HIV superinfection in chronically infected patients reported

Investigators have found evidence of HIV superinfection in chronically-infected individuals. The cases are reported in November edition of Public Library of Science Pathogens - the article is freely available online here

Prior to this study superinfection had been reported in a little over 20 patients worldwide, and in nearly all of these cases superinfection occurred within three years of initial HIV infection. But the prospective design of the current study enabled longer-term follow-up and the investigators found evidence of superinfection more than five years after patients first became infected with HIV.

The investigators from the University of Washington believe that their findings could have important implications for the development of vaccines that aim to provide protect immunity against HIV.

Although the design of the study did not allow the investigators to comment on the clinical implications of superinfection, they noted that viral load remained stable in the majority of patients after they were infected with a second strain of HIV.

Background to the study

Superinfection has been reported in over 20 HIV-positive individuals around the world. These cases show that infection with one strain of HIV does not always provide a protective immune response against the acquisition of a second strain. This has important implications for HIV vaccine development as most other viruses for which vaccines exist provide protective immunity against subsequent infection.

It is still unclear how often HIV superinfection occurs, with studies providing contradictory findings regarding incidence. Nearly all the cases of superinfection reported to date involve individuals recently infected with HIV, but there has been a reported case of superinfection in a chronically-infected patient, meaning that it is uncertain if the risk of superinfection is restricted to the few years after primary HIV infection.

In most of the cases reported so far, the superinfecting strain of HIV has been from a second distinct subtype. Detecting superinfecting strain of HIV from the same subtype can be much harder.

Given these uncertainties investigators from the University of Washington conducted a prospective study lasting five years involving 36 HIV-positive female sex workers in Kenya.

Viral sequences from the gag and env sequences of HIV’s genome were examined at two distinct time periods, the first soon after initial infection with HIV, the second approximately five years later.

Results – superinfection incidence 4%

The investigators found evidence of superinfection in seven women with an incidence of a little under 4% per year. This is half the 8% incidence of primary HIV infection seen in the wider cohort of sex workers. But the frequency of intercourse decreased in women in this cohort after infection with HIV and the investigators speculate that the rate of superinfection per exposure to HIV may be similar to that of primary infection.

Detailed analysis of the seven cases of superinfection was conducted.

Case 1

This individual’s initial HIV infection was with HIV subtype A/D. Between two and three years after primary infection, this patient was superinfected with a second strain of HIV belonging to subtype A.

Case 2

Analysis showed that this woman was initially infected with a D/A2 recombinant HIV strain. Between 4.5 and 5.5 years later she was superinfected with a subtype A1 strain of the virus.

Case 3

Initial infection was with HIV subtype D, with superinfection with a subtype A/D strain occurring two months later.

Case 4

Primary involved a subtype A strain, with superinfection with subtype D occurring approximately five years later.

Case 5

Both primary and superinfection involved HIV subtype A. The patient was superinfected between two to three years after first acquiring HIV.

Case 6

Once again, both the initial and superinfecting strains of HIV were subtype A. Superinfection occurred between a year and three years after primary infection.

Case 7

The patient was initially infected with a C/A recombinant strain of HIV and analysis showed that superinfection occurred between the second and sixth months after primary infection.

Clinical consequences of superinfection?

Median viral load before superinfection was 32,000 copies/ml, increasing to a median of 126,000 copies/ml after superinfection.

But the investigators noted that superinfection did not lead to any significant chance in viral load in five individuals.

CD4 cell counts were available for five individuals, and all had a CD4 cell count above 200 cells/mm³ at the time of superinfection.

Comments

“This study represents the most in-depth population-level assessment of the incidence and timing of superinfection to date”, write the investigators, “HIV superinfection occurs during acute infection and during primary infection, as late as five years post-infection.”

Importantly, “immune response to natural infection was not sufficient to protect against re-infection.”

The investigators suggest that their study has implications for HIV vaccine research and believe it “calls into question the likelihood of success of an HIV-1 vaccine that is predicated on mimicking the immune response to natural HIV infection.”

A total of ten cases of superinfection have now been identified by the University of Washington investigators and these cases “provide an excellent opportunity to compare the immune responses in individuals who became superinfected and those who do not” and could provide insights that could help develop an effective HIV vaccine.