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Antiretroviral resistance

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https://www.readbyqxmd.com/read/28628529/appraising-viral-load-thresholds-and-adherence-support-recommendations-in-the-world-health-organization-guidelines-for-detection-and-management-of-virologic-failure
#1
Suzanne M McCluskey, Yap Boum, Nicholas Musinguzi, Jessica E Haberer, Jeffrey N Martin, Peter W Hunt, Vincent C Marconi, David R Bangsberg, Mark J Siedner
BACKGROUND: The World Health Organization defines HIV virologic failure as two consecutive viral loads >1,000 copies/mL, measured 3-6 months apart with interval adherence support. We sought to empirically evaluate these guidelines using data from an observational cohort. SETTING: The Uganda AIDS Rural Treatment Outcomes study observed adults with HIV in southwestern Uganda from the time of antiretroviral therapy (ART) initiation, and monitored adherence with electronic pill bottles...
June 15, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/28628034/clonal-expansion-of-genome-intact-hiv-1-in-functionally-polarized-th1-cd4-t-cells
#2
Guinevere Q Lee, Nina Orlova-Fink, Kevin Einkauf, Fatema Z Chowdhury, Xiaoming Sun, Sean Harrington, Hsiao-Hsuan Kuo, Stephane Hua, Hsiao-Rong Chen, Zhengyu Ouyang, Kavidha Reddy, Krista Dong, Thumbi Ndung'u, Bruce D Walker, Eric S Rosenberg, Xu G Yu, Mathias Lichterfeld
HIV-1 causes a chronic, incurable disease due to its persistence in CD4+ T cells that contain replication-competent provirus, but exhibit little or no active viral gene expression and effectively resist combination antiretroviral therapy (cART). These latently infected T cells represent an extremely small proportion of all circulating CD4+ T cells but possess a remarkable long-term stability and typically persist throughout life, for reasons that are not fully understood. Here we performed massive single-genome, near-full-length next-generation sequencing of HIV-1 DNA derived from unfractionated peripheral blood mononuclear cells, ex vivo-isolated CD4+ T cells, and subsets of functionally polarized memory CD4+ T cells...
June 19, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28627486/the-association-between-detected-drug-resistance-mutations-and-cd4-t-cell-decline-in-hiv-positive-individuals-maintained-on-a-failing-treatment-regimen
#3
Anna Schultze, Roger Paredes, Caroline Sabin, Andrew N Phillips, Deenan Pillay, Nicola Mackie, Antonella Castagna, David Chadwick, Karolin Falconer, Anna Maria Geretti, Frank A Post, Teresa Hill, Ole Kirk, Anton Pozniak, Mark Nelson, Anna Tostevin, David Dunn, Jens Lundgren, Alessandro Cozzi-Lepri
BACKGROUND: To analyse the effect of drug resistance mutations (DRM) on CD4 cell trends in HIV-positive people maintained on virologically failing antiretroviral therapy (ART). METHODS: Individuals from two large cohorts experiencing virological failure (VF) while maintained on ART with >1 CD4 count and >1 resistance test were included. CD4 cell slopes were estimated using linear mixed models. Principal component analysis (PCA) was used to assess the effect of clusters of mutations, defined using extracted component based scores from the PCA, on CD4 cell decline...
June 19, 2017: Antiviral Therapy
https://www.readbyqxmd.com/read/28627427/144-week-efficacy-and-safety-of-a-once-daily-single-tablet-regimen-of-tenofovir-lamivudine-and-efavirenz-among-arv-na%C3%A3-ve-and-arv-experienced-hiv-1-infected-thai-adults
#4
Anchalee Avihingsanon, Wirach Maek-A-Nantawat, Sivaporn Gatechompol, Vorapot Sapsirisavat, Wanida Thiansanguankul, Jiratchaya Sophonphan, Narujakorn Thammajaruk, Sasiwimol Ubolyam, David M Burger, Kiat Ruxrungtham
OBJECTIVES: To assess the efficacy and safety of a new single tablet regimen(STR) of tenofovir disoproxil fumarate(TDF) 300mg, lamivudine(3TC) 300mg and efavirenz(EFV) 600mg in HIV-infected Thais. METHODS: This was a 144 week, prospective study among 51 treatment naïve and 49 experienced patients on separated pill of TDF, 3TC and EFV with HIV RNA<50 copies/ml. CD4, HIV RNA, liver, renal functions and lipid profiles were assessed at baseline, weeks 12, 24, 48 and then every 24 weeks...
June 13, 2017: International Journal of Infectious Diseases: IJID
https://www.readbyqxmd.com/read/28614778/the-human-immunodeficiency-virus-hiv1-protease-inhibitor-sanquinavir-activates-autophagy-and-removes-lipids-deposited-in-lipid-droplets
#5
A Polus, M Bociaga-Jasik, U Czech, J Goralska, U Cialowicz, M Chojnacka, M Polus, K Jurowski, A Dembinska-Kiec
Reduction in mortality and increased average life span of the human immunodeficiency virus (HIV)-infected patients treated with antiretroviral therapy (ART) are associated with the risk of unwanted effects, such as insulin resistance and dyslipidemia with cardiovascular complications. Antiretroviral therapy may also be associated with lipodystrophy characterized as peripheral lipoatrophy with central fat accumulation. Understanding the molecular mechanisms of lipodystrophy caused by ART is important for therapeutic strategy and the prediction of side-effects...
April 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/28610939/outcome-of-challenging-hiv-case-consultations-provided-via-teleconference-by-the-clinician-consultation-center-to-the-federal-bureau-of-prisons
#6
Betty J Dong, Michelle R Williams, J Tyler Bingham, Jason Tokumoto, Jeffery D Allen
OBJECTIVES: To describe the collaboration and prospective outcome of challenging human immunodeficiency virus (HIV) cases presented by Board of Prisons (BOP) pharmacists in consultation with Clinician Consultation Center (CCC) clinical pharmacists and physicians to improve correctional patient care. SETTING: Federal correctional facilities. PRACTICE DESCRIPTION: Pharmacists improve care of incarcerated persons infected with HIV. PRACTICE INNOVATION: Pharmacists evaluate, implement, and provide successful oversight of HIV/hepatitis C virus (HCV) care...
June 10, 2017: Journal of the American Pharmacists Association: JAPhA
https://www.readbyqxmd.com/read/28605418/should-we-be-testing-for-baseline-integrase-resistance-in-patients-newly-diagnosed-with-hiv
#7
Yiannis Koullias, Paul E Sax, Naomi F Fields, Rochelle P Walensky, Emily P Hyle
Background: Current guidelines recommend genotype resistance testing at diagnosis to guide initial selection of antiretroviral therapy (ART). Many standard resistance genotypes exclude testing for resistance to integrase inhibitors ("IR-testing"), although this class of drugs is a component of most recommended first-line regimens. Methods: We compared the 96-week clinical outcomes and cost-effectiveness of two strategies: no IR-testing vs. IR-testing performed at HIV diagnosis...
June 9, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28605172/pharmacy-refill-data-can-be-used-to-predict-virologic-failure-for-patients-on-antiretroviral-therapy-in-brazil
#8
David Martin, Paula M Luz, Jordan E Lake, Jesse L Clark, Dayse P Campos, Valdilea G Veloso, Ronaldo I Moreira, Sandra W Cardoso, Jeffrey D Klausner, Beatriz Grinsztejn
INTRODUCTION: Pharmacy adherence measures such as pharmacy dispensing ratios (PDRs) have previously been shown to be predictive of virologic outcomes. We aimed to determine the optimal interval of PDR assessment for predicting virologic failure for HIV-infected patients on antiretroviral therapy (ART). METHODS: Using national Brazilian ART pharmacy refill data, we examined PDRs for patients ≥18 years of age with at least one HIV RNA level ≥180 days after ART initiation on or after 1 January 2011...
June 5, 2017: Journal of the International AIDS Society
https://www.readbyqxmd.com/read/28604824/decline-in-cd4-t-lymphocytes-with-monotherapy-bridging-strategy-for-non-adherent-adolescents-living-with-hiv-infection-results-of-the-impaact-p1094-randomized-trial
#9
Allison L Agwu, Meredith G Warshaw, Elizabeth J McFarland, George K Siberry, Ann J Melvin, Andrew A Wiznia, Lee Fairlie, Sandra Boyd, Paul Harding, Hans M L Spiegel, Elaine J Abrams, Vincent J Carey
INTRODUCTION: Management of persistently non-adherent youth living with HIV (YLHIV) with virologic failure (VF) on combination antiretroviral therapy (cART) remains challenging. One strategy has been using 3TC/ FTC monotherapy (3TC/FTC), which in the presence of the M184V resistance mutation, does not suppress viral replication nor select for additional drug resistance mutations, and reduces viral fitness with limited side effects. P1094 compared the immunologic outcome of continuing failing cART vs...
2017: PloS One
https://www.readbyqxmd.com/read/28598790/croi-2017-advances-in-antiretroviral-therapy
#10
Joyce Jones, Barbara S Taylor, Hong-Van Tieu, Timothy J Wilkin
The 2017 Conference on Retroviruses and Opportunistic Infections (CROI) featured exciting preclinical data on investigational antiretroviral agents with good in vitro efficacy and long half-lives. Investigational medications, including bictegravir, demonstrated excellent efficacy and tolerability, as did dual-agent therapy with dolutegravir paired with rilpivirine or with lamivudine. Dolutegravir monotherapy proved inadvisable due to virologic failure and resistance. The gap between high- and low-income settings along the HIV care continuum is narrowing, with Zimbabwe, Malawi, and Zambia approaching the 90-90-90 targets established by the joint United Nations Programme on HIV/AIDS (UNAIDS), whereas communities in the Southern United States are falling behind...
May 2017: Topics in Antiviral Medicine
https://www.readbyqxmd.com/read/28591401/an-overview-of-the-molecular-and-epidemiological-features-of-hiv-1-infection-in-two-major-cities-of-bahia-state-brazil
#11
Amanda Gm Amaral, Isabele B Oliveira, Diego C Carneiro, Luiz Cj Alcantara, Joana P Monteiro-Cunha
BACKGROUND: The high mutation rate of the human immunodeficiency virus (HIV) has created a public health challenge because the use of antiretroviral drugs can generate selective pressure that drives resistance in these viruses. OBJECTIVE: The aim of this work was to characterise the molecular and epidemiological profile of HIV in Bahia, Brazil. METHODS: DNA sequences from regions of HIV gag, pol, and env genes were obtained from previous studies performed in this area between 2002 and 2012...
June 2017: Memórias do Instituto Oswaldo Cruz
https://www.readbyqxmd.com/read/28589513/prevalence-of-hiv-1-transmitted-drug-resistance-in-recently-infected-treatment-na%C3%A3-ve-persons-in-the-southwest-of-iran-2014-2015
#12
Shokouh Ghafari, Arash Memarnejadian, Alireza Samarbaf-Zadeh, Ehsan Mostafavi, Manoochehr Makvandi, Shokrolah Salmanzadeh, Ata Ghadiri, Michael R Jordan, Elham Mousavi, Fatemeh Jahanbakhsh, Kayhan Azadmanesh
The emergence and transmission of drug resistant HIV mutants is a major concern, especially in resource-limited countries with expanding antiretroviral therapy. Studies have recently reported the prevalence of HIV-1 transmitted drug resistance (TDR) mutations in certain Iranian cities; however, no information is currently available about the level of TDR, as well as the nature of the circulating HIV-1 subtypes, in the Southwestern bordering province of Iran, Khuzestan. Herein, we used a WHO-recommended TDR survey method to classify the prevalence of TDR in indigenous people of Khuzestan province...
June 6, 2017: Archives of Virology
https://www.readbyqxmd.com/read/28588979/determinants-of-adherence-to-antiretroviral-therapy-among-hiv-positive-adults-in-sub-saharan-africa-a-systematic-review
#13
Tessa Heestermans, Joyce L Browne, Susan C Aitken, Sigrid C Vervoort, Kerstin Klipstein-Grobusch
OBJECTIVE: The rapid scale up of antiretroviral treatment (ART) in sub-Saharan Africa (SSA) has resulted in an increased focus on patient adherence. Non-adherence can lead to drug-resistant HIV caused by failure to achieve maximal viral suppression. Optimal treatment requires the identification of patients at high risk of suboptimal adherence and targeted interventions. The aim of this review was to identify and summarise determinants of adherence to ART among HIV-positive adults. DESIGN: Systematic review of adherence to ART in SSA from January 2002 to October 2014...
November 2016: BMJ Global Health
https://www.readbyqxmd.com/read/28585361/prevalence-of-hiv-1-transmitted-drug-resistance-in-the-incarcerated-population
#14
J Sapozhnikov, J D Young, M Patel, T D Chiampas, P Vaughn, M E Badowski
OBJECTIVES: The aim of the study was to determine the prevalence of transmitted drug resistance (TDR)-associated mutations among treatment-naïve, incarcerated individuals with HIV-1 infection in the USA as well as the class TDR and antiretroviral (ARV) mutations present at baseline. METHODS: Patients over the age of 18 years were included in the study if they had been diagnosed with HIV infection, if their HIV infection was managed through telemedicine and if they were incarcerated in the State of Illinois Department of Corrections between 10 July 2010 and 29 April 2016...
June 6, 2017: HIV Medicine
https://www.readbyqxmd.com/read/28583191/hiv-drug-resistance-against-strand-transfer-integrase-inhibitors
#15
REVIEW
Kaitlin Anstett, Bluma Brenner, Thibault Mesplede, Mark A Wainberg
Integrase strand transfer inhibitors (INSTIs) are the newest class of antiretroviral drugs to be approved for treatment and act by inhibiting the essential HIV protein integrase from inserting the viral DNA genome into the host cell's chromatin. Three drugs of this class are currently approved for use in HIV-positive individuals: raltegravir (RAL), elvitegravir (EVG), and dolutegravir (DTG), while cabotegravir (CAB) and bictegravir (BIC) are currently in clinical trials. RAL and EVG have been successful in clinical settings but have relatively low genetic barriers to resistance...
June 5, 2017: Retrovirology
https://www.readbyqxmd.com/read/28582463/drug-resistance-testing-through-remote-genotyping-and-predicted-treatment-options-in-human-immunodeficiency-virus-type-1-infected-tanzanian-subjects-failing-first-or-second-line-antiretroviral-therapy
#16
Jenny Svärd, Sabina Mugusi, Doreen Mloka, Ujjwal Neogi, Genny Meini, Ferdinand Mugusi, Francesca Incardona, Maurizio Zazzi, Anders Sönnerborg
INTRODUCTION: Antiretroviral therapy (ART) has been successfully introduced in low-middle income countries. However an increasing rate of ART failure with resistant virus is reported. We therefore described the pattern of drug resistance mutations at antiretroviral treatment (ART) failure in a real-life Tanzanian setting using the remote genotyping procedure and thereafter predicted future treatment options using rule-based algorithm and the EuResist bioinformatics predictive engine. According to national guidelines, the default first-line regimen is tenofovir + lamivudine + efavirenz, but variations including nevirapine, stavudine or emtricitabine can be considered...
2017: PloS One
https://www.readbyqxmd.com/read/28579286/hiv-aids-infection-the-beginning-of-the-end-for-today-s-greatest-pandemic
#17
F Gutiérrez
Recently, there have been significant advances in the fight against human immunodeficiency virus, which have increased the hopes of definitively halting its dissemination and of starting the decline of the epidemic it has caused. Transmission of the infection was drastically reduced when infected patients were given antiretroviral treatments, which boosted the diffusion of treatments to middle- and low-income countries. Global therapy coverage has doubled in recent years; meanwhile the incidence of new infections has decreased...
June 1, 2017: Revista Clínica Española
https://www.readbyqxmd.com/read/28576126/effective-treatment-of-sivcpz-induced-immunodeficiency-in-a-captive-western-chimpanzee
#18
Hannah J Barbian, Raven Jackson-Jewett, Corrine S Brown, Frederic Bibollet-Ruche, Gerald H Learn, Timothy Decker, Edward F Kreider, Yingying Li, Thomas N Denny, Paul M Sharp, George M Shaw, Jeffrey Lifson, Edward P Acosta, Michael S Saag, Katharine J Bar, Beatrice H Hahn
BACKGROUND: Simian immunodeficiency virus of chimpanzees (SIVcpz), the progenitor of human immunodeficiency virus type 1 (HIV-1), is associated with increased mortality and AIDS-like immunopathology in wild-living chimpanzees (Pan troglodytes). Surprisingly, however, similar findings have not been reported for chimpanzees experimentally infected with SIVcpz in captivity, raising questions about the intrinsic pathogenicity of this lentivirus. FINDINGS: Here, we report progressive immunodeficiency and clinical disease in a captive western chimpanzee (P...
June 2, 2017: Retrovirology
https://www.readbyqxmd.com/read/28572840/low-levels-of-viral-suppression-among-refugees-and-host-nationals-accessing-antiretroviral-therapy-in-a-kenyan-refugee-camp
#19
Joshua B Mendelsohn, Paul Spiegel, Alison Grant, Sathyanarayanan Doraiswamy, Marian Schilperoord, Natasha Larke, John Wagacha Burton, Jully A Okonji, Clement Zeh, Bosco Muhindo, Ibrahim M Mohammed, Irene N Mukui, Njogu Patterson, Egbert Sondorp, David A Ross
BACKGROUND: Refugees and host nationals who accessed antiretroviral therapy (ART) in a remote refugee camp in Kakuma, Kenya (2011-2013) were compared on outcome measures that included viral suppression and adherence to ART. METHODS: This study used a repeated cross-sectional design (Round One and Round Two). All adults (≥18 years) receiving care from the refugee camp clinic and taking antiretroviral therapy (ART) for ≥30 days were invited to participate. Adherence was measured by self-report and monthly pharmacy refills...
2017: Conflict and Health
https://www.readbyqxmd.com/read/28569550/ultra-deep-sequencing-analysis-on-hiv-drug-resistant-associated-mutations-among-hiv-infected-individuals-first-report-from-the-philippines
#20
Ivo Novita SahBandar, Genesis Samonte, Elizabeth Telan, Nalyn Siripong, Mahdi Belcaid, David Schanzenbach, Susan Leano, Haorile Chagan-Yasutan, Toshio Hattori, Cecilia Shikuma, Lishomwa C Ndhlovu
OBJECTIVE: A sharp increase in the number of people living with HIV (PLHIV) has been documented in the Philippines. In response, the government has instituted antiretroviral therapy (ART) nationwide through HIV treatment hubs. However, no data presently exists on the status of ART drug-resistant-associated mutations (DRMs). In this study, we aim to analyze DRM profiles in the Philippines and provide comprehensive data on DRMs to guide treatment decisions and prevent viral failures. DESIGN AND METHODS: We conducted a cross-sectional study in 119 volunteers tested positive for HIV from over 8,000 participants screened for HIV across the nation through 2013 Integrated HIV Behavioral and Serologic Surveillance (IHBSS) program...
June 1, 2017: AIDS Research and Human Retroviruses
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