Blood, semen harbor distinct HIV mutations.

Research on AIDS has hinted that HIV can evolve along distinct lines in an infected man's blood and semen. Studies also have shown that the virus mutates in ways that make it resistant to some drugs. U.S. and Swiss researchers now report findings that combine these concepts: Genetic mutations sometimes lead to different patterns of drug resistance in a man's blood and semen.

The scientists find, for example, that viral mutations providing resistance to anti-HIV drugs emerge in the blood but not the semen of some men, that the opposite also occurs, and that sometimes two distinct mutations bestowing resistance against the same drug arise in the different locations in the same man. They report this compartmentalization of HIV mutations in the Oct. 22 journal AIDS.

The drug-resistant HIV probably derives from a mutated virus that survived the drugs that killed off the main viral population, says Ann A. Kiessling, a virologist at Harvard Medical School and Beth Israel Deaconess Medical Center in Boston. In a study released last year, Kiessling and her colleagues analyzed semen and blood from an HIV-positive man who had taken antiviral drugs for several years and a protease inhibitor for 4 months. The man's blood revealed HIV resistance to protease inhibitors, but his semen didn't.

In the new, larger study led by researchers at the University of North Carolina (UNC) at Chapel Hill, HIV showed mutations associated with resistance to medication in 8 of 11 HIV-positive men whose blood and semen were tested periodically for up to 58 weeks. As in Kiessling's study, not all of the mutations arose on parallel tracks in blood and semen.

Of the eight men who developed resistance to anti-HIV drugs, seven had viral substrains in their semen that were different from those in their blood. For example, one patient developed viral mutations indicating resistance to the drug AZT in his blood but not in his semen. Three other men developed AZT-resistance mutations in both semen and blood, but the timing varied. Surprisingly, one showed resistance in his semen earlier than in his blood.

Resistance to protease inhibitors, drugs that dramatically slow replication of virus-infected cells, varied as well. In two patients, mutations subverting these drugs appeared only in the blood. "This suggests the possibility that the protease inhibitors were not getting into the semen [in these men]," says study coauthor Myron S. Cohen, an infectious disease specialist at UNC.

The compartmentalization indicates that blood tests for HIV may not reveal a drug-resistant virus in semen. "If men are sexually active and pass it on, the next person will have that much more difficulty benefiting from the drugs," Cohen says.

"This underscores [the point] that just because you're on antiviral therapy, it doesn't mean you don't have to practice safe sex," says Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases in Bethesda, Md.