Laboratory markers of antiviral activity

Quantitative assays for viral nucleic acids have been instrumental in monit oring the response of patients to various antiviral therapies. The level of viraemia is predictive of clinical outcome in that a reduced risk of progr ession to AIDS or death was observed with lower plasma human immunodeficien cy virus (HIV) RNA levels. Rebound in viral levels often signals therapeuti c failures, some of which are associated with the development of drug resis tance. Quantitative plasma assays for HIV, hepatitis C virus (HCV), cytomeg alovirus (CMV) and hepatitis B virus (HBV) have been developed. Over time, modifications to these assays have been required to meet new demands. For e xample, as antiviral therapies have become more effective, HIV and HCV assa ys of greater sensitivity are required in order to follow patients for long er periods of time and to fully assess the extent of viral suppression. For HIV-1, a large percentage of patients treated with combination therapies h ad viral loads that were below the detection limit of the ultrasensitive as say (50 copies/ml). To assess the residual viral burden in this patient pop ulation an assay to quantify HIV-1 proviral DNA in peripheral blood mononuc lear cells was developed. Studies to date indicate that proviral DNA remain s easily detectable despite undetectable plasma RNA and may be useful in mo nitoring this patient population. To increase assay throughput, a new gener ation of quantitative assays that will provide real-time detection and a 6 log(10) detection range from a single amplification is under development.