Undetectable viral load is one of the aims of antiretroviral therapy. However, the definition of 'undetectable' viral load is constantly changing as the technology used to measure viral load improves.

An undetectable viral load result indicates that a specific viral load test cannot find any HIV in a given blood sample. An undetectable result does not mean that the blood is free of HIV. In fact, most people with 'undetectable' viral load have HIV in their blood, as well as in blood cells, tissue and bodily fluids.

For each viral load test, there is a lower limit of detection - a limit below which it is not possible to measure the amount of HIV present. Samples with very low levels of HIV, for example below 50 copies/ml, are described as having a viral load that is 'undetectable', or 'below the level of detection'.

This lower threshold depends on the sensitivity of the test. The two key ultra-sensitive tests, or assays, measure as low as 50 copies/ml. The older, standard assays, which may still be in use in some United Kingdom clinics, measure down to 500 copies/ml using the bDNA assay and down to 400 copies/ml using the polymerase chain reaction (PCR) assay. Consequently, an 'undetectable' result with a standard assay may not mean an 'undetectable' result using an ultra-sensitive assay. One study found that in the majority of cases, people with undetectable viral load using the standard tests do have measurable viral load using the more sensitive assays. In other words, their true viral load is in the range 20 to 500, indicating a very low level of ongoing viral replication (Imamichi).

Why aim for undetectable viral load?

Undetectable viral load has been proposed as the gold standard of HIV treatment by many sets of guidelines in the past few years. Several meta-analyses of trials of dual therapy have shown that suppressing viral load below the limits of detection results in the greatest reduction in the risk of death or illness.

One of the most important reasons to suppress viral load as far as possible may be to minimise the risk of HIV developing resistance to the drugs that you are taking. As discussed in Anti-HIV therapy: Resistance, HIV can only develop resistance to a drug if it is continuing to replicate in the presence of that drug. By suppressing viral replication as far as possible, the emergence of resistant mutants should be delayed, prolonging the effectiveness of therapy. For this reason, British HIV Association treatment guidelines now suggest that it is preferable to aim for viral load below 50 copies after 24 weeks of treatment.

Achieving undetectable viral load

The higher an individual's viral load before starting treatment, the greater the reduction in viral load required to bring it down to undetectable levels. For this reason, some clinicians recommend more aggressive treatment to people with very high viral load compared to people with lower viral load.

An analysis of data from the Frankfurt HIV Clinic Cohort has indicated that many people can sustain undetectable viral load if they adhere to their treatment regimen. The observational study followed 406 treatment-naive people who commenced triple combination therapy. Despite a relatively high average baseline viral load of 250,000 copies, 91% had achieved viral load below 500 copies by week 24 of treatment. Twenty percent of these (69 of 342) experienced viral rebound, defined as two consecutive viral load results over 500 copies, during two years of follow-up. However, the likelihood of rebound fell over time. The authors concluded that so long as complete adherence can be maintained over the long-term, today's HAART regimens appear able to suppress viral replication for more than ten years (Phillips).

See Suppression of HIV and durability of antiretroviral therapy in Anti-HIV therapy: Effectiveness of HIV therapy for further discussion of the durability of undetectable viral load on HAART.

Viral load blips above the limits of detection

It is not unusual for viral load which has been suppressed below 50 copies/ml to rise above 50 copies. In the majority of cases, viral load falls below 50 copies again by the time the next viral load test is conducted, and these blips do not appear to be predictive of an increased risk of treatment failure in the future. It is only when viral load remains above 50 copies after several tests, and keeps rising, that treatment failure can be diagnosed.

See Viral load blips in Anti-HIV therapy: Changing treatment for further discussion of this issue.

References

Imamichi H et al. Continued evolution of HIV-1 during combination therapy despite levels of HIV-1 RNA less than 500 copies/ml. International Workshop on Drug Resistance, Treatment Strategies and Eradication, Florida, abstract 63, 1997.

Natarajan V et al. HIV-1 replication in patients with undetectable plasma virus receiving HAART. Highly active antiretroviral therapy. Lancet 353(9147): 119-120, 1999.

Phillips AN et al. Durability of HIV-1 viral suppression over 3.3 years with multi-drug antiretroviral therapy in previously drug-naive individuals. AIDS 15(18): 2379-2384, 2001.