Coinfection with Herpes Simplex Virus Type 2 Is Associated with Reduced HIV‐Specific T Cell Responses and Systemic Immune Activation

Sheth, Prameet M.; Sunderji, Sherzana; Shin, Lucy Y.; Rebbapragada, Anu; Huibner, Sanja; Kimani, Joshua; MacDonald, Kelly S.; Ngugi, Elizabeth; Bwayo, Job J.; Moses, Stephen; Kovacs, Colin; Loutfy, Mona; Kaul, Rupert

doi:10.1086/587697

Cited by 62 publications

(50 citation statements)

References 49 publications

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“…Indeed, this has been demonstrated for HSV-1; skin biopsy specimens coinfected with HSV-1, and HIV obtained from AIDS patients, have revealed HIV virions within keratinocytes -a cell type that is normally incapable of being infected by HIV due to the lack of CD4 receptors (44). Third, both the breadth and magnitude of HIV-specific CD8+ T cell proliferative and interferon-gamma responses are reduced in HSV-2-HIV-coinfected persons, suggesting a potential mechanism through which this coinfection impairs the immune response to HIV and facilitates ongoing viral replication (45). Furthermore, the severity of symptomatic HSV disease in the setting of HIV infection is known to correlate with immune dysregulation (ie, low CD4 counts) rather than with HIV viremia (12,46).…”

Section: Evidence That Hsv-2 Infection May Impact On Hiv Prognosismentioning

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: Evidence That Hsv-2 Infection May Impact On Hiv Prognosismentioning

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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“…Viral coinfections among an HIV-infected individual may affect the disease progression of HIV/AIDS and may accelerate the progression of these other viral infections to more severe illness due to HIV coinfection (1)(2)(3)(4)(5)(6)(7)(8)(9)(10). Among the list of viruses that are likely to be co-infected with HIV, hepatitis B virus (HBV), hepatitis C virus (HCV), herpes simplex virus including type 1 (HSV-1) and type 2 (HSV-2), and the Epstein-Bar virus (EBV) are the most important coinfections among HIV/ AIDS patients due to their pathogenicity and relatively high prevalence in populations affected by HIV.…”

Section: Introductionmentioning

confidence: 99%

Multiple viral coinfections among HIV/AIDS patients in China

Chen

Lin

et al. 2011

BST

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“…The synergistic interaction between HSV2 and HIV infections is supported by epidemiological data (2,3,(5)(6)(7)(8)10,21). These studies demonstrate that HSV2 predisposes individuals to HIV acquisition and transmission, and accelerates HIV disease progression.…”

Section: Hsv2/hiv Synergy Epidemiologymentioning

confidence: 83%

“…One study showed HSV2 to be associated with a two-to three-fold increase in the risk of HIV infection (5). A metaanalysis of 18 longitudinal studies found the HSV2 infection to be associated with an increased risk of HIV infection, with a relative risk of 3.1 in women, 2.7 in heterosexual men and 1.7 in homosexual men (7). Mathematical modeling has projected that the peak incidence of HIV may double in the next ten years due to the presence of HSV2 (2).…”

Section: Hsv2/hiv Synergy Epidemiologymentioning

confidence: 99%

Drug-resistant herpes simplex virus in HIV infected patients

Lolis

L²,

Cohen³

et al. 2011

Journal of the American Academy of Dermatology

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summary Herpes simplex virus type 2 (HSV2) infection is a major source of morbidity in human immunodeficiency virus (HIV)-infected patients, since reactivations -whether symptomatic or asymptomatic -are associated with increased HIV viral load and viral shedding. Acyclovir, valacyclovir and famcyclovir are indicated for the treatment of HSV2 in HIV patients. This class of drugs has been shown to enhance survival in HIV-infected individuals. However, with the emergence of drug-resistant strains of HSV2, the rates of resistance among HIV patients are almost ten-fold those in immunocompetent individuals, comparing 0.6% to 6%. These HSV2 infections tend to be more severe and to recur. More ominously, disease progression of HIV is promoted by concurrent infection with HSV2. Intravenous foscarnet and cidofovir may be used for acyclovir-resistant HSV; however, resistance to these drugs has been documented. Newer therapies such as the toll-like receptor agonist imiquimod and immunomodulating dipeptides offer promise for the treatment of HSV2 in HIV-infected individuals.

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Coinfection with Herpes Simplex Virus Type 2 Is Associated with Reduced HIV‐Specific T Cell Responses and Systemic Immune Activation

Abstract: HSV-2 coinfection was associated with reduced HIV-specific T cell responses and systemic inflammation. The immune effects of HSV-2 may underlie the negative impact that this coinfection has on the clinical course of HIV infection.

Cited by 62 publications

References 49 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?

Multiple viral coinfections among HIV/AIDS patients in China

Drug-resistant herpes simplex virus in HIV infected patients

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