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.

Treatment persistence of bictegravir/emtricitabine/tenofovir alafenamide and efavirenz + lamivudine + tenofovir disoproxil among HIV-1 patients newly starting treatment in Hunan Province in China

“…Our study finding about the treatment discontinuation due to drug resistance in EFV + 3TC + TDF group is consistent with the previous studies about the drug resistance to free NRTI and NNRTI in China [ 28 – 34 ]. Drug resistance is a big threat to HIV patients in China, especially in HIV patients not taking drug resistance test before treatment initiation.…”

HIV-1 drug resistance and genetic transmission network among newly diagnosed people living with HIV/AIDS in Ningbo, China between 2018 and 2021

“…In our study, the prevalence of TDR was 6.1% and TDR-associated mutations to NNRTI was 7.9%, which was moderate (5-15%) according to the WHO de nition [26]. It was higher than the prevalence determined in Sichuan [27], Guangdong [28] and Jiangsu [29] in China.…”

“…The sequences were submitted to the Stanford University HIV Resistance Database (http://hivdb.stanford.edu/) to describe and interpret HIV-1 TDR. TDR level was classi ed according to the Stanford Penalty Score as high (60), intermediate , or low (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29) to the following drugs: PI, Protease inhibitor; NRTI, Nucleoside reverse transcriptase inhibitor; NNRTI, Non-nucleoside reverse transcriptase inhibitor; NFV: Nel navir; ABC: Abacavir; AZT: Zidovudine; D4T: Stavudine; DDI: Didanosine; FTC: Emtricitabine; 3TC, Lamivudine; TDF: Tenofovir; DOR: Doravirine; EFV: Efavirenz; ETR: Etravirine; RPV: Rilpivirine. Drug resistance mutations were analyzed using the CRP tool (http://cpr.stanford.edu/cpr.cgi).…”

Analysis of clinical manifestations and risk factors of HIV-1 associated thrombocytopenia in a general teaching hospital in western China

“…Sichuan province has one of the highest rates of HIV-1 infection in China and a high incidence of thrombocytopenia [9–10] . Thrombocytopenia, a common hematological disease, may be the first clinical sign in HIV-1-infected patients.…”

“…Table 2 and Figure 3 compared patients with HAT-related neuroinflammation and without neuroinflammation. Sichuan province has one of the highest rates of HIV-1 infection in China and a 160 high incidence of thrombocytopenia [9][10] . Thrombocytopenia, a common hematological disease, may be the first clinical sign in HIV-1-infected patients.…”