Researchers at the University of Texas (UT) Southwestern Medical Center in Dallas are offering the first plausible, molecular explanation of the behavior of the human immunodeficiency virus (HIV) in people with syphilis. The virus is transmitted more easily to or from people infected with syphilis. This knowledge could lead to treatments that slow the progression of HIV disease, they say.
"Syphilis, too, is a chronic, systemic illness in which the bacteria migrate rather freely throughout the body causing inflammation at numerous sites," said Dr. Michael Norgard, acting chairman of microbiology at UT Southwestern Medical Center. "By estimating what probably occurs in the genital ulcers caused by syphilis, we surmise that systemic levels of bacteria from that disease may actually activate immune cells throughout the body. Higher levels of HIV, which then result, could interfere with the efficacy of HIV treatment and even accelerate the course of AIDS."
Latent HIV Gene Expression
In a collaborative effort, Drs. Richard Gaynor and Justin Radolf, scientists in the laboratories of Dr. Norgard and professors of internal medicine and microbiology, looked at immune cells in laboratory dishes to determine whether the syphilis bacterium or its membrane lipoproteins could trigger latent HIV gene expression. Drs. Gaynor and Radolf were interested in seeing whether gene expression appeared in the primary genital ulcers, or chancres, of syphilis.
"We think the lipoproteins, a class of cell-membrane proteins in the syphilis bacterium, predominantly cause the inflammatory processes that typify the disease," said Dr. Norgard. "What is implied in our findings is that syphilis may predispose a person toward more rapid progression of HIV disease," he said.
No other studies of the effect of syphilis on the progression of HIV into acquired immunodefiency syndrome (AIDS) have been done. What is known, however, is that patients with chronic secondary infections associated with AIDS exhibit higher HIV levels because of the constant stimulation of the body’s immune system.
"This research is especially significant because we combined two areas of molecular biology--HIV and syphilis--so that we could develop experimental models and determine more fully the association between the two diseases," said Dr. Radolf.
Connection Between HIV and Syphilis
According to the Centers for Disease Control and Prevention (CDC), people with syphilis are two to five times more likely to transmit or contract HIV than are individuals not infected with a sexually transmitted disease. Epidemiologic studies have attributed this phenomenon to the open sores on the genitals or oral cavities of people with syphilis.
Future research could involve a clinical study designed to find out whether patients infected with both HIV and syphilis have higher levels of the virus before they are treated for the syphilis bacterium. Identifying people with syphilis, however, is more difficult than curing them because many people avoid seeking help due to fear, lack of money, or the absence of convenient medical facilities.
Syphilis has a long progression and can lay dormant for years if untreated. If the bacterium enters the nervous system, it can lead to blindness, impotence, or insanity and can be fatal. But the disease is usually curable with an intramuscular injection of a slow-acting penicillin.
Although the number of cases of syphilis in the United States have declined steadily over the past few years, it remains a major public-health problem. The CDC reports that the disease is more prevalent among blacks, and the region of the country with the highest rate of the disease, the South, is also the area with the largest number of heterosexually transmitted cases of HIV. According to Dr. Anthony Fauci, director of the National Insititute of Allergy and Infectious Diseases, the number of HIV cases transmitted through male-female sexual contact in the United States increased from 4.8% in 1988 to 20.3% in 1997. About 860,000 US residents have the AIDS virus.
"Our research is a first step toward understanding the molecular events that may trigger activation of the immune cells that support HIV replication in the setting of syphilis co-infection," said Dr. Norgard.
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