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

Objectives: The aim was to evaluate the evolution of transmitted HIV-1 drug resistance (TDR) prevalence in antiretroviral therapy (ART)-na\uefve 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/\u3bcL [interquartile range (IQR) 169\u2013521 cells/\u3bcL], and the median viral load was 4.7 log10 HIV-1 RNA copies/mL (IQR 4.1\u20135.3 log10 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\u20134.39; P < 0.001], lower viral load (per log10 higher: AOR 0.86; 95% CI 0.75\u20130.99; P = 0.03), site in northern Italy (AOR for southern Italy/island vs. northern Italy, 0.61; 95% CI 0.40\u20130.91; P = 0.01), and earlier calendar year (per 1 year more recent: AOR 0.95; 95% CI 0.91\u20130.99; P = 0.02). Conclusions: The prevalence of HIV-1 TDR has declined during the last 10 years in Italy

The role of baseline HIV-1 RNA, drug resistance, and regimen type as determinants of response to first-line antiretroviral therapy

The factors influencing virological response to first-line combined antiretroviral therapy (cART) in an Italian cohort of HIV-1-infected patients were examined. Eligible patients were those enrolled in a national prospective observational cohort (Antiretroviral Resistance Cohort Analysis), starting first-line cART between 2001 and 2011 and who had at least one follow-up of HIV-1 RNA. The primary endpoint was virological success, defined as the first viral load 100,000 copies/ml, virologic success was only associated with the use of integrase inhibitors in the first cART regimen. Independent predictors of immunological success were baseline CD4+ cell count and wGSS <3. High baseline HIV-1 RNA, predicted activity of the first-line regimen based on genotypic resistance testing, gender, and use of new agents were found to predict time to achieve virological success. The type of initial nucleoside analog backbone was not found to predict virological response