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

12th World AIDS Conference

Abstracts 42151-42155 803

42151 | Retrospective and long term study of HIV and HCV RNA
levels in haemophiliacs (Grehco Study)
Anne-Marie Berthier', I. Renard2, M. Vicariot3, O. Guist'hau2, R. Colimon2,
P. Gueret4, A.M. Ruffault2. 1GREHCO: Centre Del'Hemophilie Rey Leroux
35340 La Bouexiere; 2Laboratoire de Virologie-CHU Rennes 35; 3CRTH CHU
Morvan Brest 29; 4Laboratorie D'Hematologie-CHU Rennes 35, France
Objective: To determine the predictive value of HIV RNA titers early in the
course of HIV disease and to evaluate the influence of HIV on HCV infection in
multitransfused haemophiliacs.
Patients and Methods: 1 ) - 58 haemophiliacs (38 HIV(+) HCV(+) and 20
HIV(-) HCV(+)) were tested between 1985 and 1997; HIV positive were classified
in 2 groups: 15 Non or Very slow Progressors (NP) all asymptomatic and never
treated and 23 Progressors (P) symptomatic or AIDS
2 ) - HIV and HCV viral loads (VL) (RT-PCR), ALT and y GT were determined
at least 3 times: 1st 1986 ~ 1 y.: 12-36 m. after estimated HIV seroconversion
2nd 1990 + 1 y. (before antiviral therapy for P). 3rd 1997 (or last date alive).
Results: Main results of viral loads (mean of Log. 10 copies/ml) are tabulated
below:
HIV 1st HIV 2nd HIV 3rd HCV 1st HCV 2nd HCV 3rd
HIV(+) NP (n = 15) 2.85 +0.6 3.07 +0.7 3.62 1 1 3.59 ~0.8 4.7 + 0.8 5.49 + 0.6
HIV(+) P (n = 23) 4.101 0.77 4.60 0.8 4.5 -0.8 4.391 1.3 5.48 0.7 5.33 +1.5
HIV() (n = 20) - - - 3.88 1.3 - 4.12 + 1.5
HIV VL: At the 1st determination we note significant higher HIV RNA titers in
Progressors (4, 10 VS 2.85 Log., p = 0.003). HCV VL: AT 1st point: no significant
difference between HIV(+) and HIV(-) patients (p = 0.8), in constrast at the end
of the follow up we note a strong difference: (3rd determination HIV(+) VS 3rd
determination HIV(-) p = 0.0026)
No correlation between liver function tests and HCV VL except for y GT increased at 3rd point in Progressors: x = 109 IU/ml in P. VS 54 in NP and 30 in
HIV neg. patients (may be related to HCV and/or HIV VL or anti-viral therapy side
effects).
Conclusion: This study shows:
- A predictive value of baseline HIV RNA levels in clinical outcome.
- A faster rate of increase of HCV RNA levels in HIV infected patients suggesting
an effect of HIV on HCV replication.
- An absence of correlation between ALT, and HCV RNA titers.
42152 CD4+ cell decline despite maintenance of stable HIV-1
RNA in HIV-1 infection prior to AIDS
William A. O'Brien1, A. Bush2, R.A. De Masi3, A.M. Hill4. 1UTMB MED/ID 301
University Blvd., Galveston, TX 77555-0835; 2Dept Biostatistics, UNC Chapel
Hill, Chapel Hill; 3Clinical Statistics, GlaxoWellcome RTP NC, USA; 4Clinical
Research, GlaxoWellcome, London, UK
Background: Both CD4+ cell count and HIV-1 RNA are prognostic of clinical
disease progression over a wide spectrum of disease stages. Moreover, although
it has been hypothesized that HIV-1 RNA remains relatively constant during the
period of AIDS-free HIV-1 infection, this so-called set-point hypothesis has not
been rigorously evaluated. The objective of the study was to evaluate whether
HIV-1 RNA and CD4 cell count remain stable over time in a cohort of untreated
HIV-1-infected subjects without AIDS.
Methods: Sixty-six untreated patients with HIV-1 infection and CD4+ cell counts
200-500/mm3 were followed longitudinally for up to two years. CD4+ cell count
and HIV-1 RNA were measured at 16 week intervals. Rate of change in CD4+ cell
count and log HIV-1 RNA for each patient was estimated using linear regression
analysis.
Results: Baseline CD4+ cell count and HIV-1 RNA were 400 cells/mm3 and
3.83 log10 copies/mL, respectively. HIV-1 RNA remained remarkably stable over
time (rate of change = 0.00 log10 copies/mL per month, p = 0.995). However,
there was a statistically significant decline in CD4+ cell count (rate of decrease =
3.6 cells/mm3 per month, p = 0.0079).
Conclusions: AIDS-free HIV infection is characterized by stable HIV-1 RNA
and declining CD4+ cell counts. As such, intervention with highly active antiretroviral therapy is warranted to stave off an otherwise deteriorating immune system
even in patients without AIDS and with relatively low and stable HIV-1 RNA.
42153 Impact of plasma HIV RNA on CD4 change and
outcome for women in the women's interagency
HIV study
Andrea Kovacs1, L. Chan', J. Bremer2, W.A. Meyer3, B. Weiser4, M. Young5,
N. Hessol6. 1 USC School of Medicine, 1640 Marengo St., Los Angeles, CA
90033; 2Rush Medical Center, Chicago, IL; 3Quest Diagnostics, Baltimore, MD;
4NYS Dept. of Health, Albany NY; 5Georgetown University Medical Center,
Washington, DC; 6UCSF, San Francisco CA, US

Objectives: To assess the impact of HIV RNA on CD4 decline and clinical
outcome for women enrolled in the Women's Interagency HIV Study (WIHS).
Methods: WIHS is a prospective natural history study with 2,641 (2066 HIV+)
women seen every 6 months. Analysis includes 1098 women with > three CD4
and RNA levels; 879 (80%) received antiretroviral therapy (treated). Plasma RNA
levels were determined using NASBA (undetectable <4,000 copies/ml). Patients
were categorized by highest RNA level over 5 visits (<4,000, 4-50,000, 50,000

to 1 M and >1 M). Significant RNA change from baseline to Visit 2 was defined
as ~ 0.5 log. Analysis of variance was performed.
Results: Overall, at the first study visit, mean CD4 was 404 cells/mm3, mean
decline was -2 cells/6 m, mean RNA was 101,836 copies/ml (median 16,600).
CD4 declined in all RNA groups for untreated women including those with persistently undetectable RNA (-10 to -33 cells/6 mos). Comparing RNA between
visits 1 and 2 CD4 declined whether RNA increased, remained stable or decreased (-31, -17, -8 cells/6 mos). Initial CD4 and RNA had an impact on
magnitude but not pattern of decline (-11 to -35 cells/mm2). For treated women
CD4 increased in those with persistently undetectable RNA (mean +7.6 cells/6
mos) but decreased for those with maximum RNA over 1 M copies/ml (mean --13
cells/6 mos). With a decrease in RNA between visits 1 and 2, CD4 increased
(mean +12 cells/6 mos) but with stable or increasing RNA CD4 remained stable
over 2 years. CD4 counts remained relatively stable over 2 years (+2 cells/6 mos;
+7 cells/6 mos), if initial RNA levels were <4,000 copies or were persistently low.
Clinical outcomes are being studied.
Conclusion: The course of CD4 change is different for treated and untreated
women over the first two years of the WIHS Study. Women who have RNA levels
persistently <4,000 copies/ml continue to have CD4 decline if untreated, but CD4
counts are stable or increase for treated women. With persistently high RNA
levels CD4 continues to decline over two years for all women.
142154 Durability of undetectable viral load (VL) in response to
antiretroviral therapy: An assessment of immunologic
and virologic parameters
Kimberly Y. Smith, B. Sha, A. Tenorio, H.A. Kessler, J. Pottage, G. Trenholme.
'Rush Medical College, Chicago, IL; 600 S. Paulina Suite, 143ACFAC, Chicago,
IL, USA
Objective: To determine factors that affect durability of response to antiretroviral
therapy.
Methods: Patients who had attained VL < 500 by Chiron 2.0 bDNA assay underwent retrospective chart reviews. Antiretroviral regimen, follow-up CD4 counts,
and VL were assessed. Pts were divided into relapsers (VL increase >3fold, i.e.
1500, on two consecutive measurements), and non- relapsers (no VL > 1500 on
two consecutive measurements).
Results: The study included 75 pts with a mean of 11 months (range 4-25) of
follow-up. 27% were relapsers, and 73% were non-relapsers. 67% of pts were on
protease inhibitor (PI) containing regimens and 33% were on non-PI containing
regimens. 22% of pts receiving PI's relapsed vs. 36% of patients on non-PI
containing regimens (p =.196).

Variable
PI-regimen
Non-PI regimen
Viral Load (pre-therapy)
Mean
Mean log
CD4
Mean (pre-therapy)
Mean change

Relapsers
22%
36%
844,213
4.93

Non-Relapsers
78%
64%
66,751
4.34

Sig.
0.196 (x2 = 1.670)
0.018
0.041
0.223 (ns)
0.370 (ns)

178 (13-360) 238 (0-973)
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Conclusions: Of pts who attained VL < 500, baseline VL was significantly
higher in pts who relapsed than in pts who did not. There was a trend toward
increased risk of relapse in pts not on Pi's (RR = 1.6) There was no significant
difference between relapsers and non-relapsers in lowest CD4 count pre-therapy
or CD4 increase following undetectable VL, and substantial increases were noted
in both groups. VL prior to antiretroviral therapy was the best predictor of durability
of response.
S42155 Viral load assays and HIV-1 subtypes in European clinical
trials
Veronique Michael, G. Anderegg, F. Campbell, A.F. Amor. Covance CIs S.A. 7,
Rue Moise Marcinhes, 1217 Geneva, Switzerland
Backgrounds: Comparison between plasma HIV RNA viral load results obtained
using the Roche Amplicor HIV-1 Monitor assay version 1.0, same assay plus
additional primer pair "Add-in Primers" distributed by Roche and Amplicor HIV-1
Monitor assay version 1.5.
Methods: Plasma Viral load of 176 HIV-1 infected patients enrolled in European
clinical trials have been determined by 2 different Roche assays: Amplicor HIV
Monitor assay version 1.0 (1.0) and same assay plus additional primer pair called
"Add-in Primers" distributed by Roche (1.0 + "Add-in Primers"). 14 additional
plasmas from patients infected by known HIV-1 subtypes (4A-subtypes, 2 C-, 2-,
5E-, 1F-) have been performed using both tests and using the Amplicor HIV-1
Monitor assay version 1.5 (1.5).
Results: Two groups of patients can be individualised: 1/ For 169/176 (96%)
of patients, no changes in viral load results between 1.0 and 1.0 + "Add-in
Primers" assays have been observed. The Loglo difference between (1.0 +
"Add-in Primers" and 1.0) was < = 0.30 for all of them. Those patients are
infected by subtypes that are well amplified by Amplicor 1.0 assay, wide majority
by B-subtype. The Log0l difference between the 2 assays is comparable with
the assay variability of the Roche PCR assay. 2/ For 7/176 (4%) of patients,
plasma viral load increases when using 1.0 + "Add-in Primers" assay compared
to 1.0 assay. The Loglo difference between (1.0 + "Add-in Primers" and 1.0)