Philadelphia researchers have reported that HIV is still replicating when viral load is undetectable on standard tests, suggesting that current therapy is still not strong enough to stop ongoing infection of new cells.
Reporting in the Journal of the American Medical Association Dr Roger Pomerantz described tests conducted with 22 individuals on HAART who had viral load below 50 copies according to the most sensitive standard tests (Amplicor PCR or Quantiplex bDNA). All individuals had been receiving triple therapy for at least 5 months, and in some cases had maintained undetectable viral load for over four years.
When researchers used an experimental assay which can reliably detect as few as 5 RNA copies per ml, they found that the mean viral load in plasma was 17 copies. However, 12/22 had no detectable HIV RNA in their genital fluids (this group included the two women in the study); 8/22 had some trace of replicating HIVin their semen, but below 5 copies, and only 2/22 had more than 5 HIV RNA copies detectable in semen by this assay.
The authors also note that this level of viral replication is very similar to the baseline calculated in a study of viral rebound after treatment interruption, where individuals with viral load below 50 copies had experienced rebound to greater than 500 copies within 10 days.
Dr Pomerantz concludes that each individual had a total viral burden estimated at 51,000 virion RNA copies, suggesting a significant degree of ongoing HIV replication. However, it is still impossible to define where these viruses are being produced, and the authors recommend that studies of both eradication and treatment interruption/immune control need to develop easily used assays which can measure even lower levels of viral replication, in order to define more accurately when treatment might be safely interrupted, and when intensification may be appropriate.
Dornadula G, Pomerantz RJ et al. Residual HIV-1 RNA in blood plasma of patients taking suppressive highly active antiretroviral therapy. Journal of the American Medical Association 282: 17 pp1627-1632, 1999.