Sensitive test finds high rate of transmitted drug-resistant HIV in UK

The rate of transmitted drug-resistant HIV in the UK may be substantially higher than previously thought, investigators report in the online edition of HIV Medicine.

Standard genotypic tests detected drug-resistant virus in 13% of anonymous blood samples collected from undiagnosed HIV-positive gay men. However, when the investigators also used resistance testing assays capable of detecting minority populations of drug-resistant virus, the proportion of individuals with transmitted resistance increased to 19%.

“This increase of 45% in drug resistant levels was statistically significant,” comment the investigators.

Rates of transmitted drug-resistant HIV in the UK peaked at approximately 12% in 2002. Improvements in HIV treatment and care are thought to be responsible for a fall in the rate of transmitted resistance to around 8% in 2006.

Nevertheless, it is recommended that all patients should be tested for drug resistance at the time of their HIV diagnosis. Drug resistance acquired at the time of HIV infection may be less easy to detect in untreated people as time goes by, because drug-resistant virus populations will tend to decline due to poorer ability to replicate compared to 'wild type' virus.

However when treatment is begun, low levels of resistance may impair the response to treatment.

The detection of resistant virus early can help guide the choice of antiretroviral therapy.

Some researchers have commented on marked differences in the patterns of resistance found in recently diagnosed patients and those with chronic HIV infection who have taken antiretroviral treatment. These differences have been attributed to the reduced “fitness” of resistant virus, meaning that it is potentially less transmissible than drug-susceptible, or wild-type virus.

However, the assays used in routine practice to test for resistance are only able to detect majority populations (above 20%) of resistant virus.

An international team of investigators wanted to see if the use of a more sensitive test would result in an increase in the proportion of infections found to involve resistance.

They therefore tested 165 blood samples obtained anonymously from gay men who attended UK sexual health clinics in 2003 and 2006. All the samples were HIV-positive and all the men were unaware of their infection.

The samples were tested using both a routine assay, and this test in combination with a much more sensitive test capable of detecting minority populations with mutations (K103N, Y181C, and M184V) that lead resistance to first-line anti-HIV drugs.

Using the standard test, 21 samples (13%) were found to involve drug resistance. This increased to 32 samples (19%) when the sensitive assay was also used. This 45% increase was highly significant (p = 0.002).

Next the investigators used the two assays to monitor the prevalence of specific mutations. The standard test showed that 6% of patients had the K103N mutation associated with resistance to efavirenz, and this increased to 7% when the samples were tested using the more sensitive assay as well. The difference between the results from the two assays was not significant.

No virus with the Y181C mutation that confers resistance to efavirenz and nevirapine was found in any samples using either of the testing assays.

Only one (0.6%) patient was found to have the M184V mutation associated with resistance to 3TC or FTC when the routine assay was used. But this increased to 13 (8%) when samples were tested both assays. This increase was highly significant (p = 0.0005).

“The findings we report here support the suggestion that M184V is as likely to be transmitted as other mutations,” write the study authors, adding: “this study contributes evidence to support the inclusion of minority assays for M184V surveillance.”

The prevalence of resistance by calendar year was monitored using both assays. The standard assay showed that 15% of samples in 2003 involved drug resistance, and this increased to 19% when the sensitive test was also used.

For 2006, use of the standard test showed resistance in 10% of men, but this figure doubled (p = 0.0078) when a combination of both testing assays was used.

Finally, the investigators compared the prevalence of resistance according to whether individuals had recent or chronic HIV infection. Resistance was detected in 19% of men recently infected with HIV and 20% of those with long-standing infections.

Buckton AJ et al. Increased detection of the HIV-1 reverse transcriptase M184V mutation using mutation-specific minority assays in a UK surveillance study suggests evidence of unrecognised transmitted drug resistance. HIV Medicine, advance online publication, DOI: 10.1111/j.1468-1293.2010.00882x, 2010 (for abstract click here).