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

12th World AIDS Conference

Abstracts 12329-12332 79

Results: daily vitamine C did not modify urinary pH. But daily Coca-Cola light
significantly lowered urinary pH. From April 97 to september 97, only 2 new
patients presented urologic complications. But urine acidification with Coca-Cola
light did not prevent the recurrences of nephrolithiasis in 2 patients (5 times in
one case and 3 in the other).
Lessons Learned: dietetic counselling decreases the risk of urologic complications due to Indinavir but the modest urine acidification induced by Coca-Cola
light could not prevent nephrolithiasis in some cases.
112329 Effect of nelfinavir/indinavir/delavirdine in HIV+ patients
with extensive antiviral experience
Larry Lyle, G. Strebel. Apogee Medica Group 3415 Sixth Avenue San Diego CA
92103, USA
Objective: To review the efficacy and safety of combination therapy with nelfinavir (NFV), indinavir (IDV), and delavirdine (DVD) in HIV+ patients with extensive
antiretroviral experience.
Design: Retrospective analysis.
Methods: The charts for 25 patients seen at a community-based HIV clinic
were reviewed. Patients were predominantly white (88%), male (96%), and homosexual (96%). Duration of HIV infection ranged from <5 years (9 patients), 5-10
years (12 patients), and -10 years (4 patients). Only 1 patient was drug naive; 24
(96%) had been extensively pretreated with multiple nucleosides. 18 (72%) of 25
patients had been treated with at least one protease inhibitor. The combination
regimen (NFV, IDV, and DVD) was administered bid to 12 patients, tid to 13
patients. In addition to the combination regimen, most patients were taking at
least two other antivirals, most commonly lamivudine (3TC) and stavudine (d4T).
Combination therapy was initiated in all patients within 30 days.
Results: The baseline viral load (VL) for all patients ranged from 1.69-6.1
log (mean, 4.25 log). The baseline CD4 cell count ranged from 12-504 cells/mL
(mean, 239). Following combination therapy, the VL decreased by 1.30 log at 1
mo, 1.05 log at 3 mo, and 1.12 log at 6 mo. The VL was undetectable (<400) in
20% of patients at baseline, 52% patients at 1 mo, and 50% of patients at both 3
mo and 6 mo. The CD4 count increased by 41 at 1 mo, 40 at 3 mo, and 28 at
6 mo. Adverse events, reported by 14 patients, included diarrhea, fatigue, rash,
and nausea. There were no discontinuations of therapy because of AEs.
Conclusions: In HIV+ patients infected for <5 years and with heavy antiviral
experience, combination therapy with NFV, IDV, and DVD appears to decrease
the VL and increase the CD4 cell count as early as 1 month after therapy is
initiated. At 1 mo, the VL was undetectable in 52% of patients treated. This effect
was sustained at 6 mo. Additional data analyses, including results of ultrasensitive
assays, will be discussed.

S12331 Changes in CD4+ cell count and the risk of opportunistic
infections or death after highly active antiretroviral
treatment
Geneviene Chene1, Christine Binquet1, J.F. Moreau2, D. Neau 3, J. Ceccaldi4,
F. Dabis3. Gesca Study Group; 1Inserm Unit 330 146 Rue Leo-Saignat, 33076
Bordeaux, Cedex; 2Laboratoire D'lmmunologie, Bordeaux; "Cisih, Bordeaux;
4Service Medecine Interne, Bordeaux, France
Objective: To study the relationship between CD4+ response after initiation of
Protease Inhibitors (PI) and the occurrence of opportunistic infections (01) and
survival.
Design: Prospective, observational cohort.
Methods: We used data of a cohort study, set up in HIV centers of Bordeaux
University Hospital (Aquitaine Cohort), Southwestern France since 1987. Patients
eligible for this analysis were HIV-1 seropositive subjects who were prescribed
at least one available PI between January and December 1996. A Cox model
estimated the independent effect of baseline covariates and CD4+ response, considered as a time-dependent covariate, on the occurrence of new AIDS-defining
01, new AIDS-defining events, Death.
Results: 556 HIV-positive patients were prescribed at least one PI: 34%
saquinavir, 52% indinavir, 14% ritonavir. Median CD4+ at baseline was 95 cells
x 106/L and mean plasma HIV RNA 5.0 log10 copies/mL. After a median follow-up of 230 days, 65 patients experienced a new episode of 01, 79 patients
experienced at least one AIDS-defining event and 24 had died. On average, the
increase in CD4+ cell count was 42 cells x 106/L (sd 74) after a median of 49
days. In the multivariate analysis, CD4+ changes remained associated with the
incidence of 01 (HR = 0.06 when CD4+ at the second measurement >200, p <
0.01), independently of CD8+ cell count >400 (HR = 0.45 vs CD8+ cell count
-400, p = 0.01), and presence of AIDS prior to PI (HR = 3.0 vs absence of AIDS,
p - 0.01). The same prognostic factors were found with progression to any new
AIDS-defining event or death.
Conclusion: In our cohort of patients who are started on PI, the level of
immunological response is linked to the risk for subsequent development of 01
the highest the changes of CD4+, the lowest the risk. It might be important to
know if the interruption of certain types of prophylaxis of 01 is possible when
patients show every sign of immunological, virological and clinical stabilisation
after having been given PI.
12332 Ongoing experience with nelfinavir substitution for
indinavir or ritonavir/saquinavir in HIV+ suppressed
below 400 copies/ml
Calvin J. Cohen1, J.A. Hellinger1, A.J. Stein2, J. Gallant3, J. Gathe4, P. Keiser5.
'CRI of New England, 320 Washinton Street, Brookline, MA; 2CRI South Florida,
Miami, FL; 3Johns Hopkins University, Baltimore, MD; 4Houston, TX; 5Dallas,
TX, USA
Background: The goal of HIV combination therapy is maximal durable suppression, which requires near complete dosing of all agents used. While regimens
using either indinavir or ritonavir/saquinavir are very successful in achieving this
degree of suppression, the side effects and/or dosing requirements may be challenging for some patients. As it has a unique schedule, side effect profile, and
resistance mutation pattern, persons may choose to switch to nelfinavir. The
success when making this switch was the focus of this retrospective chart review.
Methodology: We reviewed records from 5 large clinical practices. Charts
were from any individuals switched from a protease containing regimen on which
the viral load was below the limit of quantification before switching to nelfinavir.
Patients may have also switched other antivirals at the same time though this was
not required. All viral load measures after the switch were recorded; measures
were grouped as week 6, 12, 18, 24 with a three week window. Reasons for
switching were noted.
Results: Data from 53 charts were included: n = 28 on indinavir [I], mean CD4
291 cells/ul (SD 179); and n = 25 on ritonavir/saquinavir [R/S] combination, mean
CD4+ 386 cells/ul (SD 303). Nelfinavir was substituted without other antiviral
changes in 78% of the I group, and 88% of the R/S group. Reasons for switching
included: PI related side effect (36%), medication preference (64%) were similar
between the 2 groups. After the I containing regimens, 18/25 (72%) were below
detection at week 6, 8/12 (67%) at week 12, 5/8 (63%) at week 18, and 1/1 at
week 24. After the R/S regimens, 16/20 (80%) were below detection at week 6.
17/19 (89%) at week 12, 6/12 (50%) at week 18, and 7/12 (58%) at week 24. No
significant difference in HIV suppression between I and R/S groups was noted at
any time point (X2 p > 0.05). CD4+ changes were similar between groups.
Conclusions: In persons with viral load measurements <400 copies/mi on
either I or R/S regimens, switching to nelfinavir resulted in continued viral load
suppression in 72-80% at 6 weeks and 67-89% at 12 weeks. These data indicate
that switching to nelfinavir after viral load suppression on another PI requires early
viral load measures in the first 6 weeks to monitor for the outcome of this switch.
A prospective study with larger numbers and longer follow-up can better define
the potential success for those switching to nelfinavir.

12330I

Efficacy and durability of ritonavir/saquinavir (RTV/SQV)
as salvage therapy after failure of initial protease
inhibitor (PI) regimen

Joel E. Gallant, S. Barnett, C. Raines, C. Hall. 'Johns Hopkins University School
Of Medicine, 600 N Wolfe St Carnegie 292 Baltimore MD 21287 - 6220, USA
Objective: To assess the efficacy and durability of RTV/SQV salvage therapy
following failure of indinavir (IDV) or nelfinavir (NFV), and to determine correlates
of success or failure of salvage therapy.
Design: Retrospective analysis of medical records identified by clinician contact
and through use of the Johns Hopkins AIDS Service computerized database.
Methods: Failure of initial regimen was defined as any detectable viral load
after 16 weeks of therapy confirmed on 2 occasions.
Results: 46 patients were identified as meeting study criteria, of whom 25
were excluded because of documented non-adherence. 12 (71%) of 17 patients
failing IDV continue to respond to RTV/SQV, with HIV viral load (VL) < 400
copies/mL, and persistence of response to a median of 33 weeks of follow-up.
Median VL at the time of switch was 13,507 copies/mL among responders vs.
17,600 copies/mL among the 5 non-responders (p >.05). Reverse transcriptase
inhibitors (RTIs) were switched in all but 1 of the responders and all but 2 of the
non-responders. Among 4 patients failing NFV median VL was 9,150 at switch
among 3 responders. The only non-responder had a viral load of 40,150 at the
time of switch. RTIs were switched in all patients except 1 of the responders.
There were no significant differences in either group between responders and
failures with respect to baseline VL, VL at time of switch, VL at switch as a
percentage of baseline VL, or time on failing regimen prior to switch (p >.05). All
patients continued to be followed to evaluate long-term response.
Conclusions: We identified a number of patients who responded to RTV/SQV
following IDV failure. Findings were similar for NFV, although numbers were
lower. In this small, retrospective study we identified no factors significantly associated with success or failure; however, the difference between our findings
and those of other investigators may be due to the relatively low viral load at the
time of switch in patients responding. Until more conclusive data are available,
RTV/SQV-containing regimens should be considered in selected patients failing
IDV or NFV, and consideration should be given to early switches.