scholarly journals Superior Efficacy of a Human Immunodeficiency Virus Vaccine Combined with Antiretroviral Prevention in Simian-Human Immunodeficiency Virus-Challenged Nonhuman Primates

2016 ◽  
Vol 90 (11) ◽  
pp. 5315-5328 ◽  
Author(s):  
Roger Le Grand ◽  
Nathalie Dereuddre-Bosquet ◽  
Stefania Dispinseri ◽  
Leslie Gosse ◽  
Delphine Desjardins ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Nonhuman Primate ◽  
Synergistic Effects ◽  
Risk Of Infection ◽  
Total Risk ◽  
Primate Model ◽  
Increased Risk ◽  
Immunodeficiency Virus ◽  
Biomedical Prevention ◽  
The Impact

ABSTRACTAlthough vaccines and antiretroviral (ARV) prevention have demonstrated partial success against human immunodeficiency virus (HIV) infection in clinical trials, their combined introduction could provide more potent protection. Furthermore, combination approaches could ameliorate the potential increased risk of infection following vaccination in the absence of protective immunity. We used a nonhuman primate model to determine potential interactions of combining a partially effective ARV microbicide with an envelope-based vaccine. The vaccine alone provided no protection from infection following 12 consecutive low-dose intravaginal challenges with simian-HIV strain SF162P3, with more animals infected compared to naive controls. The microbicide alone provided a 68% reduction in the risk of infection relative to that of the vaccine group and a 45% reduction relative to that of naive controls. The vaccine-microbicide combination provided an 88% reduction in the per-exposure risk of infection relative to the vaccine alone and a 79% reduction relative to that of the controls. Protected animals in the vaccine-microbicide group were challenged a further 12 times in the absence of microbicide and demonstrated a 98% reduction in the risk of infection. A total risk reduction of 91% was observed in this group over 24 exposures (P= 0.004). These important findings suggest that combined implementation of new biomedical prevention strategies may provide significant gains in HIV prevention.IMPORTANCEThere is a pressing need to maximize the impact of new biomedical prevention tools in the face of the 2 million HIV infections that occur each year. Combined implementation of complementary biomedical approaches could create additive or synergistic effects that drive improved reduction of HIV incidence. Therefore, we assessed a combination of an untested vaccine with an ARV-based microbicide in a nonhuman primate vaginal challenge model. The vaccine alone provided no protection (and may have increased susceptibility to a simian-HIV vaginal challenge), while the microbicide reduced the infection risk compared to that of vaccinated and naive animals. Importantly, the combined interventions provided the greatest level of protection, which was sustained following withdrawal of the microbicide. The data suggest that provision of ARV prophylaxis during vaccination reduces the potential for unexpected increased risks of infection following immunization and augments vaccine efficacy. These findings are important for the potential adoption of ARV prophylaxis as the baseline intervention for future HIV/AIDS vaccines.

scholarly journals Simian-Human Immunodeficiency Virus Containing a Human Immunodeficiency Virus Type 1 Subtype-E Envelope Gene: Persistent Infection, CD4+ T-Cell Depletion, and Mucosal Membrane Transmission in Macaques

2000 ◽  
Vol 74 (17) ◽  
pp. 7851-7860 ◽  
Author(s):  
Sunee Himathongkham ◽  
Nancy S. Halpin ◽  
Jinling Li ◽  
Michael W. Stout ◽  
Christopher J. Miller ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cell ◽  
Nonhuman Primate ◽  
Coreceptor Usage ◽  
Nonhuman Primate Model ◽  
Primate Model ◽  
Recombinant Clone ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT The envelope (env) glycoprotein of human immunodeficiency virus type 1 (HIV-1) determines several viral properties (e.g., coreceptor usage, cell tropism, and cytopathicity) and is a major target of antiviral immune responses. Most investigations on env have been conducted on subtype-B viral strains, prevalent in North America and Europe. Our study aimed to analyze env genes of subtype-E viral strains, prevalent in Asia and Africa, with a nonhuman primate model for lentivirus infection and AIDS. To this end, we constructed a simian immunodeficiency virus/HIV-1 subtype-E (SHIV) recombinant clone by replacing the env ectodomain of the SHIV-33 clone with theenv ectodomain from the subtype-E strain HIV-1CAR402, which was isolated from an individual in the Central African Republic. Virus from this recombinant clone, designated SHIV-E-CAR, replicated efficiently in macaque peripheral blood mononuclear cells. Accordingly, juvenile macaques were inoculated with cell-free SHIV-E-CAR by the intravenous or intravaginal route; virus replicated in these animals but did not produce hematological abnormalities. In an attempt to elicit the pathogenic potential of the recombinant clone, we serially passaged this viral clone via transfusion of blood and bone marrow through juvenile macaques to produce SHIV-E-P4 (fourth-passage virus). The serially passaged virus established productive infection and CD4+ T-cell depletion in juvenile macaques inoculated by either the intravenous or the intravaginal route. Determination of the coreceptor usage of SHIV-E-CAR and serially passaged SHIV-E-P4 indicated that both of these viruses utilized CXCR4 as a coreceptor. In summary, the serially passaged SHIV subtype-E chimeric virus will be important for studies aimed at developing a nonhuman primate model for analyzing the functions of subtype-E env genes in viral transmission and pathogenesis and for vaccine challenge experiments with macaques immunized with HIV-1 env antigens.

HUMAN IMMUNODEFICIENCY VIRUS AND PREGNANCY: PATHOMORPHOLOGICAL FEATURES AND OBSTETRIC AND GYNECOLOGICAL TACTICS

2021 ◽  
pp. 178-184
Author(s):  
Spiridenko G.Yu. ◽  
Petrov Yu.A. ◽  
Bragina T.V.
Keyword(s):  
Human Immunodeficiency Virus ◽  
Viral Load ◽  
Antiretroviral Therapy ◽  
Hiv Infection ◽  
Reverse Transcriptase ◽  
Reproductive Age ◽  
Risk Of Infection ◽  
Pathological Effect ◽  
Increased Risk ◽  
Immunodeficiency Virus

Currently, due to the increase in the incidence of HIV infection in women of reproductive age, the number of desired pregnancies in such patients has increased. This makes it necessary to study the pathological effect of the human immunodeficiency virus on the placenta, fetus and the female body as a whole. HIV belongs to retroviruses and contributes to the discoordination of a woman's immune mechanisms. Using the gp41 and gp120 glycoproteins, reverse transcriptase, integrase, and protease, the virus destroys CD4 cells and increases the viral load. It founded that the risk of infection of the fetus decreases from 45% to 1% with HIV infection before pregnancy and with antiretroviral therapy throughout its duration. Vertical infection is possible in the intrauterine, intranatal and postnatal periods, the main of which is the period of childbirth-up to 70%. Viral, maternal, placental, fetal, obstetric and neonatal factors contribute to an increased risk of transmission of the pathogen to the fetus. High viral load and antiretroviral therapy lead in the 3rd trimester of pregnancy to the development of chronic placental insufficiency due to the formation of focal and diffuse deciduitis, membranitis, intervillusitis and chorionamnionitis and damage to the hematoplacental barrier. Early diagnosis before 12 weeks of gestation, timely therapy with nucleoside and non-nucleoside reverse transcriptase inhibitors, as well as protease inhibitors during pregnancy, childbirth and in the postpartum period are the main aspects of preventing HIV infection and further disorders of the child's growth and development. The timely choice of the method of delivery, indications and contraindications to delivery through the natural birth canal helps to reduce the risk of infection in a particularly dangerous period - the intrapartum.

scholarly journals Hemozoin Differentially Regulates Proinflammatory Cytokine Production in Human Immunodeficiency Virus-Seropositive and -Seronegative Women with Placental Malaria

2004 ◽  
Vol 72 (12) ◽  
pp. 7022-7029 ◽  
Author(s):  
Julie M. Moore ◽  
Sujittra Chaisavaneeyakorn ◽  
Douglas J. Perkins ◽  
Caroline Othoro ◽  
Juliana Otieno ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Immune Function ◽  
Cytokine Production ◽  
Placental Malaria ◽  
High Density ◽  
Increased Risk ◽  
Tnf Α ◽  
Immunodeficiency Virus ◽  
Ifn Γ ◽  
The Impact

ABSTRACT Pregnant women are at an increased risk for malarial infection. Plasmodium falciparum accumulates in the placenta and is associated with dysregulated immune function and poor birth outcomes. Malarial pigment (hemozoin) also accumulates in the placenta and may modulate local immune function. In this study, the impact of hemozoin on cytokine production by intervillous blood mononuclear cells from malaria-infected placentas was investigated. There was a dose-dependent, suppressive effect of hemozoin on production of gamma interferon (IFN-γ), with less of an effect on tumor necrosis factor alpha (TNF-α) and interleukin-10, in human immunodeficiency virus-seronegative (HIV−) women. In contrast, IFN-γ and TNF-α production tended to increase in HIV-seropositive women with increasing hemozoin levels. Production patterns of cytokines, especially IFN-γ in HIV− women, followed different trends as a function of parasite density and hemozoin level. The findings suggest that the influences of hemozoin accumulation and high-density parasitemia on placental cytokine production are not equivalent and may involve different mechanisms, all of which may operate differently in the context of HIV infection. Cytokine production dysregulated by accumulation of hemozoin or high-density parasitemia may induce pathology and impair protective immunity in HIV-infected and -uninfected women.

scholarly journals Mutational Alteration of Human Immunodeficiency Virus Type 1 Vif Allows for Functional Interaction with Nonhuman Primate APOBEC3G

2006 ◽  
Vol 80 (12) ◽  
pp. 5984-5991 ◽  
Author(s):  
Bärbel Schröfelbauer ◽  
Tilo Senger ◽  
Gerard Manning ◽  
Nathaniel R. Landau
Keyword(s):  
Human Immunodeficiency Virus ◽  
Amino Acid ◽  
Nonhuman Primate ◽  
Virus Assembly ◽  
Primate Model ◽  
Mutant Proteins ◽  
Conserved Sequence ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Human APOBEC3F (hA3F) and APOBEC3G (hA3G) are antiretroviral cytidine deaminases that can be encapsidated during virus assembly to catalyze C→U deamination of the viral reverse transcripts in the next round of infection. Lentiviruses such as human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) have evolved the accessory protein Vif to induce their degradation before packaging. HIV type 1 (HIV-1) Vif counteracts hA3G but not rhesus macaque APOBEC3G (rhA3G) or African green monkey (AGM) APOBEC3G (agmA3G) because of a failure to bind the nonhuman primate proteins. The species specificity of the interaction is controlled by amino acid 128, which is aspartate in hA3G and lysine in rhA3G. With the objective of overcoming this species restriction, mutations were introduced into HIV-1 Vif at amino acid positions that differed in charge between HIV-1 Vif and SIV Vif. The mutant proteins were tested for the ability to counteract hA3G, rhA3G, and agmA3G. Alteration of the conserved sequence at positions 14 to 17 from DRMR to SERQ, which is the sequence in AGM Vif, caused HIV-1 Vif to functionally interact with rhA3G and agmA3G. Mutation of three residues to the sequence SEMQ allowed interaction with rhA3G. SEMQ Vif also counteracted D128K mutant hA3G and wild-type hA3G. Introduction of the sequence into an infectious molecular HIV-1 clone allowed the virus to replicate productively in human cells that expressed rhA3G or hA3G. These findings provide insight into the interaction of Vif with A3G and are a step toward the development of a novel primate model for AIDS.

scholarly journals Simian-Tropic HIV as a Model To Study Drug Resistance against Integrase Inhibitors

2015 ◽  
Vol 59 (4) ◽  
pp. 1942-1949 ◽  
Author(s):  
Melissa Wares ◽  
Said Hassounah ◽  
Thibault Mesplède ◽  
Paul A. Sandstrom ◽  
Mark A. Wainberg
Keyword(s):  
Drug Resistance ◽  
Nonhuman Primate ◽  
Hiv Treatment ◽  
Replication Capacity ◽  
Primate Model ◽  
Primary Resistance ◽  
Immunodeficiency Virus ◽  
The Impact ◽  
Hiv 1

ABSTRACTDrug resistance represents a key aspect of human immunodeficiency virus (HIV) treatment failure. It is important to develop nonhuman primate models for studying issues of drug resistance and the persistence and transmission of drug-resistant viruses. However, relatively little work has been conducted using either simian immunodeficiency virus (SIV) or SIV/HIV recombinant viruses for studying resistance against integrase strand transfer inhibitors (INSTIs). Here, we used a T-cell-tropic SIV/HIV recombinant virus in which the capsid andvifregions of HIV-1 were replaced with their SIV counterparts (simian-tropic HIV-1 [stHIV-1](SCA,SVIF)) to study the impact of a number of drug resistance substitutions in the integrase coding region at positions E92Q, G118R, E138K, Y143R, S153Y, N155H, and R263K on drug resistance, viral infectivity, and viral replication capacity. Our results show that each of these substitutions exerted effects that were similar to their effects in HIV-1. Substitutions associated with primary resistance against dolutegravir were more detrimental to stHIV-1(SCA,SVIF)infectiousness than were resistance substitutions associated with raltegravir and elvitegravir, consistent with data that have been reported for HIV-1. These findings support the role of stHIV-1(SCA,SVIF)as a useful model with which to evaluate the role of INSTI resistance substitutions on viral persistence, transmissibility, and pathogenesis in a nonhuman primate model.

Breaking Bad News — Skills and Evidence

2009 ◽  
Vol 2 (10) ◽  
pp. 605-612 ◽  
Author(s):  
Jill Thistlethwaite
Keyword(s):  
Human Immunodeficiency Virus ◽  
Communication Skills ◽  
Human Immunodeficiency Virus Status ◽  
Bad News ◽  
Breaking Bad News ◽  
Breaking Bad ◽  
Immunodeficiency Virus ◽  
The Future ◽  
The Patient’S View ◽  
The Impact

Bad or unfavorable news may be defined as ‘any news that drastically and negatively alters the patient's view of her or his future’( Buckman 1992 ). When GPs talk about breaking bad news, they usually mean telling patients that they have cancer, though in fact similar communication skills may be employed when informing patients about a positive human immunodeficiency virus status, or that a relative has died. Of key importance in the process is the doctor gaining an understanding of what the patient's view of the future is or was — the expectation that now might not be met. A doctor should not assume the impact of the diagnosis without exploring the patient's worldview.

scholarly journals The Potential Role of Nonhuman Primate Models to Better Comprehend Early Life Immunity and Maternal Antibody Transfer

Vaccines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 306
Author(s):  
Julie Sartoretti ◽  
Christiane S. Eberhardt
Keyword(s):  
Nonhuman Primate ◽  
Early Life ◽  
Cost Effective ◽  
Maternal Antibody ◽  
Maternal Antibodies ◽  
Immunological Methods ◽  
Human Pathogens ◽  
Childhood Immunization ◽  
Primate Model ◽  
The Impact

Early life immunity is a complex field of research and there are still gaps in knowledge regarding the detailed mechanism of maternal antibody transfer, the impact of maternal antibodies on infant vaccine responses and the ontogeny of human early life immunity. A comprehensive understanding is necessary to identify requirements for early life vaccines and to improve early childhood immunization. New immunological methods have facilitated performing research in the youngest, however, some questions can only be addressed in animal models. To date, mostly murine models are used to study neonatal and infant immunity since they are well-described, easy to use and cost effective. Given their limitations especially in the transfer biology of maternal antibodies and the lack of infectivity of numerous human pathogens, this opinion piece discusses the potential and prerequisites of the nonhuman primate model in studying early life immunity and maternal antibody transfer.

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