Evolution of transmitted HIV-1 drug resistance and viral subtypes circulation in Italy from 2006 to 2016

Rossetti, B.; Di Giambenedetto, S.; Torti, C.; Postorino, M. C.; Punzi, G.; Saladini, F.; Gennari, W.; Borghi, V.; Monno, L.; Pignataro, A. R.; Polilli, E.; Colafigli, M.; Poggi, A.; Tini, S.; Zazzi, M.; De Luca, A.; Mellace, V.; Capetti, A.; Gismondo, M. R.; Biondi, M. L.; Mussini, C.; Pecorari, M.; Gianotti, N.; Sacchini, D.; Parruti, G.; Baldelli, F.; Zanussi, S.; Nerli, A.; Lenzi, L.; Calzetti, C.; Vivarelli, A.; Maserati, R.; Baldanti, F.; Poletti, F.; Mondino, V.; Malena, M.; Cascio, A.; Filice, G.; Magnani, G.; Zerbini, A.; Lombardi, F.; Di Gaimbenedetto, S.; Andreoni, M.; Montano, M.; Vullo, V.; Turriziani, O.; Gonnelli, A.; Boeri, E.; Bonora, S.; Ghisetti, V.; Francisci, D.; Grossi, P.; Bagnarelli, P.; Butini, L.; del Gobbo, R.; Giacometti, A.; Tacconi, D.; Callegaro, A.; Maggiolo, F.; Zoncada, A.; Paolini, E.; Sighinolfi, L.; Colao, G.; Corsi, P.; Blanc, P.; Galli, L.; Meraviglia, P.; Tosti, A.; Bruzzone, B.; Setti, M.; Penco, G.; Di Biagio, A.; Nencioni, C.; Pardelli, R.; Arcidiacono, I.; Degiuli, A.; De Gennaro, M.; Soria, A.; Foc, A.; Latella, S.; Cosco, L.; Malandrin, S.; Milini, P.; Cicconi, P.; Rusconi, S.; Micheli, V.

doi:10.1111/hiv.12640

Objectives: The aim was to evaluate the evolution of transmitted HIV-1 drug resistance (TDR) prevalence in antiretroviral therapy (ART)-naïve patients from 2006 to 2016. Methods: HIV-1 sequences were retrieved from the Antiviral Response Cohort Analysis (ARCA) database and TDR was defined as detection of at least one mutation from the World Health Organization (WHO) surveillance list. Results: We included protease/reverse transcriptase sequences from 3573 patients; 455 had also integrase sequences. Overall, 68.1% of the patients were Italian, the median CD4 count was 348 cells/μL [interquartile range (IQR) 169–521 cells/μL], and the median viral load was 4.7 log 10 HIV-1 RNA copies/mL (IQR 4.1–5.3 log 10 copies/mL). TDR was detected in 10.3% of patients: 6% carried mutations to nucleos(t)ide reverse transcriptase inhibitors (NRTIs), 4.4% to nonnucleos(t)ide reverse transcriptase inhibitors (NNRTIs), 2.3% to protease inhibitors (PIs), 0.2% to integrase strand transfer inhibitors (INSTIs) and 2.1% to at least two drug classes. TDR declined from 14.5% in 2006 to 7.3% in 2016 (P = 0.003): TDR to NRTIs from 9.9 to 2.9% (P = 0.003) and TDR to NNRTIs from 5.1 to 3.7% (P = 0.028); PI TDR remained stable. The proportion carrying subtype B virus declined from 76.5 to 50% (P < 0.001). The prevalence of TDR was higher in subtype B vs. non-B (12.6 vs. 4.9%, respectively; P < 0.001) and declined significantly in subtype B (from 17.1 to 8.8%; P = 0.04) but not in non-B subtypes (from 6.1 to 5.8%; P = 0.44). Adjusting for country of origin, predictors of TDR were subtype B [adjusted odds ratio (AOR) for subtype B vs. non-B 2.91; 95% confidence interval (CI) 1.93–4.39; P < 0.001], lower viral load (per log 10 higher: AOR 0.86; 95% CI 0.75–0.99; P = 0.03), site in northern Italy (AOR for southern Italy/island vs. northern Italy, 0.61; 95% CI 0.40–0.91; P = 0.01), and earlier calendar year (per 1 year more recent: AOR 0.95; 95% CI 0.91–0.99; P = 0.02). Conclusions: The prevalence of HIV-1 TDR has declined during the last 10 years in Italy.

Evolution of transmitted HIV-1 drug resistance and viral subtypes circulation in Italy from 2006 to 2016

Rossetti B.;Di Giambenedetto S.;Torti C.;Postorino M. C.;Punzi G.;Saladini F.;Gennari W.;Borghi V.;Monno L.;Pignataro A. R.;Polilli E.;Colafigli M.;Poggi A.;Tini S.;Zazzi M.;De Luca A.;Mellace V.;Capetti A.;Gismondo M. R.;Biondi M. L.;Mussini C.;Pecorari M.;Gianotti N.;Sacchini D.;Parruti G.;Baldelli F.;Zanussi S.;Nerli A.;Lenzi L.;Calzetti C.;Vivarelli A.;Maserati R.;Baldanti F.;Poletti F.;Mondino V.;Malena M.;Cascio A.;Filice G.;Magnani G.;Zerbini A.;Lombardi F.;Di Gaimbenedetto S.;Andreoni M.;Montano M.;Vullo V.;Turriziani O.;Gonnelli A.;Boeri E.;Bonora S.;Ghisetti V.;Francisci D.;Grossi P.;Bagnarelli P.;Butini L.;del Gobbo R.;Giacometti A.;Tacconi D.;Callegaro A.;Maggiolo F.;Zoncada A.;Paolini E.;Sighinolfi L.;Colao G.;Corsi P.;Blanc P.;Galli L.;Meraviglia P.;Tosti A.;Bruzzone B.;Setti M.;Penco G.;Di Biagio A.;Nencioni C.;Pardelli R.;Arcidiacono I.;Degiuli A.;De Gennaro M.;Soria A.;Foc A.;Latella S.;Cosco L.;Malandrin S.;Milini P.;Cicconi P.;Rusconi S.;Micheli V.

2018-01-01

Abstract

Objectives: The aim was to evaluate the evolution of transmitted HIV-1 drug resistance (TDR) prevalence in antiretroviral therapy (ART)-naïve patients from 2006 to 2016. Methods: HIV-1 sequences were retrieved from the Antiviral Response Cohort Analysis (ARCA) database and TDR was defined as detection of at least one mutation from the World Health Organization (WHO) surveillance list. Results: We included protease/reverse transcriptase sequences from 3573 patients; 455 had also integrase sequences. Overall, 68.1% of the patients were Italian, the median CD4 count was 348 cells/μL [interquartile range (IQR) 169–521 cells/μL], and the median viral load was 4.7 log 10 HIV-1 RNA copies/mL (IQR 4.1–5.3 log 10 copies/mL). TDR was detected in 10.3% of patients: 6% carried mutations to nucleos(t)ide reverse transcriptase inhibitors (NRTIs), 4.4% to nonnucleos(t)ide reverse transcriptase inhibitors (NNRTIs), 2.3% to protease inhibitors (PIs), 0.2% to integrase strand transfer inhibitors (INSTIs) and 2.1% to at least two drug classes. TDR declined from 14.5% in 2006 to 7.3% in 2016 (P = 0.003): TDR to NRTIs from 9.9 to 2.9% (P = 0.003) and TDR to NNRTIs from 5.1 to 3.7% (P = 0.028); PI TDR remained stable. The proportion carrying subtype B virus declined from 76.5 to 50% (P < 0.001). The prevalence of TDR was higher in subtype B vs. non-B (12.6 vs. 4.9%, respectively; P < 0.001) and declined significantly in subtype B (from 17.1 to 8.8%; P = 0.04) but not in non-B subtypes (from 6.1 to 5.8%; P = 0.44). Adjusting for country of origin, predictors of TDR were subtype B [adjusted odds ratio (AOR) for subtype B vs. non-B 2.91; 95% confidence interval (CI) 1.93–4.39; P < 0.001], lower viral load (per log 10 higher: AOR 0.86; 95% CI 0.75–0.99; P = 0.03), site in northern Italy (AOR for southern Italy/island vs. northern Italy, 0.61; 95% CI 0.40–0.91; P = 0.01), and earlier calendar year (per 1 year more recent: AOR 0.95; 95% CI 0.91–0.99; P = 0.02). Conclusions: The prevalence of HIV-1 TDR has declined during the last 10 years in Italy.