Association between cervical shedding of herpes simplex virus and HIV-1

International AIDS Research and Training Program, Department of Medicine, University of Washington, Box 359909, 325 9th Avenue, Seattle, WA 98104, USA.
AIDS (Impact Factor: 5.55). 01/2003; 16(18):2425-30. DOI: 10.1097/00002030-200212060-00007
Source: PubMed


To investigate the association between the cervical shedding of herpes simplex virus (HSV) and HIV-1.
A cross-sectional study on 200 women seropositive for both HSV-2 and HIV-1 was conducted in a family planning clinic at the Coast Provincial General Hospital, Mombasa, Kenya.
Quantities of HSV DNA (types 1 and 2) and HIV-1 RNA as well as the presence or absence of HIV-1 proviral DNA in cervical secretions were determined and compared.
There was a significant correlation between the quantities of HSV DNA and HIV-1 RNA in the cervical secretions of HSV-shedding women (Pearson's r = 0.24, P = 0.05). A 10-fold increase in the quantity of cervical HSV DNA was associated with 1.35-fold higher cervical HIV-1-RNA levels (95% CI 1.00-1.81; P = 0.05), and with 1.36-fold greater odds of detection of HIV-1 proviral DNA (95% CI 1.05-1.75; P = 0.02).
Higher levels of cervical HSV were associated with higher levels of expressed HIV-1 and with the more frequent detection of HIV-1-infected cells in cervical secretions. Prospective studies are needed to explore further the association between non-ulcerative cervical HSV reactivation and HIV-1 shedding. Such a relationship may have important implications for interventions designed to slow the spread of HIV-1.

1 Follower
4 Reads
    • "The group of women with evidence of HSV-2 genital shedding had higher genital HIV-1 RNA loads than control women, in agreement with other reports [8] [10]. Compartmentalization was observed between genital HIV-1 RNA, genital HIV-1 DNA, and plasma HIV-1 RNA, independently of HSV-2 genital reactivation , suggesting that HSV-2 genital replication did not significantly affect the tissue adaptation of HIV-1 variants. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Clinical and subclinical genital HSV-2 reactivations have been associated with increases of HIV-1 genital shedding. Whether herpes simplex virus type 2 (HSV-2) shedding contributes to the selection of specific genital HIV-1 variants remains unknown. We evaluated the genetic diversity of genital and blood HIV-1 RNA and DNA in 14 HIV-1-/HSV-2- co-infected women, including 7 with HSV-2 genital reactivation and 7 without as controls. HIV-1 DNA and HIV-1 RNA env V1-V3 sequences in paired blood and genital samples were compared. The Herpes selection pressure on HIV was estimated with the number of synonymous (dS) and non-synonymous substitutions (dN) and the dS/dN ratio within HIV quasi-species. HIV-1 RNA levels in cervicovaginal secretions were higher in women with HSV-2 replication than in controls (p=0.02). Plasma HIV-1 RNA and genital HIV-1 RNA and DNA were genetically compartmentalized. No difference in dS, dN and dS/dN ratios was observed between the study groups for both genital HIV-1 RNA and plasma HIV-1 RNA. In contrast, dS and dN in genital HIV-1 DNA were significantly higher in patients with genital herpes reactivation (p<0.01 and p<0.05, respectively). The mean of dS/dN ratio in genital HIV-1 DNA was slightly higher in patients with herpetic genital replication, indicating a trend for a purifying selection (p=0.056). HSV-2 increased genetic diversity of genital HIV-1 DNA. These observations confirm molecular interactions between HSV-2 and HIV-1 at the genital tract level. Copyright © 2015. Published by Elsevier Ltd.
    No preview · Article · May 2015 · Clinical Microbiology and Infection
  • Source
    • "Moreover, other infections might have additional mechanisms in which they could affect the transmission of HIV. For example, the genital reactivations of HSV-2 generate local immune activations in genital ulcerations that might increment HIV shedding in the genital tracks [72]. This STI infection not only affects the risk of transmission but also increases the risk of acquisition in HIV-negative individuals, a characteristic that considerably affects the mode in which HSV-2 influences the pattern of HIV transmission at the population level [36,59]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Recent studies have implicated viral characteristics in accounting for the variation in the HIV set-point viral load (spVL) observed among individuals. These studies have suggested that the spVL might be a heritable factor. The spVL, however, is not in an absolute equilibrium state; it is frequently perturbed by immune activations generated by co-infections, resulting in a significant amplification of the HIV viral load (VL). Here, we postulated that if the HIV replication capacity were an important determinant of the spVL, it would also determine the effect of co-infection on the VL. Then, we hypothesized that viral factors contribute to the variation of the effect of co-infection and introduce variation among individuals. We developed a within-host deterministic differential equation model to describe the dynamics of HIV and malaria infections, and evaluated the effect of variations in the viral replicative capacity on the VL burden generated by co-infection. These variations were then evaluated at population level by implementing a between-host model in which the relationship between VL and the probability of HIV transmission per sexual contact was used as the within-host and between-host interface. Our within-host results indicated that the combination of parameters generating low spVL were unable to produce a substantial increase in the VL in response to co-infection. Conversely, larger spVL were associated with substantially larger increments in the VL. In accordance, the between-host model indicated that co-infection had a negligible impact in populations where the virus had low replicative capacity, reflected in low spVL. Similarly, the impact of co-infection increased as the spVL of the population increased. Our results indicated that variations in the viral replicative capacity would influence the effect of co-infection on the VL. Therefore, viral factors could play an important role driving several virus-related processes such as the increment of the VL induced by co-infections. These results raise the possibility that biological differences could alter the effect of co-infection and underscore the importance of identifying these factors for the implementation of control interventions focused on co-infection.
    Full-text · Article · Mar 2012 · Theoretical Biology and Medical Modelling
  • Source
    • "There is currently a great effort focused on the development of microbicides to prevent sexually transmitted diseases (STDs). Epidemiological studies consistently demonstrated that recurrent infection by herpes simplex virus (HSV) increases the risk of HIV-1 acquisition and enhances HIV-1 replication[25,26]. PRO 2000, a synthetic naphthalene sulfonic polymer, interacts with viral glycoproteins gp120 of HIV and glycoprotein B of HSV-2 and has been tested as microbicide to prevent viral infection. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Current small animal models for studying HIV-1 infection are very limited, and this continues to be a major obstacle for studying HIV-1 infection and pathogenesis, as well as for the urgent development and evaluation of effective anti-HIV-1 therapies and vaccines. Previously, it was shown that HIV-1 can infect cotton rats as indicated by development of antibodies against all major proteins of the virus, the detection of viral cDNA in spleen and brain of challenged animals, the transmission of infectious virus, albeit with low efficiency, from animal to animal by blood, and an additional increase in the mortality in the infected groups. Using in vitro experiments, we now show that cotton rat cell lines engineered to express human receptor complexes for HIV-1 (hCD4 along with hCXCR4 or hCCR5) support virus entry, viral cDNA integration, and the production of infectious virus. These results further suggest that the development of transgenic cotton rats expressing human HIV-1 receptors may prove to be useful small animal model for HIV infection.
    Full-text · Article · Jun 2009 · Virology Journal
Show more