scholarly journals Phylogenetic Methods Inconsistently Predict the Direction of HIV Transmission Among Heterosexual Pairs in the HPTN 052 Cohort

2018 ◽  
Vol 220 (9) ◽  
pp. 1406-1413 ◽  
Author(s):  
Rebecca Rose ◽  
Matthew Hall ◽  
Andrew D Redd ◽  
Susanna Lamers ◽  
Andrew E Barbier ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Maximum Parsimony ◽  
Hiv Transmission ◽  
Index Patient ◽  
Single Pair ◽  
Bootstrap Analysis ◽  
Phylogenetic Methods ◽  
Immunodeficiency Virus ◽  
Ancestral Node ◽  
Time Point

AbstractBackgroundWe evaluated use of phylogenetic methods to predict the direction of human immunodeficiency virus (HIV) transmission.MethodsFor 33 pairs of HIV-infected patients (hereafter, “index patients”) and their partners who acquired genetically linked HIV infection during the study, samples were collected from partners and index patients close to the time when the partner seroconverted (hereafter, “SC samples”); for 31 pairs, samples collected from the index patient at an earlier time point (hereafter, “early index samples”) were also available. Phylogenies were inferred using env next-generation sequences (1 tree per pair/subtype). The direction of transmission (DoT) predicted from each tree was classified as correct or incorrect on the basis of which sequences (those from the index patient or the partner) were closest to the root. DoT was also assessed using maximum parsimony to infer ancestral node states for 100 bootstrap trees.ResultsDoT was predicted correctly for both single-pair and subtype-specific trees in 22 pairs (67%) by using SC samples and in 23 pairs (74%) by using early index samples. DoT was predicted incorrectly for 4 pairs (15%) by using SC or early index samples. In the bootstrap analysis, DoT was predicted correctly for 18 pairs (55%) by using SC samples and for 24 pairs (73%) by using early index samples. DoT was predicted incorrectly for 7 pairs (21%) by using SC samples and for 4 pairs (13%) by using early index samples.ConclusionsPhylogenetic methods based solely on the tree topology of HIV env sequences, particularly without consideration of phylogenetic uncertainty, may be insufficient for determining DoT.

scholarly journals Novel Strategy To Adapt Simian-Human Immunodeficiency Virus E1 Carryingenvfrom an RV144 Volunteer to Rhesus Macaques: Coreceptor Switch and Final Recovery of a Pathogenic Virus with Exclusive R5 Tropism

2018 ◽  
Vol 92 (14) ◽  
Author(s):  
Hanna B. Scinto ◽  
Sandeep Gupta ◽  
Swati Thorat ◽  
Muhammad M. Mukhtar ◽  
Anthony Griffiths ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Placebo Recipient ◽  
T Cell ◽  
Hiv Transmission ◽  
Rhesus Macaques ◽  
Phase Iii ◽  
Immunodeficiency Virus ◽  
Coreceptor Switch ◽  
Novel Strategy ◽  
Hiv Acquisition

ABSTRACTThe phase III RV144 human immunodeficiency virus (HIV) vaccine trial conducted in Thailand remains the only study to show efficacy in decreasing the HIV acquisition risk. In Thailand, circulating recombinant forms of HIV clade A/E (CRF01_AE) predominate; in such viruses,envoriginates from clade E (HIV-E). We constructed a simian-human immunodeficiency virus (SHIV) chimera carryingenvisolated from an RV144 placebo recipient in the SHIV-1157ipd3N4 backbone. The latter contains long terminal repeats (LTRs) with duplicated NF-κB sites, thus resembling HIV LTRs. We devised a novel strategy to adapt the parental infectious molecular clone (IMC), R5 SHIV-E1, to rhesus macaques: the simultaneous depletion of B and CD8+cells followed by the intramuscular inoculation of proviral DNA and repeated administrations of cell-free virus. High-level viremia and CD4+T-cell depletion ensued. Passage 3 virus unexpectedly caused acute, irreversible CD4+T-cell loss; the partially adapted SHIV had become dual tropic. Virus and IMCs with exclusive R5 tropism were reisolated from earlier passages, combined, and used to complete adaptation through additional macaques. The final isolate, SHIV-E1p5, remained solely R5 tropic. It had a tier 2 neutralization phenotype, was mucosally transmissible, and was pathogenic. Deep sequencing revealed 99% Env amino acid sequence conservation; X4-only and dual-tropic strains had evolved independently from an early branch of parental SHIV-E1. To conclude, our primate model data reveal that SHIV-E1p5 recapitulates important aspects of HIV transmission and pathobiology in humans.IMPORTANCEUnderstanding the protective principles that lead to a safe, effective vaccine against HIV in nonhuman primate (NHP) models requires test viruses that allow the evaluation of anti-HIV envelope responses. Reduced HIV acquisition risk in RV144 has been linked to nonneutralizing IgG antibodies with a range of effector activities. Definitive experiments to decipher the mechanisms of the partial protection observed in RV144 require passive-immunization studies in NHPs with a relevant test virus. We have generated such a virus by insertingenvfrom an RV144 placebo recipient into a SHIV backbone with HIV-like LTRs. The final SHIV-E1p5 isolate, grown in rhesus monkey peripheral blood mononuclear cells, was mucosally transmissible and pathogenic. Earlier SHIV-E passages showed a coreceptor switch, again mimicking HIV biology in humans. Thus, our series of SHIV-E strains mirrors HIV transmission and disease progression in humans. SHIV-E1p5 represents a biologically relevant tool to assess prevention strategies.

scholarly journals DC-SIGN Interactions with Human Immunodeficiency Virus: Virus Binding and Transfer Are Dissociable Functions

2001 ◽  
Vol 75 (21) ◽  
pp. 10523-10526 ◽  
Author(s):  
Stefan Pöhlmann ◽  
George J. Leslie ◽  
Terri G. Edwards ◽  
Todd Macfarlan ◽  
Jacqueline D. Reeves ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Cell Surface ◽  
Hiv Transmission ◽  
Virus Transmission ◽  
Underlying Mechanism ◽  
Virus Binding ◽  
Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Virus

ABSTRACT The C-type lectins DC-SIGN and DC-SIGNR capture and transfer human immunodeficiency virus (HIV) to susceptible cells, although the underlying mechanism is unclear. Here we show that DC-SIGN/DC-SIGNR-mediated HIV transmission involves dissociable binding and transfer steps, indicating that efficient virus transmission is not simply due to tethering of virus to the cell surface.

Immunocompromised Hosts and Microorganism-Specific Syndromes

2016 ◽  
pp. 475-490
Author(s):  
Pritish K. Tosh ◽  
M. Rizwan Sohail
Keyword(s):  
Human Immunodeficiency Virus ◽  
Herpes Simplex ◽  
Occupational Exposure ◽  
Male Circumcision ◽  
Hiv Transmission ◽  
Sexual Transmission ◽  
Intravenous Drug ◽  
Immunodeficiency Virus ◽  
Immunocompromised Hosts ◽  
Intravenous Drug Injection

Human immunodeficiency virus (HIV) is transmitted sexually, perinatally, through parenteral inoculation (eg, intravenous drug injection, occupational exposure), through blood products, and, less commonly, through donated organs or semen. Sexual transmission is the most common means of infection. Conditions that may increase the risk of sexually acquiring HIV infection include traumatic intercourse (ie, receptive anal), ulcerative genital infections (including syphilis, herpes simplex, and chancroid), and lack of male circumcision. The proper use of latex condoms substantially reduces the risk of HIV transmission.

scholarly journals Modelling the epidemiologic impact of achieving UNAIDS fast-track 90-90-90 and 95-95-95 targets in South Africa

2019 ◽  
Vol 147 ◽  
Author(s):  
N. N. Abuelezam ◽  
A. W. McCormick ◽  
E. D. Surface ◽  
T. Fussell ◽  
K. A. Freedberg ◽  
...  
Keyword(s):  
South Africa ◽  
Human Immunodeficiency Virus ◽  
Fast Track ◽  
Viral Suppression ◽  
Hiv Transmission ◽  
Hiv Positive ◽  
Agent Based ◽  
Percentage Points ◽  
Immunodeficiency Virus ◽  
The Continuum

AbstractUNAIDS established fast-track targets of 73% and 86% viral suppression among human immunodeficiency virus (HIV)-positive individuals by 2020 and 2030, respectively. The epidemiologic impact of achieving these goals is unknown. The HIV-Calibrated Dynamic Model, a calibrated agent-based model of HIV transmission, is used to examine scenarios of incremental improvements to the testing and antiretroviral therapy (ART) continuum in South Africa in 2015. The speed of intervention availability is explored, comparing policies for their predicted effects on incidence, prevalence and achievement of fast-track targets in 2020 and 2030. Moderate (30%) improvements in the continuum will not achieve 2020 or 2030 targets and have modest impacts on incidence and prevalence. Improving the continuum by 80% and increasing availability reduces incidence from 2.54 to 0.80 per 100 person-years (−1.73, interquartile range (IQR): −1.42, −2.13) and prevalence from 26.0 to 24.6% (−1.4 percentage points, IQR: −0.88, −1.92) from 2015 to 2030 and achieves fast track targets in 2020 and 2030. Achieving 90-90-90 in South Africa is possible with large improvements to the testing and treatment continuum. The epidemiologic impact of these improvements depends on the balance between survival and transmission benefits of ART with the potential for incidence to remain high.

scholarly journals Epidemiology of Human Immunodeficiency Virus in the United States

2007 ◽  
Vol 20 (3) ◽  
pp. 478-488 ◽  
Author(s):  
Susan Hariri ◽  
Matthew T. McKenna
Keyword(s):  
United States ◽  
Human Immunodeficiency Virus ◽  
Hiv Infection ◽  
Hiv Transmission ◽  
The United States ◽  
Population Based ◽  
True Incidence ◽  
Immunodeficiency Virus ◽  
Sex With Men ◽  
Fundamental Shift

SUMMARY The human immunodeficiency virus (HIV) epidemic emerged in the early 1980s with HIV infection as a highly lethal disease among men who have sex with men and among frequent recipients of blood product transfusions. Advances in the treatment of HIV infection have resulted in a fundamental shift in its epidemiology, to a potentially chronic and manageable condition. However, challenges in the prevention of this infection remain. In particular, increasing evidence suggests that transmission of drug-resistant virus is becoming more common and that the epidemic is having a profound impact on morbidity and mortality in ethnic and racial minority subgroups in the United States. New population-based data collection systems designed to describe trends in behaviors associated with HIV transmission and better methods for measuring the true incidence of transmission will better elucidate the characteristics of HIV infection in the United States and inform future public health policies.

scholarly journals Plasmodium falciparum Infection Does Not Affect Human Immunodeficiency Virus Viral Load in Coinfected Rwandan Adults

2014 ◽  
Vol 1 (2) ◽  
Author(s):  
Krishanthi Subramaniam ◽  
Rebeca M. Plank ◽  
Nina Lin ◽  
Adam Goldman-Yassen ◽  
Emil Ivan ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Viral Load ◽  
Malaria Infection ◽  
Hiv Transmission ◽  
Falciparum Infection ◽  
Resistance Testing ◽  
Plasmodium Falciparum Infection ◽  
Immunodeficiency Virus

Abstract Background.  Plasmodium falciparum infection has been reported to increase human immunodeficiency virus (HIV) viral load (VL), which can facilitate HIV transmission. We prospectively studied the impact of mild P falciparum coinfection on HIV VL in Rwanda. Methods.  We measured plasma HIV VL at presentation with malaria infection and weekly for 4 weeks after artemether-lumefantrine treatment in Rwandan adults infected with HIV with P falciparum malaria. Regression analyses were used to examine associations between malaria infection and HIV VL changes. Samples with detectable virus underwent genotypic drug-resistance testing. Results.  We enrolled 28 HIV-malaria coinfected patients and observed 27 of them for 5 weeks. Three patients (11%) were newly diagnosed with HIV. Acute P falciparum infection had no significant effect on HIV VL slope over 28 days of follow-up. Ten patients with VL <40 copies/mL at enrollment maintained viral suppression throughout. Seventeen patients had a detectable VL at enrollment including 9 (53%) who reported 100% adherence to ARVs; 3 of these had detectable genotypic drug resistance. Conclusions.  Unlike studies from highly malaria-endemic areas, we did not identify an effect of P falciparum infection on HIV VL; therefore, malaria is not likely to increase HIV-transmission risk in our setting. However, routine HIV testing should be offered to adults presenting with acute malaria in Rwanda. Most importantly, we identified a large percentage of patients with detectable HIV VL despite antiretroviral (ARV) therapy. Some of these patients had HIV genotypic drug resistance. Larger studies are needed to define the prevalence and factors associated with detectable HIV VL in patients prescribed ARVs in Rwanda.

scholarly journals Association of Selected Phenotypic Markers of Lymphocyte Activation and Differentiation with Perinatal Human Immunodeficiency Virus Transmission and Infant Infection

2005 ◽  
Vol 12 (5) ◽  
pp. 622-631 ◽  
Author(s):  
John S. Lambert ◽  
Jack Moye ◽  
Susan F. Plaeger ◽  
E. Richard Stiehm ◽  
James Bethel ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
Hiv Transmission ◽  
Virus Transmission ◽  
Lymphocyte Activation ◽  
Phenotypic Markers ◽  
Perinatal Hiv ◽  
Hla Dr ◽  
Increased Risk ◽  
Immunodeficiency Virus

ABSTRACT This study of a subset of women and infants participating in National Institutes of Health Pediatric AIDS Clinical Trials Group protocol 185 evaluated lymphocyte phenotypic markers of immune activation and differentiation to determine their association with the likelihood of human immunodeficiency virus (HIV) transmission from the women to their infants and the potential for early identification and/or prognosis of infection in the infants. Lymphocytes from 215 human immunodeficiency virus type 1 (HIV)-infected women and 192 of their infants were analyzed by flow cytometry with an extended three-color panel of monoclonal antibodies. Women who did not transmit to their infants tended to have higher CD4+ T cells. Most notably, levels of total CD8+ T cells and CD8+ CD38+ cells made significant independent contributions to predicting the risk of mother-to-child transmission. Adjusting for HIV-1 RNA level at entry, a one percentage-point increase in these marker combinations was associated with a nine percent increase in the likelihood of maternal transmission. Total as well as naïve CD4+ T cells were significantly higher in uninfected than infected infants. Total CD8+ cells, as well as CD8+cells positive for HLA-DR+, CD45 RA+ HLA-DR+, and CD28+ HLA-DR+ were elevated in infected infants. Detailed immunophenotyping may be helpful in predicting which pregnant HIV-infected women are at increased risk of transmitting HIV to their infants. Increasing differences in lymphocyte subsets between infected and uninfected infants became apparent as early as six weeks of age. Detailed immunophenotyping may be useful in supporting the diagnosis of HIV infection in infants with perinatal HIV exposure.

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