News Release

HIV variant in U.S. and Europe found rare in Africa AIDS cases

Peer-Reviewed Publication

University of North Carolina Health Care

CHAPEL HILL, N.C. - A genetic variant of HIV that is tied to more rapid disease progression in the United States and Europe is rare in Africa, according to a new study headed by researchers at the University of North Carolina at Chapel Hill.

The findings published in the August issue of the Journal of Virology add important new knowledge to HIV subtype C, which now infects more than half the people infected with HIV in the world. The new study may make scientists re-think certain aspects of the design of HIV vaccines and AIDS therapies for underdeveloped regions, particularly sub-Saharan Africa and India, where the epidemic is expanding.

In the United States and Western Europe, subtype, or "clade," B is the major subtype of HIV and the most extensively studied. About 50 percent of people infected with this subtype develop a genetic variant that is altered in that portion of the virus envelope that binds it to the host's cell. When the variant appears, the number of immune system CD4 T cells drops rapidly, which implies that the disease is progressing more rapidly. With immunity reduced, the individual becomes increasingly susceptible to potentially lethal infections, such as pneumonia.

"As we studied clade B, we thought that as it evolved it became more aggressive and killed the host. Not so in Malawi where HIV didn't change but people still died," said Dr. Myron Cohen, study co-author, professor of medicine and director of the Center for Infectious Diseases at the UNC-CH School of Medicine.

"One might say that if you don't have the variants, maybe the disease course should be longer. But, in fact, in sub-Saharan Africa, the little data that is out there suggests that it's faster, not slower," said Dr. Ronald Swanstrom, UNC professor of biochemistry and biophysics, director of the UNC Center for AIDS Research and senior author of the study.

The specific envelope region in which the virus shows changes in its gene sequences is known as V3. The virus uses this region to gain entry into the host's T cells by way of cellular co-receptors known as CCR5. However, the clade B HIV variant associated with rapid AIDS progression switches co-receptor usage - from CCR5 to CXCR4. (This switch lends the variant its name: X4)

"V3 determines which one of these receptors is used. When you find a population of viruses that only use CCR5, then there's almost no variability in V3," said Swanstrom.

"Over the years, we've been asking what's the real role of V3," he added. "Its variability is associated with the switch in co-receptors. Now we know it's clearly not the primary neutralization target for a vaccine."

Cohen raised the possibility that the X4 variant's presence might lower the chances of HIV transmission. He pointed out that in the United States, the variant is very rarely transmitted.

"So one can imagine that the fraction of people late in disease who develop this variant potentially become less infectious," Swanstrom noted. "And the flip side is if that doesn't happen in Africa, you have the potential for higher transmission rates."

Swanstrom acknowledged that this is still conjecture requiring further collaborative research with UNC's infectious disease division. "We're starting to look at blood and semen samples from patients with late-stage disease to find out if, when you see a predominance of X4 variants in the blood, you also see a predominance of X4 variants in the semen."

"It's surprising that different subtypes of HIV in different parts of the world would have different biological properties," Swanstrom said. "It's likely to impact on features of the epidemic in ways that we don't understand right now."

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The study was supported by grants from the Swiss National Science Foundation, the National Institutes of Health, the UNC Center for STD Research, and the UNC Center for AIDS Research.

Note to the media: Dr. Ronald Swanstrom can be reached at 919-966-5710 or email risunc@med.unc.edu. Dr. Myron Cohen can be reached at 919-966-2536 or email MSCohen@med.unc.edu. UNC School of Medicine media contact is Lynn Wooten, 919-966-6046 or email LWooten@unch.unc.edu.


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