Rationale for Anti-AIDS Chemotherapy Directed at HIV-1 Infected Dendritic Cells in Seropositive Individuals Prior to the Appearance of ARC and AIDS

Abstract

An approach to anti-AIDS chemotherapy is presented from the point of view of treating seropositive individuals by eliminating the infected dendritic cells that are the in vivo target of HIV-1. Special attention is given to the treatment of Langerhans (dendritic) cells in the skin and epithelia that are infected in vivo by HIV and are involved in the development of the symptoms leading to AIDS and ARC. Since HIV is released through the cervical and vaginal epithelia in seropositive women, it is suggested that combined local treatment of vaginal epithelium with steroids that inactivate dendritic cells and azidothymidine (AZT) that inhibits HIV-1 replication might prevent virus dissemination. Abrogation of HIV-1 transmission will help to prevent its spread throughout the heterosexual population. Thus a new rationale for anti-AIDS treatment is presented, namely selective elimination of HIV-1 infected dendritic cells in the skin and epithelia of infected individuals before the appearance of ARC or AIDS. Subsequent restoration of dendritic cells in HIV-1-infected persons (and in AIDS patients) by means of orally administered retinoids in combination with an antiviral drug might be a useful approach to prevent or delay AIDS.

Management of Occupational Exposures to Blood-Borne Viruses

“…79,80 There is no evidence that these approaches would be of any benefit, and some might even paradoxically promote HIV infection by interfering with normal host defenses. 81 Passive immunization with hyperimmune globulin is an attractive concept in the light of the success of this approach to HBV prophylaxis, but it must await the development of antigens that can generate antibodies capable of reacting with wild-type HIV strains.…”

Reduced numbers of Langerhans cells and increased HLA‐DR expression in keratinocytes in the oral gingival epithelium of HIV‐infected patients with periodontitis

“…HLA-DR expression by gingival KC has been demonstrated in several forms of gingival and periodontal diseases, such as chronic gingivitis, CMP, and rapidly progressive periodontitis (Walsh et al 1985, Johannessen et al 1986, Katz et al 1987. Although HIV can not infect KC (Becker 1990), HIV causes increased production of proinflammatory cytokines in vitro by the cells (Dreno et al 1990), and may thereby induce skin and mucosal inflammatory diseases that are often seen in AIDS patients. It is conceivable that increased production of proinflammatory cytokines by gingival KC may amplify pre-existing periodontal disease in HIV π patients and lead to exacerbation.…”

Role of Langerhans cells and other dendritic cells in viral diseases

“…In addition, preliminary data indicate that several immunomodutators, such as OK-432 and retinoids, hold promise in the treatment of HSV-1 and HIV-1 infection [6,61,129,141] while agents inhibiting dendritic cell function may serve in the management of chronic viral diseases [47,55,145]. Finally, dendritic cells have been recently used as a "physiological adjuvant" in a new vaccination approach based on extracorporeal pulsing of autologous dendritic cells with whole antigens and subsequent immunization to trigger cellular and humoral responses [53,125].…”

“…Although zidovudine therapy reverses some defects in peripheral dendritic cell function [68], it does not restore normal Langerhans cell density in HIV-l-infected individuals [34]. Thus, correction of Langerhans cell dysfunction by administration of various immunomodulators [43,44,110,120,141,144] could serve as a useful adjuvant therapy in the treatment of AIDS patients affected by opportunistic infections [6,128,141].…”