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Sudden Viral Load Increases Usually Is Not a Sign of HIV Superinfection

By Liz Highleyman

The issue of HIV superinfection or reinfection (contracting a new strain of HIV when already infected) and coinfection (infection with more than 1 HIV  strain at the same time) -- sometimes used interchangeably and also called dual infection -- remains controversial.

To the extent that there is a consensus, most experts believe superinfection is rare (only about 2 dozen cases have been identified) and usually occurs within 3 years of initial infection. However, dual infection may be more common than suspected, since most people with HIV do not have their viral strains sequenced and compared.

One signal that has prompted doctors to do the testing necessary to establish superinfection is a sudden, unexpected increase in viral load in a patient who had previously been doing well. If this happens while off treatment, it could suggest a new infection, since viral load typically rises slowly over time.

As described in the advance online edition of the Journal of Acquired Immune Deficiency Syndromes, researchers in the Netherlands conducted a retrospective study of nearly 1600 patients seen between 1996 and 2006. They conducted further assessment of 14 untreated HIV-infected individuals who experienced sudden viral load rises of 5 logs or more, analyzing HIV-1 quasispecies in plasma samples before and at peak levels.

Results

·         12 of the 14 patients had no evidence of superinfection.

o        In 4, viral load increases were attributable to other causes including upper respiratory infections or vaccination.

o        8 had no medical conditions accompanying the viral load increase, and the researchers attributed it to HIV disease progression.

·         2 of the 14 patients had evidence of possible superinfection based on viral sequencing and phylogenetic analysis of HIV env-V3 fragments.

·         Specifically, their dominant V3 population at the peak level clustered separately from the V3 sequences in a sample predating the peak level.

·         Both individuals (who continued to practice unsafe sex) had experienced sudden viral load increases about 6 months after their initial HIV infection.

Conclusion

“This study suggests that an unexpected rapid rise in the plasma HIV-1 viral load of untreated patients can infrequently be ascribed to an HIV-1 superinfection,” the authors concluded. They added that even minor medical conditions -- such as a respiratory infection -- can trigger an increase in HIV replication.

In a related report, Spanish researchers described 2 individuals with long-term non-progressive HIV disease who they believe had dual HIV infections. The first patient was diagnosed as already coinfected with more than 1 HIV strain, based on the first sample analyzed, but a previous superinfection could not be ruled out. The second patient was diagnosed as having a superinfection based on the 9-year difference between the viral dating of the 2 strains.

“Dual infections occur in patients with long-term, non-progressive disease, with no immediate clinical manifestations,” these authors concluded. “Such occurrences could indicate a general phenomenon in natural HIV-1 infections.”

Laboratory of Experimental Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Amsterdam, Netherlands; Department of Internal Medicine, Division of Infectious Diseases, Tropical Medicine and AIDS, Academic Medical Center of the University of Amsterdam, Netherlands; International Antiviral Therapy Evaluation Centre (IATEC), Amsterdam, Netherlands.