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Prevalence and characteristics of HIV drug resistance among antiretroviral treatment (ART) experienced adolescents and young adults living with HIV in Ndola, Zambia.

ABSTRACT: BACKGROUND:HIV drug resistance (HIVDR) poses a threat to the HIV epidemic control in Zambia especially in sub-populations such as the 15-24 years where there is poor virological suppression. Understanding the prevalence and patterns of HIVDR in this population (15-24 years) will contribute to defining effective antiretroviral therapy (ART) regimens, improving clinical decision making, and supporting behavioral change interventions needed to achieve HIV epidemic control. METHODS:A cross-sectional analysis of study enrollment data from the Project YES! Youth Engaging for Success randomized controlled trial was conducted. Participants were 15 to 24 years old, who knew their HIV status, and had been on ART for at least 6 months. All participants completed a survey and underwent viral load (VL) testing. Participants with viral failure (VL ?1,000 copies/mL) underwent HIVDR testing which included analysis of mutations in the protease and reverse transcriptase genes. RESULTS:A total of 99 out of 273 analyzed participants receiving ART had VL failure, of whom 77 had successful HIVDR amplification and analysis. Out of the 77, 75% (58) had at least one drug resistant mutation, among which 83% (48/58) required a drug change. Among the 58 with HIVDR mutations, the prevalence of at least one HIVDR mutation to nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) were 81%, 65.5% and 1.7%. The mutation M184V which confers resistance to NRTI drugs of lamivudine (3TC) and emtricitabine (FTC) was the most common (81%) among NRTI associated mutations followed by K65R (34.5%) which is associated with both tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide fumarate (TAF) resistance. Thymidine analogue mutations (TAMs) which confer resistance primarily to zidovudine (AZT), stavudine (d4T) and other NRTIs were observed at 32.8%. Common TAMs were K70RTQNE (32.8%), K219QE (22.4%), D67N (17.2%) and T215IT (15.5%). The most common NNRTI associated mutation was the K103N (65.5%) which confers resistance to both efavirenz (EFV) and nevirapine (NVP). There was a relatively high occurrence of other NNRTI mutations V106A (36.2%), as well as Y188C (36.2%) and Y181C (36.2%) which confer resistance to etravirine. CONCLUSIONS:There is a high prevalence of HIVDR including TAMs despite majority of these patients (90.48%) being on AZT or d4T sparing first line ART among the youth. Emergence of these mutations including the NNRTI associated mutations (Y181C and Y188C) may compromise future second- and third-line regimens in the absence of routine HIVDR testing. HIVDR monitoring at start of ART or at first-line failure can better inform clinical decision making and ART programing.

SUBMITTER: Miti S

PROVIDER: S-EPMC7430722 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Prevalence and characteristics of HIV drug resistance among antiretroviral treatment (ART) experienced adolescents and young adults living with HIV in Ndola, Zambia.

Miti Sam S Handema Ray R Mulenga Lloyd L Mwansa Jonathan K JK Abrams Elizabeth E Frimpong Christiana C Burke Virginia M VM Zulu Mangani M Siwingwa Mpanji M Mwakazanga David D Kalibala Sam S Denison Julie A JA

PloS one 20200817 8

<h4>Background</h4>HIV drug resistance (HIVDR) poses a threat to the HIV epidemic control in Zambia especially in sub-populations such as the 15-24 years where there is poor virological suppression. Understanding the prevalence and patterns of HIVDR in this population (15-24 years) will contribute to defining effective antiretroviral therapy (ART) regimens, improving clinical decision making, and supporting behavioral change interventions needed to achieve HIV epidemic control.<h4>Methods</h4>A ...[more]

PMID: 32804970

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Project description:BackgroundLittle is known about violence against HIV-positive adolescents and young adults (AYA) in sub-Saharan Africa. This analysis examines experiences of violence victimization, and the perpetrators of this violence, among AYA living with HIV, aged 15-24 years, in Zambia.MethodsWe analyzed baseline data from 272 AYA (60.1% female, 71.0% perinatally infected) enrolled in Project YES! (Youth Engaging for Success), a randomized controlled trial conducted in four HIV clinics in Ndola, Zambia. Violence measures were adapted from the ICAST-C and the WHO Multi-Country Study on Women's Health and Domestic Violence. Youth could report up to 12 perpetrator types for past-year experiences of violence. We estimated lifetime and past-year prevalence of physical violence, psychological abuse, and forced sex, disaggregated by sex and age group. Estimates were weighted using sex and age data from the 2013-14 Zambian Demographic and Health Survey to be representative of HIV-positive AYA in Zambia.ResultsEstimated lifetime prevalence of any violence victimization was 78.2%. Past-year prevalence was 72.0% among males and 74.5% among females. Almost half of AYA (46.1%) had ever experienced polyvictimization (2+ types of violence). Psychological abuse was most common (70.4% lifetime, 65.3% past-year), followed by physical violence (50.8% lifetime, 44.7% past-year) and forced sex (10.4% lifetime, 4.7% past-year). Among past-year victims, males experienced more violence than females from a friend/peer (74.3% vs. 45.1%, p<0.001); females experienced more violence than males from a romantic partner (33.3% vs. 5.0%, p<0.001), parent/caregiver (32.4% vs. 17.6%, p = 0.02), and stranger (19.7% vs. 5.2%, p<0.001).ConclusionThe widespread and overlapping prevalence of multiple types of violence highlights the critical need for prevention and response efforts that are tailored to youths' sex and the perpetrator type. Future research should explore violence victimization and HIV outcomes, and the measurement of psychological abuse and sexual violence, among HIV-positive AYA in the region.

Project description:IntroductionHIV infection causes pathological changes in the natural killer (NK) cell compartment that can be only partially restored by antiretroviral therapy (ART). We investigated NK cells phenotype and function in children with perinatally acquired HIV (PHIV) and long-term viral control (five years) due to effective ART in a multicentre cross-sectional European study (CARMA, EPIICAL consortium). The impact of age at ART start and viral reservoir was also evaluated.MethodsPeripheral blood mononuclear cells (PBMCs) from 40 PHIV who started ART within two years of life (early treated patients (ET), ≤6 months; late treated patients (LT), > 6 months), with at least five years of HIV-1 suppression (<40 HIV copies/mL), were collected between November 2017 and August 2018. NK phenotype and function were analysed by flow cytometry and transcriptional profile of PBMCs by RNA-Seq. HIV-1 DNA was measured by real-time polymerase chain reaction (Data were analysed by Spearman correlation plots and multivariable Poisson regression model (adjusted for baseline %CD4 and RNA HIV viral load and for age at ART start as an interaction term, either ET or LT) to explore the association between NK cell parameters and HIV reservoir modulated by age at ART start.ResultsA significantly higher frequency of CD56neg NK cells was found in LT compared with ET. We further found in LT a positive correlation of CD56neg NK cells with HIV-1 DNA. LT also displayed increased expression of the NKG2D and NKp46 activating receptors and perforin compared with ET. Moreover, CD107a+ and IFN-γ+ frequencies in non-stimulated NK were associated with HIV-1 DNA in LT patients. Finally, RNA-Seq analysis showed in LT an up-regulation of genes related to NK-activating pathways and susceptibility to apoptosis compared with ET.ConclusionsWe show that early initiation of ART during infancy preserves the NK compartment and is associated with lower HIV-1 reservoir. Such condition persists over adolescence due to long-term viral control achieved through effective ART.

Project description:BackgroundThe authors examined associations between structural characteristics and HIV disease management among a geographically diverse sample of behaviorally and perinatally HIV-infected adolescents and young adults in the United States.MethodsThe sample included 1891 adolescents and young adults living with HIV (27.8% perinatally infected; 72.2% behaviorally infected) who were linked to care through 20 Adolescent Medicine Trials Network for HIV/AIDS Interventions Units. All completed audio computer-assisted self-interview surveys. Chart abstraction or blood draw provided viral load data. Geographic-level variables were extracted from the United States Census Bureau (e.g., socioeconomic disadvantage, percent of Black and Latino households, percent rural) and Esri Crime (e.g., global crime index) databases as Zip Code Tabulation Areas. AIDSVu data (e.g., prevalence of HIV among youth) were extracted at the county-level. Using HLM v.7, the authors conducted means-as-outcomes random effects multi-level models to examine the association between structural-level and individual-level factors and (1) being on antiretroviral therapy (ART) currently; (2) being on ART for at least 6 months; (3) missed HIV care appointments (not having missed any vs. having missed one or more appointments) over the past 12 months; and (4) viral suppression (defined by the corresponding assay cutoff for the lower limit of viral load at each participating site which denoted nondetectability vs. detectability).ResultsFrequencies for the 4 primary outcomes were as follows: current ART use (n = 1120, 59.23%); ART use for ≥6 months (n = 861, 45.53%); at least one missed HIV care appointment (n = 936, 49.50); and viral suppression (n = 577, 30.51%). After adjusting for individual-level factors, youth living in more disadvantaged areas (defined by a composite score derived from 2010 Census indicators including percent poverty, percent receiving public assistance, percent of female, single-headed households, percent unemployment, and percent of people with less than a high school degree) were less likely to report current ART use (OR: 0.85, 95% CI: 0.72-1.00, p = .05). Among current ART users, living in more disadvantaged areas was associated with greater likelihood of having used ART for ≥6 months. Participants living in counties with greater HIV prevalence among 13-24 year olds were more likely to report current ART use (OR: 1.32, 95% CI: 1.05-1.65, p = .02), ≥6 months ART use (OR: 1.32, 95% CI: 1.05-1.65, p = .02), and to be virally suppressed (OR: 1.50, 95% CI: 1.20-1.87, p = .001); however, youth in these areas were also more likely to report missed medical appointments (OR: 1.32, 95% CI: 1.07-1.63, p = .008).ConclusionsThe findings underscore the multi-level and structural factors associated with ART use, missed HIV care appointments, and viral suppression for adolescents and young adults in the United States. Consideration of these factors is strongly recommended in future intervention, clinical practice, and policy research that seek to understand the contextual influences on individuals' health behaviors.

Project description:BackgroundWhereas many adolescents and young people with HIV require the transfer of care from paediatric/adolescent clinics to adult ART clinics, this transition is beset with a multitude of factors that have the potential to hinder or facilitate the process, thereby raising ethical challenges of the transition process. Decisions made regarding therapy, such as when and how to transition to adult HIV care, should consider ethical benefits and risks. Understanding and addressing ethical challenges in the healthcare transition could ensure a smooth and successful transition. The purpose of this study was to analyze the ethical challenges of transitioning HIV care for adolescents into adult HIV clinics.MethodsData presented were derived from 191 adolescents attending nine different health facilities in Uganda, who constituted 18 focus group discussions. In the discussions, facilitators and barriers regarding adolescents transitioning to adult HIV clinics were explored. Guided by the Silences Framework for data interpretation, thematic data analysis was used to analyze the data. The principles of bioethics and the four-boxes ethics framework for clinical care (patient autonomy, medical indications, the context of care, and quality of life) were used to analyze the ethical issues surrounding the transition from adolescent to adult HIV care.ResultsThe key emerging ethical issues were: reduced patient autonomy; increased risk of harm from stigma and loss of privacy and confidentiality; unfriendly adult clinics induce disengagement and disruption of the care continuum; patient preference to transition as a cohort, and contextual factors are critical to a successful transition.ConclusionThe priority outcomes of the healthcare transition for adolescents should address ethical challenges of the healthcare transition such as loss of autonomy, stigma, loss of privacy, and discontinuity of care to ensure retention in HIV care, facilitate long-term self-care, offer ongoing all-inclusive healthcare, promote adolescent health and wellbeing and foster trust in the healthcare system. Identifying and addressing the ethical issues related to what hinders or facilitates successful transitions with targeted interventions for the transition process may ensure adolescents and young people with HIV infection remain healthy across the healthcare transition.

Project description:BACKGROUND:Studies from sub-Saharan Africa (SSA) document how barriers to ART adherence present additional complications among adolescents and young adults living with HIV. We qualitatively explored barriers to ART adherence in Uganda among individuals age 14-24 to understand the unique challenges faced by this age group. METHODS:We conducted focus group (FG) discussions with Community Advisory Board members (n = 1), health care providers (n = 2), and male and female groups of adolescents age 14-17 (n = 2) and youth age 18-24 (n = 2) in Kampala, Uganda. FGs were transcribed verbatim and translated from Luganda into English. Two investigators independently reviewed all transcripts, developed a detailed codebook, achieved a pooled Cohen's Kappa of 0.79 and 0.80, and used a directed content analysis to identify key themes. RESULTS:Four barriers to ART adherence emerged: 1) poverty limited adolescents' ability to buy food and undercut efforts to become economically independent in their transition from adolescence to adulthood; 2) school attendance limited their privacy, further disrupting ART adherence; 3) family support was unreliable, and youth often struggled with a constant change in guardianship because they had lost their biological parents to HIV. In contrast peer influence, especially among HIV-positive youth, was strong and created an important network to support ART adherence; 4) the burden of taking multiple medications daily frustrated youth, often leading to so-called 'drug holidays.' Adolescent and youth-specific issues around disclosure emerged across three of the four barriers. CONCLUSIONS:To be effective, programs and policies to improve ART adherence among youth in Uganda must address the special challenges that adolescents and young adults confront in achieving optimal adherence. For example, training on budgeting and savings practices could help promote their transition to financial independence. School staff could develop strategies to help students take their medications consistently and confidentially. While challenging to extend the range of services provided by HIV clinics, successful efforts will require engaging the family, peers, and larger community of health and educational providers to support adolescents and young adults living with HIV to live longer and healthier lives. TRIAL REGISTRATION:ClinicalTrials.gov Identifier: NCT02514356 . Registered August 3, 2015.

Dataset Information

Prevalence and characteristics of HIV drug resistance among antiretroviral treatment (ART) experienced adolescents and young adults living with HIV in Ndola, Zambia.

Publications

Prevalence and characteristics of HIV drug resistance among antiretroviral treatment (ART) experienced adolescents and young adults living with HIV in Ndola, Zambia.

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