Genotypic resistance testing is more than 90% successful in individuals with a viral load between 200-1000 copies/ml using standard testing and it should be offered earlier than is currently practised to everyone failing antiretroviral therapy in order to inform a treatment switch sooner and prevent the possible development of further resistance, according to investigators from London's Chelsea & Westminster Hospital, writing in the March 21st issue of the journal, AIDS.
Viral load monitoring has become an integral part of HIV care in well-resourced countries. Currently, an HIV viral load below 50 copies/ml is considered to be one of the main aims of care, since two HIV viral load tests above 50 copies/ml suggests the emergence of genotypic mutations that may eventually lead to clinically significant drug resistance and treatment failure.
Historically, clinics using standard genotyping resistance tests only do so when viral load is above 1,000 copies/ml. However, the letter's authors argue, this number is arbitrary and based on clinician experience and anecdotal evidence rather than research or clinical trials.
Since there is evidence that continuing on a regimen that is failing to suppress viral load to below 50 copies/ml leads to the accumulation of resistance mutations, the risk of resistance would be minimised if a failing regimen were changed sooner rather than later.
The ideal solution would be to use standard genotypic resistance testing earlier to help provide an accurate assessment of drug resistance even when viral load levels are low, and this is what appears to have happening at the United Kingdom's largest HIV clinic for several years.
The letter's authors used the hospital's HIV database to identify 112 genotype resistance tests performed on individuals with at least two consecutive viral loads above 50 copies/ml but less than 1000 copies/ml, between July 2001 and July 2003.
Standard genotype testing was used (an UAI 3730XL sequencer using Virco's proprietary primer mixers), and viral loads at the time of resistance testing were stratified into three ranges: 50-200, 200-600, and 600-1000 copies/ml. Overall, 73% of samples were clade B and 27% were non-B.
A total of 36 samples in the 50-200 range were tested and almost 70% (95% CI, 51.9-83.6) were successful in detecting genotypic resistance. This increased to just over 90% (95% CI, 77.8-96.6) for samples in the 200-600 range and just under 93% (95% CI, 75.7-99.1) for samples in the 600-1000 range. The likelihood of successful genotyping was significantly greater for a viral load between 200 and 1000 copies/ml compared with 50 and 200 copies/ml (p= 0.009).
Given such a high level of success, the authors conclude that they "recommend genotypic testing on all individuals with a viral load in excess of 200 copies/ml and also for individuals with persistent viraemia below 200 copies/ml."
Waters L et al. Successful use of genotypic resistance testing in HIV-1-infected individuals with detectable viraemia between 50 and 1000 copies/ml. AIDS 20 (5): 773-782, 2006.