Transmitted drug-resistant HIV stabilising in Europe

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The transmission of drug-resistant strains of HIV in Europe has stabilised, and in some cases declined, an international team of investigators reports in the November 15th edition of the Journal of Infectious Diseases, which is now online.

Blood samples were collected from individuals newly diagnosed with HIV between 2002 and 2006 in 20 European countries and Israel.

An analysis of these samples showed that there was a modest fall in the transmission of HIV that was resistant to nucleoside reverse transcriptase inhibitors (NRTIs). It also indicated that transmitted non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance peaked in 2004 before falling, and that the transmission of virus resistant to protease inhibitors fell significantly throughout the period of the study.

Glossary

subtype

In HIV, different strains which can be grouped according to their genes. HIV-1 is classified into three ‘groups,’ M, N, and O. Most HIV-1 is in group M which is further divided into subtypes, A, B, C and D etc. Subtype B is most common in Europe and North America, whilst A, C and D are most important worldwide.

drug resistance

A drug-resistant HIV strain is one which is less susceptible to the effects of one or more anti-HIV drugs because of an accumulation of HIV mutations in its genotype. Resistance can be the result of a poor adherence to treatment or of transmission of an already resistant virus.

representative sample

Studies aim to give information that will be applicable to a large group of people (e.g. adults with diagnosed HIV in the UK). Because it is impractical to conduct a study with such a large group, only a sub-group (a sample) takes part in a study. This isn’t a problem as long as the characteristics of the sample are similar to those of the wider group (e.g. in terms of age, gender, CD4 count and years since diagnosis).

reverse transcriptase

A retroviral enzyme which converts genetic material from RNA into DNA, an essential step in the lifecycle of HIV. Several classes of anti-HIV drugs interfere with this stage of HIV’s life cycle: nucleoside reverse transcriptase inhibitors and nucleotide reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). 

nucleoside

A precursor to a building block of DNA or RNA. Nucleosides must be chemically changed into nucleotides before they can be used to make DNA or RNA. 

This pattern of declining transmitted resistance coincided with lower rates of resistance amongst patients taking HIV therapy. The investigators therefore write: “This concordance is reassuring and indicates that our observed time trends in transmitted drug resistance are a genuine consequence of improved clinical care of treated patients”.

Modern antiretroviral therapy is so effective that both patients starting treatment with anti-HIV drugs for the first time and those with an extensive history of HIV treatment have an excellent chance of achieving and maintaining an undetectable viral load.

However, treatment with older regimens did not have such impressive results, meaning that a proportion of patients developed virus that was resistant to HIV and potentially transmissible to partners.

Investigators from the SPREAD Programme wished to determine the prevalence, trends, and risk factors for transmitted drug resistance between 2002 and 2006.

Their analysis was based upon blood samples obtained from 2793 patients newly diagnosed with HIV. These patients were demographically representative of the populations most affected by HIV in Europe and Israel.

These blood samples were subjected to genotypic analysis to determine the presence of resistance to NRTIs, NNRTIs, and protease inhibitors.

Most of the patients born in western Europe were gay men (60%), whereas 98% of patients involved in the study who originated from sub-Saharan Africa were heterosexuals.

Between 2002 and 2006, the overall prevalence of transmitted resistance was 8%. NRTI resistance was present in 5% of patients, whereas 2% had resistance to NNRTIs and 3% were resistant to protease inhibitors.

Resistance to two classes of anti-HIV drugs was present in approximately 1% of patients, and less than 0.5% of patients had triple-class resistance.

Statistical analysis showed that there was a modest decline in the proportion of newly diagnosed patients with transmitted resistance to NRTIs during the period of the study. The number of patients with resistance to NNRTIs peaked in 2004, but fell significantly thereafter (p = 0.02). The investigators also observed that between 2002 and 2006 the number of newly diagnosed patients with resistance to protease inhibitors fell significantly (p = 0.04).

HIV subtype B was the most prevalent strain of the virus (67%), followed by subtype A (10%) and subtype C (7%).

Unsurprisingly, gay men were the group most likely to be infected with subtype B (p

Furthermore, gay men with subtype B were the group most likely to have transmitted drug resistance (p

“The representative data provide evidence of a stabilising trend over time in the overall transmitted resistance in Europe,” comment the investigators.

They conclude, “the prevalence of overall transmitted resistance among patients in Europe in whom HIV-1 infection was newly diagnosed was found to be stabilising at under 10%...transmitted NRTI resistance also seems to be stabilising, whereas transmitted NNRTI and protease inhibitor resistance decreased over time. Subtype B infection was the strongest predictor of transmission of resistance.”

It is worth noting that the investigators' analysis stopped in 2006. Since then, several new antiretroviral drugs have become available that mean that even the most treatment-experienced patient has the chance of suppressing their viral load to undetectable levels. This is likely to reduce of the transmission of resistant virus, and also of HIV itself.

References

Vercauteren J et al. Transmission of drug-resistant HIV-1 is stabilizing in Europe. J Infect Dis 200 (online edition), 2009.