Genotypic tests are able to detect resistance to antiretroviral drugs in patients with low viral load, UK research published in the May 1st edition of the Journal of Infectious Diseases suggests.
A number of major resistance mutations were just as likely to be detected when a patient’s viral load was below 1000 copies/ml as they were at higher viral loads.
“The finding of major resistance mutations supports the practice of HIV genotyping among patients with low-level viremia to guide the choice of an effective alternative regimen”, write the investigators.
The goal of HIV treatment is a viral load below 50 copies/ml. If viral load increases above this level, resistance to antiretroviral drugs can develop. The prompt identification and characterisation of such resistance can help ensure that a patient receives the most appropriate treatment.
Current genotypic resistance tests are most accurate when viral load is above 1000 copies/ml.
However, it is possible to modify these tests so that they are able to detect resistance at lower viral loads.
Little information is available about the use of these tests at lower viral loads. Therefore investigators from the UK performed retrospective analyses to characterise patients having resistance tests when their viral load was below 1000 copies/ml; the resistance profiles of such patients; and the factors associated with the detection of resistance mutations.
A total of 7861 resistance test results from 3791 patients were included. Results were stratified according to viral load (<300 copies, 300-999, 1000-2999, 3000-9999, 10,000-29,999, 30,000-99,999, >100,000).
Overall, 13% of resistance test results were obtained from patients with a viral load below 1000 copies/ml. The proportion of tests performed at low viral loads increased from 4% before 1999 to 22% in 2006.
Other factors associated with having a resistance test when viral load was below 1000 copies/ml included treatment centre (three centres accounted for over 80% of tests at lower viral loads); more recent calendar year; antiretroviral therapy that included a ritonavir-boosted protease inhibitor; and no previous virological failure.
The proportion of all tests detecting resistance fell from 75% in 1999 to 48% in 2006. The prevalence of NRTI resistance closely mirrored this trend. However, NNRTI resistance fluctuated over time, increasing from 68% in 1999 to 76% in 2003, but then falling to 56% in 2006. In 1999, 52% of tests showed resistance to protease inhibitors, but this had fallen to 24% in 2006.
Factors independently associated with the detection of resistance included earlier year of testing (p < 0.001), treatment with an NNRTI-containing regimen (p < 0.001), and never having achieved a viral load below 50 copies/ml (p < 0.001).
The prevalence of resistance mutations varied according to viral load. A resistance mutation was most likely to develop when a patient had a viral load between 300 and 10,000 copies/ml.
When the investigators conducted an analysis to see if the level of viral load affected the total number of resistance mutations present, they found that this varied little. Patients with a viral load below 300 copies/ml had a median of three mutations, those with a viral load between 300 – 10,000 copies/ml had a median of four mutations, and individuals with higher viral loads above this level had a median of three resistance mutations.
Individual resistance profiles varied according to viral load. Amongst patients experiencing NRTI failure, the M41L, L210W and T215Y mutations occurred more often in patients with a viral load below 1000 copies/ml. Other NRTI mutations had a similar prevalence regardless of viral load.
Although uncommon, the L74V mutation was more likely to emerge when a patient’s viral load was above 1000 copies/ml (7% vs. 3%, p < 0.001).
Amongst patients experiencing NNRTI treatment failure, the most common mutation was K103N, which was detected in 35% of individuals. However, the occurrence of this mutation did not vary by viral load.
Common resistance mutations in patients taking a protease inhibitor were L90M, M461, V82A, and D30N. Of these, L90M occurred more frequently at lower viral loads (p < 0.001), whereas the others were more likely to be present in patients with a viral load above 1000 copies/ml.
“To our knowledge, this paper provides the first substantive analysis of the prevalence of major resistance mutations at viral loads of below 1000 copies/ml among patients accessing routine care”, comment the investigators. “The highest rates of detection of resistance mutations were observed at viral loads of 300-10,000 copies/ml…several major resistance mutations were as likely to be detected at viral loads of below 1000 copies/ml as they were at viral loads above this level.”
The investigators believe that their findings have implications for routine HIV care and conclude, “the use of HIV genotypic resistance testing among patients with low viral loads may be helpful in clinical practice to allow a timely and optimized change and may improve outcomes.”
Mackie NE et al. Antiretroviral drug resistance in HIV-1 infected patients with low-level viremia. J Infect Dis 201: 1303-07, 2010.