Dataset Information

Drug Resistance and Virological Failure among HIV-Infected Patients after a Decade of Antiretroviral Treatment Expansion in Eight Provinces of China.

ABSTRACT:

Background

China's National Free Antiretroviral Treatment Program (NFATP) has substantially increased the survival rate since 2002. However, the emergence of HIV drug resistance (HIVDR) limits the durability and effectiveness of antiretroviral treatment (ART) in at risk patients.

Method

A cross-sectional survey was conducted among patients having received a median of 13.9 months of ART in eight provinces in China. Demographic and clinical information was collected, and venous blood was sampled for CD4 cell counts, measurement of the HIV viral load (VL), and HIV drug resistance (HIVDR) genotyping. Possible risk factors for HIVDR were analyzed by the logistic regression model.

Results

The study included 765 patients. Among them, 65 patients (8.5%) had virological failure (VLF) defined as ?1,000 copies/ml. Among the individuals with VLF, 64 were successful genotyped, and of these, 33 had one or more HIVDR mutations. The prevalence of HIVDR mutations among patients receiving first-line ART was 4.3% (33/765). All of the patients with HIVDR mutations were resistant to non-nucleoside transcriptase inhibitors, 81.8% were resistant to nucleoside reverse transcriptase inhibitors, and only 3% had mutations that caused resistance to protease inhibitors. Having lower ratios of drug intake in the past month and dwelling in two southwestern provinces were factors independently associated with the emergence of HIVDR.

Conclusion

Most patients receiving first-line ART treatment achieved sound virological and immunological outcomes. However, poor adherence is still a key problem, which has led to the high rate of HIVDR. It was notable that the proportion of drug resistance widely varied among the provinces. More studies are needed to focus on adherence.

SUBMITTER: Zuo Z

PROVIDER: S-EPMC5172524 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Drug Resistance and Virological Failure among HIV-Infected Patients after a Decade of Antiretroviral Treatment Expansion in Eight Provinces of China.

Zuo Zhongbao Z Liang Shu S Sun Xianguang X Bussell Scottie S Yan Jing J Kan Wei W Leng Xuebing X Liao Lingjie L Ruan Yuhua Y Shao Yiming Y Xing Hui H

PloS one 20161220 12

<h4>Background</h4>China's National Free Antiretroviral Treatment Program (NFATP) has substantially increased the survival rate since 2002. However, the emergence of HIV drug resistance (HIVDR) limits the durability and effectiveness of antiretroviral treatment (ART) in at risk patients.<h4>Method</h4>A cross-sectional survey was conducted among patients having received a median of 13.9 months of ART in eight provinces in China. Demographic and clinical information was collected, and venous bloo ...[more]

PMID: 27997554

Similar Datasets

Project description:First-line antiretroviral therapy (ART) failure often results from the development of resistance-associated mutations (RAMs). Three patterns, including thymidine analogue mutations (TAMs), 69 Insertion (69Ins) and the Q151M complex, are associated with resistance to multiple-nucleoside reverse transcriptase inhibitors (NRTIs) and may compromise treatment options for second-line ART.We investigated patterns and factors associated with multi-NRTI RAMs at first-line failure in patients from The TREAT Asia Studies to Evaluate Resistance - Monitoring study (TASER-M), and evaluated their impact on virological responses at 12 months after switching to second-line ART. RAMs were compared with the IAS-USA 2013 mutations list. We defined multi-NRTI RAMs as the presence of either Q151M; 69Ins; ? 2 TAMs; or M184V+? 1 TAM. Virological suppression was defined as viral load (VL) <400 copies/ml at 12 months from switch to second-line. Logistic regression was used to analyze (1) factors associated with multi-NRTI RAMs at first-line failure and (2) factors associated with virological suppression after 12 months on second-line.A total of 105 patients from 10 sites in Thailand, Hong Kong, Indonesia, Malaysia and Philippines were included. There were 97/105 (92%) patients harbouring ? 1 RAMs at first-line failure, 39/105 with multi-NRTI RAMs: six with Q151M; 24 with ? 2 TAMs; and 32 with M184V+? 1 TAM. Factors associated with multi-NRTI RAMs were CD4 ? 200 cells/µL at genotyping (OR=4.43, 95% CI [1.59-12.37], p=0.004) and ART duration >2 years (OR=6.25, 95% CI [2.39-16.36], p<0.001). Among 87/105 patients with available VL at 12 months after switch to second-line ART, virological suppression was achieved in 85%. The median genotypic susceptibility score (GSS) for the second-line regimen was 2.00. Patients with ART adherence ? 95% were more likely to be virologically suppressed (OR=9.33, 95% CI (2.43-35.81), p=0.001). Measures of patient resistance to second-line ART, including the GSS, were not significantly associated with virological outcome.Multi-NRTI RAMs at first-line failure were associated with low CD4 level and longer duration of ART. With many patients switching to highly susceptible regimens, good adherence was still crucial in achieving virological response. This emphasizes the importance of continued adherence counselling well into second-line therapy.

Project description:ImportanceWorldwide, the nonnucleoside reverse transcriptase inhibitors (NNRTIs) efavirenz and nevirapine are commonly used in first-line antiretroviral regimens in both adults and children with human immunodeficiency virus (HIV) infection. Data on the comparative effectiveness of these medications in children are limited.ObjectiveTo investigate whether virological failure is more likely among children who initiated 1 or the other NNRTI-based HIV treatment.Design, setting, and participantsRetrospective cohort study of children (aged 3-16 years) who initiated efavirenz-based (n = 421) or nevirapine-based (n = 383) treatment between April 2002 and January 2011 at a large pediatric HIV care setting in Botswana.Main outcomes and measuresThe primary outcome was time from initiation of therapy to virological failure. Virological failure was defined as lack of plasma HIV RNA suppression to less than 400 copies/mL by 6 months or confirmed HIV RNA of 400 copies/mL or greater after suppression. Cox proportional hazards regression analysis compared time to virological failure by regimen. Multivariable Cox regression controlled for age, sex, baseline immunologic category, baseline clinical category, baseline viral load, nutritional status, NRTIs used, receipt of single-dose nevirapine, and treatment for tuberculosis.ResultsWith a median follow-up time of 69 months (range, 6-112 months; interquartile range, 23-87 months), 57 children (13.5%; 95% CI, 10.4%-17.2%) initiating treatment with efavirenz and 101 children (26.4%; 95% CI, 22.0%-31.1%) initiating treatment with nevirapine had virological failure. There were 11 children (2.6%; 95% CI, 1.3%-4.6%) receiving efavirenz and 20 children (5.2%; 95% CI, 3.2%-7.9%) receiving nevirapine who never achieved virological suppression. The Cox proportional hazard ratio for the combined virological failure end point was 2.0 (95% CI, 1.4-2.7; log rank P < .001, favoring efavirenz). None of the measured covariates affected the estimated hazard ratio in the multivariable analyses.Conclusions and relevanceAmong children aged 3 to 16 years infected with HIV and treated at a clinic in Botswana, the use of efavirenz compared with nevirapine as initial antiretroviral treatment was associated with less virological failure. These findings may warrant additional research evaluating the use of efavirenz and nevirapine for pediatric patients.

Project description:INTRODUCTION:Antiretroviral treatment (ART) has been scaled up over the last decade but compared to adults, children living with HIV are less likely to receive ART. Moreover, children and adolescents are more vulnerable than adults to virological failure (VF) and emergence of drug resistance. In this study we determined virological outcome in perinatally HIV-1-infected children and adolescents receiving ART in Togo. METHODS:HIV viral load (VL) testing was consecutively proposed to all children and adolescents who were on ART for at least 12 months when attending HIV healthcare services for their routine follow-up visit (June to September 2014). Plasma HIV-1 VL was measured using the m2000 RealTime HIV-1 assay (Abbott Molecular, Des Plaines, IL, USA). Genotypic drug resistance was done for all samples with VL>1000 copies/ml. RESULTS AND DISCUSSION:Among 283 perinatally HIV-1-infected children and adolescents included, 167 (59%) were adolescents and 116 (41%) were children. The median duration on ART was 48 months (interquartile range: 28 to 68 months). For 228 (80.6%), the current ART combination consisted of two nucleoside reverse transcriptase inhibitors (NRTIs) (zidovudine and lamivudine) and one non-nucleoside reverse transcriptase inhibitor (NNRTI) (nevirapine or efavirenz). Only 28 (9.9%) were on a protease inhibitor (PI)-based regimen. VL was below the detection limit (i.e. 40 copies/ml) for 102 (36%), between 40 and 1000 copies/ml for 35 (12.4%) and above 1000 copies/ml for 146 (51.6%). Genotypic drug-resistance testing was successful for 125/146 (85.6%); 110/125 (88.0%) were resistant to both NRTIs and NNRTIs, 1/125 (0.8%) to NRTIs only, 4/125 (3.2%) to NNRTIs only and three harboured viruses resistant to reverse transcriptase and PIs. Overall, 86% (108/125) of children and adolescents experiencing VF and successfully genotyped, corresponding thus to at least 38% of the study population, had either no effective ART or had only a single effective drug in their current ART regimen. CONCLUSIONS:Our study provided important information on virological outcome on lifelong ART in perinatally HIV-1-infected children and adolescents who were still on ART and continued to attend antiretroviral (ARV) clinics for follow-up visits. Actual conditions for scaling up and monitoring lifelong ART in children in resource-limited countries can have dramatic long-term outcomes and illustrate that paediatric ART receives inadequate attention.

Dataset Information

Drug Resistance and Virological Failure among HIV-Infected Patients after a Decade of Antiretroviral Treatment Expansion in Eight Provinces of China.

Background

Method

Results

Conclusion

Publications

Drug Resistance and Virological Failure among HIV-Infected Patients after a Decade of Antiretroviral Treatment Expansion in Eight Provinces of China.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets