Test Early. Test Sensitive

[jmjm530]

From the Boston Meeting, ID #170. Again, the importance of early and *sensitive* viral load testing -- in this case weeks 4 and 12 -- to help manage therapy -- in this case to predict SVR.

"The application of the highly sensitive HCV RNA tests must be considered to be now mandatory because this new test helps to evaluate in a much more refined way treatment response as well as relapse rates and provides better clues for an individualized tailored treatment strategy."

Again, the trend is clear -- test early and test using only sensitive tests. And if your doc doesn't appreciate the signficance, then either try and educate them or find another.

BTW the Group "B" figures seem a bit bogus to me as they are derived from what seems like an arbitrary extension rule of mutiplying the week one becomes UND by Bdna (615 IU/ml) times 6. By this rule, I should have only treated 12 weeks (I was <600 at week 2). No wonder the relapse rates were so high in this group.


Importance of a Minimal Residual Viremia for the Relapse Prediction in HCV Type 1 Patients Receiving Standard or Individualized Treatment Duration
T. Berg1; V. Weich1; G. Teuber2; H. Klinker3; B. Möller4; J. Rasenack5; H. Hinrichsen6; T. Gerlach7; U. Spengler8; P. Buggisch9; H. Balk10; M. Zankel10; C. Sarrazin2; S. Zeuzem2
1. Charite, Campus Virchow Klinikum, Berlin, Germany.
2. Medizinische Universitätsklinik, Frankfurt, Germany.
3. Klinikum der Universität Würzburg, Würzburg, Germany.
4. Hepatologische Schwerpunktpraxis, Berlin, Germany.
5. Medizinische Universitätsklinik, Freiburg, Germany.
6. Christian-Albrecht-Universität, Kiel, Germany.
7. Universitätsklinik, Zürich, Switzerland.
8. Medizinische Universitätsklinik, Bonn, Germany.
9. Universitätsklinik Eppendorf, Hamburg, Germany.
10. essex GmbH, München, Germany.


The exact estimation of early virologic response rates in the course of antiviral therapy is an important goal in order to improve individualized therapeutic strategies in HCV infection. The sensitive TMA test could provide better advantage to distinguish at early stages sustained from non-sustained responders. We evaluated HCV type 1 patients who took part in a prospective study asking whether the application of TMA in bDNA-negative patients may be a better indicator to predict long-term outcome of the HCV infection. Methods 433 patients were randomized to receive either 1.5ug/kg PEG-INFa-2b plus 800-1400 mg RBV for 48 weeks (n=225, group A) or an individualized tailored treatment duration (n=208, group B). In the latter group treatment duration was calculated by the time required to become for the first time HCV RNA negative as defined by bDNA assay (detection limit 615 IU/mL) multiplied by the factor 6. HCV RNA levels were quantified weekly until week 8, at week 12 and 24. For all those patients who were bDNA negative the more sensitive TMA test (detection limit 5.3 IU/mL) was also prospectively assessed. The different response groups were classified according to the HCV RNA levels at week 4 and 12 (Table). Results Table shows the relevant data and refers to the relative relapse rates in group A and B at week 4 and 12 in relation to the treatment schedule. There is clear evidence for a high relapse rate in patients with a positive TMA within the first 12 weeks of therapy being more pronounced when treatment duration shortened in the individualized treatment group. In contrast patients shown to respond as early as week 4 evidenced by a negative TMA test had relapse rates below 10% irrespectively from treatment group. Conclusion The application of the highly sensitive HCV RNA tests must be considered to be now mandatory because this new test helps to evaluate in a much more refined way treatment response as well as relapse rates and provides better clues for an individualized tailored treatment strategy. Thus our study clearly indicates that patients even with a minimal amount of HCV RNA detected at week 12 can suffer from relapse rates greater than 50%. These patients may indeed benefit when their treatment duration is adapted to their individual needs.

response groups relative relapse rate (%)

week 4
response >= log decline,
bDNA positive 36%
(all patients) 19%
(group A) 63%
(group B)
bDNA negative,
TMA positive 38%
(all patients) 22%
(group A) 49%
(group B)
bDNA negative,
TMA negative 4%
(all patients) 0%
(group A) 8%
(group B)
week 12
response >= 2log decline,
bDNA positive 77%
(all patients) 78%
(group A) 75%
(group B)
bDNA negative,
TMA positive 64%
(all patients) 56%
(group A) 69%
(group B)
bDNA negative,
TMA negative 20%
(all patients) 9%
(group A) 32%
(group B)

[geterdone]

Looking back in my records, LabCorp uses QuantaSure Plus (Serial)
Looking on the graph chart provided It shows <10 but says that it can detect RTPCR RNA from 10-100m.
Comments: Less than 10 iu/ml indicates either complete absence of HCV RNA or in rare cases, low copy numbers below the detectable limit of the assay. Brain fog the first read of numbers. Thanks for the post above, got me thinking anyway.

jasper

[jmjm530]

I think "<10" is very sensitive and wouldn't worry. That said, may of us test to "<5", using tests like Heptimax and some test to ""<2" with a LabCorp test. However, never heard of someone testing postive with let's say a viral load of 7 IU/ml, but that does not mean it can't happen. The test I preferred after becoming UND is Quest's Diagnositc's "HCV RNA QUALITATIVE TMA" written usually " HCV RNA QUAL TMA". Because it's a qualitative, you don't get the viral load, just either "Virus Dectected" or "Virus Not Detected". It goes down to 5 IU/ml.

-- Jim

[geterdone]

What is the lowest that the present PCR will go when showing UND. My beginning vl was 4.7 and by week 8 it was <10. and the same for week 12. and will find out where I’m at here in the next couple of days. Should I be looking for something lower than <10?

jasper