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

XIV International AIDS Conference

Abstracts WePeB5898-WePeB5901 55

WePeB5898 Extended treatment interruption in HIV-infected
patients with maximal viral suppression
C. Achenbach, M. Deloria Knoll, M. Till, S. Terp, F. Palella, A. Kalnins,
R. Murphy. Northwestern University, 676 N. St. Clair St., Suite 200, Chicago, IL,
60611, United States
Background: Relatively short-term treatment interruption (TI) has been studied
as a strategy aimed at boosting immune responses and minimizing drug-related
toxicities. This study describes the results of long-term TI where treatment was
resumed when CD4 counts declined and/or HIV-RNA (VL) increased significantly.
Methods: Prospective observational cohort study at a university AIDS clinic. Eligible patients (pts) had VL <500 (c/mL) for >6 m while on ART before initiating
a TI lasting for >28 d. Demographics, CD4 (per mm3), and VL were analyzed
before, during and after the TI. Hypothesis testing was performed using Wilcoxon
rank scores.
Results: 20 pts were eligible for analysis including 10 women, 9 with lipodystrophy, 8 with prior AIDS and 5 on a PI-based regimen. Pre-TI, nadir CD4 mean=299
(27-926) and zenith VL median=25,279 (400-375,000). Immediate pre-TI, CD4
mean=755 (276-1135). Median TI duration was 30 wks (4-168). Overall, mean
change in CD4 during TI was -299. Median max
VL during TI was 75,000. End-TI, CD4 mean=360 (69-596) and VL median=83,653. Pts who resumed therapy had a max mean change in CD4 of +374
and all on HAART resuppressed VL to <500. 4 pts developed uncomplicated
herpes virus outbreaks during TI. Parameters associated with greater declines in
CD4 during TI were male gender (-419 v -179, P=.05), PI-based therapy (-562 v
-211, P=.012), and hx of lipodystrophy (-440 v -183, P=.03).
Conclusions: 50% of pts with maximal VL suppression remained off treatment
for >30 wks. Despite a significant decline in CD4 and increase in VL during an
extended TI, therapy was reintroduced safely and effectively. Significantly larger
declines in CD4 were observed in particular pts. Neither nadir CD4 nor zenith
VL impacted the duration of TI. These findings suggest that, in selected pts, TI
may be a safe and effective means of reducing drug exposure, which may impact
long-term complications, quality of life and cost of therapy.
Presenting author: Chad Achenbach, 676 N. St. Clair St., Suite 200, Chicago,
IL, 60611, United States, Tel.: [phone], Fax: [phone], E-mail:
c-achenbach @ md.northwestern.edu
WePeB5899 Antiviral potency and tolerability of a convenient
once a day direct observed therapy with
amprenavir containing haart regimen in an
antiretroviral naive, inner-city minority patients
with poor HIV knowledge and very advanced AIDS
D. Jayaweera1, T Tanner', A.M. Nowak2, M. Brill2, J. Pottage2, R. Campo',
A. Rodriquez', M. Kolber'. 'Division of Infectious Diseases, University of Miami,
1500 nw 12th avenue, 8 west, miami, fl 33136, United States; 2Vertex
Pharmaceuticals Incorporated, Cambridge, United States
Background: Inner-city minority patients with, multiple social problems, substance abuse and poor HIV specific knowledge tend to be non adherent with
antiretrovirals. Once a day direct observed therapy (DOT) may improve the adherence and outcomes. We evaluated a HAART regimen in patients with advanced
disease and most with multiple opportunistic infections (01).
Methods: Prospective, nonrandomized, pilot study in an inner city, hospital based
clinic. Antiretroviral naive patients were treated with Amprenavir 1200mg, Ritonavir 200mg, Videx ECTM 400mg and lamivudine 300mg once a day. Patients were
given DOT and the non-compliant patients were discontinued from the study
Results: Twenty patients were enrolled. Mean age was 38 years and 85% were
men. All were minority patients. Heterosexuals accounted for 80%. Two months
before and within 2 months after enrollment patients had 13 Ols. The median,
mean and mode of the HIV VL are given below with CD4 cell changes. The median. VL decreased from 177,500 copies/mm3 to 56 copies at week 24 while the
CD4 cell count increased from 88 to 141 cells/mm3 at week 24. There were no
limiting adverse events except one case of grade 2 hepatitis. At week 24, 70%
had the HIV VL <400 copies/mm3.
BL(20) W4(19) W8(19) W12(19) W16(17) W20(14) w24(10)
VL Mean 273783 1555 653 554 5327 470 2782
Median 177500 766 369 110 67 138 56.5
Mode 750000 400 400 50 50 50 50
CD4 Mean 88 210 198 164 169 135 141
Cells S.E. 30.2 56.4 41.5 26.2 29.9 16.3 18.6
Median 20 145 156 128 134.5 124 132
Number of subjects in parenthesis, w = weeks, BL = baseline
Conclusion: This regimen of once a day DOT with Amprenavir, Ritonavir, Videx
ECTM and Epivir shows good potency and tolerability in a very challenging population to treat. Larger study with a more compliant population without DOT should

be undertaken.
Presenting author: dushyantha jayaweera, 1500 nw 12th avenue, 8 west, miami, fl 33136, United States, Tel.: [phone], Fax: [phone], E-mail:
[email protected]

WePeB5900 The effect of mycophenolic acid and ribavirin on
the anti-HIV activity of amdoxovir (DAPD)
J. Harris, K. Borroto-Esoda, F. Myrick, G. Painter. Triangle Pharmaceuticals, Inc.,
4611 University Dr., PO. Box 50530, Durham, NC 27717-0530, United States
Background: Amdoxovir (DAPD, (-)-p-D-2,6-diaminopurine dioxolane) is a selective inhibitor of HIV-1 replication in vitro and in vivo. DAPD is deaminated by
adenosine deaminase to yield (-)-p-D-dioxolane guanine (DXG) which is subsequently converted to the corresponding 5-triphosphate DXG-TP, a potent inhibitor
of the HIV-RT (Ki = 0.019 VM). Mycophenolic Acid (MPA) and ribavirin inhibit the
de novo synthesis of guanosine nucleotides by inhibition of inosine monophosphate dehydrogenase (IMPDH). Reduction of intracellular dGTP levels through
inhibition of IMPDH may effectively increase the intracellular concentration of
DXG-TP thereby augmenting inhibition HIV replication.
Methods: The effects of MPA and ribavirin on the antiviral activity of DAPD and
DXG against wild type (WT) and mutant strains of HIV-1 were analyzed in PBMC
and in the laboratory adapted T-cell line MT2.
Results: When tested against WT HIV-1 in MT2 cells, both MPA and ribavirin
decreased the apparent EC50 for DXG by 1 log. Assays in PBMCs showed that
addition of 0.25 ItM MPA or 20 IM ribavirin completely inhibited virus replication
at all concentrations of DXG tested. HIV-1 isolates containing the L74V, K65R or
Q151M mutations are 4-10 fold less sensitive to inhibition by DXG than WT virus.
Addition of 0.25 IM MPA or 20 IM ribavirin completely reversed the DXG resistance observed with these isolates. Similarly, when tested against a virus fully
resistant to inhibition by DXG (K65R/Q151M, EC50 =80kM) MPA and ribavirin
decreased the apparent EC50 for DXG to within 5-fold of WT The combination
of 0.25 VM MPA or 20 IM ribavirin was not cytotoxic to the cells in these assays.
In addition, when tested at physiologically relevant concentrations, neither compound demonstrated mitochondrial toxicity, alone or in combination with DAPD or
DXG.
Conclusions: These data suggest a role for the use of IMPDH inhibitors in combination therapy with amdoxovir for the treatment of HIV.
Presenting author: Phyllis McDade, 4611 University Dr., PO. Box 50530,
Durham, NC 27717-0530, United States, Tel.: [phone], Fax: +1 919
493 5925, E-mail: [email protected]
WePeB5901I Protease inhibitor-sparing regimens containing
nevirapine, Efavirenz, or Abacavir achieve
long-term HIV-1 Aviremia and CD4 stabilization but
do not improve metabolic complications
P. Greiger-Zanlungo', G. Blick2, T. Garton3, S. Sharfuddin4, Z. Arzu4. 1Mt.
Vernon Hospital/New York Medical College, Teaneck, NJ, United States; 2Blick
Medical Associates, Stamford CT; 3Blick Medical Associates, Stamford CT
United States; 4Mt Vernon Hospital, Mt. Vernon NY, United States
Background: Protease inhibitor (PI)-containing regimens have reduced mortality
for patients with HIV/AIDS and made HIV a chronic and manageable disease.
PIs have been implicated in causing metabolic complications. This trial assessed
whether HIV-1 aviremia and CD4 can be maintained long-term (>12 months)
and if metabolic complications can be reversed in HIV/AIDS pts switched from
PI-containing to PI-sparing regimens.
Methods: Pts who had been successfully treated with PI-containing regimens for
at least 1 year and had PCR<500 copies/ml for at least 6 mos on these regimens were analyzed. 28 patients were switched from PI-containing to PI-sparing
regimens composed of 2 NRTI plus either nevirapine (NVP, Arm A, n=14), or
Efavirenz (EFV, Arm B, n=6), or Abacavir (ABC, Arm C, n=8). Pts had PCR, CD4,
and metabolic assessments every 3 mos.
Results: After a median follow-up of 37 mos., 86% of pts. in all 3 Arms maintained
PCR<600 and had stable CD4 counts with increased CD4%. 7/8 pts in Arm C
and 4/6 in Arm B maintained PCR<50, the exceptions maintaining PCR<600;
10/14 Arm A pts. kept PCR<50, with 3 pts staying <2000 and 1 <20,000. CD4
count remained stable in ARMs B and C but increased in ARM A, while all 3
ARMS had mean increased CD4% from baseline (ARM A +11.6%, ARM B +7%
and ARM C +36.4%). Metabolic complications (elevated cholesterol, triglycerides,
and AST/ALT) initially improved, but after 12 mos returned to baseline and were
similar in all groups.
Conclusions: Long-term treatment greater than 3 years with PI-sparing regimens containing either NVP, EFV, or ABC were equally effective in maintaining
aviremia and stable CD4 in HIV/AIDS pts, but ABC increased CD4% more than
NVP or EFV. Metabolic complications did not improve over the long-term when
compared to previous PI-containing regimens.
Presenting author: Paola Greiger-Zanlungo, 1333 Somerset Rd, Teaneck, New
Jersey, 7666, United States, Tel.: [phone], Fax: [phone], Email: [email protected]