Acquired HIV Antiretroviral Resistance Is a 'Well-Controlled Relic' in Switzerland

Estimated prevalence of acquired resistance to HIV antiretrovirals in Switzerland fell from 56.2% among people who started antiretroviral therapy (ART) before 1999 to 9.7% in those who started between 2007 and 2013, according to an 11,084-person analysis of the Swiss HIV Cohort Study (SHCS). New resistance mutations emerged in 401 antiretroviral-treated people in 1999 and in 23 people in 2013, a trend making resistance "a well-controlled relic," SHCS investigators write in an article published in the May 15 issue of Clinical Infectious Diseases.

HIV resistance to antiretrovirals emerged rapidly in the early years of ART, when regimens consisted of one or two nucleosides or an unboosted protease inhibitor (PI) added to an already failing nucleoside combination. In more recent years, development of ritonavir-boosted PI strategies, more potent and convenient antiretrovirals and antiretrovirals in new classes often permitted control of resistant HIV and stopped emergence of newly resistant virus. SHCS investigators conducted this 15-year analysis to track trends in acquired resistance.

The study included all antiretroviral-experienced SHCS members (72% of all treated people in Switzerland) who made at least one study visit between January 1999 and December 2013. Researchers collected genotypic resistance data from the SHCS resistance database and from a national database that includes all resistance genotypes performed in Switzerland from 2003 through 2013. The SHCS team divided study participants into (1) those who started ART before January 1, 1999, (2) those who started between January 1999 and December 2006 and (3) those who started from 2007 through 2013. For antiretroviral-treated people without resistance data, the researchers imputed resistance prevalence by stratifying participants into groups with low, high or unknown resistance risk. For SHCS members active in 2013, the researchers also calculated remaining antiretroviral options based on the Stanford resistance algorithm, which ranks antiretrovirals as having full activity, intermediate activity or no activity against resistant strains.

The 11,084 SHCS participants had a median age of 47 (interquartile range 39 to 53); 29% were women; and 19.5% were nonwhite. Similar proportions acquired HIV through sex between men (39.6%) and sex between men and women (37.6%), while 18.8% became infected while injecting drugs.

About one-third of study participants fell into each of the three treatment periods. Prevalence of at least one resistance mutation fell from 56.2% in the pre-1999 group, to 19.7% in the 1999-2006 group and to 9.7% in the 2007-2013 group. In the most recent group, only 1.6% with a resistance test before starting ART acquired resistant virus during therapy. Among SHCS members who had resistant virus in 2013, 59.8% started ART before 1999 and 25.4% started from 1999 through 2006. Among people with antiretroviral experience in 1999, 401 had newly acquired resistant HIV; that number dropped to 23 among treated people in 2013.

Among SHCS members active in 2013, prevalence of resistance to three antiretroviral classes fell from 10.7% in those who started ART before 1999, to 1.6% in the 1999-2006 group and to 0.2% in the 2007-2013 group. In the pre-1999 cohort, 33.8% did not have a fully active nucleoside available and 14.4% did not have a fully active nonnucleoside. Those proportions fell to 6.0% and 9.9% in 1999-2006 and to 0.7% and 8.2% in 2007-2013. Starting in 1999, almost all cohort members had a fully active PI and integrase inhibitor available. Reflecting these declining resistance trends, proportions of people who died of AIDS-related complications fell from 4.0% in those who started ART before 1999, to 2.4% in the 1999-2006 group and to 0.5% in the 2007-2013 group. Respective proportions who died of any cause were 18.6%, 10.3% and 2.1%.

The SHCS investigators conclude that acquired resistance in antiretroviral-treated people in Switzerland "is a well-controlled relic from the era before combination ART." In more recent periods, the researchers observe, most people had a genotypic resistance test before starting ART and began therapy with a suppressive regimen. They warn, though, that resistance transmission and multiclass-resistant HIV remain global threats "because of ART scale-up in settings with limited options for potent drugs, monitoring, and diagnostic tests."