Abstracts Vol. 1 [International Conference on AIDS (11th: 1996: Vancouver, Canada)]

Track B: Clinical Science

Tu.B.2372 -Tu.B.2376

significant differences in averages between each group of patients staged according to the
1993 CDC revised classification.We observed concordant results with the initiation
(n=44) or the modification (n=6) of therapeutic. Discordant results between HIV-RNA
copy numbers and p24 antigen concentration were often revealed. In the 445 samples, we
found 46 negative p24 antigen detections with HIV-RNA copy number> 100000/ml; whereas 32 samples had p24 antigen values greater (> 100pg/ml) than expected by the HIV-RNA
copy number (< 100000/ml).
Conclusion: HIV-RNA plasmatic level seems to be a reproducible, individual and independant marker of interest for patients follow-up. Discordant results between viral load and
p24 antigenemia and predictive value of this parameter need further investigations.
Bocket Laurence, Service DeVirologie-Chru De Lille Bat; Irfpps- 59045 Lille, Cedex, France.
Tu.B.2372
ROUTINELY USE OF VIRAL LOAD IN THE MANAGEMENT OF HIV-I INFECTED
INDIVIDUALS:A ONEYEAR PROSPECTIVE STUDY IN THE NORTH FRANCE AIDS
REFERENCE CENTER.
Gerard Y.(*), Bocket L.(**), Ajana F.(*), Beuscart C.(*), Leclerc P(***), De LaTribonniere
X.(*), Bourez J.M.(*),Valette M.(*), Senneville E.(*), Chidiac C.(*),Wattre P(**), Mouton
Y(*). *North Aids Reference Center-C. H Tourcoing- I 35, rue du President Coty-59208
Tourcoing Cedex-France. **Laboratoire de Virologie-C.H.R.U. Lille-59037 Lille CedexFrance. ***C.H.U. Grenoble-38043 Grenoble Cedex 09.
Objective: to assess the impact of antiretroviral drugs on plasma HIV RNA levels and the
potential clinical utility of this marker in the follow-up of HIV-infected individuals.
Methodology: 50 HIV- I seropositive and antiretroviral-naive subjects were enrolled, within
January through December 1995. Serial samples were collected before, and after initiating
antiretroviral therapy Virologic parameters were monitored: plasma HIV RNA quantitation
by the reverse transcriptase PCR assay, serum p24 antigen concentration after immune
complex dissociation, and CD4 cell count.
Results: 24 subjects were treated with an antiretroviral monotherapy (group A). 26 subjects
were treated with a two drugs combination therapy (group B). 6 subjects from the former
group were switched to a two drugs regimen.We found a marked decrease in plasma HIV
RNA levels (log-transformed) after initiating therapy, in the great majority of individuals (46
subjects/50).This marked decrease seemed to be transient especially in group A after five
months of therapy
The mean regression during the first 4 months of follow-up was -0.68 log RNA copies/ml
in group A and -1.29 log RNA copies/ml in group B.The difference between the 2 groups
(mono vs bitherapy) was significative (p < 0.01). Furthermore, 6 subjects from group A
experienced a - 0.33 log RNA copies/ml reduction after 2 months of monotherapy, then
were switched to a two drugs regimen, responsible for a mean reduction of -1,06 log RNA
copies/ml.
Conclusions: measurement of viral load seems to be a reliable and quick method to assess
the efficacy of different antiretroviral regimens, here pointing out the potential superiority of
the combination therapy Further studies are required to know if HIV RNA levels can predict the clinical course of the disease or the occurrence of clinical events.
Gerard Yann - Service Des Maladies Infectieuses 135, Rue Du Prdsident Coty - F-59208
Tourcoing
Tu.B.2373
HIVVIREMIA: RELATIONSHIP WITH CLINICAL STAGE AND BIOLOGICAL MARKERS
Dubuis Olivier **,Yerly S *, PernegerT *, Matter L **, Perrin L *, the Swiss HIV Cohort
Study * Geneva University Hospital, Switzerland; ** University of Bern, Switzerland.
Objective: To investigate the cross-sectional associations between HIV viremia and currently
used markers.
Methods: 398 patients who had frozen plasma collected between 1991-93 were selected
after stratification by CD4 cell counts (0-49, 50-199, 200-499, and > 500/mm3). Clinical
stage and biological parameters (CD4, CD8, CD4/CD8 ratio, -2-microglobulin, soluble p24
antigen, immune complex dissociation (ICD) p24 antigen) were assessed for univariate
association with log HIV RNA (Roche Amplicor) using scatterplots. A multivariate regression
analysis identified variables associated independently with HIV viremia.
Results: The sample included 309 men and 89 women, mean age 35, SD 8; 158 were in
stage A, 116 in stage B, and 1 24 in stage C. Log HIV RNA ranged from 2.00 to 6.24 (mean
4.34, SD 0.80). In univariate analysis, all variables were associated with log RNA. For CD8
count and 3-2-microglobulin, the association was not linear, but involved a change in slope.
This multivariate model explains 44% of log HIV RNA variance.
Variables independently associated with log RNA
(Multivariate model)
Variables Comparison Alog RNA 95% CI
Clinical stage: B vs A 0.23 0.05 to 0.40
C vs A 0.37 0.18 to 0.56
ICD p24: pos. vs neg. 0.56 0.4 I to 0.71
CD4 count: + 100/mm3 -0.05 - 0.08 to -0.02
0-2-micro:
range 0-4 mg/I + I 0.19 0.08 to 0.30
range >4 mg/I + I -0.03 -0. I I to 0.05
Conclusion: Clinical stage, ICD p24, CD4 cell count and B-2-microglobulin were independently associated with viremia levels.
O. Dubuis, Institute for Medical Microbiology, University of Bern, Friedbhl stnr 5 I, 3010
Bern, Switzerland.Tel: [phone], Fax: 4 I 3 I -382-00-63
Tu.B.2374
EARLY DIAGNOSIS OF PERINATAL HIV INFECTION COMPARING DNA-POLYMERASE CHAIN REACTION AND PLASMA VIRAL RNA AMPLIFICATION.

Brown,Teresa M, Steketee RW, Abrams EJ,Thea D, Lambert G, Greenberg B, Schoenbaum

E, Bamji M,Thomas P Rapier JM, Orloff 5, Kalish ML. the NewYork City Perinatal HIV
Transmission Collaborative Study Group. MHRA, New York and CDC, Atlanta, GA.
Objective: Early diagnosis of perinatal HIV infection is increasingly important because interventions are available to infants in the first months of life. Passive transfer of maternal antibodies renders HIV antibody testing inaccurate until the second year of life; polymerase
chain reaction amplification of proviral DNA from peripheral blood mononucleocytes
(DNA-PCR) is highly sensitive and specific by age 3-6 months. Extracellular HIV RNA has
been shown to increase to high levels soon after primary and perinatal infections. We compared DNA-PCR and plasma viral RNA for early detection of infant HIV infection.
Methods: In a prospective study of perinatal HIV transmission where diagnostic DNA-PCR
testing is routinely performed on early infant specimens, a total of 94 same-blood-draw
specimens in the first year of life from 44 HIV-infected infants and 9 uninfected infants were
examined by DNA-PCR and viral RNA amplification and detection (NASBA, OrganonTeknika).
Results: Of 23 specimens collected between 0-14 days of age, 4 (1I7%) were positive by
DNA-PCR and 8 (35%) were positive for viral RNA; in 17 specimens collected between
21-34 days of age, 12 (71%) were DNA-PCR positive and 16 (94%) were viral RNA positive; in 54 specimens collected at > 35 days of age, 47 (87%) were DNA-PCR positive and
53 (98%) were viral RNA positive. No specimens were DNA-PCR(+) and viral RNA(-).
Older infant age and higher viral RNA load were associated with DNA-PCR-positivity Nine
specimens from uninfected infants (aged 3-6 months) whose mothers had high HIV viral
RNA load at or near delivery or had AIDS were negative by both DNA-PCR and viral
RNA load testing.
Conclusions: Our results suggest that HIV viral RNA is present in plasma early in infant
infection. HIV- I viral RNA testing may allow for detection of infant HIV infection earlier
than other currently available assays.
Teresa M. Brown CDC. Mailstop D-12, 1600 Clifton Rd. Atlanta GA 30333 USA
Telephone:[phone] FAX:[phone]
Tu.B.2375
INTRA-AND INTER-ASSAY VARIATION IN ESTIMATES OF VIRAL TITERS FROM
QUANTITATIVE MICROCULTURES.
Brambilla Donald |*, Bremer JW**, Staes B**, Michels C***, Reichelderfer P:****. for the
DAIDS-sponsored Virology Laboratories. *New England Res Inst, Watertown, MA, USA;
**Rush Medical College, Chicago, IL, USA; ***Dataworks Development Inc. Seattle, WA,
USA; ****NIH/NIAID, Bethesda, MD, USA.
Objective: To ascertain the intra- and inter-assay variability of estimates of viral titer
obtained from quantitative microculture of peripheral blood mononuclear cells (PBMC).
Methods: Data were obtained on 21 proficiency panels from 54 laboratories participating
in the Virology Quality Assurance Program. At monthly intervals, laboratories were sent four
coded whole blood samples. Samples were assayed using the ACTG consensus protocol,
which is based on 1:5 (0.7 Iog 10) serial dilutions. Results were expressed as Infectious Units
per Million Cells (IUPM). Cultures with goodness of fit p<0.05 were excluded from the
analysis. Long-term variability of estimates of log 10 IUPM for each laboratory was assessed
by calculating the standard deviation (SD) of the residuals formed by subtracting median
log 10 IUPM for each sample from the individual estimates. Intra- and inter-assay variability
was assessed in five panels by including duplicate samples (n=8 pairs). Intra-assay SD's were
estimated from the differences within pairs of titers, while inter-assay SD's were estimated
by combining titers across laboratories. Robust estimators of SD were employed to avoid
problems with outliers.
Results: The median long term SD was 0.53 (range: 0.23-1I.03) which was based on 990
cultures from the 54 laboratories (median: 17 cultures/lab). Fifty percent of these SD's fell
between 0.43 and 0.59.The median intra-assay SD of log l0 IUPM was 0.39 (range: 0.07 -0.54) which was based on II 5 pairs of assays from 38 laboratories (median: 3 pairs/lab).
The median inter-assay SD for the pairs was 0.53 (range: 0.23-0.88).These SD's imply that
about half the variance in log10 IUPM is attributable to inter-assay variability and the other
half to intra-assay variability
Conclusions: At the observed median inter-assay SD, the difference between titers on two
sequential cultures from a patient must be 30-fold to be significant. Smaller differences may
be considered significant in laboratories that perform consistently better than the median.
However, given the difference between the intra- and inter-assay SD, it may be preferable to
batch test quantitative cultures, in spite of potential losses of titer in stored specimens.
D.J. Brambilla, New England Research Institutes Inc. 9 Galen St, Watertown, MA, USA
Telephone: [phone] X230 Fax: [phone] email: donb%[email protected]
Tu.B.2376
COMPENSATED HYPOGONADISM:A COMMON FINDING IN HIV INFECTION
Falutz, Julian M. Immune DeficiencyTreatment Centre, Montreal General Hospital, Montreal,
Quebec, Canada
Objective: Both primary (I~) and secondary (2~) hypogonadism occur in HIV disease, contributing to common clinical manifestations such as fatigue, malnutrition and depression.This
study determined the spectrum of pituitary-gonadal relationships in men with a wide range
of CD4 counts and varied HIV-associated complications.
Methods: Serum testosterone (T), luteinizing hormone (LH) and follicle stimulating hormone (FSH) were measured by RIA in 160 HIV seropositive men. Repeat determinations
were available on 23 men. Clinical status, whether (ASx) or symptomatic (Sx), according to
CDC criteria, was assessed concurrently CD4+ T helper cells were measured by flow cytometric analysis using monoclonal antibodies.
Results: Overall, of the 160 men, 89 (56%) were eugonadal, 14 (9%) had Io and I3 (8%)
had 2o hypogonadism. Compensated hypogonadism (T-normal; LH and/or FSH increased)
was found in 44 (28%) men.This was seen at all CD4 levels (> or <200/mm3), regardless
of clinical status (ASx or Sx), occurring in I 1/49 (22%) ASx men with CD4 >200 and in
27/78 (35%) of Sx men with <200 CD4. Of 23 men with compensated hypogonadism
who had repeat T LH and FSH after a mean follow-up of 5m., 9 (39%) developed lowT
This occurred in 1/6 (17%) of men with initial CD4>200, and in 8/17 (47%) of men with
initial CD4<200. In 2 I initially eugonadal men, follow-up evaluations after 5m. showed that
18/21 (86%) remained eugonadal; this occurred in 10/10 (100%) of men with >200 CD4,
and 8/I I (73%) of men with <200 CD4.

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