Washington Post

Tuesday, February 1, 2000

Africa Studies Raise AIDS Vaccine Hopes

By David Brown

SAN FRANCISCO, Jan. 31 -- A low concentration of the AIDS virus in the bloodstream greatly decreases the chance that an infected man or woman will transmit the disease to a heterosexual partner, according to two studies from Africa presented at a scientific meeting here.

That observation raises the possibility that an imperfect AIDS vaccine may yet be useful in the region where 70 percent of the world's cases of human immunodeficiency virus (HIV) infection occur. Specifically, it suggests that a vaccine that fails to block initial infection--but does manage to lower a person's "viral load"--may reduce that person's ability to pass the virus on to someone else.

Nearly 70 percent of the 34 million people living with HIV live in sub-Saharan Africa, where heterosexual intercourse is the dominant mode of virus transmission. The two studies, presented at the Seventh Conference on Retroviruses and Opportunistic Infections, looked at the experience of African couples in which one person was infected with HIV and the other was not.

In a study from the rural Rakai district of Uganda, researchers followed 415 "HIV-discordant" couples for 30 months. In slightly more than half, the man was the partner infected. In 90 of the couples (about 22 percent), the uninfected partner ultimately acquired the infection. Male-to-female transmission was as likely as female-to-male.

The big determinant of transmission was viral load. People with more than 50,000 viruses per milliliter of blood had 10 times the chance of transmitting their infection as people with fewer than 3,500 viruses per milliliter. In the 50 couples in which one partner had a viral load less than 1,500, there were no transmissions at all.

A study in Lusaka, Zambia, produced nearly the same results. There, 109 individuals in 500 discordant couples became infected. The average viral load in the transmitting partner was 38,000. For every 10-fold increase in bloodstream virus concentration, the risk of transmission more than doubled. No one with less than 1,000 viruses per milliliter passed on the infection.

"Reduction of viral load by [antiviral] therapy or by therapeutic vaccines could reduce transmission," said Thomas C. Quinn of Johns Hopkins University, who helped conduct the study in Uganda. He emphasized, however, that there's no direct evidence that a low viral load achieved by drug treatment behaves the same as a low viral load achieved "naturally" by native immune defenses.

Nevertheless, the findings injected some hope into the generally dispiriting field of HIV vaccine development.

No experimental vaccine to date has reliably blocked infection in large-scale studies of laboratory animals. Several, however, have sufficiently stimulated immunity that virus growth is dampened after infection takes hold. This is especially true in vaccines that stimulate the production of immune-system cells directed at HIV-infected cells, as opposed to vaccines that stimulate antibodies that attack free-floating virus.

Two such studies were described here. One used vaccinia virus (the microbe that for years was used as a vaccine against smallpox) into which genes of simian immunodeficiency virus (SIV), the monkey equivalent of HIV, had been spliced. The other used fragments of "naked" SIV DNA. In both cases, monkeys that were vaccinated and then injected with SIV became infected. However, their viral loads were lower than those in unvaccinated infected animals. In the case of the DNA vaccine, the viral load in some animals dropped into the undetectable range after an initial burst of growth.

These various lines of research are a reason to test HIV vaccines that, by conventional measures, might seem less than promising, said Gary Nabel, head of the Vaccine Research Center at the National Institutes of Health.

Because laboratory studies haven't revealed what immune system response is the optimal one, only field trials of "candidate" vaccines in places where HIV prevalence is high and many people are at risk will reveal whether imperfect ones have real utility.

"We don't want to tie ourselves to some laboratory tests, whose significance is not known," said Nabel.

In other research, a scientist at the Centers for Disease Control and Prevention gave further evidence that recent advances in the treatment of HIV infection may be lulling some people into thinking they can participate in unsafe activities with relative impunity.

In a seven-state survey of equal numbers of male homosexuals, intravenous drug users, and heterosexuals, 31 percent said they were "less concerned" now about becoming infected than they were in the past, and 17 percent said they were "less safe" in their habits.

The highest proportion of people expressing less worry was among drug users, especially African American drug users. Among homosexual men, about 70 percent of those who said they were being less careful had participated in unprotected anal intercourse, compared with about 45 percent of those who said they weren't being any less careful than in the past.