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Defective virus may explain rare couple
One LTNP and one elite suppressor
A husband and wife HIV transmission pair offer researchers a rare look at what happens when a long-term nonprogressor is compared over time with an elite suppressor.
In a study presented recently at the 18th Conference on Retroviruses and Opportunistic Infections (CROI) in Boston, MA, investigators described a long-term non-progressor (LTNP) who maintained a stable CD4 T cell count of greater than 500 and a viral load from 1,000 to 5,000 copies/mL.1
The spouse to whom the LTNP transmitted HIV was an elite suppressor with a viral load of fewer than 50 copies/mL without antiretroviral treatment.
"Both patients are infected with the virus, but one maintains elite suppression while the other can control it, but not to clinically-undetectable levels," says Robert Buckheit III, a graduate student researcher at the Johns Hopkins University School of Medicine in Baltimore, MD.
"We're not sure when the virus was transmitted," Buckheit says. "It could have been during acute infection when the viral load was higher."
Even patients who can control HIV without antiretroviral therapy will have a peak viremia period, although it is extremely reduced compared to patients who have progressive HIV, he adds.
The couple had been infected for about a decade, and the wife, who was the elite suppressor, had been on antiretroviral therapy twice during pregnancies. There had been no change in her viral load or CD4 T cell counts, Buckheit says.
The husband had never been on antiretroviral therapy.
"In this case we believe their virus is defective relative to typical HIV," Buckheit says. "We've done assays with the virus cultured out of these patients, and it seems less fit than laboratory reference strain."
This might partially explain the couple's resistance to progressive HIV disease.
"We hypothesized that infection with attenuated virus can increase your likelihood of progression to control, but there still are unique host factors that lead to elite suppression," Buckheit says.
"I think in the grand scheme of things this is a very unique case in which an attenuated virus infected both of these patients," he adds.
Although the discovery of such a pair of HIV patients raises questions about whether HIV's evolution might one day lead to increases in attenuated virus, Buckheit says that is unlikely to happen.
"Imagine the whole spectrum of HIV viruses out theresome will not be replication competent, but the majority are replication competent," he says. "Some are very pathogenic and cause severe disease in patients, so I don't think we'll see a withering away of HIV; HIV will continue."
In another case, investigators observed a patient with progressive HIV who transmitted the competent virus to an elite suppressor, he notes.
"The elite suppressor's host T cell response maintained mutations that made the virus less fit compared to the progressor, a phenomenon where elite suppressors truly have host mechanisms that can either diminish the fitness of HIV or control very robust HIV replications," Buckheit explains.
The next step in studies of elite suppressors would be to focus on the evolution of virus in these patients and to look at their latent reservoir and viral factors, including viral fitness, he says.
"My research will continue along that line," he adds. "Is the virus fit in elite suppressors, and what affect does elite suppression have on viral fitness?"