Guidelines for Clinical Management Using Plasma HIV RNA Quantitation

viral load, which are being provided to physicians in the CPCRA 036 study described above. These guidelines will be reviewed periodically throughout the study, and will be changed as new information becomes available.]

The goal of utilizing plasma HIV RNA quantitation in patient management is to keep viral burden AS LOW AS POSSIBLE FOR AS LONG AS POSSIBLE. At present, there are no clear thresholds for "high" or "low" HIV RNA viral burden. The following points represent the state of the art in this area:

* Levels of <10,000 copies (10 Keq/ml) are associated with LOW risk of progression (Mellors J. and others. Quantitation of HIV-1 RNA in plasma predicts outcome after seroconversion. ANNALS OF INTERNAL MEDICINE. 1995; volume 122, pages 573- 579.)

* Levels of >100,000 copies (100 Keq/ml) are associated with HIGH risk of progression (Mellors and others, reference cited).

* The observed biologic variability of the HIV RNA assays may be as high as threefold. Therefore, a change of more than threefold is considered significant, and a change of less than threefold may be due to assay variability. (Todd J. and others. Quantitation of human immunodeficiency virus plasma RNA by branched DNA and reverse transcription coupled polymerase chain reaction assay methods: A critical evaluation of accuracy and reproducibility. SERODIAG. IMMUNOTHER. INFECT. DIS. 1994; volume 6, number 4, pages 233- 239. * Pachl C. and others. Rapid and precise quantification of HIV-1 RNA in plasma using branched DNA signal amplification assay. JOURNAL OF APPLIED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY 1995; volume 8, pages 445- 454. * D. Chernoff, personal communication, 1995.)

* Repeating the assay improves reliability. It is recommended that the assay be repeated, rather than relying on a single value, before the value is used for decisionmaking to initiate or change therapy. (Todd and others, reference cited. * Dewar R.L. and others. Application of branched DNA signal amplification to monitor human immunodeficiency virus type 1 burden in human plasma. JOURNAL OF INFECTIOUS DISEASES 1994; volume 170, pages 1172-1179. * Pachl and others, reference cited.)

* Changes in plasma HIV RNA are seen as early as two to four weeks after the initiation of a new therapy with antiviral activity. Obtaining a plasma HIV RNA quantitation at this time may indicate whether the therapy has been effective in acutely decreasing plasma HIV RNA.

* Obtaining HIV RNA measurements during any acute intercurrent illness or within four weeks after a patient receives a vaccination (including influenza) may impact on the interpretation of plasma HIV RNA results.