Bulletin of Experimental Treatments for AIDS Important note: Information in this article was accurate in April 1999. The state of the art may have changed since the publication date.
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HIV Transmission and Origins

Bulletin of Experimental Treatments for AIDS, Spring, 1999
Harvey S. Bartnof, MD


New CCR5 Gene Mutation Increases Risk of Mother-to-Newborn Transmission

Researchers from the Aaron Diamond AIDS Research Center in New York presented new information at CROI that may help to explain higher rates of HIV transmission among people of African descent. In the past two years, the discovery of a specific CCR5-D3 double gene mutation affecting immune cells helped to explain why certain high-risk gay men remained HIV negative. Now, a third CCR5 mutation has been discovered. However, instead of decreasing HIV transmission risk, this new mutation appears to increase the rate of HIV transmission, at least from mothers to newborns.

The new mutation is called CCR5-59356-C/T. The researchers examined the rate of the new mutation in 1,435 infants born to HIV positive mothers in the U.S. Among the 663 African-American infants whose mothers did not take AZT, 48% became infected with HIV when they had two copies of the mutant gene. This was significantly greater than the 14% transmission rate among African-American infants who had no copies or only one copy of the mutant gene, even when their mothers did not take AZT. The researchers reported that approximately 20% of African-Americans carry the newly discovered mutation. They also commented that the mutation appears to be common in West Africa. The new findings may help to explain the higher rates of perinatal HIV transmission in sub-Saharan Africa.

The occurrence of the new mutation must be examined in other racial/ethnic groups and in sexual transmission cohort studies. It is also possible that the new mutation may be a co-factor in the rate of HIV disease progression.

Kostrikis, L.G. and others. "Polymorphisms in the regulatory regions of the CCR5 influence perinatal transmission of HIV", 6th CROI. Abstract 263.


Four Persons Infected with HIV at Physician's Office in 1989

The final confirmation of HIV transmission to four persons in a health-care setting was presented at CROI. While an initial report appeared in the Lancet in the early 1990s, definitive proof was only recently documented. The initial report indicated that four of 17 persons who had minor skin surgery in a general practitioner's medical office in Australia on November 13, 1989, were HIV antibody positive. A fifth patient was a man known to have AIDS. The physician was HIV antibody negative, as were the remaining 12 patients. Most of the 17 had skin biopsy procedures.

Nitin Saksena, PhD, from the University of Sydney presented detailed PCR analyses of the HIV strains originally isolated from the four HIV positive persons. HIV proviral (integrated into the human chromosome) DNA was used from blood lymphocytes and plasma. A sample from the man with AIDS was not available, since he had died. When compared with 20 random HIV isolates from other HIV positive persons in the community, the isolates from the skin surgery patients were significantly different; however, the strains from these four persons were distinctly similar to each other. Saksena and colleagues concluded that the case histories plus the new laboratory findings confirm a likely single source of HIV transmission, as had been strongly suspected. Saksena believes that the outbreak likely occurred due to a breach in infection control procedures by the physician. A biopsy instrument, needle, syringe, or anesthetic bottle first used on the person with AIDS likely became contaminated with HIV. Due to inadequate sterilization or cross-contamination, the four others became infected with HIV later that day when the same instrument or anesthetic bottle was used on them.

The other two examples of documented HIV transmission in a health-care setting include a Florida dentist and a French orthopedic surgeon. Since the 1989 Australian case, physicians and surgeons in developed countries are much more knowledgeable regarding appropriate infection control guidelines to prevent HIV transmission in health-care settings.

Saksena, N.K. and others. "Significance of simultaneous use of multiple HIV-1 genomic regions from cell-free and cell-associated virus in establishing epidemiologic linkage between four individuals who acquired HIV via surgical procedure", 6th CROI. Abstract 280.


Origin of HIV is Traced to Chimpanzees

Beatrice Hahn, PhD, from the University of Alabama presented research indicating that HIV originated in a subspecies of chimpanzees from western equatorial Africa. She and her colleagues determined that the DNA genetic sequence of SIV from the chimpanzee subspecies Pan troglodytes troglodytes is very closely related to HIV-1. Chimpanzee and human genes are 98.5% identical.

Hahn's presentation indicated that SIV crossed into humans in western equatorial Africa at least three times in the past. She believes that this most likely occurred due to blood exposure during the hunting or possibly eating of chimpanzees in that region. Since these chimpanzees do not become ill from SIV infection, Hahn emphasized that studying their immune systems could provide key insights leading to new HIV treatments and an HIV vaccine for humans. She commented that this may be difficult, however, due to the small remaining number of these chimpanzees. The population of this species has decreased significantly due to lax enforcement of local poaching laws and the progressive loss of rain forests due to urban growth. As a result of Hahn's report, the Rainforest Action Network of San Francisco declared that preserving African rain forests and the chimpanzees is extremely important, or "the cure for AIDS may be lost forever." Hahn's report was published in the February 4, 1999 issue of Nature.

Gao, F. and others. "Origin of HIV-1 in Pan troglodytes troglodytes", Nature 1999 Feb 4;397(6718):436-41.

Hahn, B. The origin of HIV-1: a puzzle solved? 6th CROI. Abstract S2.

Harvey S. Bartnof, MD, has been a member of the Scientific Advisory Committee of the San Francisco AIDS Foundation since 1987.

DT 19990410
DOCN BE990412


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