Effects of Cotrimoxazole Prophylaxis Initiation and Discontinuation on Mortality and Attrition Rates among HIV Patients Who Initiate ART in Southwest China:An Observational Cohort Study

Combination antiretroviral therapy(ART)reduced AIDS-related mortality and increased survival among patients living with HIV by interrupting HIV replication,enhancing immune recovery,and preventing the onset of opportunistic infections[1].In China,ART has rapidly been scaled up since the beginning of the National Free Antiretroviral Treatment Program(NFATP)in 2003[2].By the end of 2016,489,411 individuals diagnosed with HIV were receiving free antiretroviral treatment in China.China is firmly committed to reducing overall AIDS-related mortality and HIV incidence within the country.However,similar to other low-and middle-income countries,the NFATP is challenged by high mortality and attrition shortly after patients initiate ART[3].

Real-time RT-PCR Assay for the Detection of Culex flavivirus

Based on the Culex flavivirus (CxFV) E gene sequences in GenBank, CxFV-specific primers and probes were designed for real-time reverse transcription-polymerase chain reaction (RT-qPCR). The specificity test revealed that CxFV could be detected using RT-qPCR with the specific CxFV primers and probes; other species of arboviruses were not detected. The stability test demonstrated a coefficient of variation of <1.5%. A quantitative standard curve for CxFV RT-qPCR was established. Quantitative standard curve analysis revealed that the lower detection limit of the RT-qPCR system is 100 copies/mu L. Moreover, RT-qPCR was used to detect CxFV viral RNA in mosquito pool samples. In conclusion, we established a real-time RT-PCR assay for CxFV detection, and this assay is more sensitive and efficient than general RT-PCR. This technology may be used to monitor changes in the environmental virus levels.

HIV-1 Transmission among Injecting Drug Users is Principally Derived from Local Circulating Strains in Guangxi, China

Objective The mode of human immunodeficiency virus(HIV) transmission via injection drug use(IDU)still exists, and the recent shift in IDU-related transmission of HIV infection is largely unknown. The purpose of this study was to analyze the spatiotemporal sources and dynamics of HIV-1 transmission through IDU in Guangxi.Methods We performed a molecular epidemiological investigation of infections across Guangxi from2009 to 2019. Phylogenetic and Bayesian time-geographic analyses of HIV-1 sequences were performed to confirm the characteristics of transmission between IDUs in combination with epidemiological data.Results Among the 535 subjects, CRF08_BC(57.4%), CRF01_AE(28.4%), and CRF07_BC(10.7%) were the top 3 HIV strains;72.6% of infections were linked to other provinces in the transmission network;93.6% of sequence-transmitted strains were locally endemic, with the rest coming from other provinces,predominantly Guangdong and Yunnan;92.1% of the HIV transmission among people who inject drugs tended to be transmitted between HIV-positive IDUs.Conclusion HIV recombinants were high diversity, and circulating local strains were the transmission sources among IDUs in Guangxi. However, there were still cases of IDUs linked to other provinces.Coverage of traditional prevention strategies should be expanded, and inter-provincial collaboration between Guangxi, Yunnan, and Guangdong provinces should be strengthened.

Changing Proportions of HIV-1 Subtypes and Transmitted Drug Resistance Among Newly Diagnosed HIV/AIDS Individuals—China,2015 and 2018

Introduction:With the expansion of human immunodeficiency virus(HIV)antiretroviral therapy(ART),HIV drug resistance is becoming more and more serious.This study describes the changing prevalence of HIV-1 subtypes and transmitted drug resistance(TDR)among newly diagnosed individuals in China,2015 and 2018.Methods:A total of 8,980 individuals in 2015 and 2018 from 31 provincial-level administrative divisions(PLADs)were enrolled in this study.Viral RNAs were amplified and sequenced using an in-house polymerase chain reaction(PCR)protocol.The Stanford HIV Drug Resistance Database(HIVdb)was used to predict susceptibility to 12 antiretroviral drugs.Results:The prevalence of TDR was not significantly increased over time.The prevalence of TDR was 3.8%and 4.4%in 2015 and 2018,respectively(P=0.13).The prevalence of CRF55_01B increased from 2.3%in 2015 to 3.9%in 2018(P<0.001).The drug resistance prevalence of nonnucleoside reverse transcriptase inhibitors(NNRTI)increased from 2.4%in 2015 to 3.3%in 2018(P<0.01).The prevalence of E138(P<0.001),H221(P=0.03),and V179(P<0.001)mutations increased from 0.30%,0.09%,and 0.70%in 2015 to 1.10%,0.30%,and 1.70%in 2018,respectively.Conclusions:HIV drug resistance affects the effect of antiretroviral treatment,so the monitoring of HIV TDR should be strengthened to control the transmission of HIV drug resistance.

Treatment outcomes of HIV patients with hepatitis B and C virus co-infections in Southwest China:an observational cohort study

Background:Antiretroviral therapy(ART)has reduced mortality among people living with HIV(PLWH)in China,but co-infections of hepatitis B virus(HBV)and hepatitis C virus(HCV)may individually or jointly reduce the effect of ART.This study aimed to evaluate the impacts of HBV/HCV coinfections on treatment drop-out and mortality among PLWH on ART.Methods:A retrospective cohort study analysis of 58,239 people living with HIV(PLWH)who initiated antiretroviral therapy(ART)during 2010-2018 was conducted in Guangxi Province,China.Data were from the observational database of the National Free Antiretroviral Treatment Program.Cox proportional hazard models were fitted to evaluate the effects of baseline infection of HBV or HCV or both on death and treatment attrition among PLWH.Results:Our study showed high prevalence of HBV(11.5%),HCV(6.6%)and HBV-HCV(1.5%)co-infections.The overall mortality rate and treatment attrition rate was 2.95[95%confidence interval(CI):2.88-3.02]and 5.92(95%CI:5.82-6.01)per 100 person-years,respectively.Compared with HIV-only patients,HBV-co-infected patients had 42%higher mortality[adjusted hazard ratio(a HR)=1.42;95%CI 1.32-1.54],HCV-co-infected patients had 65%higher mortality(a HR=1.65;95%CI:1.47-1.86),and patients with both HCV and HBV co-infections had 123%higher mortality(a HR=2.23;95%CI:1.87-2.66).Conclusions:HBV and HCV coinfection may have an additive effect on increasing the risk of all-cause death among PLWH who are on ART.It is suggested that there is need for primary prevention and access to effective hepatitis treatment for PLWH.

Changes in HIV-1 Subtypes/Sub-Subtypes,and Transmitted Drug Resistance Among ART-Naïve HIV-Infected Individuals—China,2004–2022

Introduction:The efficacy of treatment and clinical outcomes may be jeopardized by factors such as transmitted drug resistance(TDR)and the genetic diversity of the human immunodeficiency virus type 1(HIV-1).This comprehensive study aims to examine the alterations in HIV-1 subtypes or sub-subtypes and TDR among Chinese individuals,who have been diagnosed with HIV infection and are previously untreated with antiretroviral therapy(ART),across the span of 2004 to 2022.Methods:Sequences of the HIV-1 pol gene region were obtained from ART-naïve HIV-positive individuals across 31 provincial-level administrative divisions between 2004 and 2022.To predict susceptibility to 12 antiretroviral drugs,the research utilized the Stanford HIV Drug Resistance Database.The Cochran-Armitage trend test facilitated the analysis of changes in HIV-1 subtype/sub-subtype prevalence and TDR.This analysis was conducted in alignment with the progression of the National Free Antiretroviral Treatment Program’s stages between 2004 and 2022.Results:Among the 57,902 ART-naïve individuals infected with HIV,there was a notable decline in the prevalence of CRF01_AE,B,and C from 37.3%,24.1%,and 1.3%respectively in 2004–2007 to 29.4%,7.3%,and 0.2%respectively in 2020–2022.Simultaneously,a significant increase was observed in the proportions of CRF07_BC,CRF08_BC,CRF55_01B,other CRFs,and URFs,from 24.1%,11.5%,0.1%,0.4%,and 0.9%respectively in 2004–2007 to 40.8%,11.5%,3.8%,3.7%,and 2.8%respectively in 2020–2022(all P<0.001 for trend).The prevalence of TDR to overall,non-nucleoside reverse transcriptase inhibitor(NNRTI),efavirenz,and nevirapine also significantly increased from 2.6%,1.8%,1.6%,and 1.8%respectively in 2004–2007 to 7.8%,6.7%,6.3%,and 6.7%respectively in 2020–2022(all P<0.001 for trend).However,there were no meaningful changes in the TDR prevalence of nucleoside reverse transcriptase inhibitor and protease inhibitor.Notably,in 2020–2022,the overall TDR prevalence exceeded 15%in Xinjiang.Conclusions:The total prevalence of TDR in China has achieved a moderate level(7.8%)from 2020 to 2022,with NNRTI resistance standing prominently at 6.7%.Consequently,measures to curb TDR are urgently required,particularly among ART-naïve HIVinfected individuals in China.

Comparison of different strategies for controlling HIV/AIDS spreading in MSM

As proposed in the UNAIDSs 2014 report,to end global AIDS epidemic by 2030,90%of people living with HIV need to be diagnosed,90%of the diagnosed need to receive antiretroviral therapy(ART),and 90%of those on treatment need to achieve viral suppression(90-90-90 strategy).The strategies focus on the reservoir.It controls HIV spreading by reducing infectiousness of HIV infected individuals via diagnosis and treatment.In this manuscript,we compared the effects of HIV/AIDS interventions that focus on different individuals in MSM population through a dynamics model.Our results showed that,the success or not of the”90-90-90”strategies depends on a very important factor:the infectious strength among individuals taking ART.Without highly effective HIV treatment,the”90-90-90”strategies are likely to fail.Therefore,we call for the combination of both primary prevention among the susceptible with the 90-90-90 strategy among the infected to curb the HIV epidemic in Chinese MSM.

Relationship Between Drug Resistance and Death in HIV-Infected Patients Receiving Antiretroviral Therapy—7 PLADs,China,2010−2019

Summary What is already known about this topic?With increasing coverage of antiretroviral therapy(ART)for HIV-infected patients,more and more attention has been paid to the impact of HIV drug resistance on death in those patients in China.What is added by this report?Among HIV-infected patients receiving ART,the risk of death is higher in patients with HIV drug resistance[adjusted odds ratio(AOR)=4.25.

A mathematical modeling study of the HIV epidemics at two rural townships in the Liangshan Prefecture of the Sichuan Province of China

Background:As a response to a severe HIV epidemic in the Liangshan Prefecture,one of the worst in China,population based HIV interventions,including two population-wide HIV screening,have been carried out since 2005 at two townships in a remote mountainous region of Liangshan.The objective of our mathematical modeling study is to assess the temporal dynamics of the HIV epidemic in the two townships based on the data collected in the study area during the period 2005e2010.Methods:A mathematical model was set up to describe the population dynamics of HIV transmission in study area.The model was calibrated by fitting it to the HIV testing and treatment data from 2005 to 2008.Validation of the model was done by comparing its predicted value of HIV prevalence in 2010 to the prevalence data obtained in the 2010 population wide HIV testing.The validated model was used to produce estimation of HIV incidence,prevalence and death.Results:Our model estimations show that population-based HIV interventions have significantly slowed down the rise of the HIV epidemic in the two townships.Over the five-year period from 2005 to 2010,the year-over-year rate of increase in HIV incidence,prevalence,and death has declined by 91.5%,28.7%,and 52.3%,respectively.Conclusion:Mathematical models,when integrated with epidemiological and surveillance data,can be an effective tool for predicting the temporal dynamics of HIV and assessing the impacts of HIV interventions.

Pretreatment HIV drug resistance in adults initiating antiretroviral therapy in China,2017

Background:After the scale-up of antiretroviral therapy(ART)for HIV infected people,increasing numbers of patients have pretreatment drug resistance(PDR).In this study,the prevalence of PDR was evaluated in adults initiating antiretroviral therapy in China.Methods:Blood samples were obtained from 1943 patients who initiated antiretroviral therapy(ART)in 2017 from 13 provinces or cities in China.Pol sequences were used to analyze drug resistance and construct transmission networks.Logistic regression model was used to estimate the potential factors associated with PDR.Results:In total,1711 eligible patients(76.0%male;87.8%aged≥25 years)were included,of which 117(6.8%)had PDR.The highest rates of PDR were 12.2%in Liangshan Prefecture of Sichuan and 9.3 and 8.9%in Dehong and Lincang Prefecture of Yunnan.A multivariate logistic regression analysis revealed that PDR was significantly higher among intravenous drug users(adjusted Odds Ratio(aOR)=2.64,95%CI:1.57–4.44)and individuals from Liangshan,Dehong,and Lincang(aOR=2.04,95%CI:1.26–3.30).In total,754 sequences were used to generate 164 transmission networks.Five transmission networks had two or three sequences containing the same mutations,two networks contained subjects from Liangshan,and one network contained subjects from Dehong.Conclusions:Overall,the PDR prevalence was moderate,with a particularly high prevalence in areas with severe HIV epidemics.These results indicate the importance of continuous PDR monitoring in patients initiating antiretroviral therapy.