HIV-1 transmitted drug resistance in newly diagnosed individuals in Italy over the period 2015-21

Abstract

Background: Transmitted drug resistance (TDR) is still a critical aspect for the management of individuals living with HIV-1. Thus, its evaluation is crucial to optimize HIV care.

Methods: Overall, 2386 HIV-1 protease/reverse transcriptase and 1831 integrase sequences from drug-naïve individuals diagnosed in north and central Italy between 2015 and 2021 were analysed. TDR was evaluated over time. Phylogeny was generated by maximum likelihood. Factors associated with TDR were evaluated by logistic regression.

Results: Individuals were mainly male (79.1%) and Italian (56.2%), with a median (IQR) age of 38 (30-48). Non-B infected individuals accounted for 44.6% (N = 1065) of the overall population and increased over time (2015-2021, from 42.1% to 51.0%, P = 0.002). TDR prevalence to any class was 8.0% (B subtype 9.5% versus non-B subtypes 6.1%, P = 0.002) and remained almost constant over time. Overall, 300 transmission clusters (TCs) involving 1155 (48.4%) individuals were identified, with a similar proportion in B and non-infected individuals (49.7% versus 46.8%, P = 0.148). A similar prevalence of TDR among individuals in TCs and those out of TCs was found (8.2% versus 7.8%, P = 0.707).By multivariable analysis, subtypes A, F, and CFR02_AG were negatively associated with TDR. No other factors, including being part of TCs, were significantly associated with TDR.

Conclusions: Between 2015 and 2021, TDR prevalence in Italy was 8% and remained almost stable over time. Resistant strains were found circulating regardless of being in TCs, but less likely in non-B subtypes. These results highlight the importance of a continuous surveillance of newly diagnosed individuals for evidence of TDR to inform clinical practice.

Figure 1.

Evaluation of HIV-1 B and non-B subtype prevalence in newly diagnosed individuals over time in the overall population (a) and in Italians (b). Chi-squared test for the trend was used to evaluate potential differences in the prevalence of B and non-B subtypes over the years 2015–2021. Pvalues in the figure are referred to the evaluation of potential differences during the periods 2015–2017 and 2018–2021.

Figure 2.

Prevalence of TDR in Italian PHW, diagnosed in the period 2015–2021, according to calendar year and drug classes. (a) Prevalence of TDR over time in the overall population. (b) Prevalence of TDR over time in individuals infected with the HIV-1 B subtype. (c) Prevalence of TDR over time in individuals infected with HIV-1 non-B subtypes. TDR was evaluated by considering the surveillance list of mutations used in HIVdb. The P values were calculated using the chi-squared test for trend.

Figure 3.

Genotypic susceptibility to antiretrovirals among HIV-1 B and non-B subtype in newly diagnosed individuals. (a) Proportion of individuals harbouring fully susceptible virus per each ARV. (b) Proportion of individuals harbouring fully susceptible virus per each first-line regimen used in clinical practice.^, The dotted line indicates a proportion of 95%.

Figure 4.

Prevalence of drug resistance mutations in HIV-1 B (a) and non-B subtypes (b) according to drug classes and presence or not in TCs. Surveillance mutations are reported that used HIVdb present in at least two individuals for PI and RTI and in at least one individual for INSTI. Each bar is divided according to (i) the presence of drug resistance mutations in clusters (in white) and (ii) the presence of drug resistance mutations out of clusters (in black).