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

52 Abstracts WePeB5885-WePeB5889

XIV International AIDS Conference

WePeB5885 I Evaluation of immunological, virological,
metabolic and clinical outcomes in HIV positive
patients with six month-structured treatment
interruption
C. Martinelli, R. Giuntini, S. Ambu, D. Bartolozzi, PG. Rogasi, A. Farese,
F. Leoncini. Unit of infectious Diseases, Careggi Hospital, Florence, Italy
Background: to evaluate virological, immunological, methabolic and clinical consequences in cronically infected HIV patients after spontaneous interruption of
ART for the presence of lipodystrophy/dyslipidemia and after the reintroduction of
antiretroviral therapy
Methods: 14 patients, 10 males and 4 females, aged between 25-51, HIV+ since
a mean of 8 years (range: 1-16), with a first mean CD4 cell count of 453/mm3
(range: 24-675), 12 treated with HAART (first protease inhibitor containing regimen) and 2 with d4T/ddl. Structured treatment interruption (STI) was started with
mean CD4 cell count of 890/mm3 (range: 542-1464) and all with viral load of <50
copies/mL (bDNA PCR); triglyceride mean value was 471 mg/dL (range:312-643);
10 patients presented mixed lipodystrophy (type Ill).
Results: after 2 month-STI CD4 cells were 528/mm3 (range: 341-1013) and median viremia was 106000 copies/mL (range: 3700-348000, 3.56-5.54 log10). After
6 months, 10 patients re-started HAART because of CD4 cells decreasing down
to 360/mm3 (range: 255-459) and viral load increasing up to 168000 copies/mL
(range: 30000-500000, 4.47-5.69 Iog10). Four patients, with a CD4 cell count
of 750/mm3 (range: 516-1177) and viremia of 28000 copies/mL (range: 3500 -61000, 3.54-4.78 log10), continued STI. In all 14 patients, triglyceride values have
decreased to 208 mg/dL (range: 112-325).
Conclusions: in our cohort of 14 patients, six month-treatment interruption, with
a periodic evaluation of immunological, virological and methabolic criteria, was
associated with a significant drop in triglyceride levels and lipodystrophy (in 8 out
of 10 patients who presented it). In all 10 patients who re-started HAART we
assisted to a rapid increase of CD4 cells to 634/mm3 (range: 424-1056) and decrease of viremia to 435 copies/mL (range: 90-830, 1.95-2.91 log10) within the
second month. Six months of STI may be useful and helpful in diminishing lipidic
abnormalities.
Presenting author: Canio Martinelli, Unit of Infectious Diseases, Viale Morgagni 85, Florence, Italy, Tel.: [phone], Fax: [phone], E-mail:
[email protected]
WePeB5886 Non-structured treatment interruptions are
associated to detectable HIV RNA in people taking
NNRTI
R. Murri, C.M.J. Drapeau, A. De Luca, M. Fantoni, R. Cauda. Catholic University
of Rome, Dept. of inf. Diseases, Rome, Italy
Background: Non-structured treatment interruptions (nonSTIs, drug discontinuations decided only by pts), could occur often. Prevalence of nonSTIs and their
effect on treatment efficacy need to be investigated.
Methods: Prospective, monocenter, cohort study A short interview was performed by a physician not involved in the pts care. NonSTI =any patient reporting to have discontinued all drugs (minimum for definition at least twice nonSTIs
during the last year). At the time of survey, CD4 and HIV-RNA (bDNA) were measured. The outcome of the study was detectable HIV RNA (HIV RNA>ge>50
copies/ml, detHIV) at the time of the survey
Results: between 7/01 and 10/01, 88 patients were enrolled: mean age 40 years
(interquartile range [IQR] 34-44), 23% females; 35% IDU, 26% CDC group C;
mean CD4 326/1l (IQR 209-564). 59% were taking at least one PI while 49% at
least one NNRTI. 26% reported a nonSTI. 57% had a nonSTI lasting not more
than 1 week, 26% not more than 1 month, 4% for 1-2 months, and 13% for more
than 2 months. The most frequent reported cause of nonSTI was side effects
(43%), particularly vomiting and gastroenteric symptoms. Other causes were being bored of therapy, and being in holiday. 41% of people had detHIV at the time of
survey. At bivariate analysis, nonSTIs were associated with detHIV in people taking NNRTI (OR 5.6; 95% C 1.1-28.8) but not in people taking PIs (OR 1.8; 95%
Cl 0.5-6.0). At multivariable analysis, nonSTIs was independently associated to
detHIV (OR 5.6; 95% C 1.2-28.7) in people taking NNRTI even after adjusting for
CD4 cell count at the time of survey.
Conclusions: NonSTI are very frequent among HIV+ taking HAART. In people
taking a NNRTI-containing regimen reporting a previous nonSTI is independently
associated with detectable HIV RNA.
Presenting author: Rita Murri, Dept. of inf. Diseases, Catholic University of
Rome, 00168 Rome, Italy, Tel.: [phone], Fax: [phone], E-mail:
ritanto@ iol.it
WePeB5887 Benefits of Treatment Interruption (TI) in Patients
with Multiple Therapy Failures, CD4 cells <200
/mm3 and HIV RNA >50 000 cp/ml (GIGHAART

ANRS 097)
C. Katlama1, S. Dominguez1, C. Duvivier', C. Delaugerre1, G. Peytavin2,
M. Legrand', V. Calvez', D. Costagliola3, GIGHAART Study Team3. 1Hopital
Pitie-Salpetriere, Paris, France; 2Hopital Bichat, Paris, France; 3/NSERM SC4,
Paris, France
Background: Megahaart was shown to rescue severe clinical situations and TI

to favour the return of wild type virus. To evaluate the impact of TI on the efficacy
of a subsequent multidrug therapy in patients (pts) with a history of failure to at
least 2 NRTI, 1NNRTI and 2 PI and severe biological failure an open, prospective,
multicentre, randomised study was conducted.
Methods: Pts were randomised to either Immediate GIGHAART therapy (Imm.G)
or Deferred GIGHAART (Def.G) after 8 weeks of TI. Gighaart regimen consisted
in 3-4 NRTI + 1 NNRTI ~ Hydroxyurea (500mg bid) + ritonavir (400 mg bid) + amprenavir (600 mg bid) or lopinavir + a third PI (indinavir 400mg bid or saquinavir
600mg bid or nelfinavir 1250mg bid). The primary end-point was a decrease in
plasma HIV-1 RNA >1 log10 after 12 weeks of therapy (W 12/20). Due to the
interim analysis, the final significance level is 0.0418
Results: 70 patients were randomised, 68 pts started study drugs and 63 were
evaluated at W12/20. At baseline, median plasma HIV RNA was 5.3 log10 cp/ml,
CD4 27/mm3, duration of ARV therapy was 6.6 years, with previous exposure to
11 ARV. During TI, the median HIV RNA increase was + 0.16 log10 cp/ml and
the median CD4 count decrease -10/mm3. By ITT missing equal failure analysis, an HIV RNA decrease >110og10 from BL to W12/20 was observed in 26% vs
62% (p= 0.007), with 15% vs 38% of pts having HIV RNA < 400 copies/ml (p=
0.053) respectively in Imm. G vs Def. G. The observed median decrease in HIV
RNA was - 0.371og10 vs -1.91 log10 (p=0.008) respectively in Imm. G and Def. G
groups. Tolerance was acceptable. Gigatherapy reduction (<6 drugs) occurred in
5 pts. Follow-up until 24 weeks is on going.
Conclusion: In patients with extensive viral resistance and no current therapeutic
options, a TI of 8 weeks followed by a multi-drug salvage regimen induces, after
12 weeks, a significantly higher benefit than no TI in terms of antiviral efficacy
Presenting author: christine katlama, Hopital Pitie-Salpetriere, 47 Bd de
I'Hopital, 75013 Paris, France, Tel.: [phone], Fax: [phone]
66, E-mail: christine.katlama @ psl.ap-hop-paris.fr
WePeB5888 Evolution of the human immunodeficiency virus
type 1 (HIV-1) env gene isolated from patients
under structured treatment interruptions
M. Arnedo1, A. Mas2, C. Gill, F. Garcia1, E. Domingo2, J.M. Gatell1,
T. Pumarala1. 1Hospital Clinic de Barcelona-IDIBAPS, Hospital Clinic de
Barcelona, Villarroel 170, Servicio Microbiologia, esc. 11 planta 5, Spain;
2Universidad Autdnoma de Madrid-CSIC, Madrid, Spain
Background: env gene of HIV-1 has a high sequence diversity, being a good region to analyze gene evolution. Virus-host interactions are one of the main forces
driving env gene evolution. The objective of the study was to analyze the HIV-1
evolution during the course of Structured Treatment Interruptions (STIs).
Methods: Six patients of a cohort of 9 early stage chronically infected HIV patients were included. Three cycles of STI were performed in this group of patients.
A control group of 4 matched CD4 and viral load antiretroviral naive patients,
with a 1 year of followed-up, were also studied. RNA was extracted from plasma
samples at different times, the C2/V4 region was amplified by RT-PCR, and the
PCR products were sequenced. Nucleotide sequences were aligned using the
CLUSTALX version 1.8 program. Pairwise DNA matrices, generated using the
Kimura two-parameter model and phylogenetic analyses, were determined with
the use of the PHYLIP package.
Results: Both genetic distances and mutation frequency were calculated for each
patient. Genetic distance (mean ~ SD) was 3.76 + 1.91 for the STI group and
3.47 ~ 3.52 for the control group. Mutation frequencies (mean ~ SD) were 0.017
~ 0.004 substitutions per nucleotide (s/nt) for the STI group and 0.017 ~ 0.008
s/nt for the control group. No significant differences between these two groups
were detected when the two parameters were compared. The phylogenetic tree
showed a topology with the samples of each patient clustered together.
Conclusion: Evolution of HIV-1 env gene does not appear to be significantly
modified by Structured Treatment Interruption.
Presenting author: Mireia Arnedo, Hospital Clinic de Barcelona, Villarroel
170, Servicio Microbiologia, esc.11 planta 5, Spain, Tel.: [phone], Fax:
[phone], E-mail: arnedo@ medicina.ub.es
WePeB5889 Effect of structured therapy interruption on HIV
rebound and CD4-mediated cell functions
D. Vincenti, S. Carrara, C. Montesano, S. Topino, C. Agrati, F Poccia,
N. Petrosillo, G. Ippolito, G. D'Offizi, D. Goletti. IRCCS L. Spallanzani, Via
Portuense 292 Roma 00149, Italy
Structured therapy interruption (STI) may boost anti-HIV specific immunity acting as an autologous live vaccine. Nevertheless, STI may present the potential
risks of HIV-mediated loss of CD4+ cells and severe constitutional symptoms. We
evaluated the effect of STI on the CD4-mediated immune function in chronically
HIV-1 infected asymptomatic patients with undetectable HIV-RNA plasma during
at least two years. A clinical and immunological follow-up was performed at the
suspension of HAART (TO), after 1 month from the suspension (Ti), at the re
sumption (T2), and after 30 days from HAART-resumption (T3). Twelve patients
were studied in terms of modulation of CD4 cell number and percentage (naive,
long term memory and effector phenotype) and HIV-load. Immune response to
mitogen, HIV protein (p24), recall antigen were studied overtime in terms of cell
proliferation and IFNg production, both evaluated at day 7 post culture in thawed
cells. The results show a statistically significant decrease of CD4 cell number
during the period of therapy interruption (TO vs T1, p=0.004) that correlated with