Drug combo routs HIV from blood to tissue.

Even after drugs have banished HIV from the bloodstream, the virus may still lurk in the lymphoid tissues of the body A successful AIDS-preventive treatment must therefore destroy HIV hiding in those tissues. If not completely routed, the virus may ultimately rebound.

A new study now demonstrates that a three-drug regimen clears nearly all of the virus from the lymphoid tissue of adults with advanced HIV infection. A second report shows that another three-drug treatment results in a striking reduction of the virus in the bloodstream of some HIV-infected babies.

Some researchers view such results as the first step toward the ultimate goal of a complete cure--for both adults and children. Others remain wary. Even if drug therapy can quash most of the virus in the body, there's still a chance that any remnants will smolder and later ignite a fire of infection, warns virologist Winston Cavert of the University of Minnesota Medical School in Minneapolis.

In the first study, Cavert's team focused on the lymphoid tissue. The researchers wanted to find out whether drug regimens that clear HIV from the blood would also shut down HIV factories in the tonsils and lymph nodes.

They studied 10 HIV-infected people who were being treated with a regimen of ritonavir, AZT, and lamivudine. Ritonavir belongs to a new class of drugs, called protease inhibitors, that has generated considerable optimism in the war on AIDS (SN: 7/13/96, p. 21). The other two drugs inhibit reverse transcriptase, an enzyme crucial to viral infection.

After 6 months, the researchers tested a snip of lymphoid tissue from the tonsils of the patients. In the May 9 Science, the scientists report that the treatment's triple whammy had eliminated 99.9 percent of HIV--even in the tissues' follicular dendritic cells, which trap and store HIV.

"That [result] tells us that antiviral therapy is having a profound effect, even at the level of lymphoid tissue," comments Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases in Bethesda, Md.

The second study, published in the May 8 New England Journal of Medicine (NEJM), looks at HIV in the bloodstream. Katherine Luzuriaga of the University of Massachusetts Medical School in Worcester and her colleagues worked with eight babies who had been infected with HIV early in life, probably at birth. Typically, doctors give such infants a single antiviral drug. Luzuriaga's team wanted to try a three-pronged attack with AZT and two other drugs that also block reverse transcriptase.

In all but one of the babies, the triple-drug therapy dramatically reduced HIV infection. The team observed a 96 percent or greater drop in the concentrations of viral RNA after the first 4 weeks of treatment. Subsequently, HIV reasserted itself in some of the seven infants, but the treatment maintained at least a 32 percent reduction in viral RNA concentrations throughout the 6-month study. In two babies, HIV was cleared to almost undetectable amounts.

The researchers did not look for HIV sequestered in the lymphoid tissues, Luzuriaga says. However, there's no reason to believe that the drug therapy failed in that quarter, according to Fauci. Luzuriaga hopes to continue the study, perhaps looking at the youngsters' tonsils after they have been on a potent drug regimen for 2 years.

Luzuriaga believes that a three-drug attack which includes a protease inhibitor might prove even more effective at clearing HIV infection in babies, and she has already modified the regimen for some of the infants. Furthermore, she says the results might have been even better if the researchers had administered the drugs in the babies' first month of life rather than starting treatment at 2 to 16 months of age.

A third study, in the same issue of NEJM, underscores the importance of immediate treatment for babies with HIV infection.

William T. Shearer of the Baylor College of Medicine in Houston and his colleagues show that the amount of HIV in the blood peaks 1 to 2 months after birth and declines only slowly during the next 2 years. This finding may explain why babies with HIV tend to get sick and die faster than adults. In adults, the amount of virus peaks and then drops dramatically.