The Origin And Transmission Of HIV-1 Subtype C And The Characteristics Of Drug Resistance In Ethiopia

Background: In the past two decades,the subtype C is still the most prevalent strain of HIV-1 in the world.Although HIV-1 subtype C strains have not caused widespread epidemics after being introduced into China,the prevalence of B/C recombinant strains in China has gradually expanded,with more complicated epidemic patterns and diverse infected populations.As an effective AIDS prevention intervention,antiretroviral therapy can significantly reduce the mortality of HIV patients and the transmission of HIV.Ethiopia is the third largest country in Africa,the dominant HIV subtypes is subtype C.With the promotion of antiretroviral therapy,the proportion of drug resistance in patients with virological suppression failure has increased,which has brought severe challenges to public health.In addition,Ethiopia,as an important partner of the“Belt and Road” initiative,has an increasing political,economic,cultural,and trade exchanges with China,which may increase the risk of HIV drug-resistant strains spreading between the two countries.Objective: Based on the collected genetic sequence data of HIV-1 C subtype,we reconstruct the origin,epidemic history and characteristics of the subtype by using Bayesian genetic system dynamics analysis.The epidemiological data of infection samples from patients with virological suppression failure in Ethiopia are integrated analyzed,in order to understand the drug resistance characteristics and influencing factors,and provide a reference for optimizing the domestic antiviral treatment programs in Ethiopia.It can also provide scientific guidance for nation in formulating public health measures to prevent and control the cross-border transmission of HIV.Methods: Sequences of subtype C of HIV-1 and some subtype A,B,D,CRFS_BC and URFS_BC from all over the world before December 31,2020 were retrieved from HIV Databases.At the same time,the CRF07_BC,CRF08_BC and URFs_BC sequences from the laboratory research project of the Chinese Center for AIDS/STD Prevention and Control and the international HIV Databases(NCAIDS)over the years were collected.The available sequences were screened through quality assessment,and Bayesian analysis was performed to construct the Maximum clade credibility volutionary tree to analyze and judge the origin and spread of HIV-1 subtype C.A cross-sectional survey was used to investigate and collect blood samples from patients with virological suppression failure(viral load ≥ 1000 copies/ml)in Ethiopia in2017.The sequence of HIV pol gene region was obtained by nucleic acid extraction and amplification sequencing.The Stanford Drug Resistance Database was used to detected the HIV drug resistance.Multivariate Logistic regression was used to analyze the influencing factors of drug resistance.Results: 1.The HIV-1 subtype C originated in central Africa around 1952(95%CI,1939-1961),and was introduced into southern Africa around 1969(95%CI,1960-1970),eastern Africa around 1973(95%CI,1968-1976)and southern Asia around 1977(95% CI,1975-1985).Then subtype C was introduced from India to China around 1986(95% CI,1985-1989)and introduced into Brazil was in 1987(95% CI,1983-1989).CRF07_BC and CRF08_BC originated from Yunnan in 1988(95%CI,1986-1991)and1990(95%CI,1988-1992),respectively.CRF64_BC originated in1993(95%CI,1990-1998),CRF61_BC in 2002(95%CI,1996-2003)and CRF62_BC in 2000(95%CI,1997-2004).2.The drug resistance rate of patients with virological suppression failure in Ethiopia in 2017 was 84.3%(425/504),which was at a high epidemic level(>15%).Most of the drugs in NRTIs and NNRTIs are highly resistant drugs.The highest drug resistance rate was NVP,and M184 V was the most frequently found resistence mutation.The multivariate logistic regression model showed that the factors significantly correlated with drug resistance were age 18-29years(AOR=5.34,95%CI: 1.75-16.29,P=0.003),the southern ethnic state(AOR=2.67,95%CI: 1.07~6.63,P=0.035),Gambella State(AOR=3.86,95%CI:1.47~10.17,P=0.006),Addis Ababa(AOR=2.78,95 %CI: 1.10~6.98,P=0.030),CD4 count before treatment 200~500 copies/μl(AOR=7.29,95%CI: 1.77-29.96,P=0.006)and CD4 count before treatment <200 copies/μl(AOR=7.67,95%CI:1.88~31.21,P=0.004),CD4 count 200~500 copies/μl during the survey(AOR=2.60,95%CI: 1.30~5.22,P=0.007)and during the survey CD4 count<200 copies/μl(AOR=3.08,95%CI: 1.40~6.80,P=0.005).Conclusions: 1.Our results reconstruct the origin and transmission history of the HIV-1 subtype C,which further supports the global pandemic of the HIV-1subtype C.In view of the importance of HIV-1 subtype C for the B/C recombinant strains in China,epidemic prevention and control measures should be developed for specific geographical and gene specificity of HIV-1 C subtype,while actively preventing the introduction of HIV-1 subtype C from Asian countries bordering China.1.Patients with virological suppression failure in Ethiopia had a high drug resistance rate.To improve the effect of antiretroviral treatment and reduce HIV resistance,the publicity and education of antiviral therapy for HIV infected people in Ethiopia should be strengthened,and intervention and monitoring measures for HIV-infected people aged 18 to 29 should be strengthened to ensure compliance with their treatment.At the same time,monitoring of drug resistance should be focused on patients with low CD4 cell counts to reduce the generation and spread of HIV drug-resistant strains.