Bridging the Gap: Conference Record [Abstract book, International Conference on AIDS (12th: 1998: Geneva, Switzerland)]

12th World AIDS Conference

Abstracts 22384-22388 341

22384 Full compliance sustains viral suppression during
tritherapy initiated at primary HIV-1 infection
Catherine Tamalet, I. Poizot Martin, N. Yahi, G. Lepeu, J. Moreau, H. Gallais,
J.A. Gaytaut. 'Hdpital Timone Laboratoire Virologie 264, Rue St Pierre 13385
Marseile Cedex 5; 2 Hdpital St Marguerite, Marseille; 3Hopital Timone, Marseille;
4 Hpital D'Avignon, Avignon; 5 Hpital Houphovet Boigny, Marseille; 5Hopital
Conception, Marseille, France
Objective: To assess viral load and CD4 count in PHI patients (pts) treated during
3 to 18 months according to 1) - the degree of compliance with the regimen drug.
2) - the resistance associated mutations detected prior to start of tritherapy.
Design/Methods: open-label study of 30 HIV-1 infected pts (15 males, 15 females) included between august 1995 and june 1997. They received RT inhibitors
with or without one protease (Pr) inhibitor initiated at early seroconversion (WB
<3 bands in 28 pts). Sequential measurements of plasma and PBMC virus load
including the Roche ultrasensitive assay. Analysis of resistance mutations by DNA
sequencing of the RT-Pr gene at baseline and in the course of follow-up. Baseline
characteristics of pts: CD4 count: 547/pl plasma viral load (PVL): 5.85 log/ml;
PBMC HIV-1 DNA: 3.91 log/106 cells; PBMC HIV-1 RNA: 3.91 log/106 cells.
Genotypic analysis prior to therapy: RT mutations in 6/27 pts (22%): T215Y/F (6
pts); M41L (3); T69D (1); M184V (1). Protease mutations: L63P (21 pts); V771/D
(10); L10I/D (4); K20M (3); D30N (3); A71D (2); M361 (1), M461 (1); V82A (1). Pr
gene: -3 mutations in 5/24 pts (21%).
Results: Viral load (VL) mean log reduction (mlr) in compliant (C) and poorly
compliant (PC) pts:

Months (M)
PVL - 50 c/ml n
PVL mlr
PBMC HIV-1 DNA (mir)
PBMC HIV-1 RNA (mlr)

M3 M6 M9
C PC C PC C PC
9/24 0/6 15/19 0/6 9/15 0/5
3.32 -0.86 3.35 0.80 -3.42 -0.87
1.02 0.76 1.21 0.38 --1.43 --0.51
1.95 --0.75 1.94 -0.58 -2.61 +0.48

M12 M18
C PC C PC
8/12 0/4 4/6 0/2
--3.71 --0.95
-1.36 -0.56
-2.00 -0.62

During the follow-up: emergence of RT mutations associated with ZDV resistance in 3 pts: K70R (2 pts); L210W (1 pt) due to a transient lack of compliance
(rebound in viral load). No additional protease mutation.
Conclusion: Maximum CD4 response at M9 (+219) in compliant pts. 79%
of compliant pts had undetectable plasma viral load at M6. Resistance associated mutations detected prior to therapy did not prevent viral load decrease in
compliant pts. No additional RT-Pr mutation emerged in compliant pts during the
follow-up.
22385 Evolution of the antiretroviral prescription in France,
from June 1994 to September 1997
Sophie Courtial-Destembert, J.M. Nadal, F. Bourdillon, L. Cavaignac. Ministere
De La Sante, 8, Avenue De Segur, Paris, France
Objectives: Since the announcement of the ACTG 175 and Delta surveys, antiretroviral prescriptions have changed considerably in France. To observe the
changes, we conducted a study from data obtained from the DMI2 information
system.
Methods: This system is a national, multicentred database localised in the
specialized HIV services known as CISIH. The evolution of antiretroviral prescriptions was observed on a yearly basis from June 1993 to June 1996 and on a
three monthly basis from June 1996 to September 1997.
Results: The following changes were observed:
- an increasing number of patients are under treatment: 59.4% in 1993, 86.7%
in September 1997;
- among the treated patients in 1993, 90% were under monotherapy, in the
third quarter of 1997, they were 1.1%;
- in 1993, 10% of the patients treated had dual therapy, in September 1997
dual therapy was prescribed for 38.6% of them, triple therapy for 54.5% and four
antiretroviral agent therapy for 5.8% of these patients;
- in September 1997, the most frequent combinations prescribed were lamivudine + indinavir + stavudine, (17.3% of patients treated) then lamivudine +
zidovudine (11.1%) and thereafter zidovudine + lamivudine + indinavir (10.9%).
Conclusions: The increase in the number of patients treated and, among
these patients, the wide prescription of antiretroviral polytherapy could be linked
to the decrease in AIDS cases and inpatient days observed in France in 1996
and 1997.
22386 Initial effectiveness and tolerability of nelfinavir (NFV) in
combination with efavirenz (EFV, SUSTIVATM, DMP 266) in
antiretroviral therapy naive or nucleoside analogue
experienced HIV-1 infected patients: Characterization in a
phase II, open-label, multicenter study at 24 weeks (Study
DMP 266-024)
Elaine Eyster', J. Jemsek2, S. Kagan3, G. Martin4, D. Seekins5, R. Steigbigel6,
D.J. Manion7. 1 The Milton's Hershey Medical Center, Hershey, PA; 2Nalle Clinic,
Charlotte, NC; 3Georgia Research Associates, Atlanta, GA; 4National Naval
Medical Center, Betjesda, MD; 5St. Joseph's Comprehensive Research Ctr,
Tampa, FL; 6Sunny Health Science Center, Stonybrook, NY; 7DuPont Merck
Pharmaceutical Company, Wilmington, DE, USA
Background: EFV is a once-daily nonnucleoside HIV-1 reverse transcriptase

inhibitor (NNRTI) that has been studied in combination with indinavir, zidovudine,
lamivudine, and stavudine.
Objectives: To characterize the effectiveness (decrease in HIV-1 RNA and
increase in CD4 cells) and safety of EFV in combination with NFV in antiretroviral
therapy naive or nucleoside analogue reverse transcriptase (NRTI) experienced
HIV-1 infected patients.
Methodology: A 48-week, open-label, single-arm, multicenter study at 10 sites
enrolling a total of 63 patients: 30 antiretroviral naive (Group A) and 33 NRTI
experienced (Group B). At the beginning of the trial, EFV (600 mg qd) and NFV
(750 mg q8h with food) were administered open-label, and all other antiretroviral
agents were discontinued.
Patient Eligibility: HIV-1 RNA > 1 x 105 copies/mL; CD4 > 50 cells/mm3.
Exclusion Criteria: Prior treatment with any NNRTI or PI; prior treatment with
any other experimental drug within 30 days prior to initiating study treatment.
Study Design: An open-label study; one arm (EFV + NFV) without randomization from nucleoside experienced and nuceloside naive patient populations.
Patient Demographics: Preliminary data, patient demographics:
Overall: Male = 93%, Caucasion = 76%, mean age = 36.5 (~10.5) years, mean
years HIV-1 (+) = 4.4 (~4.68), mean log HIV-1 RNA = 4.57 (~0.6), mean CD4
count = 370 (~198) cells/mm3.
NRTI naive: Male = 93%, Caucasion = 77%, mean age = 37.4 (~9.2) years,
mean years HIV-1 (+) = 3.2 (~5.1), mean logo1 HIV-1 RNA = 4.61 (~0.5), mean
CD4 count = 418 (~214) cells/mm3
NRTI experienced: Male = 92%, Caucasion = 75%, mean age = 35.3 (~12.0)
years, mean years HIV-1 (+) = 5.8 (~3.9), mean loglo HIV-1 RNA = 4.52 (~0.6),
mean CD4 count = 314 (~164) cells/mm3.
Results - Activity: HIV-1 RNA. At 24 weeks, mean HIV-1 RNA decrease
(truncated analysis, where a value of 400 is assigned to <400 copies/mL) and
percent BQL (<400 copies/mL) will be presented.
CD4. Mean increase of CD4 cells observed will be presented.
Results - Tolerability: After 24 weeks, the treatment has been generally
well-tolerated. Adverse events (AEs) and early withdrawals from the treatment
regimen will be presented.
Conclusions: The combination of EFV and NFV is effective and safe in the
treatment of HIV-1. Concomitant administration of EFV and NFV does not require
any dose alterations. The combination is generally well-tolerated and offers an
NRTI sparing approach in both therapy naive and NRTI experienced patients.
22387 Predictors of maximal viral suppression in clinical
practice
Alexandra Moses1'2, V. Waring2, I. Salit2, K. Logue2, A. Humar2, S. Walmsley2.
'The Toronto Hospital, CW-g - 315, 200 Elizabeth St., Toronto, ON M5G 2C4,
2University of Toronto, Toronto, ON, Canada
Background: Following the publication of the International AIDS Society-USA
guidelines for antiretroviral (AR) therapy and the availability of viral load (VL)
testing many patients (pts) changed their AR therapy in attempts to achieve
maximal VL suppression (<500 copies/ml).
Objective: To determine what portion of pts in clinical practice achieve maximal VL suppression with a change in therapy in response to a detectable VL. To
identify factors which predict which pts reach this goal.
Methods: Retrospective case review of 296 randomly selected pts attending a
hospital based tertiary care HIV clinic. Pt data was collected from the time of their
first VL determination (available in our centre in 11/96) until 12/97.
Results: Of the 296 pts, 48 (16%) had a VL < 500 copies/ml through the entire
study period and are excluded. An additional 14 pts with only one VL measure
and are also excluded. Of the remaining 234 pts, 185 had a change in therapy
in response to a detectable VL and form the cohort for the analysis. Suppression
of VL to <500 copies/ml was achieved in 118 (64%) pts. Univariate analysis
demonstrated that pts who achieved maximal viral suppression with a change
in therapy were more likely to have a higher mean baseline CD4 count (279 vs
165/mm3, p <.001) and lower mean baseline VL (4.2 log copies/ml vs 4.5 log
copies/ml, p =.008). Prior use of PI was strongly predictive of failure to maximally
suppress VL (54% vs 75%, p =.006). The number of AR agents changed was
not different between the 2 groups (2.27 vs 2.33, p >.05). Logistic regression
confirmed baseline CD4 (OR 1.4 per 100/mm3 cell increase, 95% Cl 1.13-1.75,
p =.003) and prior lack of PI use (OR 1.96, 95% Cl 1.02-3.80, p =.045) as
predictors of maximal suppression.
Conclusion: Maximal viral suppression was possible for the majority of pts in
our out-patient clinic setting. This response was more likely for pts with higher
CD4 counts and was less likely for those with PI experience.
S22388 HIV replication persists in patients receiving HAART
despite undetectable plasma virus
Ven Nata Rajan', T.W. Chun2, D.P. O'Neill1, J.A. Metcalf2, J. Mican2, D. Engel2.
A.S. Fauci2, H.C. Lane2, J.A. Kovacs2. 1 NCI - FCRDC - S AIC, O. Box B.
Frederick, Maryland;2 National Institute of Health Bethesda, MD, USA

Objective: To determine if there is ongoing HIV replication in patients receiving
highly active antiretroviral therapy (HAART) who have less than 50 HIV RNA
copies/ml in plasma.
Methods: Cells from eleven patients receiving HAART for a year or longer, nine
of whom had also received intermittent interleukin-2 therapy, who had less than 50
copies of viral RNA in plasma, as determined by RT-PCR, were examined for the
presence of HIV RNA using a nested RT-PCR assay (sensitivity, 20 copies/106