Characterization of drug resistance and the defective HIV reservoir in virally suppressed vertically infected children in Mali

2020 ◽  
Vol 75 (5) ◽  
pp. 1272-1279
Author(s):  
Josephine Brice ◽  
Mariam Sylla ◽  
Nathalie Desire ◽  
Sophie Sayon ◽  
Fatoumata Telly ◽  
...  
Keyword(s):  
Stop Codon ◽  
Dried Blood Spots ◽  
Viral Population ◽  
Genotypic Resistance ◽  
Hiv Reservoir ◽  
Hiv Dna ◽  
Art Initiation ◽  
High Prevalence ◽  
Resistance Patterns ◽  
Hiv 1

Abstract Background In the perspective of ART-free HIV remission, vertically infected children treated with suppressive ART from early infancy represent an optimal population model to better understand the genetic complexity of the reservoir. Objectives To evaluate the proportion of defective viral population and the genotypic resistance patterns in cell-associated HIV DNA. Methods In a cohort including 93 ART-treated vertically HIV-infected (VHIV) children in Mali with plasma HIV-1 RNA ≤50 copies/mL for at least 6 months, we studied total HIV DNA, percentage of defective genomes and resistance by reverse transcriptase and protease bulk sequencing from whole blood in dried blood spots. Results Children had a median age of 9.9 years at the time of inclusion (IQR = 7.6–13.4) and 3.3 years (IQR = 2–7) at ART initiation; median ART duration was 5.5 years (IQR = 3.7–7.3). The median level of total HIV DNA was 470 copies/106 cells with one patient presenting undetectable HIV DNA (<66 copies/106 cells). We observed the presence of at least one stop codon in viruses from 34 patients (37%). The presence of stop codons was not correlated with the level of HIV DNA or duration of ART. We showed a high prevalence of HIV-1 resistance in DNA with 26% of children harbouring virus resistant to at least one NRTI and 40% to at least one NNRTI. Conclusions While these VHIV children were successfully treated for a long time, they showed high prevalence of resistance in HIV DNA and a moderate defective HIV reservoir.

scholarly journals Continuous Prophylactic Antiretrovirals/Antiretroviral Therapy Since Birth Reduces Seeding and Persistence of the Viral Reservoir in Children Vertically Infected With Human Immunodeficiency Virus

2020 ◽  
Author(s):  
Marta Massanella ◽  
Thanyawee Puthanakit ◽  
Louise Leyre ◽  
Thidarat Jupimai ◽  
Panadda Sawangsinth ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Antiretroviral Therapy ◽  
Cross Sectional Study ◽  
Viral Reservoir ◽  
Cross Sectional ◽  
Hiv Reservoir ◽  
Hiv Dna ◽  
Art Initiation ◽  
Immunodeficiency Virus ◽  
Infected Cells

Abstract Background Early antiretroviral therapy (ART) restricts the size of the human immunodeficiency virus (HIV) reservoir in infants. However, whether antiretroviral (ARV) prophylaxis given to exposed vertically infected children exerts similar effects remains unknown. Methods We measured total and integrated HIV DNA, as well as the frequency of CD4 T cells producing multiply spliced RNA (msRNA) after stimulation (inducible reservoir) in vertically infected Thai infants. Eighty-five infants were followed longitudinally for up to 3 years. We compared the size of the reservoir in children who received continuous ARV prophylaxis since birth vs those who never received or discontinued prophylaxis before initiating ART. We used samples from a cross-sectional cohort of 37 Thai children who had initiated ART within 6 months of life to validate our findings. Results Before ART, levels of HIV DNA and the frequencies of cells producing msRNA were significantly lower in infants who received continuous ARV prophylaxis since birth compared to those in whom ARV prophylaxis was discontinued or never initiated (P < .020 and P < .001, respectively). Upon ART initiation, total and integrated HIV DNA levels decayed significantly in both groups (P < .01 in all cases). Interestingly, the initial differences in the frequencies of infected cells persisted during 3 years on ART. The beneficial effect of prophylaxis on the size of the HIV reservoir was confirmed in the cross-sectional study. Importantly, no differences were observed between children who discontinued prophylactic ARVs before starting ART and those who delayed ART initiation without receiving prior prophylaxis. Conclusions Neonatal ARV prophylaxis with direct transition to ART durably limits the size of the HIV reservoir.

scholarly journals Prolonged Post-Treatment Virologic Control and Complete Seroreversion after Advanced HIV-1 Infection

2020 ◽  
Author(s):  
Analia Uruena ◽  
Isabel Cassetti ◽  
Neena Kashyap ◽  
Claire Deleage ◽  
Jacob D Estes ◽  
...  
Keyword(s):  
T Cells ◽  
Lymph Node ◽  
Mononuclear Cells ◽  
Brain Biopsy ◽  
Post Treatment ◽  
Hiv Diagnosis ◽  
Hiv Reservoir ◽  
Hiv Rna ◽  
Hiv Dna ◽  
Hiv 1

Abstract Background Possible human immunodeficiency virus (HIV)-1 clearance has been rarely reported. Here we describe a unique case of an HIV-positive, combination antiretroviral therapy (cART)-experienced woman with prior acquired immunodeficiency syndrome (AIDS) who has not experienced viral rebound for over 12 years since discontinuing cART. Methods Leukapheresis, colonoscopy, and lymph node excision were performed for detailed examination of virologic (including HIV reservoir) and immunologic features. Comparisons were made with chronically infected patients and healthy controls. Results No HIV-specific antibodies were detected in serum. Plasma HIV RNA levels were <0.2 copies/mL and, except for low-frequency HIV DNA + cells in lymph node tissue (1 copy/3 x 10 6 cells), HIV antigen could not be detected by quantitative virus outgrowth (<0.0025 infectious units/10 6 CD4 + T cells) or by most measurements of HIV RNA or DNA in blood, lymph node or gut-associated mononuclear cells. HIV-specific T-cell responses were detectable, but low. Brain imaging revealed a prior biopsy site and persistent white matter disease since 1996. HIV DNA + cells in the 1996 brain biopsy specimen confirmed her identity and initial HIV diagnosis. Conclusions This represents the first report of complete seroreversion, prolonged post-treatment virus suppression, a profoundly small HIV reservoir and persistent HIV-specific T cells in an adult with prior AIDS.

The burden of neuropsychiatric disorders in patients living with HIV-1 treated with antiretroviral therapies—A perspective from US Medicaid data

2021 ◽  
pp. 095646242110528
Author(s):  
Wing Chow ◽  
Hélène Hardy ◽  
Ji Song ◽  
Nancy Connolly ◽  
Bingcao Wu
Keyword(s):  
Antiretroviral Therapy ◽  
Primary Outcome ◽  
Neuropsychiatric Disorders ◽  
Administrative Claims ◽  
Art Initiation ◽  
Immunodeficiency Virus ◽  
High Prevalence ◽  
The Mean ◽  
Living With Hiv ◽  
Hiv 1

Background People with human immunodeficiency virus (HIV)-1 face challenges with treatment adherence for various reasons, including consideration of neuropsychiatric disorders and neuropsychiatric adverse reactions associated with antiretroviral therapy (ART). Methods A retrospective cohort study was conducted using administrative claims data from the IBM MarketScan® Multi-State Medicaid Database (1/1/2014–12/31/2017). Adults (≥18 years) diagnosed with HIV-1 and newly initiated on antiretroviral therapy with continuous health plan enrollment were included. Primary outcome was the 6-month period prevalence of neuropsychiatric events (NPEs) of interest after ART initiation. Results Among 1971 newly treated patients included in the study, mean age (standard deviation [SD]) was 38.5 (12.7) years, and 41.4% were female. During the 6 months after ART initiation, 51.4% of patients had a claim for ≥1 NPE versus 30.3% of matched patients without HIV. Among newly treated patients, the most common (≥10%) NPE claims were for depression (42.2%), anxiety (15.8%), headache (11.9%), and bipolar/manic depression (10.1%). Also in this group, the mean (SD) total all-cause healthcare cost during the 6-month post-ART initiation was $16,632 ($33,928), of which $2914 ($18,233) was NPE-related. Conclusions In summary, in this Medicaid study of people newly initiated on ART, there was a high prevalence of NPEs, and incremental NPE-associated costs were considerable.

scholarly journals Human Immunodeficiency Virus (HIV)-Antibody Repertoire Estimates Reservoir Size and Time of Antiretroviral Therapy Initiation in Virally Suppressed Perinatally HIV-Infected Children

2018 ◽  
Vol 8 (5) ◽  
pp. 433-438 ◽  
Author(s):  
Salvatore Rocca ◽  
Paola Zangari ◽  
Nicola Cotugno ◽  
Anita De Rossi ◽  
Bridget Ferns ◽  
...  
Keyword(s):  
Viral Proteins ◽  
Antibody Responses ◽  
Hiv Dna ◽  
Art Initiation ◽  
Therapy Initiation ◽  
Immunodeficiency Virus ◽  
Dna Size ◽  
Hiv 1 ◽  
Plasma Assay

Different specific antibody responses against 10 HIV-1 viral proteins detected by Western blot, plasma assay on a very small amount of plasma (20 μL) can estimate HIV-DNA size and timing of ART initiation in long-term virally suppressed children.

scholarly journals Comprehensive Characterization of HIV-1 Molecular Epidemiology and Demographic History in the Brazilian Region Most Heavily Affected by AIDS

2016 ◽  
Vol 90 (18) ◽  
pp. 8160-8168 ◽  
Author(s):  
Tiago Gräf ◽  
Hegger Machado Fritsch ◽  
Rúbia Marília de Medeiros ◽  
Dennis Maletich Junqueira ◽  
Sabrina Esteves de Matos Almeida ◽  
...  
Keyword(s):  
Molecular Epidemiology ◽  
Demographic History ◽  
Phylogenetic Analyses ◽  
Viral Population ◽  
Subtype C ◽  
Capital Cities ◽  
Subtype B ◽  
High Prevalence ◽  
Hiv 1 ◽  
South Brazil

ABSTRACTThe high incidence of AIDS cases and the dominance of HIV-1 subtype C infections are two features that distinguish the HIV-1 epidemic in the two southernmost Brazilian states (Rio Grande do Sul [RS] and Santa Catarina [SC]) from the epidemic in other parts of the country. Nevertheless, previous studies on HIV molecular epidemiology were conducted mainly in capital cities, and a more comprehensive understanding of factors driving this unique epidemic in Brazil is necessary. Blood samples were collected from individuals in 13 municipalities in the Brazilian southern region. HIV-1envandpolgenes were submitted to phylogenetic analyses for assignment of subtype, and viral population phylodynamics were reconstructed by applying Skygrid and logistic coalescent models in a Bayesian analysis. A high prevalence of subtype C was observed in all sampled locations; however, an increased frequency of recombinant strains was found in RS, with evidence for new circulating forms (CRFs). In the SC state, subtype B and C epidemics were associated with distinct exposure groups. Although logistic models estimated similar growth rates for HIV-1 subtype C (HIV-1C) and HIV-1B, a Skygrid plot reveals that the former epidemic has been expanding for a longer time. Our results highlight a consistent expansion of HIV-1C in south Brazil, and we also discuss how heterosexual and men who have sex with men (MSM) transmission chains might have impacted the current prevalence of HIV-1 subtypes in this region.IMPORTANCEThe AIDS epidemic in south Brazil is expanding rapidly, but the circumstances driving this condition are not well known. A high prevalence of HIV-1 subtype C was reported in the capital cities of this region, in contrast to the subtype B dominance in the rest of the country. This study sought to comparatively investigate the HIV-1 subtype B and C epidemics by sampling individuals from several cities in the two states with the highest AIDS incidences in Brazil. Our analyses showed distinct epidemic growth curves for the two epidemics, and we also found evidence suggesting that separate transmission chains may be impacting the viral phylodynamics and the emergence of new recombinant forms.

scholarly journals Therapeutic options in heavily pretreated HIV-1 patients based on the genotypic resistance patterns

2008 ◽  
Vol 11 (Suppl 1) ◽  
pp. P47
Author(s):  
D Paraskevis ◽  
E Magiorkinis ◽  
G Magiorkinis ◽  
V Paparizos ◽  
MC Lazanas ◽  
...  
Keyword(s):  
Therapeutic Options ◽  
Genotypic Resistance ◽  
Resistance Patterns ◽  
Heavily Pretreated ◽  
Hiv 1

Phenotypic and genotypic resistance patterns of HIV-1 isolates derived from individuals treated with didanosine and stavudine

AIDS ◽  
2000 ◽  
Vol 14 (2) ◽  
pp. F9-F15 ◽  
Author(s):  
Eoin P. Coakley ◽  
Jacqueline M. Gillis ◽  
Scott M. Hammer
Keyword(s):  
Genotypic Resistance ◽  
Resistance Patterns ◽  
Hiv 1

scholarly journals HIV reservoir size is determined prior to ART initiation and linked to CD8 T cell activation and memory expansion

2019 ◽  
Author(s):  
Genevieve E Martin ◽  
Matthew Pace ◽  
Freya Shearer ◽  
Eva Zilber ◽  
Jacob Hurst ◽  
...  
Keyword(s):  
T Cell ◽  
Hiv Infection ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cd8 T Cell ◽  
Effector Memory ◽  
Hiv Reservoir ◽  
Hiv Dna ◽  
Art Initiation ◽  
One Year

AbstractInitiation of antiretroviral therapy (ART) in early compared with chronic HIV infection is associated with a smaller HIV reservoir. This longitudinal analysis of 63 individuals who commenced ART during primary HIV infection (PHI) investigates which pre-and post-therapy factors associate most closely with reservoir size (HIV DNA) following treatment initiation during PHI. The best predictor of reservoir size at one-year was pre-ART HIV DNA which was in turn significantly associated with CD8 memory differentiation (effector memory, naïve and T-betnegEomesnegsubsets), CD8 T cell activation (CD38 expression) and PD-1 and Tim-3 expression on memory CD4 T cells. No associations were found for any immunological variables following one-year of ART. HIV reservoir size is determined around the time of ART initiation in individuals treated during PHI. CD8 T cell activation and memory expansion are linked to HIV reservoir size, suggesting the importance of the initial host-viral interplay in eventual reservoir size.

scholarly journals Characterization of viral rebounds on dual etravirine/raltegravir maintenance therapy (ANRS-163 ETRAL trial)

2020 ◽  
Vol 75 (7) ◽  
pp. 1943-1949
Author(s):  
Cathia Soulie ◽  
Lambert Assoumou ◽  
Basma Abdi ◽  
Sophie Sayon ◽  
Thuy Nguyen ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
Resistance Testing ◽  
Daily Regimen ◽  
Hiv Viral Load ◽  
Genotypic Resistance ◽  
Hiv Dna ◽  
Genotypic Resistance Testing ◽  
Hiv 1 ◽  
Switch Study

Abstract Background The ANRS-163 ETRAL trial, a switch study to an etravirine 200 mg/raltegravir 400 mg twice-daily regimen in 165 patients with HIV-1 infection, showed durable efficacy until Week 96. The aim of this work was to investigate in detail the virological rebounds (VRs), defined as at least one plasma HIV viral load (VL) >50 copies/mL. Methods Quantification of HIV-DNA level was assessed at baseline, Week 48 and Week 96 (n = 157). VLs were measured in seminal plasma at Week 48 (n = 26). Genotypic resistance testing by ultra-deep sequencing (UDS) for reverse transcriptase (RT) and integrase regions was performed at baseline and at the time of VR. Results In this study, 19 patients experienced VR, with 2 patients having virological failure (VF; two consecutive VLs >50 copies/mL). For the first patient with VF, UDS detected minority resistant variants only in RT (K103N, 9.6%; Y181C, 4.9%) at baseline. Some RT variants became dominant at VF (K101E, 86.3%; Y181C, 100.0%; G190A, 100.0%) and others emerged in integrase (Y143C, 2.4%; Q148R, 6.2%; N155H, 18.8%). For the second patient with VF, neither RT nor integrase mutations were detected at baseline and VF. Median HIV-DNA level was similar at baseline, Week 48 and Week 96 (2.17, 2.06 and 2.11 log10 copies/106 cells, respectively). Only one patient had a detectable seminal HIV VL (505 copies/mL). Conclusions The dual etravirine/raltegravir regimen as maintenance therapy was effective and the emergence of mutations in cases of VF was similar to that seen in other dual-regimen studies. No HIV-DNA level modification was evidenced by Week 96.

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