Resistance to anti-HIV drugs in steep decline in Switzerland

Prevalence of antiretroviral drug resistance has declined significantly among patients in Switzerland, investigators report in the online edition of Clinical Infectious Diseases. As many as 57% of patients taking HIV therapy in 1999 had resistance to at least one anti-HIV drug, but prevalence had declined to 37% in 2013 when most cases of resistance involved either individuals with a history of sub-optimal therapy or transmitted resistance.

“Our results showed that the burden of drug resistance and multi-class resistance…is mainly a relic from the era before highly active antiretroviral therapy was introduced,” write the authors. “We demonstrated that the vast majority of treated patients who initiated treatment in more recent years did not acquire resistance. These patients usually had a pre-treatment resistance test done and were treated with highly effective first-line ART.”

Resistance is a major limitation of antiretroviral therapy (ART). It can emerge when viral load remains detectable in the presence of treatment. This can be because the treatment is sub-optimal or because of poor patient adherence.

Modern HIV therapy is potent and easy to take. This means that the risk of new resistance cases is reduced.

Investigators from the Swiss HIV Cohort Study wanted to establish a clearer understanding of changing prevalence of drug resistance among ART-treated patients between 1999 and 2013.

They therefore designed a study involving all ART-treated individuals enrolled in the cohort who had at least one follow-up visit between 1999 and 2013.

Patients were classified as having drug resistance if they had a strain of virus with at least one major resistance mutation.

There were major improvements in HIV treatment and care during the study period. Therefore patients were divided into three groups according to the year in which they initiated treatment:

• Before 1999: sub-optimal therapy (mono- or dual-therapy or treatment based on an unboosted protease inhibitor).
• 1999-2006: combination treatment based on an early NNRTI or first-generation boosted protease inhibitor.
• 2007 onwards: modern treatment, characterised by the availability of potent drugs with high barriers to resistance and simple adherence schedules.

The total study population comprised 11,084 patients and approximately a third started therapy in each of the treatment eras.

The absolute number of treatment-experienced patients with drug resistance remained very stable at approximately 2000 individuals each year. This was despite the absolute number of ART-treated patients increasing from 5,516 in 2003 to 8,189 in 2013.

Overall, 29% of patients had resistance detected. Prevalence was highest among individuals who initiated treatment before 1999 (56%), declining to 20% among individuals who started therapy between 1999 and 2006 and to 10% among those first taking treatment after 2007. In the most recent treatment group, only 1.6% of patients developed resistance when taking ART. The vast majority of patients with resistance in the post-2007 group had been infected with a drug-resistant strain of virus (278 of 323, 86%).

Of the patients in care in 2013 with resistance, 60% started therapy before 1999 and 25% initiated treatment between 1999 and 2006. Only 15% of cases involved patients who started antiretrovirals in the most recent period.

The number of cases of newly diagnosed resistance declined from 401 patients in 1999 to 23 individuals in 2013. In 1999 there were 69 diagnoses of triple-class resistance, but there were just three diagnoses of this type in 2013.

The authors estimated that up to 57% of patients in care in 1999 carried a drug-resistant strain but that this had fallen to 37% in 2013.

Prevalence of triple-class resistance fell by half from 9% in 1999 to 4% in 2013.

Most patients – 97% – had enough treatment options available to construct a viable ART regimen, including 95% of patients who started therapy before 1999.

“The expansion of treatment indications is not expanding drug resistance; it is resulting in less drug resistance,” writes the author of an editorial. “This can be attributed to more potent drugs, less side effects, fixed dose of combinations and higher treatment success rates in those initiating treatment at earlier stages of disease.”