Significant fall in transmitted drug-resistant HIV in UK; may be due to better treatment

National surveillance data show for the first time a significant and sustained decline in the prevalence of transmitted drug-resistant HIV in the United Kingdom. A study published in the May 11^th edition of AIDS found that the proportion of antiretroviral-naïve HIV-positive individuals in the UK with drug-resistant virus fell significantly between 2002 and 2004.

The study also found that two years earlier there was a significant fall in the number of newly infected individuals acquiring drug-resistant HIV. The investigators attribute the decline in transmitted drug-resistant HIV to the wider use of anti-HIV treatment regimens that are able to suppress viral load to below infectious levels.

Routine genotypic resistance tests performed on antiretroviral-naïve patients in the United States and many European countries have shown that the prevalence of drug-resistance HIV has increased as use of anti-HIV drugs has expanded. In the UK, all the results of all resistance tests performed as part of routine HIV are held in the UK Drug Resistance Database. Investigators from the UK database performed an analysis of resistance tests performed on antiretroviral-naïve individuals to the end of 2005.

Particular attention was paid to the test results of patients who were recently infected with HIV. They defined a test as relating to recent HIV infection if a patient was enrolled on the UK Register of HIV Seroconverters and their blood sample for resistance testing was obtained within 18 months of a previous HIV-negative result.

The investigators had a total of 4,454 samples available for analysis. These samples were obtained between early 1996 and late 2004 and included the results of 316 tests performed on individuals with recent HIV infection.

In 1996, only 310 resistance tests on untreated individuals were performed, increasing to 519 in 2002. Thereafter, however, there was a significant increase in the number of tests (767 tests in 2003 and 1,185 in 2004) following the publication of guidelines from the British HIV Association (BHIVA) recommending that all HIV-positive individuals should be monitored for transmitted drug resistance before starting antiretroviral treatment.

A peak in the number of individuals with transmitted drug resistance was observed in 2001 – 2002, when one or more major resistance mutations were detected in 14% of patients. By the end of 2004, however, only 8% of untreated individuals had resistance, a highly significant decline (P_trend

Among patients with recent infection, a similar pattern was detected, but the downward trend in the transmission of resistance occurred approximately two years earlier, from 2000 onwards (P_trend = 0.002).

Particularly notable was a decline in the prevalence of transmitted NRTI resistance over time, with NNRTI resistance becoming as common as NRTI resistance by 2004 (4%). The prevalence of resistance to protease inhibitors peaked at approximately 4% in 2001 – 2002, but by 2004 had fallen to below 2%.

Three possible reasons for the decline in the prevalence of transmitted drug resistance in the UK are advanced by the investigators:

• Earlier estimates may have had an upward bias if individuals were selectively tested if their partner was known to be on antiretroviral therapy or if retrospective testing was performed on a patient who had experienced treatment failure.
• There has been an increase in the prevalence of non-B HIV subtypes in the UK. Preliminary analysis suggests that transmitted resistance is less common in non-B subtypes, but when the investigators restricted their analysis to type B samples they found that their principal findings remained unaltered.
• There has been a genuine reduction in transmitted drug resistance, due to “the wider use of, and improved adherence to, regimens that suppress viral load concentration to below infectious levels.”

However, the investigators “caution against over-optimistic interpretation of our findings from a public health perspective”, noting that the fall in transmitted resistance needs to be seen within the context of a doubling of new HIV diagnoses in the UK in recent years. They conclude, “the persistence of resistance mutations is a key factor in the epidemiology of transmitted drug resistance; if they persist indefinitely the absolute number of infections with resistant virus will inevitably increase if the average number of new infections per index case exceeds one.”