Frequent Recovery of HIV-1 From Genital Herpes Simplex Virus Lesions in HIV-1–Infected Men

Schacker, Timothy W.; Ryncarz, Alexander J.; Goddard, James L.; Diem, Kurt; Shaughnessy, Mary; Corey, Lawrence

doi:10.1001/jama.280.1.61

Cited by 284 publications

(159 citation statements)

References 40 publications

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“…The first eight patients seen at the University of Washington Primary Infection Clinic who presented within 66 days (median, 42.5 days) of onset of acute HIV-1 infection were studied. The enrollment criteria, detailed demographic characteristics, and definition of onset of infection of this cohort have been reported (21,22). In brief, all had an acute symptomatic illness associated with HIV-1 primary viremia that was followed by seroconversion.…”

Section: Methodsmentioning

confidence: 99%

“…HIV-1 RNA concentrations in plasma were determined by the branched DNA (bDNA) assay (limit of detection of 500 copies/ml; Chiron Corporation, Emeryville, Calif.) as described previously (10,22). For genetic analysis, DNA was purified from peripheral blood mononuclear cells (PBMCs), or viral RNA was extracted from plasma, reverse tran-scribed, and then amplified by nested PCR as previously described (10).…”

Section: Methodsmentioning

confidence: 99%

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Virus Population Homogenization following Acute Human Immunodeficiency Virus Type 1 Infection

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Muthui²,

Brodie³

et al. 2002

J Virol

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Understanding the properties of human immunodeficiency virus type 1 (HIV-1) variants capable of establishing infection is critical to the development of a vaccine against AIDS. Previous studies of men have shown that the HIV-1 env gene is homogeneous early in infection, leading to the suggestion that infection is established by a single transmitted variant. However, we report here that all of eight homosexual men evaluated beginning 3.7 to 9 weeks following onset of symptoms of acute infection harbored diverse virus populations in their blood, with median genetic distances averaging 1.08% in the env C2V5 region and 0.81% in the gag p17 gene. Within another 4.7 to 11 weeks, the variant lineage in env became more homogeneous, while gag sequences continued to diversify. Thus, the homogenization that has been reported to characterize acute infection is actually preceded by the replication of multiple virus variants. This early selective process focuses on viral properties within Env but not Gag p17. Hence, the viral homogeneity observed early in HIV-1 infection results from a selective process that occurs during the establishment of infection.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Virus Population Homogenization following Acute Human Immunodeficiency Virus Type 1 Infection

Learn

Muthui²,

Brodie³

et al. 2002

J Virol

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show abstract

“…Higher numbers of target cells likely contribute to the increased HIV susceptibility observed in HSV-2-infected persons. Finally, among individuals who become HSV-2-HIV coinfected, HSV-2 has been associated with increases in HIV viral load in both plasma and genital secretions of up to 0.5 log 10 copies/mL (12,(29)(30)(31)(32), thus increasing the likelihood of secondary HIV transmission to HIV-uninfected partners. Taken together, these findings provide a strong epidemiological and pathophysiological rationale for studying pharmacological HSV-2 suppression as a therapeutic strategy for preventing HIV acquisition.…”

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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“…Latent virus can reactivate and cause recurrent symptoms, including genital lesions; however, subclinical infection and asymptomatic viral shedding also occur (11,35,40,53). HSV-2 has gained increasing interest in the light of evidence that it is a major risk factor for human immunodeficiency virus type 1 (HIV-1) acquisition and transmission and for the progression of HIV-1 infection (8, 9,17,25,37,55,56). In addition, there is evidence that anti-HSV therapy can reduce the amount of infectious HIV-1 in the genital tracts of women (9,45).…”

mentioning

confidence: 99%

Mucosal Innate and Adaptive Immune Responses against Herpes Simplex Virus Type 2 in a Humanized Mouse Model

Kwant-Mitchell

Ashkar

Rosenthal

2009

J Virol

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Genital herpes, caused by herpes simplex virus type 2 (HSV-2), is one of the most prevalent sexually transmitted diseases worldwide and a risk factor for acquiring human immunodeficiency virus. Although many vaccine candidates have shown promising results in animal models, they have failed to be effective in human trials. In this study, a humanized mouse strain was evaluated as a potential preclinical model for studying human immune responses to HSV-2 infection and vaccination. Immunodeficient mouse strains were examined for their abilities to develop human innate and adaptive immune cells after transplantation of human umbilical cord stem cells. A RAG2 ؊/؊ ␥c ؊/؊ mouse strain with a BALB/c background was chosen as the most appropriate model and was then examined for its ability to mount innate and adaptive immune responses to intravaginal HSV-2 infection and immunization. After primary infection, human cells in the lymph nodes were able to generate a protective innate immune response and produce gamma interferon (IFN-␥). After intravaginal immunization and infection, human T cells and NK cells were found in the genital tract and iliac lymph nodes. In addition, human T cells in the spleen, lymph nodes, and vaginal tract were able to respond to stimulation with HSV-2 antigens by replicating and producing IFN-␥. Human B cells were also able to produce HSV-2-specific immunoglobulin G. These adaptive responses were also shown to be protective and reduce local viral replication in the genital tract. This approach provides a means for studying human immune responses in vivo using a small-animal model and may become an important preclinical tool.

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Frequent Recovery of HIV-1 From Genital Herpes Simplex Virus Lesions in HIV-1–Infected Men

Cited by 284 publications

References 40 publications

Virus Population Homogenization following Acute Human Immunodeficiency Virus Type 1 Infection

Virus Population Homogenization following Acute Human Immunodeficiency Virus Type 1 Infection

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

Mucosal Innate and Adaptive Immune Responses against Herpes Simplex Virus Type 2 in a Humanized Mouse Model

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