Acceptance and Factors Associated With Participation in Functional Cure–Related Trials Among People Living With HIV: A Cross-sectional Study in Southern China

HIV remains a global health challenge,and research efforts directed towards a functional cure require people living with HIV(PLHIV)in-volvement in clinical trials.Our study assessed willingness to participate in HIV functional cure–related clinical trials and associated fac-tors among PLHIV in Guangzhou,China,using a questionnaire survey approach.We analyzed responses from 718 questionnaires,finding that 71.2%were willing to participate in Phase Ⅲtrials,while 51.7%were willing to participate in Phase I trials and 42.9%expressed acceptability for analytic treatment interruption.Multivariate logistic regression demonstrated that male PLHIV,those with awareness of functional cure,and PLHIV,who had been on antiretroviral therapy(ART)for less than 1 year,were more willing to partic-ipate in Phase Ⅲtrials.Those with a body mass index greater than 24,and those without resistance to ART drug were more willing to participate in Phase I trials.The major motivations for participation in Phase Ⅲtrials were access to cutting-edge treatments(62.6%)and supporting research(55.3%).Safety was the main concern contributing to hesitancy.Our study revealed a high willingness to participate in HIV functional cure–related trials among PLHIV in Guangzhou,China,and willingness varied across different trial phases and was in-fluenced by multiple factors.This study provides valuable references for future clinical trial recruitment strategies and public health policy formulation.

Immediate and long-term outcomes after treat-all among people living with HIV in China:an interrupted time series analysis

Background In 2003,China implemented free antiretroviral therapy(ART)for people living with HIV(PLHIV),establishing an eligibility threshold of CD4<200 cells/μl.Subsequently,the entry criteria were revised in 2012(eligibility threshold:CD4≤350 cells/μl),2014(CD4≤500 cells/μl),and 2016(treat-all).However,the impact of treat-all policy on HIV care and treatment indicators in China is unknown.We aimed to elucidate the immediate and long-term impact of the implementation of treat-all policy in China.Methods Anonymized programmatic data on ART initiation and collection in PLHIV who newly started ART were retrieved between 1 January 2015 and 31 December 2019,from two provincial and municipal Centers for Disease Control and Prevention and ten major infectious disease hospitals specialized in HIV care in China.We used Poisson and quasi-Poisson segmented regression models to estimate the immediate and long-term impact of treat-all on three key indicators:monthly proportion of 30-day ART initiation,mean CD4 counts(cells/μl)at ART initiation,and mean estimated time from infection to diagnosis(year).We built separate models according to gender,age,route of transmission and region.Results Monthly data on ART initiation and collection were available for 75,516 individuals[gender:83.8%males;age:median 39 years,interquartile range(IQR):28-53;region:18.5%Northern China,10.9%Northeastern China,17.5%Southern China,49.2%Southwestern China].In the first month of treat-all,compared with the contemporaneous counterfactual,there was a significant increase in proportion of 30-day ART initiation[+12.6%,incidence rate ratio(IRR)=1.126,95%CI:1.033-1.229;P=0.007]and mean estimated time from infection to diagnosis(+7.0%,IRR=1.070,95%CI:1.021-1.120;P=0.004),while there was no significant change in mean CD4 at ART initiation(IRR=0.990,95%CI:0.956-1.026;P=0.585).By December 2019,the three outcomes were not significantly different from expected levels.In the stratified analysis,compared with the contemporaneous counterfactual,mean CD4 at ART initiation showed significant increases in Northern China(+3.3%,IRR=1.033,95%CI:1.001-1.065;P=0.041)and Northeastern China(+8.0%,IRR=1.080,95%CI:1.003-1.164;P=0.042)in the first month of treat-all;mean estimated time from infection to diagnosis showed significant increases in male(+5.6%,IRR=1.056,95%CI:1.010-1.104;P=0.016),female(+14.8%,IRR=1.148,95%CI:1.062-1.240;P<0.001),aged 26-35(+5.3%,IRR=1.053,95%CI:1.001-1.109;P=0.048)and>50(+7.8%,IRR=1.078,95%CI:1.000-1.161;P=0.046),heterosexual transmission(+12.4%,IRR=1.124,95%CI:1.042-1.213;P=0.002)and Southwestern China(+12.9%,IRR=1.129,95%CI:1.055-1.208;P<0.001)in the first month of treat-all.Conclusions The implementation of treat-all policy in China was associated with a positive effect on HIV care and treatment outcomes.To advance the work of rapid ART,efforts should be made to streamline the testing and ART initiation process,provide comprehensive support services,and address the issue of uneven distribution of medical resources.

Correlates of Sexual Lifestyles Among Older Adults Living With HIV in China: Findings From the Sexual Well-being (SWELL) Study

Sexual lifestyles are closely related to overall human health and well-being.Few studies have focused on sexual lifestyles among older adults living with HIV(OALHIV),especially in low-and middle-income countries.This study is a part of the sexual well-being among older adults in China(SWELL)study,which is a multicenter cross-sectional study focused on sexual health among older adults aged 50 years and older.Participants were 680 OALHIV(≥50 years old)from the SWELL study conducted from June 2020 to December 2022.Data were collected through one-on-one interviews.We used logistic regression to assess the correlates of sexual activity and sexual satis-faction.Among all participants,37.1%were sexually active.Being older,male,in a steady relationship and employed were associated with being sexually active.The prevalence of sexual satisfaction was 69.8%among sexually active OALHIV.Being homosexual and reporting a better general health status were associated with sexual satisfaction.The OALHIV who have depressive symptoms were less likely to report sexual satisfaction.To support holistic healthy aging among OALHIV,it is important for healthcare providers to be educated about the importance of enquiring about sexual activity,satisfaction and problems and addressing concerns while conveying sex-positive attitudes during clinical reviews,as these are still critical aspects of their health and well-being.

A three-dose inactivated SARS-CoV-2 vaccine is sufficient to elicit humoral immune responses in people living with HIV-1

To the Editor:Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is the virus that caused the 2019 coronavirus disease(COVID-19)pandemic.Over two years after the initial outbreak,several more infectious variations of the virus continue to pose a grave threat to global public health.[1]Intense,worldwide efforts for vaccine development have led to several candidate vaccines utilizing a variety of platforms.

Human umbilical cord mesenchymal stem cell transfusion in immune non-responders with AIDS:a multicenter randomized controlled trial

We examined the safety and efficacy of human umbilical cord mesenchymal stem cell(hUC-MSC)infusion for immune nonresponder(INR)patients with chronic HIV-1 infection,who represent an unmet medical need even in the era of efficient antiretroviral therapy(ART).Seventy-two INR patients with HIV were enrolled in this phase II randomized,double-blinded,multicenter,placebo-controlled,dose-determination trial(NCT01213186)from May 2013 to March 2016.They were assigned to receive high-dose(1.5 x 106/kg body weight)or low-dose(0.5 x 106/kg body weight)hUC-MSC,or placebo.Their clinical and immunological parameters were monitored during the 96-week follow-up study.We found that hUC-MSC treatment was safe and well-tolerated.Compared with baseline,there was a statistical increase in CD4+T counts in the high-dose(P<0.001)and low-dose(P<0.001)groups after 48-week treatment,but no change was observed in the control group.Kaplan-Meier analysis revealed a higher cumulative probability of achieving an immunological response in the low-dose group compared with the control group(95.8%vs.70.8%,P=0.00A).However,no significant changes in CD4/CD84-T counts and CD4/CD8 ratios were observed among the three groups.In summary,hUC-MSC treatment is safe.However,the therapeutic efficacy of hUC-MSC treatment to improve the immune reconstitution in INR patients still needs to be further investigated in a large cohort study.

COVID-19 induces new-onset insulin resistance and lipid metabolic dysregulation via regulation of secreted metabolic factors

Abnormal glucose and lipid metabolism in COVID-19 patients were recently reported with unclear mechanism.In this study,we retrospectively investigated a cohort of COVID-19 patients without pre-existing metabolic-related diseases,and found new-onset in suli n resista nee,hyperglycemia,and decreased HDL-C in these patie nts.Mecha nistically,SARS-CoV-2 infecti on in creased the expression of RE1-silencing transcription factor(REST),which modulated the expression of secreted metabolic factors including myeloperoxidase,apelin,and myostatin at the transcriptional level,resulting in the perturbation of glucose and lipid metabolism.Furthermore,several lipids,including(±)5-HETE,(±)12-HETE,propionic acid,and isobutyric acid were identified as the potential biomarkers of COVID-19-induced metabolic dysregulation,especially in insulin resistance.Taken together,our study revealed insulin resistance as the direct cause of hyperglycemia upon COVID-19,and further illustrated the underlying mechanisms,providing potential therapeutic targets for COVID-19-induced metabolic complications.

Incidence and factors associated with hepatitis B surface antigen seroclearance in patients co-infected with HBV/HIV during antiretroviral therapy in Guangdong,China

Background:Hepatitis B surface antigen(HBsAg)clearance is vital for a functional cure of hepatitis B virus(HBV)infection.However,the incidence and predictors of HBsAg seroclearance in patients co-infected with HBV and human immunodeficiency virus(HIV)remain largely unknown in Guangdong,China.Methods:Between 2009 and 2019,patients co-infected with HBV/HIV undergoing antiretroviral therapy(ART)in Guangzhou Eighth People’s Hospital affiliated to Guangzhou Medical University were retrospectively reviewed with the endpoint on December 31,2020.The incidence and risk factors for HBsAg seroclearance were evaluated using Kaplan-Meier and multivariate Cox regression analyses.Results:A total of 1550 HBV/HIV co-infected patients were included in the study,with the median age of 42 years and 86.0%(1333/1550)males.Further,98.3%(1524/1550)received ART containing tenofovir disoproxil fumarate(TDF)plus lamivudine(3TC).HBV DNA was examined in 1283 cases at the last follow-up.Over the median 4.7 years of follow-up,8.1%(126/1550)patients achieved HBsAg seroclearance,among whom 50.8%(64/126)obtained hepatitis B surface antibody,28.1%(137/488)acquired hepatitis B e antigen seroconversion,and 95.9%(1231/1283)undetectable HBV DNA.Compared with patients who maintained HBsAg positive,cases achieving HBsAg seroclearance showed no differences in age,gender,CD4+T cell count,alanine aminotransferase(ALT)level,or fibrosis status;however,they presented lower HBV DNA levels,lower HBsAg levels,and higher rates of HBV genotype B at the baseline.Multivariate analysis showed that baseline HBsAg<1500 cutoff index(COI)(adjusted hazard ratio[aHR],2.74,95%confidence interval[95%CI]:1.48-5.09),ALT elevation>2×upper limit of normal during the first six months after receiving ART(aHR,2.96,95%CI:1.53-5.77),and HBV genotype B(aHR,3.73,95%CI:1.46-9.59)were independent predictors for HBsAg seroclearance(all P<0.01).Conclusions:Long-term TDF-containing ART has high anti-HBV efficacy including relatively high overall HBsAg seroclearance in HBV/HIV co-infected patients.Lower baseline HBsAg levels,HBV genotype B,and elevated ALT levels during the first six months of ART are potential predictors of HBsAg seroclearance.

Transcriptome analysis of CD4^(+)T cells from HIV-infected individuals receiving ART with LLV revealed novel transcription factors regulating HIV-1 promoter activity

Some HIV-infected individuals receiving ART develop low-level viremia(LLV),with a plasma viral load of 50-1000 copies/mL.Persistent low-level viremia is associated with subsequent virologic failure.The peripheral blood CD4^(+)T cell pool is a source of LLV.However,the intrinsic characteristics of CD4^(+)T cells in LLV which may contribute to low-level viremia are largely unknown.We analyzed the transcriptome profiling of peripheral blood CD4^(+)T cells from healthy controls(HC)and HIV-infected patients receiving ART with either virologic sup-pression(VS)or LLV.To identify pathways potentially responding to increasing viral loads from HC to VS and to LLV,KEGG pathways of differentially expressed genes(DEGs)were acquired by comparing VS with HC(VS-HC group)and LLV with VS(LLV-VS group),and overlapped pathways were analyzed.Characterization of DEGs in key overlapping pathways showed that CD4^(+)T cells in LLV expressed higher levels of Th1 signature transcription factors(TBX21),toll-like receptors(TLR-4,-6,-7 and-8),anti-HIV entry chemokines(CCL3 and CCL4),and anti-IL-1βfactors(ILRN and IL1R2)compared to VS.Our results also indicated activation of the NF-κB and TNF signaling pathways that could promote HIV-1 transcription.Finally,we evaluated the effects of 4 and 17 tran-scription factors that were upregulated in the VS-HC and LLV-VS groups,respectively,on HIV-1 promoter activity.Functional studies revealed that CXXC5 significantly increased,while SOX5 markedly suppressed HIV-1 tran-scription.In summary,we found that CD4^(+)T cells in LLV displayed a distinct mRNA profiling compared to that in VS,which promoted HIV-1 replication and r+eactivation of viral latency and may eventually contribute to virologic failure in patients with persistent LLV.CXXC5 and SOX5 may serve as targets for the development of latency-reversing agents.

Pure Red Cell Aplasia Caused by Parvovirus B19 in Patients with Human Immunodeficiency Virus Infection: A Series of Four Cases

Parvovirus B19(B19V)infection can cause pure red cell aplasia(PRCA)in patients with human immunodeficiency virus(HIV)infection.Intravenous immunoglobulin(IVIG)is a preferred treatment option.From July 2019 to March 2022,four patients with HIV infection were admitted to Guangzhou Eighth People’s Hospital with dizziness and fatigue and were diagnosed with PRCA.Blood investigations revealed severe anemia and the B19V genome.Therefore,the four patients were diagnosed with B19V-induced PRCA.All four patients received red blood cell transfusion in the setting of antiretroviral therapy,and two of the four patients received intravenous immunoglobulin(IVIG).After 3-7 months of treatment,all four patients recovered,although two did not receive IVIG.This suggests that IVIG is not always necessary for the treatment of PRCA in patients with HIV infection and that effective antiretroviral therapy and immunological reconstitution play an important role in the eradication of parvovirus.

Persistently low CD4 cell counts are associated with hepatic events in HCV/HIV coinfected patients: data from the national free antiretroviral treatment program of China

Background: Chronic liver disease has emerged as a leading cause of non-acquired immune deficiency syndrome (AIDS)-related mortality in hepatitis C virus (HCV)/human immunodeficiency virus (HIV)-coinfected patients. The relationship between CD4 cell count and HIV-related opportunistic infections and tumors has been well characterized;however, it is unclear whether CD4 cell count is associated with HCV-related hepatic events.Methods: This observational cohort study enrolled HCV/HIV-coinfected patients from the National Free Antiretroviral Treatment Program of China from 2004 to 2019 in Guangzhou. The primary outcome was a composite of hepatic events, including cirrhosis complications, hepatocellular carcinoma (HCC), and liver-related mortality. Kaplan-Meier survival and multivariate logistic regression analyses were performed.Results: Among the 793 patients, 43 developed hepatic events during a median follow-up of 6.7 years, including 35 cirrhosis complications, 13 HCC cases, and 14 cases of liver-related mortality. The 5-year and 10-year cumulative incidences of hepatic events were 4.2% and 9.3%, respectively. Patients who developed hepatic events had a less satisfactory increase in CD4 cell count, lower peak CD4 (354.5 cells/μLvs. 560.0 cells/μL,P < 0.001), and lower percentage of peak CD4 > 500 cells/μL (30.2%vs. 60.7%,P < 0.001) after the initiation of antiretroviral therapy (ART) than those who did not. The cumulative incidences of hepatic events were higher in patients with lower peak CD4 levels with adjusted odds ratios of 3.96 (95% confidence interval [CI]: 1.51-10.40), 2.25 (95% CI: 0.87-5.86), and 0.98 (95% CI: 0.35-2.74) for patients with peak CD4 at <200 cells/μL, 200-350 cells/μL, and 351 to 500 cells/μL, respectively, relative to those with peak CD4 > 500 cells/μL. Peak CD4 was negatively associated with the risk of hepatic events in a dose-response manner (P-value for trend = 0.004).Conclusion: Persistently low CD4 cell counts after ART are independently associated with a high risk of hepatic events in HCV/HIV-coinfected patients, highlighting the important role of immune reconstitution in improving liver outcomes.

Advances in diagnosis andtreatment of talaromycosis in patients WithAIDS

Talaromycosis(formerly named penicilliosis)is an important invasive mycosis caused by Talaromyces marneffei(formerly Penicillium marneffei,T.marneffei).[1]The World Health Organization and Food and Drug Administration have recently paid increasing attention to the disease as a neglected tropical disease due to the growing burden of T.marneffei infection globally.[1,2]Talaromycosis is a common opportunistic disease and a leading cause of death in patients with acquired immune deficiency syndrome(AIDS)in endemic regions;moreover,it is increasingly being reported in human immunodeficiency virus(HIV)-negative individuals and outside of epidemic areas.[3,4]The mortality of talaromycosis is up to 30%in both HIV-positive and HIV-negative individuals,which is associated with late diagnosis and untimely or ineffective antifungal therapy.[5]Therefore,early diagnosis and effective antifungal treatment are critical to reduce the mortality.

Alteration of the respiratory microbiome in COVID-19 patients with different severities

Coronavirus disease 2019(COVID-19) is rampant worldwide and has affected more than 215 countries and regions. According to the World Health Organization's report, there were 226,018,919 COVID-19 cases and 4,654,898 deaths as of March 14, 2021, although300,002,228 vaccines have been administered globally. COVID-19patients have different clinical phenotypes and can be divided into asymptomatic, normal, mild, severe, and critical patients.

Pre-treatment Drug Resistance Could Impact the 96-Week Antiretroviral Efficacy in Treatment-Naive HIV-1–Infected Patients in Guangdong,China

Background:With the high prevalence of pre-treatment drug resistance(PDR)and the potential impact to the virological inhibition,the detection of PDR was particularly necessary.This study aimed to determine the prevalence of PDR in Guangdong,China,and its impact on antiretroviral therapy(ART)in treatment-naive HIV patients.Methods:A retrospective cohort study was conducted.A total of 1936 HIV-1-infected treatment-naive patients in the clinic of the infectious department,Guangzhou Eighth People’s Hospital,between August 2018 and December 2019 were assayed for PDR mutations before initiating ART.Patients with PDR mutations(PDR arm)were screened and compared with those without drug-resistant mutations(non-PDR arm).The rate of HIV-1 virologic failure(VF)and CD4^(+)T-cell counts of the 2 arms were compared at the 96th week after ART to evaluate the impact of PDR on the efficacy of ART.Results:Pretreatment drug resistance was detected in 125 cases(6.46%)from the 1936 enrolled participants,most of which were resistant to non-nucleoside reverse transcriptase inhibitors(64.00%,80/125).One hundred and eight of 125 completed the follow-up of 96 weeks(PDR arm).In this cohort,52 patients whose ART regimen containing the resistant drug were grouped as con-PDR arm,and the remaining 56 patients whose ART regimen did not contain the resistant drug were grouped as non-con-PDR arm.A total of 125 patients without PDR were randomly selected as the control group(non-PDR arm),112 of whom had completed the 96-week followup.At the 96th week after ART initiation,7 patients(6.5%,7/108)in the PDR arm and 1 patient(0.9%,1/112)in the non-PDR arm developed VF,exhibiting a significant difference(χ^(2)=4.901,P=0.029).Meanwhile,3 patients(5.8%,3/52)in the con-PDR arm developed VF;the rate was also higher than that in the non-PDR arm,but without a significant difference(χ^(2)=3.549,P=0.095).The CD4^(+)T-cell count in the non-PDR arm increased more than the PDR arm(386.6 vs.319.1 cells/μL,t=2.448,P=0.015)or the con-PDRarm(386.6 vs.325.1 cells/μL,t=1.821,P=0.070)at 12weeks afterART.However,no significant differenceswere observed in the CD4^(+)T-cell count from the 24th week after ART onward.Conclusions:Pretreatment drug resistance was moderately prevalent in Guangdong,China,and could affect the antiretroviral efficacy during a 96-week observation period,indicating the need to closely monitor PDR before ART initiation.