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

XIV International AIDS Conference

Abstracts ThOrB1439-ThOrB1442 379

ThOrBi439 Prolonged treatment interruption after immunologic
response to HAART
M.A. Parish1, P Tarwater2, M. Lu2, C. Raines1, J.E. Gallant1. 'Johns Hopkins
University School of Medicine, Baltimore, United States; 2Johns Hopkins
Bloomberg School of Public Health, Baltimore, United States
Background: There is growing interest in treatment interruption (TI) after response to HAART. We present data on 75 patients who stopped HAART and
assess predictors of reinitiation (RI) and CD4 decline.
Methods: Patients entered an observational database when the clinician interrupted HAART with the plan to reinitiate based on lab parameters. CD4 count
and viral load (VL) were evaluated pre-HAART, on HAART, during TI and following RI.
Results: 75 patients underwent TI. Med. pre-HAART CD4 was 426 and med. VL
was 27,000. Med. CD4 at TI was 677 and VL was 263 (<50 in 24 [32%]). Of the
23 (31%) who have resumed therapy (mean TI 30 wks), med. CD4 decline was
258 and med. VL increase was 122,000. Med. CD4 at RI was 258 and med. VL
was 160,500. Among the 52 (69%) who remain off therapy (mean TI 69 wks),
med. CD4 is 508 with a med. decline of 255 and med. VL is 22,151. 14 (64%)
of resumers and 17 (33%) of non-resumers met current DHHS criteria for initiation pre-HAART. By univariate analysis correlates of RI included CD4 pre-HAART
(OR 0.6, p=.003) and on HAART (OR 0.73, p=.003). VL and CD4 during TI were
also correlated with resumption (p<.01). VL during TI was associated with rate
of CD4 decline (p=.042). By multivariate analysis a lower CD4 count at HAART
initiation predicted RI (OR=.64, 95% Cl 0.46-0.87). The rate of CD4 decline was
314/yr for resumers and 115/yr for non-resumers (p=.003), with estimated med.
times to CD4 <200 assuming continued
TI of 0.7 yrs and 3.9 yrs for non-resumers (p<.001).
Conclusions: 69% of our cohort remain off therapy after a mean TI of 69 weeks.
Low pre-HAART CD4 predicted RI and VL rebound was correlated with rate of
CD4 decline. Thus the best candidates for prolonged TI are those with higher
baseline CD4 counts and lower viral loads, patients who are less likely to be
treated based on current guidelines. Randomized trials are needed to assess the
safety and durability of prolonged TI and the related strategy of pulse therapy.
Presenting author: Joel Gallant, Johns Hopkins University School of Medicine,
Division of Infectious Diseases, 1830 E. Monument St. #443, Baltimore, MD
21287, United States, Tel.: [phone], Fax: [phone], E-mail: [email protected]
I ThOrB1440 Treatment discontinuation in patients who started
antiretroviral therapy following the 1996 IAS-USA
Recommendations. A prospective randomized trial
A.J. Krolewiecki1, C. Zala1, A. Gun1, C. Ochoa1, H. Perez', M.B. Bouzas',
I. Cassetti2, R Cahn1. 'Fundacion Huesped, peluffo 3932, (1202), Buenos
Aires, Argentina; 2FUNCEI, Buenos Aires, Argentina
Background: HIV treatment guidelines have evolved to a delayed indication to
start therapy. Patients who have started therapy under older guidelines might benefit from treatment discontinuation. Toxicity, cost, quality of life (QOL) and drug
preservation are areas where these discontinuations might have an impact.
Methods: HIV+ individuals on HAART for >6 months and no history of failure,
with a nadir CD4 count >350 cells and a pre-therapy viral load (VL) under 60000
copies/mL are randomized to stop (DISC) or continue (CON) with current HAART.
The CON group receives standard care; and the DISC is followed at monthly intervals for 24 weeks and every 8 weeks until week (W) 48. Clinical, virologic,
immunologic and metabolic parameters are followed in both groups. QOL and
economic analysis are performed. Patients are re-started on therapy when they
reach clinical or laboratory endpoints (CD4<350 or VL >1 log from pre-therapy
at 2 consecutive visits).
Results: Accrual as of 12/2001 was 28 patients. Baseline CD4 counts were 610
and 618 in the DISC and CON groups respectively No clinical events were seen
and no clinical or laboratory endpoints were reached. VL in the DISC group became detectable with peaks between weeks 4 and 12. At W12 and W24 all patients had VLs within 1 log of the pre-therapy values (mean VL of 4.28, 4.20 and
3,79 at pre-therapy, W12 and W24 respectively). Mean CD4 was 544 cells at
W12. LDL showed a decrease from a mean of 132mg/dl at baseline to 116 and
90 in W12 and W24. In the CON group CD4 and metabolic parameters remained
stable. Lipodystrophy developed in 2 patients after discontinuation. Two patients

interrupted therapy in the CON group due to side effects. Economic and QOL
analysis are ongoing.
Conclusions: Patients who would not have been started on HAART with current
guidelines can safely stop therapy and remain off-drugs for at least 24 weeks.
Longer follow-up is warranted to confirm these preliminary results.
Presenting author: alejandro krolewiecki, peluffo 3932, -1202, Buenos Aires,
Argentina, Tel.: [phone], Fax: [phone], E-mail: alekrol@hotmail.
com
ThOrB1441 Dynamics of viral rebound in plasma and semen
after stopping effective antiretroviral therapy
G. Liuzzi, G. D'Offizi, S. Topino, A. Amendola, M. Capobianchi, C.F. Perno,
P. Narciso, A. Antinori. NIID-L. Spallanzani, INMI - L. Spallanzani, Via Portuense
292, 00149 Roma, Italy
Background: The persistence of a reservoir of HIV in genital tract compartment
can be considered as an impediment to the long-term control and/or eradication
of HIV in infected individuals who are receiving HAART: The pathogenic significance of this reservoir as well as its involvement in the rebound of plasma viremia
after discontinuation of HAART remain to be fully delineated.
Structured interruptions of antiretroviral therapy of HIV-1 infected individuals are
currently being tested in clinical trials to study the effect interruptions have on the
immune responses and control of virus replication.
Methods: We examined the dynamic of viral load rebound in plasma and semen in 12 HIV-1-infected patients who decided to discontinue HAART after 1
year of HAART treatment and effective virologic response. We also assessed the
response after reintroducing the same therapy. Peripheral blood and semen specimens were collected at baseline and every 4 weeks for determination of viral load
by bDNA methodology.
Results: See table below.
Conclusions: We reported preliminary observations about rebound of HIV-RNA
in semen during discontinuation of HAART Our data suggest that discontinuation
of treatment is always associated with viral rebound in plasma and semen and
that after reintroduction of HAART is possible to obtain an effective virologic response also in semen.These data reinforce the body of evidence that during the
viral replication the male genital tract is a separate compartment to plasma.
Presenting author: Giuseppina Liuzzi, INMI - L. Spallanzani, Via Portuense 292,
00149 Roma, Italy, Tel.: [phone], Fax: [phone], E-mail: giusi.
liuzzi @ libero.it
ThOrB1442 Expansion of pre-terminally differentiated CTL in
HIV-infected persons presenting a rapid viral
rebound during structured treatment interruption
F. Poccia, C. Montesano, C. Gioia, M. Amicosante, C. Agrati, S. Topino,
P. Narciso, G. Ippolito, L.P. Pucillo, G. DOffizi. National Institute for Infectious
Diseases "Lazzaro Spallanzani" - IRCCS, National Institute for Infectious
Diseases, Lab. Immunopathology, Rome, Italy
Background: Since structured antiretroviral treatments (STI) may boost anti-HIV
specific immunity, we analysed the influence of STI on CD8 T cell dynamics and
HIV viral rebound.
Methods: Twenty-six chronically HIV-1 infected asymptomatic patients with undetectable HIV-RNA plasma during at least two years of HAART were divided in
two groups: one group of patients with a rapid viral rebound and a second group
of patients with a delayed viral rebound during STI. A clinical and immunological
follow-up was performed at the suspension of HAART (tO), after 1 month from
the suspension (ti), at the resumption of HAART (t2), and after 30 days from
HAART-resumption (t3). HIV-specific CD8 T cell frequencies were measured by
flow cytometry as intracellular cytokine-staining. Naive, central and effector memory CD8 T cell subsets were monitored using specific differentiation markers:
CD45RA, CD27 and CCR7.
Results: We observed a delayed viral rebound in a relevant fraction of our
STI patients, presenting no significant changes in the immunological parameters
during a prolonged drug-free period. In contrast, we observed a rapid expansion of circulating CD8 T lymphocytes in HIV-infected persons presenting a sustained viral rebound during STI. In these patients, the frequencies of CD8 T cells

Abstract ThOrB1441 - Table
Pts Plasma VL Semen VL Highest plasma VL Highest semen VL Nadir plasma VL Nadir semen VL STI time Time from restarting
at STI at STI during STI during STI after restarting after restarting (days) (days)
001 729 <50 34,184 1,566 105 <50 118 35
002 <50 <50 17,822 17,736 <50 <50 77 281
003 <50 <50 22,563 2,248 <50 202 114 33
004 <50 <50 254,025 >1,000,000 440 412 120 27
005 <50 <50 42,943 154,730 112 82 89 27
006 69 <50 163,421 6,384 n.e. n.e. n.d. n.d.
007 80 <50 >500,000 2,120 774 <50 34 34
008 <50 <50 45,055 32,636 n.e. n.e. n.d. n.d.
009 <50 <50 93,000 4,118 100 <50 192 253
010 <50 110 39,000 6,020 n.e. n.e. n.d. n.d.
011 2,500 <50 15,670 2,650 n.e. n.e. n.d. n.d.
012 <50 <50 15,266 1,096 n.e. n.e. n.d. n.d.