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.”