Sudden increases in viral load in first two years of infection could indicate superinfection

A sudden increase in viral load is rarely due to HIV superinfection, researchers from Amsterdam report in study published in the online edition of the Journal of Acquired Immune Deficiency Syndromes. Minor medical conditions, such as upper respiratory tract infections appeared to be the most likely explanation for sudden viral load increases.

However, the investigators did find evidence of superinfection in two patients. Both these individuals had contracted HIV only six months before their superinfection, and reported unprotected sex since their primary HIV infection.

Sudden increases in viral load amongst patients taking potent antiretroviral therapy are usually due to poor adherence. Individuals who are not taking anti-HIV drugs can also experience rapid increases in viral load, and it is thought that opportunistic infections, sexually transmitted infections including syphilis, and vaccinations are amongst the reasons.

It has also been suggested that superinfection – or reinfection – with a second strain of HIV may also be a possible explanation.

To see if this was the case, investigators at the Academic Medical Centre in Amsterdam conducted a retrospective study including 1596 patients with follow-up data from 1996 to 2006.

Only individuals who were treatment naïve or had been on a treatment break for at least a year were eligible for inclusion in the investigators’ analysis. Furthermore, it was necessary for a patient to have experienced a fivefold increase in their viral load.

A total of 14 patients were eligible for inclusion in the study. The average duration of follow-up was seven years. Blood samples obtained before and after the peak in viral load were analysed by reverse transcriptase polymerase chain reaction amplification and sequencing. Phylogenetic analysis was also performed to confirm any cases of suspected superinfection.

None of the patients experiencing sudden increases in viral load switched from having HIV with the CCR5 co-receptor to CXCR-4 receptor. And analysis found no evidence of superinfection in twelve patients.

In the other two, however, both viral sequencing and phylogenetic analysis indicated superinfection. Both patients had been infected with HIV for approximately six months.

The investigators comment, “there are many reasons for a sudden, substantial increase in HIV-1 plasma viral load, and…HIV-1 superinfection is at best only a minor explanation.”

However, firm evidence of superinfection was found in two patients, both of whom “reported continuing unsafe sexual practices after their primary HIV-infection.”

Case reports appear to suggest that the risk of superinfection is greatest in the first few or so years after acquisition of HIV, although there has been a report of superinfection in a patient with chronic HIV infection.

The investigators searched the medical records of the other twelve patients to see if they could identify reasons for the sudden increases in viral load. Three of the patients had an upper respiratory tract infection and an additional patient had recently had travel vaccinations. No explanation could be identified for the other individuals.

One of the superinfected patients also had recent infection with syphilis and the investigators speculate that this could have facilitated his HIV superinfection.

“Unexpected plasma viral load peaks occurring in chronically HIV-1-infected patients are infrequently associated with HIV-superinfection”, conclude the investigators, “minor medical conditions…or vaccinations appear more likely to increase HIV-1 replication. Our two superinfections occurred within half a year of the original HIV infection, consistent with prior observations. Thus, sudden increased HIV-1 levels in the first one or two years after primary infection may be more suggestive for HIV-1 superinfection than those occurring later.”