HIV-1 Subtype Diversity and Factors Affecting Drug Resistance among Patients with Virologic Failure in Antiretroviral Therapy in Hainan Province,China,2014–2020

Objective This study aimed to determine the HIV-1 subtype distribution and HIV drug resistance(HIVDR)in patients with ART failure from 2014 to 2020 in Hainan,China.Methods A 7-year cross-sectional study was conducted among HIV/AIDS patients with ART failure in Hainan.We used online subtyping tools and the maximum likelihood phylogenetic tree to confirm the HIV subtypes with pol sequences.Drug resistance mutations(DRMs)were analyzed using the Stanford University HIV Drug Resistance Database.Results A total of 307 HIV-infected patients with ART failure were included,and 241 available pol sequences were obtained.Among 241 patients,CRF01_AE accounted for 68.88%,followed by CRF07_BC(17.00%)and eight other subtypes(14.12%).The overall prevalence of HIVDR was 61.41%,and the HIVDR against non-nucleoside reverse transcriptase inhibitors(NNRTIs),nucleotide reverse transcriptase inhibitors(NRTIs),and protease inhibitors(PIs)were 59.75%,45.64%,and 2.49%,respectively.Unemployed patients,hypoimmunity or opportunistic infections in individuals,and samples from 2017 to 2020 increased the odd ratios of HIVDR.Also,HIVDR was less likely to affect female patients.The common DRMs to NNRTIs were K103N(21.99%)and Y181C(20.33%),and M184V(28.21%)and K65R(19.09%)were the main DRMs against NRTIs.Conclusion The present study highlights the HIV-1 subtype diversity in Hainan and the importance of HIVDR surveillance over a long period.

Immuno-haematologic and virologic responses and predictors of virologic failure in HIV-1 infected adults on first-line antiretroviral therapy in Cameroon

Background:Contemporary data on the immunologic,haematologic and virologic responses and predictors of virologic failure after initiation of free antiretroviral treatment in Cameroon are needed to evaluate the current treatment-monitoring algorithm and to complement efforts to scale-up and improve on the management of HIV infections.Methods:This was a cross-sectional study conducted between October 2010 and June 2012.A total of 951 participants aged 18-74 years were recruited from selected approved HIV treatment centres of the Northwest and Southwest regions.This comprised 247 males and 704 females.Demographic,self-reported risk behaviours and socioeconomic data were obtained using a structured questionnaire.Full blood and CD4+T-cell counts were done using standard automated techniques.Determination of viral load(VL)was done using Abbott RealTime HIV-1 m2000™system.Data was analysed using SPSS version 17.The statistical significance level was P<0.05.Results:The median duration of antiretroviral therapy(ART)was 24 months.The population mean CD4+T-cell count was 255.3 cells/μL[95%CI,236.8-273.9].Overall,45.9%,43.8%and 10.2%of the participants had CD4+T-cell counts of<200 cells/μL,200-499 cells/μL and>500 cells/μL respectively.Anaemia was present in 26.2%of the participants with 62.3%,25.7%and 12%described as mild,moderate and severe anaemia respectively.Virologic failure occurred in 23.2%of the participants with 12.3%having VL>10,000 RNA copies/mL.Meanwhile 76.8%of patients attained adequate viral suppression with 40.8%having undetectable viral load.The age group 18-29 years(p=0.024),co-infection with tuberculosis(p=0.014),anaemia(p=0.028)and distance from the treatment centre(p=0.011)independently predicted virologic failure.Conclusion:The majority of the participants achieved adequate viral suppression after≥6 months of ART.Despite these favourable immuno-haematologic and virologic outcomes,the National AIDS Control Program should step-up efforts to improve on antiretroviral drug distribution,as well as proper assessment and management of anaemia,foster early diagnosis and treatment of tuberculosis and enhance treatment adherence counselling especially in younger patients.

Factors associated with DAA virological treatment failure and resistance-associated substitutions description in HIV/HCV coinfected patients

AIMTo describe factors associated with treatment failure and frequency of resistance-associated substitutions （RAS）.METHODSHuman immunodefciency virus （HIV）/hepatitis C virus （HCV） coinfected patients starting a first direct-acting antiviral （DAA） regimen before February 2016 and included in the French ANRS CO13 HEPAVIH cohort were eligible. Failure was defned as： （1） non-response [HCV-RNA remained detectable during treatment, at end of treatment （EOT）]; and （2） relapse （HCV-RNA suppressed at EOT but detectable thereafter）. Sequencing analysis was performed to describe prevalence of drug class-specifc RAS. Factors associated with failure were determined using logistic regression models.RESULTSAmong 559 patients, 77% had suppressed plasmaHIV-RNA 〈 50 copies/mL at DAA treatment initiation41% were cirrhotic, and 68% were HCV treatmentexperienced. Virological treatment failures occurred in22 patients and were mainly relapses （17, 77%） thenundefined failures （3, 14%） and non-responses （29%）. Mean treatment duration was 16 wk overall. Posttreatment NS3, NS5A or NS5B RAS were detected in10/14 patients with samples available for sequencinganalysis. After adjustment for age, sex, ribavirin useHCV genotype and treatment duration, low platelecount was the only factor signifcantly associated with ahigher risk of failure （OR： 6.5; 95%CI： 1.8-22.6）. CONCLUSIONOnly 3.9% HIV-HCV coinfected patients failed DAAregimens and RAS were found in 70% of those failingLow platelet count was independently associated withvirological failure.

Virological Therapeutic Failure and Associated Factors in People Living with HIV Followed up at the Regional Hospital and University of Borgou (RHU-B) in 2019

Introduction: Antiretroviral treatment has made a considerable reduction in morbidity and mortality in HIV patients, but its effectiveness is compromised by the emergence of cardiovascular and metabolic diseases and also treatment failure. The goal is to study Virological therapeutic failure and the factors associated with HIV patients followed at RUH-B. Methods: This was a cross-sectional, descriptive and analytical study covering the period from 21st July to 21st September 2019. The study enrolled patients 18 years old and above, on antiretroviral treatment for at least 6 months. For the survey, a questionnaire and review of the medical records were used. The variable studied was virological treatment failure. Data analysis was performed using EPI-INFO version 7 and STATA 11 software. The significance level was 5%. Results: A total of 498 patients were included in the study. The mean age was 40 ± 9.90 years. The sex ratio was 0.3. The frequency of treatment failure was 15.3%. The factors associated with the occurrence of treatment failure were: phytotherapy, occurrence of opportunistic infections during follow-up, poor compliance with antiretrovirals, lack of weight gain and anemia during follow-up. Conclusion: This study had shown that treatment failure was frequent in patients. The systematic investigation for failure should be done in all people living with HIV patients on antiretrovirals.

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.