No evidence of HIV-1 strain cross transmission

Superinfection is very rare occurrence

Researchers in one recent study have found no evidence of HIV superinfection between chronically-infected sexual partners.

Sixteen HIV-infected men who have sex with men (MSM), recruited from a Seattle cohort for a study about HIV and anal dysplasia, reported having long-term sexual partners, says Mary Campbell, MD, a senior fellow in infectious diseases at the University of Washington in Seattle.

"So we had sexual behavioral data, data about the length of their partnerships, and we also had quite a bit of clinical data about any AIDS-defining or HIV symptoms they had prior to the study and in follow-up," Campbell says. "And we had data on antiretroviral treatment and CD4 cell counts and viral load."

Investigators screened HIV envelop sequences derived from mononuclear cells at the initial and final study visits, and they analyzed those sequences biogenetically to determine the relatedness between individuals and their partners, Campbell explains.

Researchers used phylogenetic methods to analyze HIV sequences.1 Most of the men were followed for three to five years, and at each study visit they completed detailed questionnaires about sexual behavior, she says.

Researchers had access to information about eight pairs of chronically HIV-infected male partners, whose partnerships were of three to 15 years duration, Campbell notes.

"The main findings were that for three of the couples it appeared that either one partner had transmitted the virus to the other partner prior to enrollment in the study, or they had a third partner in common who had transmitted to them both because the viral sequences were very similar and unable to be separated biogenetically," Campbell says.

"For the remaining pairs there was no evidence of epidemiologic linkage between viral strains at either time point, which suggested no transmission," she adds.

The data are consistent with the hypothesis investigators have had for several years about how superinfection is a very special case and not a frequent event, says James I. Mullins, PhD, a professor of microbiology at the University of Washington. Mullins was a co-investigator in the study.

When infection with multiple HIV strains has occurred, in almost all instances it has been reported early after acquisition of the first strain or during a drug holiday after a period of suppression, Mullins says.

"The situation that is found in the naïve or newly-infected host or the host that has been on antiretroviral suppression for a long time is the high abundance of susceptible target cells," Mullins explains. "So someone who has been chronically infected for some time will have a low level of uninfected susceptible cells."

Typically, when a cell becomes infected it is less susceptible to being re-infected, Mullins adds. "Superinfection is certainly less common in chronically infected individuals," Campbell says.

When superinfection has been detected in a person with established infection it has been a very unique circumstance of the person having gone off their antiretroviral drugs for weeks or days and then encountering a new strain, Mullins says.

Since the small study did not find evidence of superinfection, its findings are consistent with the idea that superinfection requires a large number of target cells to be susceptible and available for infection by a new strain, Mullins says.

This might reassure clinicians that under normal circumstances their patients won’t become re-infected, although they might be concerned when there’s a possibility of therapy interruption, Mullins notes.

"We are not trying to say this study is definitive or that superinfection does not occur following the establishment of initial infection, but we’re building up a data set to give us an idea of what are the windows of opportunity for superinfection," Mullins says. "And so far, the windows are very early after acquisition of first infection and during drug holidays, and we have no evidence of it occurring at other times."

Reference

  1. Campbell M, Wong K, Nickle DC, et al. Lack of evidence of HIV transmission between chronically-infected sexual partners. Presented at the 13th Conference on Retroviruses and Opportunistic Infections, held Feb. 5-8, 2006, in Denver, CO. Abstract: 293.