term supervised treatment interruption on these adverse effects and on
the CD4+ development.
Methods: 25 patients on successful PI-ART with HIV-RNA < 50 copies/ml for a
mean of 37~11 months and mean CD4 407 cells/mm3 stopped PI-ART as part of
a clinical trial and were monitorded closely regarding serum fasting Cholesterol,
Triglycerides (TG), Lipoprotein a (Lp(a)), Glucos, Insulin, a single cut computed
tomography (CT) scan at the level of the umbilicus (n=10) and the rate of CD4
change (slope; decline or increase), assessed using a linear regression analysis
model.
Results: The mean time without PI-ART is now 11 months. 21/25 patients have
not restarted ART Cholesterol, TG and Lp(a) decreased (p<0,001; p<0,01;
p=0,068), while Insulin increased (p<0,05). There was a trend for the amount of
visceral adipose tissue (VAT) to decrease (p=0,105). The monthly CD4 change,
which was +10~7cells/mm3 during PI-ART changed after treatment interruption
to -212~176 cells/mm3 during month 0-1 and to -16~21 cells/mm3 per month
during the period: month 1 to the latest month. The CD4 decline during the treatment interruption positively correlated to the CD4 increase during PI-ART and the
CD4 level before treatment interruption (p<0,001).
Conclusion: Treatment interruption of successful PI-ART results in a biphasic
CD4 decline, which is inverse to the increase during ART. Lipid levels normalise,
VAT tend to decrease, while insulin resistance possibly persists. Treatment programs with prolonged periods on/off therapy might be considered in the future
HIV care.
Presenting author: Goran Bratt, Venhalsan, Sodersjukhuset, 118 83 Stockholm,
Sweden, Sweden, Tel.: [phone], Fax: [phone], E-mail: goran.bratt
@venh.sos.sll.se
SWePeB5880 ICD4 Disadvantage and Improved Blood Lipids in a
Large Controlled 18-Month Trial of Treatment
Interruptions (TIs)
H. Jaeger', E. Wolf', C. Hoffmann2, E. Gersbacher3, M. Procaccianti4,
F. Mosthaf4, A. Ulmer5, J. Schardt3, M. Karwat6, E. Jaegel-Guedes1.
' KIS-Curatorium for Immunedeficiency, MUC Research GmbH, Karsplatz 8,
80335 Mdnchen, Germany; 2Uni. of Kiel, Kiel, Germany; 3MUC Research GmbH,
Munich, Germany; 4private practice, Karlsruhe, Germany; 5private practice,
Stuttgart, Germany; 6private practice, Munich, Germany
Objectives: To assess the long-term effects of TIs on viral load (VL), CD4 cells,
metabolic parameters and clinical outcome in chronically infected HIV+patients
(pts).
Methods: Multicenter, prospective, controlled, frequency-matched 18-month
study of HIV+pts with TI (for any reason) versus a control group remaining on
ART. Both, TI-pts and controls were subdivided on the basis of their baseline (BL)
VL (< 50 vs >50 cop/ml).
Results: Analysis of N = 379 pts (127 TI- pts, 252 controls) with an overall observation time of 445 patient years (PY) (148 PY in TI-pts, 297 PY in controls).
18-month follow-up was available for 73 TI-pts and 135 controls. BL data were
comparable in TI-pts and controls: mean CD4 count 431/Rl vs 431/1l, 30% vs
36% AIDS cases, 47% vs 44% with a BL VL < 50 cop/ml.
Mean duration of the first TI was 1.3 months, 40% of TI-pts had > 2 TIs. After
4 weeks of TI, CD4 cells had declined by an average of -72/id (p < 0.001) and
returned to BL during follow-up. By month 18, in the controls with a BL VL <
50 cop/ml, CD4 count had increased by +127/p1 (p=0.04), whereas in the corresponding TI-pts change from BL was +5/tl (p=ns).
Mean VL-increase during TI was +1.9 log (p<0.001). In 65% of the TI-pts with
undetectable BL VL vs 82% of the corresponding controls, a VL< 50 cop/mI was
reinstated at month 18 (p=0.08).
In pts with elevated BL blood lipids, total cholesterol and triglycerides had declined by -54 and -218 mg/dl (p<0.001), respectively.
AIDS incidence rate was 2/100 PY in TI-pts, and 1/100 PY in controls (p=ns).
Conclusion: This large controlled trial showed a significant decrease in blood
lipids during TIs but also a long-term CD4 disadvantage for TI-pts compared to
their frequency matched controls. Thus, in considering TIs in pts with successful ART, the improvement in metabolic parameters should be carefully weighed
against the absence of the CD4 increase seen without TIs.
Presenting author: Hans Jaeger, MUC Research GmbH, Karsplatz 8, 80335

M0nchen, Germany, Tel.: [phone], Fax: [phone], E-mail: info
@mucresearch.de