Scientists have proved what they long suspected: The less virus in an HIV-infected person's blood, the less his or her chance of passing it on to a partner of the opposite sex.
The large study, done by Johns Hopkins researchers in rural Uganda, found that with every 10-fold rise in the concentration of HIV in the bloodstream, transmission more than doubled.
This common-sense notion has been shown in mother-to-baby HIV infection, but it had never been examined in sexual transmission, the predominant way people get HIV.
Its implications are far-reaching, since certain medicines are able to lower the amounts of the human immunodeficiency virus in the bloodstream. Experts say that could be one way to slow the epidemic.
"This is an incredibly important finding," said Dr. Tom Coates, director of the AIDS Research Institute at the University of California, San Francisco.
"It points to the possibility that not only do we get clinical benefit for the individual, but maintaining people on drug regimens may also have enormous public health benefit in terms of reducing infections."
The study, published in today's New England Journal of Medicine, is part of larger work Hopkins investigators were doing in rural Uganda. They were trying to find out whether treating other sexually transmitted diseases could lower HIV transmission rates. It did not.
In trying to figure out why, researchers analyzed 415 heterosexual couples. One partner in each couple was HIV-negative; the other was HIV-positive.
The data on the couples, who had been monitored for 2 1/2 years, showed that those who had fewer than 1,500 copies of the virus per milliliter of blood didn't transmit HIV to their partners.
Like most in Uganda, none of those people had access to the expensive drugs that can lower the viral level in a person's blood. Some just had higher levels in their blood than others. The key question for scientists is whether lowering a person's viral level with the drugs would accomplish the same thing.
"It offers hope to everyone globally who is infected with HIV or those at risk for HIV," said Dr. Thomas C. Quinn, the study's lead author and a professor of medicine at Hopkins, "because on the basis of this study, more work will be done to try and develop other means, not just the drugs, but vaccines and microbicides, to effectively lower the viral load in infected people."
Virus down but not out
In the United States, Quinn and others said, doctors are using anti-viral medicines to push the level down as far as 50 copies per milliliter of blood and lower. But even when researchers have pushed HIV down so far it is undetectable in blood, they have found the virus in semen and cervical secretions, said Dr. Ronald Valdiserri, deputy director of the National Center for HIV, STD and TB Prevention.
He and others cautioned HIV patients to remember that they are still at risk.
"None of these lowers your risk to zero. You may get lucky a few times, but you hit it at just the right time and your luck unfortunately can run out. It's really a crap shoot," said Dr. David Butcher, director of clinical affairs at Chase-Brexton Health Services.
He said he sees many HIV patients who, because they are being treated, have the misconception that they can't pass on the virus.
Worse, an increasing number of HIV patients in Baltimore, particularly injection drug users, are going on and off their anti-viral drugs, creating resistant strains that they are transmitting to others, said Dr. William A. Blattner, associate director of the Institute of Human Virology at the University of Maryland.
The Hopkins study found that circumcised men had a sharply lower chance of getting the virus. Of the 50 HIV-negative male partners who had been circumcised, none became infected despite exposure to an HIV-positive partner, no matter how high the woman's HIV level.
Quinn thinks that is because men who are not circumcised still have the soft foreskin that is susceptible to tiny breaks during intercourse, allowing viruses in. This might explain why, in heterosexual sex, American men are less likely than women to contract HIV, because most American men are circumcised.
Not absolute protection
Doctors stressed that circumcision does not give men absolute protection. But an accompanying editorial suggested that countries where HIV is endemic consider promoting circumcision for the benefit of reduced infections.
The writer, Dr. Myron S. Cohen of the University of North Carolina at Chapel Hill, also noted that this would raise cultural and medical issues, including the risk of complications, that would be difficult to handle.
The Hopkins report also sparked an unusual second editorial, written by the journal's editor, Dr. Marcia Angell. She questioned the ethics of the study, including whether Hopkins researchers should have informed the HIV-negative subjects of their risk, or whether HIV-positive subjects should have received anti-viral drugs.