The case of an HIV-positive Baltimore married couple appears to rule out the competing notion -- that so-called "elite suppressors" were infected with a weaker strain of the virus, according to Joel Blankson, M.D., Ph.D., of Johns Hopkins, and colleagues.
Both partners are infected with the same HIV strain, but in the case of the male it has led to progressive disease that is controlled by highly active antiretroviral therapy (HAART), Dr. Blankson and colleagues wrote in the August issue of the Journal of Virology.
The female partner, on the other hand, has never had symptoms of HIV disease, has consistently had levels of HIV RNA in her blood that are below the level of detectability, and has never needed drug treatment, the researchers said.
A series of experiments showed that the woman has a robust CD8-positive T cell response to the virus. At the same time, she had an antibody response to HIV that "wasn't impressive, by any stretch of the imagination," Dr. Blankson said.
The implication is that "immune control of the virus is possible," he said, but through T cells, not neutralizing antibodies. Such a T-cell vaccine would be used therapeutically, rather than to prevent infection.
Recent trials aimed at eliciting a T-cell response have not come up with a successful vaccine candidate, but Dr. Blankson said he thinks this study gives "cause for optimism." (See NIAID Urges 'Accelerated' HIV Vaccine Research)
The man and woman in the study are monogamous, but the husband has a history of injection drug use, while the only risk factor for the wife is sexual activity in the marriage, the researchers said.
The man was diagnosed with HIV 10 years ago after two opportunistic infections. At the time, his viral load was higher than 200,000 copies of viral RNA per milliliter of blood and his CD4-positive T-cell count was 266 cells per microliter.
The woman also tested positive by an HIV antibody test, but her viral load was always less than 50 copies per milliliter and her CD4 count was always greater than 800 cells per microliter.
While isolating virus from the woman was "challenging," the researchers said, a home-grown method that is more sensitive than standard approaches allowed them to obtain replication-competent samples.
Viral isolates from the partners were genetically more similar to each other than to any other isolate from a large library, suggesting that both were infected with the same strain.
One immediate implication is that the woman's immune system is controlling a viral strain that is pathogenic, because it caused disease in her husband. Dr. Blankson said.
Genetic analysis showed that both have the immune allele HLA-*B5703, which is associated with protection against the virus. Dr. Blankson said the allele is clearly not enough to control HIV, because the husband has it as well as his wife.
On the other hand, the wife has the immune system allele HLA-*B2703 -- also associated with protection -- and her husband does not. It's possible, Dr. Blankson said, that the HLA-*B2703 allele allows infected cells to present viral antigens that rev up a CD8 response and prevent the wholesale infection of immune cells characteristic of HIV.
When the woman's CD8 cells were isolated and tested against a laboratory strain of HIV, they completely blocked its replication. They had a similar effect -- although not as complete -- against virus isolated from her husband.
The results also suggest that a qualitatively superior HIV-1-speciï¬c immune response that limits viral replication will prevent evolution of the virus toward greater ï¬tness.
On the other hand, titers of neutralizing antibodies to the Env protein of their virus in both partners were "relatively low," ranging from less than 1:20 to 1:125, the researchers reported.
Taken together, the findings "tell us that hypothetically, a vaccine is possible, without a robust antibody response," Dr. Blankson said.
|The study was supported by the National Institutes of Health and the Howard Hughes Medical Institute. The researchers did not report any conflicts.|
Zalman S. Agus, MD Emeritus Professor
University of Pennsylvania School of Medicine
Journal of VirologySource Reference: Bailey JR, et al "Transmission of Human Immunodeficiency Virus Type 1 from a Patient Who Developed AIDS to an Elite Suppressor" J Virol 2008; 82: 7395-7410.