Characterization of HIV-1 molecular epidemiology and transmitted drug-resistance in newly diagnosed HIV-infected patients in Sichuan, China

Abstract

Background: Sichuan province is one of the highest AIDS epidemic provinces in China, with a large number of floating population. The annual number of cases of HIV/AIDS reported in Sichuan has been the highest province in China for several successive years. There is a lack of widespread and representative data on the distribution of HIV genotypes in Sichuan. We aim to investigate the characteristics of HIV-1 molecular epidemiology and transmitted drug-resistance in newly diagnosed HIV-infected patients in Sichuan, China.

Method: Archived plasma samples (n = 1524) from HIV-1 newly-diagnosed individuals in April 2019 were selected by cross-sectional investigation from all 21 cities in Sichuan province. Phylogenetic relationship, transmission cluster, and genotypic drug resistance analyses were performed using HIV-1 polymerase (pol) gene sequences. We also analysed the association of demographic and virological factors with transmitted drug-resistance (TDR) and transmission clusters.

Results: Partial pol gene sequences were obtained from 1297 cases. HIV-1 epidemic strains in Sichuan province: the majority of genotypes were circulating recombinant form (CRF) 07_BC (675, 52.04%), CRF01_AE (343, 26.45%), CRF08_BC (115, 8.87%), CRF85_BC (67, 5.17%), subtype B (33, 2.54%), the other genotypes only accounted for 4.93%, and unique recombinant forms (URFs) (23, 1.77%) were observed in the study, and the difference of age, ethnicity, education, occupation, region and transmission pathway of different genotypes were statistically significant. According to WHO HIVDR surveillance threshold, the level of TDR has reached a medium level, with 72 of 1297 (5.55%) cases carrying drug-resistance mutation sites, TDR mutation frequency to nonnucleoside reverse transcriptase inhibitors (NNRTIs, 3.85%) was much higher than nucleoside reverse transcriptase inhibitors (NRTIs, 0.31%) and protease inhibitors (PIs, 1.70%), and CRF08_BC was a risk factor for TDR (odds ratio, 8.32; 95% CI 4.38-15.80 for CRF07_BC, P < 0.05). The most common drug resistance HIV-1 mutation pattern for NNRTI was V106 (1.31%, 17/1297) and E138 (1.16%, 15/1297), and for PI was M46 (0.69%, 9/1297). A total of 205 (15.8%) pol sequences were involved in the genetic transmission network clusters, CRF01_AE (odds ratio, 2.369; 95% CI 1.659-3.382; P < 0.05), subtype B (odds ratio, 13.723; 95% CI 6.338-29.71; P < 0.05), drug resistance (odds ratio, 0.306; 95% CI 0.106-0.881; P < 0.05) and different levels of education (P < 0.05) were significantly associated to be in clusters.

Conclusion: The distribution of HIV-1 genotypes in Sichuan is more diverse and complex, and the Men who have sex with men (MSM) is underrated, arguing for behavior scaling up intervention in this specific population besides the elderly people with heterosexual transmission risk groups. The risk of TDR mutation frequency increased in newly diagnosed patients highlights the significance of genotypic drug resistance monitoring and molecular surveillance of pretreatment HIV-1 drug resistance. The regimen composed of TDF, 3TC and EFV was still currently the preferred solution used free first-line therapy.

Keywords: Genotype; HIV-1; Molecular epidemiology; Transmitted drug resistance.

Fig. 1

The phylogenetic tree of HIV-1 pol sequences obtained from Sichuan. The maximum-likelihood tree obtained using 1062 bp corresponded to the protease region and part of the reverse transcriptase. A total of 675 HIV-1 sequences branched with CRF07_BC reference sequences (depicted in blue). 342 HIV-1 query sequences branched with CRF01_AE reference sequences (depicted in red). 115 HIV-1 CRF08_BC query sequences were identified (depicted in light blue). 67 HIV-1 CRF85_BC query sequences were identified (depicted in brown). 36 query sequences clustered with HIV-1 subtype B reference sequences (depicted in yellow). Other subtypes and URFs were not depicted color. The reference sequences from the Los Alamos HIV sequence database (http://hiv-web.lanl.gov/content/index)

Fig. 2

Distribution of HIV-1 genotypes in different cities of Sichuan

Fig. 3

Transmitted drug resistance mutations sites in treatment-naive patients

Fig. 4

The resistance of HIV-1 to antiretroviral drugs. 3TC: lamivudine; ABC: abacavir; AZT: zidovudine; d4T: stavudine; ddI: didanosine; FTC: emtricitabine; TDF: tenofovir disoproxil fumarate; EFV: efavirenz; DOR: doravirine; NVP: nevirapine; RPV: Rilpivirine; ETR: etravirine; ATV/r: atazanavir/ritonavir; FPV/r: Fosamprenavir/ritonavir; IDV/r: indinavir/ritonavir; LPV/r: lopinavir/ritonavir, NFV: nelfinavir, SQV/r: saquinavir/ritonavir; TPV/r: tipranavir/ritonavir

Fig. 5

TDR and clustering rate of different cities in Sichuan