Prevalence of drug-resistant HIV has fallen dramatically among antiretroviral-experienced patients in Western Europe

There has been a significant fall in the proportion of HIV-positive people in Western Europe with experience of HIV treatment who have resistance to antiretroviral drugs, investigators report in the online edition of the Journal of Infectious Diseases. The prevalence of triple-class resistance peaked at below 5% in 2005 before falling, and in 2008 at most 1% of patients had exhausted their treatment options.

The study shows the durability of modern antiretroviral therapy and will give confidence to patients that currently available treatments will work for a lifetime. The results stand in contrast to those of a recent Australian study that predicted prognosis would be reduced due to the exhaustion of treatment options.

HIV can become resistant to antiretroviral drugs. The presence of drug-resistant virus can allow HIV to replicate, reducing CD4 cell count, and possibly increasing the risk of illness and death.

Glossary

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.

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. 

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). 

retrospective study

A type of longitudinal study in which information is collected on what has previously happened to people - for example, by reviewing their medical notes or by interviewing them about past events. 

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.

Resistance was a serious problem in the years immediately after the introduction of triple-drug antiretroviral treatment in 1996. This was because many people had previously received suboptimal therapy with one or two drugs. This treatment could not suppress HIV in the long term, leading to the development of resistance. Moreover, early triple regimens often lacked potency, had a demanding adherence schedule and were associated with severe side-effects.

There have been major improvements to HIV treatment and care in the past decade. These include the introduction of powerful, safe, easy-to-take new drugs which often work against drug-resistant virus. These improvements mean that virological control of HIV is now the aim of therapy for almost all people with HIV.

Investigators wished to establish trends and predictors of drug resistance among people taking antiretroviral therapy in Europe. They therefore designed a retrospective study involving 20,323 people treated with anti-HIV drugs between 1997 and 2008 in seven Western European countries.

Most of the participants were men (74%) and were infected with HIV subtype B (64%). Their median age was 40 years, median CD4 cell count was 277 cells/mm3 and median viral load was approximately 8000 copies/ml. Participants had been taking antiretroviral therapy for a median of 64 months when their virus was genotyped for drug resistance. Over half had had received mono or dual therapy.

Overall, 80% of participants had at least one major resistance mutation to at least one drug from the three major classes of antiretrovirals – nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs).  Specifically, two-thirds carried resistance to an NRTI, 50% to an NNRTI and 33% to a protease inhibitor.

However, there was “clear evidence” of a reduction in resistance to NRTIs and protease inhibitors after 2001 (p < 0.001). Resistance to NNRTIs peaked in 2004 and then fell significantly (p < 0.001).

The prevalence of triple-class resistance reached a high of 4.5% in 2005 before falling.

The overall proportion of participants who had exhausted their treatment options was 11%. This peaked at between 27 and 32% in 2000, but had fallen to just 0.3 to 1% in 2008. The authors attributed this dramatic reduction to the availability of new anti-HIV drugs.

“HIV drug resistance mutations to all historical drug classes decline during the most recent calendar years,” write the investigators. “This effect emerged despite accumulating drug exposure over time, involved all classes and almost all different mutation patterns, and persisted after adjustment for potential confounders.”

References

De Luca A et al. Declining prevalence of HIV-1 drug resistance in antiretroviral treatment-exposed individuals in Western Europe. J Infect Dis, online edition, 2013.