New ways of preventing HIV infection: thinking simply, simply thinking

HIV infection is the greatest health crisis in human history. It continues to spread unchecked among the poor in the developing world because we have failed to design simple preventative methods that are available and affordable to those living on under $2 a day. Five new methods are discussed. (i) A natural microbicide . Intravaginal lime or lemon juice has been used for centuries as a traditional contraceptive. The juice can also kill HIV in the laboratory, but clinical trials are needed to see if vaginal application is acceptable, safe and effective. (ii) Intravaginal oestrogen . Monkeys can be protected from Simian immunodeficiency virus (SIV) infection by keratinizing the vagina with topical oestrogen. If women take the oral contraceptive pill vaginally it retains its contraceptive efficacy, and the oestrogen it contains should thicken the vagina and protect against HIV infection. Clinical trials are needed. (iii) Male circumcision . Removal of the inner foreskin removes the main site of HIV entry into the penis, resulting in a sevenfold reduction in susceptibility to infection. The practice needs to be promoted. (iv) Post-coital penile hygiene . Wiping the penis immediately after intercourse with lime or lemon juice or vinegar should kill the virus before it has had a chance to infect. A clinical trial of efficacy is needed. (v) PhotoVoice . Asking schoolchildren in developing countries to photograph their impressions of HIV/AIDS is a powerful way of getting them to discuss the subject openly, and develop their own preventative strategies.

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Reduced neuronal population in the dorsolateral prefrontal cortex in infant macaques infected with simian immunodeficiency virus (SIV)

Journal of NeuroVirology ◽

10.1007/s13365-021-01019-2 ◽

2021 ◽

Author(s):

Alexandra Haddad ◽

Brittany Voth ◽

Janiya Brooks ◽

Melanie Swang ◽

Heather Carryl ◽

...

Keyword(s):

Prefrontal Cortex ◽

Hiv Infection ◽

Simian Immunodeficiency Virus ◽

Dorsolateral Prefrontal Cortex ◽

Neuronal Population ◽

Pediatric Hiv ◽

Health Crisis ◽

Immunodeficiency Virus ◽

Dorsolateral Prefrontal ◽

Siv Infection

AbstractPediatric HIV infection remains a global health crisis with an estimated 150,000 new mother-to-child (MTCT) infections each year. Antiretroviral therapy (ART) has improved childhood survival, but only an estimated 53% of children worldwide have access to treatment. Adding to the health crisis is the neurological impact of HIV on the developing brain, in particular cognitive and executive function, which persists even when ART is available. Imaging studies suggest structural, connectivity, and functional alterations in perinatally HIV-infected youth. However, the paucity of histological data limits our ability to identify specific cortical regions that may underlie the clinical manifestations. Utilizing the pediatric simian immunodeficiency virus (SIV) infection model in infant macaques, we have previously shown that early-life SIV infection depletes the neuronal population in the hippocampus. Here, we expand on these previous studies to investigate the dorsolateral prefrontal cortex (dlPFC). A total of 11 ART-naïve infant rhesus macaques (Macaca mulatta) from previous studies were retrospectively analyzed. Infant macaques were either intravenously (IV) inoculated with highly virulent SIVmac251 at ~1 week of age and monitored for 6–10 weeks or orally challenged with SIVmac251 from week 9 of age onwards with a monitoring period of 10–23 weeks post-infection (19–34 weeks of age), and SIV-uninfected controls were euthanized at 16–17 weeks of age. Both SIV-infected groups show a significant loss of neurons along with evidence of ongoing neuronal death. Oral- and IV-infected animals showed a similar neuronal loss which was negatively correlated to chronic viremia levels as assessed by an area under the curve (AUC) analysis. The loss of dlPFC neurons may contribute to the rapid neurocognitive decline associated with pediatric HIV infection.

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Human Immunodeficiency Virus (HIV)-Resistant CD4+ UT-7 Megakaryocytic Human Cell Line Becomes Highly HIV-1 and HIV-2 Susceptible Upon CXCR4 Transfection: Induction of Cell Differentiation by HIV-1 Infection

Blood ◽

10.1182/blood.v89.8.2670 ◽

1997 ◽

Vol 89 (8) ◽

pp. 2670-2678 ◽

Cited By ~ 17

Author(s):

Marta Baiocchi ◽

Eleonora Olivetta ◽

Cristiana Chelucci ◽

Anna Claudia Santarcangelo ◽

Roberta Bona ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Hiv Infection ◽

Cell Line ◽

Viral Entry ◽

Human Cell Line ◽

Immunodeficiency Virus ◽

Hiv Entry ◽

Stromal Cell Derived Factor ◽

Hiv 1

Abstract Recent findings have shown that the expression of the seven trans-membrane G-protein–coupled CXCR4 (the receptor for the stromal cell-derived factor [SDF]-1 chemokine) is necessary for the entry of T-lymphotropic human immunodeficiency virus (HIV) strains, acting as a coreceptor of the CD4 molecule. In the human system, the role of CXCR4 in HIV infection has been determined through env-mediated cell fusion assays and confirmed by blocking viral entry in CD4+/CXCR4+ cells by SDF-1 pretreatment. We observed that the human megakaryoblastic CD4+ UT-7 cell line fails to express CXCR4 RNA and is fully resistant to HIV entry. Transfection of an expression vector containing the CXCR4 c-DNA rendered UT-7 cells readily infectable by different T-lymphotropic syncytium-inducing HIV-1 and HIV-2 isolates. Interestingly, HIV-1 infection of CXCR4 expressing UT-7 cells (named UT-7/fus) induces the formation of polynucleated cells through a process highly reminiscent of megakaryocytic differentiation and maturation. On the contrary, no morphologic changes were observed in HIV-2–infected UT-7/fus cells. These findings further strengthen the role of CXCR4 as a molecule necessary for the replication of T-lymphotropic HIV-1 and HIV-2 isolates and provide a useful model to study the functional role of CD4 coreceptors in HIV infection.

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SIV infection aggravates malaria in a Chinese rhesus monkey coinfection model

BMC Infectious Diseases ◽

10.1186/s12879-019-4465-6 ◽

2019 ◽

Vol 19 (1) ◽

Author(s):

Guangjie Liu ◽

Youjia Li ◽

Li Qin ◽

Yongxiang Yan ◽

Yijian Ye ◽

...

Keyword(s):

T Cells ◽

Body Weight ◽

Body Temperature ◽

Hiv Infection ◽

Malaria Infection ◽

Rhesus Monkeys ◽

Immunological Mechanism ◽

Immunodeficiency Virus ◽

Siv Infection ◽

The Impact

Abstract Background The co-occurrence of human immunodeficiency virus (HIV) infection and malaria in humans in endemic areas raises the question of whether one of these infections affects the course of the other. Although epidemiological studies have shown the impact of HIV infection on malaria, the mechanism(s) are not yet fully understood. Using a Chinese rhesus macaque coinfection model with simian immunodeficiency virus (SIV) and Plasmodium cynomolgi (Pc) malaria, we investigated the effect of concurrent SIV infection on the course of malaria and the underlying immunological mechanism(s). Methods We randomly assigned ten Chinese rhesus monkeys to two groups based on body weight and age. The SIV-Pc coinfection animals (S + P group) were infected intravenously with SIVmac251 eight weeks prior to malaria infection, and the control animals (P group) were infected intravenously with only Pc-infected red blood cells. After malaria was cured with chloroquine phosphate, we also initiated a secondary malaria infection that lasted 4 weeks. We monitored body weight, body temperature and parasitemia, measured SIV viral loads, hemoglobin and neopterin, and tracked the CD4+, CD8+, and CD4+ memory subpopulations, Ki67 and apoptosis by flow cytometry. Then, we compared these parameters between the two groups. Results The animals infected with SIV prior to Pc infection exhibited more severe malaria symptoms characterized by longer episodes, higher parasitemia, more severe anemia, greater body weight loss and higher body temperature than the animals infected with Pc alone. Concurrent SIV infection also impaired immune protection against the secondary Pc challenge infection. The coinfected animals showed a reduced B cell response to Pc malaria and produced lower levels of Pc-specific antibodies. In addition, compared to the animals subjected to Pc infection alone, the animals coinfected with SIV and Pc had suppressed total CD4+ T cells, CD4+CD28highCD95high central memory T cells, and CD4+CD28lowCD95− naïve T cells, which may result from the imbalanced immune activation and faster CD4+ T cell turnover in coinfected animals. Conclusions SIV infection aggravates malaria physiologically and immunologically in Chinese rhesus monkeys. This nonhuman primate SIV and Pc malaria coinfection model might be a useful tool for investigating human HIV and malaria coinfection and developing effective therapeutics.

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Cytomegalovirus (CMV) and Human Immunodeficiency Virus (HIV) Burden, CMV End-Organ Disease, and Survival in Subjects with Advanced HIV Infection (AIDS Clinical Trials Group Protocol 360)

Clinical Infectious Diseases ◽

10.1086/375843 ◽

2003 ◽

Vol 37 (4) ◽

pp. 567-578 ◽

Cited By ~ 49

Author(s):

A. Erice ◽

C. Tierney ◽

M. Hirsch ◽

A. M. Caliendo ◽

A. Weinberg ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Clinical Trials ◽

Hiv Infection ◽

Immunodeficiency Virus ◽

Aids Clinical Trials

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Magnitude and Quality of Cytokine and Chemokine Storm during Acute Infection Distinguish Nonprogressive and Progressive Simian Immunodeficiency Virus Infections of Nonhuman Primates

Journal of Virology ◽

10.1128/jvi.01061-16 ◽

2016 ◽

Vol 90 (22) ◽

pp. 10339-10350 ◽

Cited By ~ 12

Author(s):

Sheila M. Keating ◽

John W. Heitman ◽

Shiquan Wu ◽

Xutao Deng ◽

Andrea R. Stacey ◽

...

Keyword(s):

Hiv Infection ◽

Simian Immunodeficiency Virus ◽

Acute Phase ◽

Area Under The Curve ◽

Host Immune System ◽

Amyloid A ◽

Infection Models ◽

Serum Amyloid A Protein ◽

Immunodeficiency Virus ◽

Siv Infection

ABSTRACTAcute human immunodeficiency virus (HIV) infection represents a period of intense immune perturbation and activation of the host immune system. Study of the eclipse and viral expansion phases of infection is difficult in humans, but studies in nonprogressive and progressive nonhuman primate (NHP) infection models can provide significant insight into critical events occurring during this time. Cytokines, chemokines, and other soluble immune factors were measured in longitudinal samples from rhesus macaques infected with either SIVmac251 (progressive infection) or SIVmac239Δnef(attenuated/nonprogressive infection) and from African green monkeys infected with SIVsab9315BR (nonpathogenic infection). Levels of acute-phase peak viral replication were highest in SIVmac251 infection but correlated positively with viremia at 3 months postinfection in all three infection models. SIVmac251 infection was associated with stronger corresponding acute-phase cytokine/chemokine responses than the nonprogressive infections. The production of interleukin 15 (IL-15), IL-18, gamma interferon (IFN-γ), granulocyte colony-stimulating factor (G-CSF), monocyte chemoattractant protein 1 (MCP-1), macrophage inflammatory protein 1β (MIP-1β), and serum amyloid A protein (SAA) during acute SIVmac251 infection, but not during SIVmac239Δnefor SIVsab9315BR infection, correlated positively with chronic viremia at 3 months postinfection. Acute-phase production of MCP-1 correlated with viremia at 3 months postinfection in both nonprogressive infections. Finally, a positive correlation between the acute-phase area under the curve (AUC) for IL-6 and soluble CD40 ligand (sCD40L) and chronic viremia was observed only for the nonprogressive infection models. While we observed dynamic acute inflammatory immune responses in both progressive and nonprogressive SIV infections, the responses in the nonprogressive infections were not only lower in magnitude but also qualitatively different biomarkers of disease progression.IMPORTANCENHP models of HIV infection constitute a powerful tool with which to study viral pathogenesis in order to gain critical information for a better understanding of HIV infection in humans. Here we studied progressive and nonprogressive simian immunodeficiency virus (SIV) infection models in both natural and nonnatural host NHP species. Regardless of the pathogenicity of the virus infection and regardless of the NHP species studied, the magnitude of viremia, as measured by area under the curve, during the first 4 weeks of infection correlated positively with viremia in chronic infection. The magnitude of cytokine and chemokine responses during primary infection also correlated positively with both acute-phase and chronic viremia. However, the pattern and levels of specific cytokines and chemokines produced differed between nonprogressive and progressive SIV infection models. The qualitative differences in the early immune response in pathogenic and nonpathogenic infections identified here may be important determinants of the subsequent disease course.

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Gastrointestinal Tract and the Mucosal Macrophage Reservoir in HIV Infection

Clinical and Vaccine Immunology ◽

10.1128/cvi.00518-14 ◽

2014 ◽

Vol 21 (11) ◽

pp. 1469-1473 ◽

Cited By ~ 20

Author(s):

Dallas Brown ◽

Joseph J. Mattapallil

Keyword(s):

Human Immunodeficiency Virus ◽

T Cells ◽

Gastrointestinal Tract ◽

Hiv Infection ◽

Simian Immunodeficiency Virus ◽

Primary Site ◽

Functional Cure ◽

Immunodeficiency Virus ◽

Siv Infection ◽

Explosive Phase

ABSTRACTThe gastrointestinal tract (GIT) is a primary site for human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) infection, replication, and dissemination. After an initial explosive phase of infection, HIV establishes latency. In addition to CD4 T cells, macrophages are readily infected, which can persist for long periods of time. Though macrophages at various systemic sites are infected, those present in the GIT constitute a major cellular reservoir due to the abundance of these cells at mucosal sites. Here, we review some of the important findings regarding what is known about the macrophage reservoir in the gut and explore potential approaches being pursued in the field to reduce this reservoir. The development of strategies that can lead to a functional cure will need to incorporate approaches that can eradicate the macrophage reservoir in the GIT.

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Genetic influences on HIV infection: implications for vaccine development

Sexual Health ◽

10.1071/sh04057 ◽

2005 ◽

Vol 2 (2) ◽

pp. 53 ◽

Cited By ~ 7

Author(s):

Miranda Z. Smith ◽

Stephen J. Kent

Keyword(s):

Hiv Infection ◽

Genetic Factors ◽

Vaccine Development ◽

Critical Role ◽

Genetic Influences ◽

Susceptibility To Infection ◽

Immunodeficiency Virus ◽

Host Genetic ◽

Host Genetic Factors

Human HIV infection is characterised by great variability in outcome. Much of this variability is due either to viral variation or host genetic factors, particularly major histocompatibility complex differences within genetically diverse populations. The study of non-human primates infected with well characterised simian immunodeficiency virus strains has recently allowed further dissection of the critical role of genetic influences on both susceptibility to infection and progression to AIDS. This review summarises the important role of many host genetic factors on HIV infection and highlights important variables that will need to be taken into account in evaluating effective HIV vaccines.

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The Results of Clinical Trials of Recombinant Vaccine Virus, MVA Strain, Expressing Genes of Human Immunodeficiency Virus

Problems of Particularly Dangerous Infections ◽

10.21055/0370-1069-2021-3-13-22 ◽

2021 ◽

pp. 13-22

Author(s):

L. F. Stovba ◽

S. A. Mel’nikov ◽

D. I. Paveli’ev ◽

V. T. Krotkov ◽

N. K. Chernikova ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Clinical Trials ◽

Immune Responses ◽

Hiv Infection ◽

Vaccine Virus ◽

Viral Reservoirs ◽

Humoral Immune ◽

Number Of Patients ◽

Immunodeficiency Virus ◽

The Usa

Although successes in antiretroviral therapy (ART) turned AIDS from lethal illness into sluggishly progressing disease, its prevention and treatment remain one of the most socially significant concerns. The increase in the number of patients infected with human immunodeficiency virus (HIV), especially in the USA, South America and Europe, determines the need in creating a vaccine against this disease. Existing vaccination practice has demonstrated efficiency of priming/boosting scheme for the development of immune responses. As anti-vector immunity of priming vector can constrain the response to boosting immunization with the same vaccine, heterologous priming/boosting vector constructs are used. An ideal AIDS vaccine would prevent virus dissemination and control viral replication, but it also must be safe for HIV-infected contingent. The vaccination of HIV-infected individuals is used for enhancing immune-mediated elimination of persistently HIV-infected CD4+ Т-cells during long-term ART in order to purge the latently infected viral reservoirs. The paper considers the results of clinical trials of DNA-anti-HIV/AIDS vaccines and recombinant MVA strain of vaccinia virus, expressing different combination of HIV genes, which demonstrated the safety and tolerability both, in HIV-infected and non-HIV-infected volunteers. All implemented schedules of vaccination induced cell-mediated and humoral immune responses in all volunteers. And though there are no data on acquiring AIDS by HIV-uninfected volunteers from groups at low risk of HIV-infection, there are no grounds to conclude the sufficiency of induced protection for the prevention of possible HIV infection.

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