HIV superinfection: more evidence

HIV superinfection is still big news but it didn’t grab the headlines this week at the Tenth Conference on Retroviruses and Opportunistic Infections despite two oral sessions and two posters.

The problem is that the proof that superinfection does occur has already been published, and the one paper that had something new to say on the subject was, in fact, about dual HIV infection, which is not exactly the same as superinfection.

Dual infection can be the result of either co-infection (when both infections occur at the same time or very close to each other) or superinfection (when a second infection occurs after the first infection is established).

Gottlieb and colleagues from the University of Washington reported that they had identified four individuals with dual HIV infection that had progressed to AIDS or death within two years of infection. This is the first time that an association has been found between dual infection and rapid disease progression.

It is not an easy task to detect dual infection within the same subtype, but the researchers appeared to satisfy the scientists in the auditorium that their methods were sound. Out of 47 patients from three different cohorts - two in the US and one in South Africa - they found three people from the US with two separate clades of subtype B and one with two separate clades of subtype C.

The researchers surmised that all four had been co-infected rather than superinfected, although they couldn’t rule out superinfection because they had no stored blood samples prior to seroconversion. All four had extremely high viral loads in common, ranging from 4.6-5.8 logs, and all developed serious opportunistic infections or died within two years of seroconversion.

Although these data are intriguing, it is still unclear whether superinfection results in equally rapid disease progression, since the immune system may already be primed by the first infection. However, a poster by Fang and colleagues suggested that a Kenyan sex worker superinfected with subtype C after subtype A had a rapid decrease in CD4 cell count after superinfection, although a clinical outcome was not reported.

The Gottlieb paper also begs the question as to whether individuals that are genetically more likely to allow dual infections are also genetically more likely to progress rapidly.

Since detection of superinfection is difficult within the same subtype, an outbreak of two distinct strains of HIV-1 (subtypes B and CRF-11) amongst intravenous drug users (IDUs) in western Switzerland provided an opportunity for researchers to see how often superinfection can occur through the blood route.

Perrin and colleagues found that two heroin and cocaine users originally infected by HIV subtype B with unexplained rises in their viral load during a stable period of HIV infection, had been superinfected with a second HIV subtype, CRF-11. Both, surprisingly, were long-term nonprogressors, since their viral load had been undetectable without antiretrovirals for several years. One, a Swiss female, had been undetectable for five years, until she experienced classic symptoms of acute antiretroviral syndrome, a rise in HIV-1 RNA to over 10 million and a rapid drop of CD4 T-cells from around 1000 cells/mm3 to 500 cells/mm³. The same was essentially true for the second individual, an African male, who had been been undetectable for three years.

The Swiss researchers did complete phylogenic analyses on these patients, and were convinced that they were seeing superinfection, rather than co-infection. Whilst many scientists in the audience appeared to agree with their methods, some were a little sceptical.

Indeed, until an article has been published in a respected, peer-reviewed journal, it is not always guaranteed that the science is not flawed in some way. This may well be the case when peers review the data by Wong and colleagues from Canada, who displayed a poster that concluded they had found two cases of superinfection in two female IDU sex workers at the Ottawa Hospital Immunodeficiency Clinic between 1997 and 2000. The poster was unclear whether these women had acquired their second infection via the blood or sexual route and was rather scant of any details. This came from the same team who reported one of the first cases of superinfection at the Seventh Conference on Retroviruses and Opportunistic Infections, which has yet to be published a peer-reviewed journal.