Prevalence of UK HIV drug resistance in antiretroviral-naive falls to 9%

The prevalence of antiretroviral-naive individuals with HIV in the United Kingdom who are resistant to at least one anti-HIV drug has declined from a peak of 16% in 2002 to 9% in 2004, according to genotypic data from the UK HIV Drug Resistance Database reported in the January 26^th edition of the UK Health Protection Agency's (HPA) CDR Weekly. The report also found that the prevalence of resistance in antiretroviral-experienced individuals is showing a downward trend.

In recent years, data have suggested that in contrast to some other European countries, like France and Spain, the prevalence of primary drug resistance in the UK has been on the rise, leading to concerns that increasing numbers of individuals in the UK who start antiretroviral therapy may have fewer options for first-line treatment.

The HPA's report is based on findings from genotypic testing undertaken as part of routine clinical care in 2004. However, the report does not include a linkage to clinical data, which is required to determine how these mutations may have affected an individual's treatment options and/or disease progression. In addition, the HPA say that the data for 2004 are incomplete.

The report defines HIV drug-resistant mutations as one or more major mutations listed in the 2005 International AIDS Society-USA guidelines, plus several additional mutations agreed by the UK Collaborative Group on HIV Drug Resistance (who also counted as a single major protease mutation any reverse transcriptase mutation at G190 or T215; a combination of protease V32I and I47V/A mutations; and seven or more minor lopinavir mutations). No data were presented on fusion inhibitor (T-20, enfuvirtide, Fuzeon) resistance, and the report excluded mother-to-child transmission and all children under 16 years of age.

Drug-experienced data

The number of resistance tests performed in treatment-experienced individuals has remained constant at around 1500 for the past few years. As in treatment-naive individuals, prevalence of resistance in treatment-experienced individuals is declining, but the 2004 data are more striking when compared to data from 1998/1999.

In 1999, only 22% of samples tested had no evidence of resistance to any class; in 2004 this had increased to 35%. Although resistance to at least one NRTI is still more prevalent than other drug classes (at around 55%) this is declining from its 1999 peak of around 70%. Similarly prevalence of resistance to at least one PI has declined from a peak of around 35% in 1998 to just under 20% in 2004.

In contrast, NNRTI resistance has remained relatively stable since 2001, with around 50% of samples tested having evidence of major NNRTI resistance mutations. The number of individuals infected with triple class resistant viruses, who are most at risk of exhausting treatment options has fallen from a peak of around 15% in 1999-2001 to around 8% in 2003-2004.

Drug-naive data

Since 2003, British HIV Association (BHIVA) guidelines have recommended baseline resistance testing for individuals suspected of having acquired transmitted drug resistance. Consequently, the number of results reported to the UK HIV Drug Resistance Database have increased from 520 in 2002 to 1185 in 2004.

Data on individuals who have never taken antiretroviral therapy include both the newly infected and chronically infected individuals who have not yet begun highly active antiretroviral therapy (HAART). However, because this report does not distinguish between the two, and because primary resistance mutations may persist for several years after infection, the results cannot be interpreted as describing the epidemiology of recently-transmitted drug resistance.

Resistance to any drug class (ie. NRTI, NNRTI, or PI) declined from 16% in 2002, and 12% in 2003, to 9% in 2004. In 2004, around 4.5% of samples showed resistance to at least one drug in the nucleoside reverse transcriptase (NRTI) and non-nucleoside (NNRTI) classes. Resistance to at least one protease inhibitor (PI) was seen in 2.1%.

Of the samples that harboured mutations, the majority were resistant to just one drug class, with 17% resistant to two classes, and 8% multiclass resistant (i.e. resistant to three classes). In line with the general decline seen in HIV drug resistance, the proportion of individuals with two and three-class resistant HIV has also declined.

Comment

One of the possible reasons for the decline of HIV drug resistance in antiretroviral-naive individuals is that clinicians are being more thorough in determining whether patients who claim they are treatment-naive have previously taken antiretroviral therapy. This may be the case when people who acquired HIV in a country outside of the UK appear to test HIV-positive for the first time when they may have been previously diagnosed and treated in their home country.

The authors of the HPA report also suggest that since most new HIV diagnoses in the UK are among those infected in sub-Saharan Africa "where availability to antiretroviral therapy is very limited...it is to be expected that the presence of pre-existing resistance is lower for such individuals than for those infected within the UK." However, the authors of a study published last year in the British Medical Journal on primary HIV drug resistance between 1996 and 2003 in the UK were surprised to find primary resistance to be equally prevalent in whites (15%) and black Africans (17%).