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HIV Resistance Prevalence Flat in Italy Over Past 5 Years
  16th European AIDS Conference, October 25-27, 2017. Milan
Mark Mascolini
Prevalence of HIV mutations conferring resistance to multiple antiretroviral classes dropped sharply over the past 15 years in Italy, but resistance rates remained stable over the past 5 years [1]. Single-class resistance edged up steadily since 2001.
Availability of several antiretroviral classes and potent new agents means higher proportions of treated people can achieve and maintain an undetectable viral load. Greater viral suppression rates suggest that prevalence of detectable resistance mutations should fall as fewer newly treated people durably control HIV. To see if that assumption is true, researchers at the University of Rome Tor Vergata and other centers conducted this 1996-2016 analysis.
The study involved 6147 antiretroviral-treated people from central and northern Italy who provided 12,839 viral samples genotyped for mutations conferring resistance to nucleos(t)ides, nonnucleosides, protease inhibitors, or integrase inhibitors. Participants were in care for various periods between 1996 and 2016. The researchers identified resistance-conferring mutations with the 2017 IAS-Stanford list. They used logistic regression to pinpoint factors associated with emergence of resistant HIV.
Of the 6147 treated participants, 69% were men, 71% were Italian, 27% became infected during heterosexual sex, 27% through drug injection, and 17% during sex between men. At genotyping, median age stood at 42 years and median viral load at 4.2 log10 copies (about 16,000 copies). The study group had taken a median of 4 previous antiretroviral regimens.
Overall, 41% of people had no detectable mutations, 21% had 1 mutation, 25% had 2 mutations, and 13% had 3 or more mutations. The proportion of participants with no detectable mutations rose significantly from 13% in or before 2001 to 58% in 2010 (P < 0.001). Over the same years, proportions with 1 mutation rose significantly from 14% to 22% (P < 0.001), but proportions with 2 mutations plunged from 42% to 14% (P < 0.001) and with 3 or more mutations from 30% to 6% (P < 0.001). From 2011 through 2016, proportions in all these groups changed little. Proportions with 1 mutation stayed flat at around 25%, with 2 mutations at around 12%, and with 3 or more mutations at around 5%.
New detection of triple-class resistance or more plummeted from 23% in 1999 to 1% in 2010 (P < 0.001) but inched up nonsignificantly from 1% to 3% from 2011 through 2016 (P = 0.222). Prevalence of resistance to one or more of the three integrase inhibitors stayed flat from 2008 through 2016 (8% to 9%, P = 0.818). After 2008 integrase resistance occurred mostly in genotypes with triple-class or more resistance.
Logistic regression analysis linked four factors to lower odds of emergent resistance in 1999-2010: female gender (P < 0.001), every additional 5 years of age at genotyping (P = 0.007), every 10-fold higher viral load (P < 0.001), and raltegravir use before genotyping (P = 0.019). Three variables predicted a greater chance of emerging resistance in 1999-2010: heterosexual HIV risk (P = 0.011), each additional regimen before genotyping (P < 0.001), and each additional nucleos(t)ide before genotyping (P = 0.003). In 2011-2016, exposure to each additional nonnucleoside, protease inhibitor, or integrase inhibitor before genotyping independently predicted detection of at least 1 resistance mutation.
In multidrug-experienced people, the researchers stressed, resistance to 3 or more antiretroviral classes "remains a recurrent concern deserving clinical attention."
1. Armenia D, Di Carlo D, Borghi V, et al. HIV drug resistance remains a relevant clinical concern, despite its dramatic drop over the years. 16th European AIDS Conference. October 25-27, 2017. Milan. Abstract PS3/2.