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Hiv and low level viremia

Francesca Falasca, Corrado De Vito, Laura Mazzuti, Daniele di Carlo, Luigi Celani, Caterina Fimiani, Gabriella d'Ettorre, Ivano Mezzaroma, Guido Antonelli, Ombretta Turriziani
BACKGROUND: Viremia copy-years (VCY) is associated with mortality and disease outcome prediction. This study evaluated the association of VCY with virological failure (VF), defined as a pVL >400 copies/mL, and with single levels of viremia. METHODS: Eight hundred and fifty ART-treated patients with plasma viral load (pVL) < 37 copies/mL [target not detected (TND) or target detected (TD)] or >37, but less than 200 copies/mL [low level viremia (LLV)], and at least 6 pVL measures during 54 months of follow-up were selected...
November 29, 2018: Journal of Acquired Immune Deficiency Syndromes: JAIDS
Truong Tam Nguyen, Véronique Lemee, Karine Bollore, Hai Vinh Vu, Karine Lacombe, Xuan Lien Truong Thi, Que Anh Luong, Charline Dubos, Jean-Christophe Plantier, Huong Duong Thi, Didier Laureillard, Maud Lemoine, Edouard Tuaillon
BACKGROUND: Nucleic acid tests performed on blood samples collected on Dried Blood Spot (DBS) and detection of HCV core antigen (HCVcAg) are two approaches that may facilitate access to HCV diagnosis in low and middle incomes countries. In this study we evaluate HCV RNA and HCV antigen testing on DBS in HIV/HCV co-infected peoples who inject drugs in Vietnam. METHOD: One hundred and four HIV/HCV seropositive patients managed in outpatient care at the Haiphong Viet Tiep hospital were included in this study from February to March, 2014 (ANRS 12262 study)...
December 4, 2018: BMC Infectious Diseases
Miriam Rosás-Umbert, Anuska Llano, Rocío Bellido, Alex Olvera, Marta Ruiz-Riol, Muntsa Rocafort, Marco A Fernández, Patricia Cobarsi, Manel Crespo, Lucy Dorrell, Jorge Del Romero, José Alcami, Roger Paredes, Christian Brander, Beatriz Mothe
Elite and Viremic HIV controllers are able to control their HIV infection and maintain undetectable or low-level viremia in the absence of antiretroviral treatment. Despite extensive studies, the immune factors responsible for such exclusive control remain poorly defined. We identified a cohort of 14 HIV controllers that suffered an abrupt loss of HIV control (LoC) to investigate possible mechanisms and virological and immunological events related to the sudden loss of control. The in-depth analysis of these subjects involved the study of cell-tropism of circulating virus, evidence for HIV super-infection, cellular immune responses to HIV as well as an examination of viral adaptation to host immunity by Gag sequencing...
November 28, 2018: Journal of Virology
Allahna Esber, Christina Polyak, Francis Kiweewa, Jonah Maswai, John Owuoth, Lucas Maganga, Yakubu Adamu, Patrick Hickey, Julie Ake, Trevor A Crowell
Background: World Health Organization (WHO) guidelines identify HIV viral load less than 1000 copies/mL as the goal of antiretroviral therapy (ART). However, the clinical implications of viremia below this threshold are unclear in the African context. We examined factors associated with persistent low level viremia (pLLV) and quantified the risk of subsequent virologic failure among participants with pLLV. Methods: The African Cohort Study enrolled HIV-infected adults at clinics in Uganda, Kenya, Tanzania, and Nigeria, with assessments every six months...
November 20, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Shilpa Buch, Palsamy Periyasamy, Minglei Guo
Despite the efficacy of combination antiretroviral therapy (cART) in controlling viremia, the central nervous system (CNS) continues to harbor viral reservoirs. The persistence of low-level virus replication leads to the accumulation of early viral proteins, including HIV-1 Transactivator of transcription (HIV-1 Tat) protein. Based on the premise that cART does not impact levels of HIV-1 Tat, and since the CNS is inaccessible to the cART regimens, HIV-1-Tat-mediated neuroinflammation has been implicated as an underlying mediator of HIV-1-associated neurocognitive disorders (HAND)...
2018: Epigenetics insights
Koen Ka Van Rompay, Said Hassounah, Brandon F Keele, Jeffrey D Lifson, Amir Ardeshir, Jennifer Watanabe, Hanh Thi Pham, Elena Chertova, Raymond Sowder, Jan Balzarini, Thibault Mesplède, Mark A Wainberg
Drug resistance remains a major concern for HIV treatment. To date, very few resistance mutations have emerged in first-line combination therapy that includes the integrase strand transfer inhibitor (INSTI) dolutegravir (DTG). In vitro, DTG selects for several primary mutations that induce low-level DTG resistance; secondary mutations, while increasing the level of resistance, however further impair replication fitness, which raised the idea that DTG monotherapy may be feasible. The simian immunodeficiency virus (SIV) rhesus macaque model of HIV infection can be useful to explore this concept...
October 31, 2018: Journal of Virology
Alessia Capone, Alessandra Lo Presti, Leonardo Sernicola, Stefania Farcomeni, Flavia Ferrantelli, Maria T Maggiorella, Edward T Mee, Nicola J Rose, Eleonora Cella, Massimo Ciccozzi, Barbara Ensoli, Alessandra Borsetti
Intra-host evolution of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) has been shown by viral RNA analysis in subjects who naturally suppress plasma viremia to low levels, known as controllers. However, little is known about the variability of proviral DNA and the inter-relationships among contained systemic viremia, rate of reservoir reseeding and specific major histocompatibility complex (MHC) genotypes, in controllers. Here, we analysed the proviral DNA quasispecies of the env V1-V2 region, in PBMCs and in anatomical compartments of 13 long-term controller monkeys after 3...
October 12, 2018: Journal of General Virology
N Margot, D Koontz, S McCallister, J W Mellors, C Callebaut
BACKGROUND: Plasma HIV-1 RNA (viral load, VL) is measured routinely in HIV-infected persons with FDA-approved commercially available assays such as the Cobas-TaqMan HIV-1 Assay v2.0. This assay provides quantification of viremia ≥20 copies/mL. More sensitive methods, able to quantify low-level persistent viremia below the detection limit of commercially available assays, are needed to assess the impact of current HIV cure strategies on viremia. OBJECTIVES: The novel integrase HIV-1 RNA single-copy assay (iSCA) was evaluated for measurement of low-level persistent viremia in clinical trial samples (n = 151) from subjects participating in Gilead HIV clinical research...
September 10, 2018: Journal of Clinical Virology: the Official Publication of the Pan American Society for Clinical Virology
Rami Kantor, Allison DeLong, Leeann Schreier, Marissa Reitsma, Emanuel Kemboi, Millicent Orido, Salome Obonge, Robert Boinett, Mary Rono, Wilfred Emonyi, Katie Brooks, Mia Coetzer, Nathan Buziba, Joseph Hogan, Lameck Diero
OBJECTIVE: Characterize failure and resistance above and below guidelines-recommended 1000 copies/ml virologic threshold, upon second-line failure. DESIGN: Cross-sectional study. METHODS: Kenyan adults on lopinavir/ritonavir-based second-line were enrolled at AMPATH (Academic Model Providing Access to Healthcare). Charts were reviewed for demographic/clinical characteristics and CD4/viral load were obtained. Participants with detectable viral load had a second visit and pol genotyping was attempted in both visits...
November 13, 2018: AIDS
Egidio Brocca-Cofano, Cuiling Xu, Katherine S Wetzel, Mackenzie L Cottrell, Benjamin B Policicchio, Kevin D Raehtz, Dongzhu Ma, Tammy Dunsmore, George S Haret-Richter, Karam Musaitif, Brandon F Keele, Angela D Kashuba, Ronald G Collman, Ivona Pandrea, Cristian Apetrei
Current approaches do not eliminate all human immunodeficiency virus type 1 (HIV-1) maternal-to-infant transmissions (MTIT); new prevention paradigms might help avert new infections. We administered maraviroc (MVC) to rhesus macaques (RMs) to block CCR5-mediated entry, followed by repeated oral exposure of a CCR5-dependent clone of simian immunodeficiency virus (SIV) mac251 (SIVmac766). MVC significantly blocked the CCR5 coreceptor in peripheral blood mononuclear cells and tissue cells. All control animals and 60% of MVC-treated infant RMs became infected by the 6th challenge, with no significant difference between the number of exposures ( P = 0...
September 1, 2018: Journal of Virology
Ruth Pereira, David A Ludwig, Sunil Mathew, Claudia Flores, Sady Dominguez, Ivan Gonzalez, Delia Rivera-Hernandez, Gwendolyn B Scott, Charles D Mitchell
Background: Less than optimal adherence with antiretroviral therapy occurs commonly among human immunodeficiency virus HIV)-infected youth. In this study, our object was to identify patterns in the prefailure measurement of viral load (VL) that can reliably predict virological failure (VF) in HIV perinatally infected youth on highly active antiretroviral therapy (HAART). Methods: We conducted a retrospective chart review of HIV-infected youth with low-level viremia (LLV), defined as an HIV VL between the lower limits of detection (20-75 copies/mL) and 1000 copies/mL...
May 19, 2018: Journal of the Pediatric Infectious Diseases Society
Palsamy Periyasamy, Annadurai Thangaraj, Ming-Lei Guo, Guoku Hu, Shannon Callen, Shilpa Buch
The present study demonstrates HIV-1 Tat-mediated epigenetic downregulation of microglial miR-124 and its association with microglial activation. Exposure of mouse primary microglia isolated from newborn pups of either sex to HIV-1 Tat resulted in decreased expression of primary miR-124-1, primary miR-124-2 as well as the mature miR-124. In parallel, HIV-1 Tat exposure to mouse primary microglial cells resulted in increased expression of DNA methylation enzymes, such as DNMT1, DNMT3A, and DNMT3B, which were also accompanied by increased global DNA methylation...
June 6, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Rajnish S Dave, Pooja Jain, Siddappa N Byrareddy
A hallmark feature of follicular dendritic cells (FDCs) within the lymph nodes (LNs) is their ability to retain antigens and virions for a prolonged duration. FDCs in the cervical lymph nodes (CLNs) are particularly relevant in elucidating human immunodeficiency virus (HIV)-1 infection within the cerebrospinal fluid (CSF) draining LNs of the central nervous system. The FDC viral reservoir in both peripheral LN and CLN, like the other HIV reservoirs, contribute to both low-level viremia and viral resurgence upon cessation or failure of combined antiretroviral therapy (cART)...
2018: Frontiers in Immunology
Marta E Bull, Caroline Mitchell, Jaime Soria, Sheila Styrchak, Corey Williams-Wietzikoski, Jillian Legard, Jennifer McKernan-Mullin, Kelli Kraft, Frankline Onchiri, Joshua Stern, Sarah Holte, Kevin J Ryan, Edward P Acosta, Alberto La Rosa, Robert W Coombs, Eduardo Ticona, Lisa M Frenkel
OBJECTIVE: During effective antiretroviral therapy (ART), low-level plasma viremias (LLV) (HIV RNA >30-1000 copies/ml) can be detected intermittently. We hypothesized that systemic inflammation is associated with LLV either as the cause or result of the production of virions from clonally expanded cells. METHODS: Prospective cohort study of HIV-infected ART-naive Peruvians enrolled prior to ART and followed for 2 years. Plasma HIV RNA and peripheral blood mononuclear cell (PBMC) HIV DNA concentrations were quantified pre-ART from individuals whose plasma HIV RNA was ART-suppressed...
July 17, 2018: AIDS
Eva Poveda, Manuel Crespo
The level of HIV-RNA in plasma (HIV viral load) is the main marker used to monitor the virological response to antiretroviral therapy (ART) in HIV-infected patients. The threshold used to define virological suppression has historically been dictated by the limits of detection of the commercial assays used to quantify the plasma viral load. Thus, as more sensitive assays have proliferated and become more widely available, the definition has shifted from < 400 cop/mL with the first generation assays, to < 50 cop/mL, to < 20 cop/mL currently...
January 2018: AIDS Reviews
Enrique Bernal, Jose M Gómez, Inma Jarrín, Alfredo Cano, Angeles Muñoz, Antonia Alcaraz, Arkaitz Imaz, Jose A Iribarren, María Rivero, Piedad Arazo, Félix Gutiérrez
BACKGROUND: The objective of this study was to investigate the long-term impact of low-level viremia (LLV) on all-cause mortality, AIDS and non-AIDS events (NAEs), and virological failure in patients receiving antiretroviral therapy (ART). METHODS: We analyzed ART-naive adults from the cohort of the Spanish AIDS Research Network (CoRIS) who initiated ART from 2004 to 2015 and achieved plasma viral load (VL) below 50 copies per milliliter. LLV50-199 was defined as 2 consecutive VL between 50 and 199 copies per milliliter, and LLV200-499 as 2 consecutive VL between 50 and 499 copies per milliliter with at least one between 200 and 499 copies per milliliter...
July 1, 2018: Journal of Acquired Immune Deficiency Syndromes: JAIDS
Ann J Hessell, Mariya B Shapiro, Rebecca Powell, Delphine C Malherbe, Sean P McBurney, Shilpi Pandey, Tracy Cheever, William F Sutton, Christoph Kahl, Byung Park, Susan Zolla-Pazner, Nancy L Haigwood
A high level of V1V2-specific IgG antibodies in vaccinees' sera was the only independent variable that correlated with a reduced risk of HIV acquisition in the RV144 clinical trial. In contrast, IgG avidity, antibody neutralization, and antibody-dependent cellular cytotoxicity each failed as independent correlates of infection. Extended analyses of RV144 samples demonstrated antiviral activity of V1V2-specific vaccine-induced antibodies. V2-specific antibodies have also been associated with protection from SIV, and the V2i-specific subset of human monoclonal antibodies (mAbs), while poor neutralizers, mediate Fc-dependent antiviral functions in vitro The objective of this study was to determine the protective efficacy of a V2i-specific human mAb 830A against mucosal SHIV challenge...
March 7, 2018: Journal of Virology
Mohammad Arif Rahman, Katherine M McKinnon, Tatiana S Karpova, David A Ball, David J Venzon, Wenjin Fan, Guobin Kang, Qingsheng Li, Marjorie Robert-Guroff
Follicular CD8+ T (fCD8) cells reside within B cell follicles and are thought to be immune-privileged sites of HIV/SIV infection. We have observed comparable levels of fCD8 cells between chronically SIV-infected rhesus macaques with low viral loads (LVL) and high viral loads (HVL), raising the question concerning their contribution to viremia control. In this study, we sought to clarify the role of SIV-specific fCD8 cells in lymph nodes during the course of SIV infection in rhesus macaques. We observed that fCD8 cells, T follicular helper (Tfh) cells, and T follicular regulatory cells (Tfreg) were all elevated in chronic SIV infection...
April 15, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Amedeo Ferdinando Capetti, Maria Vittoria Cossu, Gaetana Sterrantino, Giorgio Barbarini, Simona Di Giambenedetto, Giuseppe Vittorio De Socio, GianCarlo Orofino, Antonio Di Biagio, Benedetto M Celesia, Stefano Rusconi, Barbara Argenteri, Giuliano Rizzardini
BACKGROUND: Data from clinical studies confirm the efficacy of switching to dolutegravir (DTG) plus rilpivirine (RPV) in selected patients. OBJECTIVE: The primary objective is to report the 96-week virological suppression in our cohort, assessing the durability of this strategy in complicated situations. The secondary objective is to describe the safety and metabolic profile. METHODS: All patients who had switched to DTG plus RPV between October 1, 2014, and September 30, 2015, were analyzed using a retrospective-prospective design, approved by ethics committees...
August 2018: Annals of Pharmacotherapy
Dionysios C Watson, Eirini Moysi, Antonio Valentin, Cristina Bergamaschi, Santhi Devasundaram, Sotirios P Fortis, Jenifer Bear, Elena Chertova, Julian Bess, Ray Sowder, David J Venzon, Claire Deleage, Jacob D Estes, Jeffrey D Lifson, Constantinos Petrovas, Barbara K Felber, George N Pavlakis
B cell follicles in secondary lymphoid tissues represent an immune privileged sanctuary for AIDS viruses, in part because cytotoxic CD8+ T cells are mostly excluded from entering the follicles that harbor infected T follicular helper (TFH) cells. We studied the effects of native heterodimeric IL-15 (hetIL-15) treatment on uninfected rhesus macaques and on macaques that had spontaneously controlled SHIV infection to low levels of chronic viremia. hetIL-15 increased effector CD8+ T lymphocytes with high granzyme B content in blood, mucosal sites and lymph nodes, including virus-specific MHC-peptide tetramer+ CD8+ cells in LN...
February 2018: PLoS Pathogens
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