Special Coverage: Retroviruses Conference 2006

HIV seroconversion time is more similar among patients than not

Very rare case prompted study question

North Carolina investigators came across a very unusual HIV case that raised the question of how long it takes for people infected with HIV to experience seroconversion.

"We had one case that was the genesis of the whole project," says Charles Hicks, MD, an associate professor at Duke University Medical Center in Durham, NC.

"This very unusual case was used to spur analysis of a larger cohort of HIV-infected patients we had been following, who were diagnosed during acute infection," Hicks says.

Hicks and co-investigators found that people infected with HIV typically will have a positive antibody test within a month's time.1

The case that started the inquiry involved a man who became sick in September, 2003, and was given the standard antibody test for HIV. The test was negative, but because of the man's history and the clinicians' suspicion that he might be HIV-positive, a viral load test was done, and it showed that the man was HIV infected, Hicks explains.

"He was acutely infected," he says. "The man didn't keep his appointment to follow-up in our clinic, and from September to December he was not seen on a regular basis."

Then in December, 2003, the man returned to the emergency room with severe shortness of breath, weight loss, and he was hospitalized with Pneumocystis carinii pneumonia (PCP), Hicks says.

"It had only been three months since he was first sick, and it looked like his disease had progressed very dramatically," Hicks says. "Also, an additional three months had lapsed, and his regular blood test continued to be negative."

The man was treated for his pneumonia and was started on antiretroviral drugs, Hicks says.

"Unfortunately and unbeknownst to his doctor, the virus the man was infected with was a virus resistant to one or more drugs, so he didn't develop a decent response," Hicks says.

In April, 2004, the man was switched to an alternative treatment, which controlled his viral load, he says.

Still, the man's HIV antibody test continued to be negative until September, 2004, a year after he was diagnosed, and this result was in conjunction with the man's virus being controlled and his body rebuilding the T-cell count, Hicks says.

"Our question was how unusual was it for people after infection to not have a detectable antibody test, and how long does it usually take for an antibody test to turn positive," Hicks says. "We wanted to know what was going on with this guy that made his situation so different."

The study involved patients with symptomatic acute HIV-1 infection who were diagnosed within 30 days of seroconversion.1

"We found that half of the patients, at the time of initial evaluation, had a negative antibody test, but in general that was quickly followed by a positive antibody test," Hicks says.

"For those who had a negative antibody test, it appeared that this was just a function of their having been diagnosed earlier," Hicks says. "With a little more time, everybody's test turned positive."

The average time from when people got sick to when the antibody test was positive was about 25 days, he adds.

Despite investigators' experiences with the man whose seroconversion took at least a year, the study showed that most seroconversions take place within one month of infection, Hicks says.

"For the vast majority of people with symptomatic acute infection, within less than a month their antibody test is positive," he says. "But it's possible in unusual circumstances, as in this one patient, it can be delayed very dramatically."

The study's take-home message is that physicians should follow their instincts when presented with a patient who appears to have symptoms of acute HIV infection and have an RNA test done if the antibody test is negative, Hicks says.

As for the one unusual case, researchers investigated several theories about why his seroconversion was so delayed, but found no definitive answers.

"Was his virus different from everybody else's, or was his genetic background one that makes it harder for him to get the antibodies?" Hicks says. "Is it the virus or host or a combination interplay between the two?"

Investigators tested the patient's antibody cells to see if they could make antibodies, and they seemed to function as well as a normal host, Hicks says.

"It did not appear that his ability to generate antibodies was in any way abnormal," Hicks says. "His virus was a little unusual, and it appeared to be a dual tropic virus."

Dual tropic viruses are uncommon, and were a prominent topic of discussion last year when mainstream media reports told of the New York City case of a man who had a multiple-drug resistant virus, combined with rapid disease progression, and his virus was a dual tropic virus, Hicks notes.

The North Carolina case involved rapid disease progression, but the drug resistance was more limited than the NYC case, he adds.

"We can't be certain when the man was infected, but I was certain it was an acute infection in September, 2003," Hicks says. "People ask, 'How do you know he wasn't infected for years and years and this is the end of a normal pattern where he gets PCP and complications?'"

There are a number of reasons why that's not true, Hicks says.

First, the man's symptoms were characteristic of a new infection: the man transmitted a resistant virus, and this was a relatively new phenomenon, he says.

Also, there was a total absence of antibodies to HIV, he says.

"We looked very hard in the literature for any cases of people who had been infected for a long time, who had antibody response, and as their infection got worse and worse they lost their antibody response," Hicks says. "But if he had a bad infection and lost his antibody response, then that was an unprecedented finding."

No one has reported cases of dual tropic virus in which the disease progression went to the point of losing antibody response, Hicks says.

Also, the man's antibody cells were able to make antibodies to tetanus and diphtheria, proving that they worked, he says.

"The man's in treatment and is doing well," Hicks says. "His T cells are above 200, and he's on a protease inhibitor regimen."

Reference:

  1. Morpeth S, et al. Time to HIV-1 seroconversion is similar among patients with acute HIV-1 infection, but there are exceptions. Presented at the 13th Conference on Retroviruses and Opportunistic Infections, held Feb. 5-8, 2006, in Denver, CO. Abstract: 389.