The genital tract immune milieu: an important determinant of HIV susceptibility and secondary transmission

Kaul, Rupert; Pettengell, Christopher; Sheth, Prameet M.; Sunderji, Sherzana; Biringer, Anne; MacDonald, Kelly S.; Walmsley, Sharon; Rebbapragada, Anu

doi:10.1016/j.jri.2007.02.002

Cited by 131 publications

(101 citation statements)

References 65 publications

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“…The mechanisms through which HSV-2 may drive the amplification of HIV transmission are multiple (27). First, both symptomatic and asymptomatic HSV-2 infections may result in the disruption of the epithelial barrier of genital mucosal surfaces, providing increased portals of entry for HIV into the HSV-2-infected person during sexual contact.…”

Section: How Hsv-2 May Fuel the Hiv Epidemicmentioning

confidence: 99%

Left out but not Forgotten: Should Closer Attention be Paid to Coinfection with Herpes Simplex Virus Type 1 and HIV?

Tan

Kaul

Walsmley

2009

Canadian Journal of Infectious Diseases and Medical Microbiolog

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Herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) are among the most common coinfections seen in individuals infected with HIV-1. Most research on HSV-HIV coinfection has focused on HSV-2, and in particular, on its impact on HIV transmission. HSV-2 is associated with micro- and macroulcerations in genital mucosal surfaces, increased numbers of HIV target cells in genital mucosal tissue and increases in plasma HIV viral load of up to 0.5 log10copies/mL, such that HSV-2 infection increases the risk of both HIV acquisition and transmission. Because plasma HIV RNA levels are a major determinant of rates of CD4 cell decline, HSV-2 coinfection may also adversely affect the progression of HIV disease. Anti-HSV medications have in fact been associated with reciprocal decreases in HIV viral load in short-term studies. These findings have led to the development of several clinical trials of HSV-2 suppression as strategies for preventing HIV transmission and slowing the rate of HIV disease progression. HSV-1 coinfection has largely been ignored from this growing body of research, yet there are several reasons that this coinfection remains an important issue for study. First, the seroprevalence of HSV-1 is consistently higher than that of HSV-2 among both HIV-infected and HIV-uninfected populations, underscoring the relevance of HSV-1 coinfection to the majority of HIV-infected persons. Second, pre-existing HSV-1 antibodies in individuals may modulate the course of subsequently acquired HSV-2 infection; the implications of such changes on HSV-HIV coinfection remain unexplored. Third, HSV-1 and HSV-2 are closely related viruses that share 83% genetic homology. Their virological and pathobiological similarities suggest that their implications on HIV pathogenesis may be similar as well. Finally, HSV-1 is becoming increasingly relevant because the incidence of genital HSV-1 has risen. Although genital herpes is traditionally associated with HSV-2, recent studies have shown that the majority of serologically confirmed primary genital herpes in some settings is attributable to HSV-1. Because the genital tract is an important site of biological interaction between HSV and HIV, this epidemiological change may be clinically important.

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Section: How Hsv-2 May Fuel the Hiv Epidemicmentioning

confidence: 99%

Left out but not Forgotten: Should Closer Attention be Paid to Coinfection with Herpes Simplex Virus Type 1 and HIV?

Tan

Kaul

Walsmley

2009

Canadian Journal of Infectious Diseases and Medical Microbiolog

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“…In a recent study, HSV-2 +/HIV− women showed an increase in genital mucosal target cells populations that are known to enhance HIV infection, even in the absence of genital ulceration or HSV2 reactivation (Rebbapragada et al 2007). Kaul et al has reviewed the evidence for negative mucosal synergy between HIV and HSV-2 (Kaul et al 2007). They conclude that the evidence supporting synergy between HSV-2 and HIV as factors driving acquisition and transmission is strong (Kaul et al 2007).…”

Section: Stress and Acquisition Of Hivmentioning

confidence: 99%

“…They conclude that the evidence supporting synergy between HSV-2 and HIV as factors driving acquisition and transmission is strong (Kaul et al 2007). Importantly, research examining whether suppressing HSV-2 can prevent HIV acquisition is now underway (Kaul et al 2007). …”

Section: Stress and Acquisition Of Hivmentioning

confidence: 99%

Population Levels of Psychological Stress, Herpesvirus Reactivation and HIV

2008

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Nearly 40,000 Americans are newly infected with Human Immunodeficiency Virus (HIV) each year. Recently, studies have demonstrated associations between group-level characteristics and the prevalence and incidence of HIV/Acquired Immune Deficiency Syndrome (AIDS) and other sexually transmitted diseases. Two mechanisms previously posited to explain these associations are neighborhood effects on risk behaviors and social or institutional policies. In this paper, we hypothesize that adversity at the population level, such as neighborhood poverty, also influences HIV risk through stress-mediated aberrations in immunological susceptibility by reviewing existing data examining each of these pathways. In particular, we review the evidence showing that: (1) Neighborhood ecologic stressors influence neighborhood-and individual-levels of mental health, psychosocial stress, and HIV/AIDS risk, (2) Individual-level psychosocial stressors influence progression from HIV to AIDS through stress-related hormonal changes, and (3) Individual-level psychosocial stressors influence HIV acquisition via stress-related reactivation of latent herpesviruses, specifically EBV and HSV-2. Our review indicates that further studies are needed to examine the joint pathways linking neighborhood-level sources of psychosocial stress, stress-related reactivation of HSV-2 and EBV, and increased acquisition rates of HIV. We suggest using a multi-level framework for targeting HIV prevention efforts that address not only behavioral risk factors, but structural, political, and institutional factors associated with neighborhood disadvantage, levels of psychosocial stress, and prevention or treatment of HSV-2 and EBV.

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“…Common bacterial STI can also increase the number of immune cells in the genital tract (9,52), and elevated counts of white blood cells in semen are associated with higher seminal HIV shedding (3,4,69,80). Since HIV principally infects and replicates in CD4 ϩ T lymphocytes, monocytes, and macrophages (16,30), an accumulation of these cells in semen is likely to increase the risk of sexual HIV transmission (40,79).…”

mentioning

confidence: 99%

Associations between Virologic and Immunologic Dynamics in Blood and in the Male Genital Tract

Gianella

Strain

Rought

et al. 2012

J Virol

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To determine the influence of asymptomatic genital viral infections on the cellular components of semen and blood, we evaluated the associations between the numbers and activation statuses of CD4 ؉ and CD8 ؉ T lymphocytes in both compartments and the seminal levels of cytomegalovirus (CMV), herpes simplex virus (HSV), and human immunodeficiency virus 1 (HIV). Paired blood and semen samples were collected from 36 HIV-infected antiretroviral-naïve individuals and from 40 HIV-uninfected participants. We performed multiparameter flow cytometry analysis (CD45, CD45RA, CD3, CD4, CD8, and CD38) of seminal and blood cellular components and measured HIV RNA and CMV and HSV DNA levels in seminal and blood plasma by real-time PCR. Compared to HIV-uninfected participants, in the seminal compartment HIV-infected participants had higher levels of CMV (P < 0.05), higher numbers of total CD3 ؉ (P < 0.01) and CD8 ؉ subset (P < 0.01) T lymphocytes, and higher CD4 ؉ and CD8 ؉ T lymphocyte activation (RA-CD38 ؉ ) (P < 0.01). Seminal CMV levels positively correlated with absolute numbers of CD4 ؉ and CD8 ؉ T cells in semen (P < 0.05) and with the activation status of CD4 ؉ T cells in semen and in blood (P < 0.01). HIV levels in semen (P < 0.05) and blood (P < 0.01) were positively associated with T-cell activation in blood. Activation of CD8 ؉ T cells in blood remained an independent predictor of HIV levels in semen in multivariate analysis. The virologic milieu in the male genital tract strongly influences the recruitment and activation of immune cells in semen and may also modulate T-cell immune activation in blood. These factors likely influence replication dynamics, sexual transmission risk, and disease outcomes for all three viruses.

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The genital tract immune milieu: an important determinant of HIV susceptibility and secondary transmission

Cited by 131 publications

References 65 publications

Left out but not Forgotten: Should Closer Attention be Paid to Coinfection with Herpes Simplex Virus Type 1 and HIV?

Left out but not Forgotten: Should Closer Attention be Paid to Coinfection with Herpes Simplex Virus Type 1 and HIV?

Population Levels of Psychological Stress, Herpesvirus Reactivation and HIV

Associations between Virologic and Immunologic Dynamics in Blood and in the Male Genital Tract

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