AIDSWEEKLY Plus, 25 March 1996 issue; Published by Charles Henderson, Publisher. Editorial & Publishing Office: P.O. Box 5528, Atlanta, GA 30307-0528 / Telephone: (800) 633-4931; Subscription Office: P.O. Box 830409, Birmingham, AL 35283-0409 / FAX: (205) 995-1588
Daniel J. DeNoon, Senior Editor

AIDS among heterosexuals would greatly increase in the U.S. and Europe if HIV strains common in most of the world became established in the west, a leading expert warns.

Nearly all HIV vaccines currently in development use antigens derived from U.S. and European strains.

But according to Harvard AIDS Institute researcher Max Essex, AIDS is not the same epidemic in all parts of the world.

"We have two distinctly different HIV epidemics," Essex said during a plenary address to the Eighth Annual Meeting of the National Cooperative Vaccine Development Groups for AIDS (NCVDG), held February 11-15, 1996, in Bethesda, Maryland.

"If other HIV-1 subtypes take hold in the United States or western Europe, a more extensive heterosexual epidemic will take place."

Essex noted that 85 to 90 percent of heterosexual HIV infections occur outside the U.S. and western Europe. In these areas, where nearly all infections are with clade B HIV- 1 viruses, no more than 10 percent of HIV infections are heterosexually transmitted.

"Heterosexual epidemics are never type B," Essex said.

In contrast, the heterosexual AIDS epidemic is spread by all other types of HIV-1: in Africa by clades A, C, and E; in India by clade D; and in southeast Asia by clade E.

To bolster his hypothesis, Essex pointed to the AIDS epidemic in Thailand. Although clade B HIV-1 strains were present there in the mid 1980s, the dramatic explosion of heterosexual HIV infections did not occur until 1987 following the introduction of clade E virus.

Clade B HIV-1 differs from other strains in that it preferentially infects blood cells, specifically lymphocytes and monocytes, via the cellular CD4 receptor.

But other HIV-1 strains can more easily infect Langerhans cells, one of two major antigen-sampling cells on the epidermis. Essex proposed that Langerhans cell tropism accounts for the greater heterosexual transmission of non-B viruses.

Essex noted that the migratory dendritic cells known as Langerhans cells:

* are present in high densities in the cervix, vagina, and penis foreskin.

* can ingest antigens, such as HIV virions.

* have the CD4 and HLA DR receptors on their surfaces.

* are one of only two types of antigen-sampling cells present on external surfaces.

Most clade B HIV-1 strains grow poorly in Langerhans cells. But all clade E HIV-1 grow significantly better in these cells than do clade B strains.

Conversely, clade B HIV-1 strains grow "a little better" in peripheral blood mononuclear cells (PBMC) than their clade E cousins.

"It is very unlikely that behavioral practices or concurrent sexually transmitted diseases alone can explain the major differences between the two epidemics," Essex said.

It originally was assumed that HIV infects Langerhans cells the same way it infects T cells: via their CD4 receptors. But subsequent studies have shown that anti-CD4 antibodies do not block HIV infection of Langerhans cells.

"Although CD4 is present on Langerhans cells, it is probably not very important for HIV to infect these cells," Essex said.

Since efficient replication in Langerhans cells is a correlate of heterosexual HIV transmission, Essex suggested that vaccines based on clade B isolates will be inappropriate for most of the world.

"Vaccine protocols including only [clade] B envelope antigens are probably quite inappropriate for preventing heterosexual transmission," he said.

"We believe that Langerhans cell tropism is quite important for heterosexual transmission. For vaccines, especially outside the U.S., it is quite important to look for epitopes important for Langerhans cell infection."

Essex was asked why there appears to be an epidemic of clade B HIV-1 infection among heterosexuals in the Caribbean. He suggested that B strains in that area may have developed a tropism for Langerhans cells. He also said that anal intercourse may be more common among heterosexuals in this region, and that concurrent sexually transmitted diseases may be more frequent.

Bonnie Mathieson, chair of the NIH Office of AIDS Research Vaccine Coordinating Committees, said that the heterosexual epidemic of clade B HIV-1 in the southern U.S. contradicts Essex's hypothesis.

She suggested that mutations improving the ability of clade B HIV-1 might occur if the strain were more widespread among heterosexuals.

Copyright (c) 1995 - Charles Henderson, Publisher. All rights Reserved. Permission to reproduce granted to AEGIS by Charles W. Henderson. Authorization to reproduce for personal use granted granted by C. W. Henderson, Publisher, provided that the fee of US$4.50 per copy, per page is paid directly to the Copyright Clearance Center, 27 Congress Street, Salem, Massachusetts 01970, USA.

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Copyright © 1996 - Charles Henderson, Publisher. All rights Reserved. Permission to reproduce granted to AEGIS by Charles W. Henderson. Authorization to reproduce for personal use granted granted by C. W. Henderson, Publisher, provided that the fee of US$4.50 per copy, per page is paid directly to the Copyright Clearance Center, 27 Congress Street, Salem, Massachusetts 01970, USA.