[e-drug] Parameter for assessing longer-term efficacy of antiretroviral

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E-drug: Parameter for assessing longer-term efficacy of antiretroviral 
treatment
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[Copied as fair use. KM]

Lancet 2001; 358: 1760-65 (24 November)

Correlation between reduction in plasma HIV-1 RNA concentration 1 week 
after
start of antiretroviral treatment and longer-term efficacy

M A Polis, I A Sidorov, C Yoder, S Jankelevich, J Metcalf, B U Mueller, M A
Dimitrov, P Pizzo, R Yarchoan, D S Dimitrov
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Laboratory of Immunoregulation, National Institute of Allergy and 
Infectious
Diseases, Building 10, Room 11C103, National Institutes of Health (NIH),
Bethesda, MD 20892, USA (Prof M A Polis MD, J Metcalf BA); Laboratory of
Experimental and Computational Biology, National Cancer Institute at
Frederick, NIH, Frederick, MD (I A Sidorov PhD, D S Dimitrov PhD); Critical
Care Medicine Department, Warren Grant Magnuson Clinical Center, NIH,
Bethesda, MD (C Yoder RN); National Institute of Allergy and Infectious
Diseases, Bethesda, MD (S Jankelevich MD); Texas Children's Cancer Center
and Hematology Service, Baylor College of Medicine, Houston, TX (Prof B U
Mueller MD); Center for Scientific Review, NIH, Bethesda, MD (Prof M A
Dimitrov PhD); School of Medicine, Stanford University, Stanford, CA (Prof 
P
Pizzo MD); and HIV and AIDS Malignancy Branch, National Cancer Institute,
NIH, Bethesda, MD (Prof R Yarchoan MD)

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Correspondence to: Dr M A Polis (e-mail:mpolis@nih.gov)
Summary

Background.  Early assessment of antiretroviral drug efficacy is important 
for
prevention of the emergence of drug-resistant virus and unnecessary 
exposure
to ineffective drug regimens. Current US guidelines for changing therapy 
are
based on measurements of plasma HIV-1 RNA concentrations 4 or 8 weeks after
the start of treatment with cut-off points of 0·75 or 1·00 log, 
respectively. We investigated the possibility of assessing drug efficacy
from measurements of plasma HIV-1 concentrations made during the first week
on therapy.

Methods. The kinetics of virus decay in plasma during the first 12 weeks of
treatment was analysed for 124 HIV-1-infected patients being treated for 
the
first time with a protease inhibitor. Patients with a continuous decline of
HIV-1 concentrations and in whom HIV-1 was either undetectable or declined
by more than 1·5 log at 12 weeks were defined as good responders; the rest
were poor responders.

Findings. The individual virus decay rate constants (k) at day 6 correlated
significantly (r>0·66, p<0·0001) with changes in HIV-1 concentrations at 4,
8, and 12 weeks, and correctly predicted 84% of the responses with a 
cut-off
value of k=0·21 per day (in log scale). Reduction in plasma HIV-1 of less
than 0·72 log by day 6 after initiation of therapy predicted poor long-term
responses in more than 99% of patients.

Interpretation. These results suggest that changes in HIV-1 concentration 
at
day 6 after treatment initiation are major correlates of longer-term
virological responses. They offer a very early measure of individual
long-term responses, suggesting that treatment could be optimised after 
only
a few days of therapy.
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Lancet comment:

These results suggest that changes in HIV-1 concentration at day 6 after
treatment initiation are major correlates of longer-term virological
responses'

In patients with HIV-1 infection, the effectiveness of antiretroviral
therapy should be assessed as early as possible to ensure that the most
appropriate regimen is being used. A marker of antiretroviral efficacy is
the concentration of HIV-1 RNA in plasma, currently measured 4 or 8 weeks
after the start of treatment. M A Polis and colleagues determined whether
earlier measurements could also predict drug efficacy. Using a simple
equation, they calculated HIV-1 RNA decay rate constants (k) for 124
patients during the first week of treatment. At day 6, k values correlated
significantly with changes in HIV-1 concentrations at 4, 8, and 12 weeks,
and correctly predicted 84% of responses to treatment at week 12 (defined 
as
either good or poor) when a cut-off value of k=0·21 per day was used.

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