Viral load during primary infection influences viral load for years after

Individuals with a high viral load during primary HIV infection have a higher subsequent viral load set point, according to a US study published in the August 1^st edition of the Journal of Acquired Immune Deficiency Syndromes. The study also showed that there was a relationship between viral load and the number of symptoms experienced during primary infection. The investigators, from the University of California San Francisco believe “innate immune factors and/or HIV viral characteristics may have contributed to determining viral load set point and subsequent disease course.”

Primary, or acute, HIV infection can include a period of ‘flu-like symptoms during the first weeks of HIV infection. Viral load reaches a peak during primary infection before declining to a set point where it remains for months or even years during which time individuals typically have few physical symptoms of HIV infection.

Earlier research suggests that patients with more symptoms or longer duration of illness during primary HIV infection have faster progression to AIDS.

Conversely, other studies have indicated that symptoms during primary infection may actually be indicative of a strong immune response to HIV and be linked to a rapid decline in viral load.

On the other hand, research involving African women with recent HIV infection found that symptoms and a high preseroconversion viral load were linked to faster progression to AIDS and death independent of subsequent viral load set point.

Investigators noted that no previous research had included data on initial viral load, primary HIV infection symptoms and viral load set point. As the relationship between these factors was therefore unclear, researchers in California designed a study involving patients with preseroconversion or recent HIV seroconversion to establish the relationship between these factors.

Individuals were classified as having preseroconversion infection if HIV tests were negative or indeterminate but they had an HIV viral load of more than 2000 copies/ml in at least two tests. Patients were categorised as having recent HIV seroconversion if they tested HIV-positive after a recent negative test result.

Individuals were asked if they had any of 21 symptoms typically associated with primary HIV infection, such as fever, rash, mouth ulcers, muscle and joint pain, sore throat, loss of appetite, fatigue, head ache and night sweats. Blood samples to measure viral load were taken every four weeks for the first 24 weeks and then at intervals of eight weeks for a median of 98 weeks.

A total of 57 patients with preseroconversion HIV infection and 120 patients with recent HIV seroconversion were included in the investigators’ analysis. Almost all were gay men, and the average age was 41 years.

Individuals with preseroconversion infection had significantly more symptoms of primary HIV infection (mean, nine versus six, p < 0.001) than those with recent seroconversion. Furthermore, patients with preseroconversion also had higher mean viral load (126,000 copies/ml versus 25,000 copies/ml).

In the investigators’ initial set of statistical analysis, each additional symptom of primary infection predicted an increase in viral load of 0.009 log₁₀. Such an increase was statistically significant (p < 0.001). In addition, the presence of symptoms, as opposed to asymptomatic primary infection, predicted an increase in viral load of 0.9 log ₁₀, and once again this was highly statistically significant (p < 0.001). However, the duration of symptoms during primary infection was not associated with a higher initial viral load.

In subsequent multivariate analysis, the researchers found that preseroconversion infection was associated with a statistically significant 0.5 log₁₀ higher viral load (p = 0.001), with fever associated with a 0.6 log₁₀ higher viral load (p < 0.001), and weight loss a 0.4 log₁₀ higher viral load (p = 0.008).

The investigators then designed a model that included the stage of infection, the number and type of symptoms, and the duration of symptoms with initial viral load as the outcome. This showed that preseroconversion illness was associated with a statistically significant increase in initial viral load of 0.48 log₁₀ (p = 0.002) compared to recent seroconversion, and that each additional symptom of primary HIV infection was associated with a significant 0.08 log₁₀ (p < 0.001) increase in viral load.

Statistical analyses were then performed to predict the viral load set point for the small number of patients who did not start antiretroviral therapy (six individuals with preseroconversion illness and 42 with recent seroconversion). The median period of follow-up was 98 weeks.

The first set of analysis showed that each 1.0 log₁₀ increase in viral load predicted a statistically significant 0.46 log₁₀ (p < 0.001) increase in viral load set point. Furthermore, each additional symptoms of primary HIV infection was associated with a 0.05 log₁₀ increase in viral load set point. Once again, this increase was statistically significant (p = 0.03).

In subsequent multivariate analysis, a higher initial viral load remained associated with a higher viral load set point (each 1.0 log₁₀ increase in initial viral load associated with a 0.44 log₁₀ increase in set point, p = 0.003).

The investigators believe that their research has practical implications. They write, “for clinicians, our results suggest that a low viral load during primary HIV infection or soon after seroconversion is a more reliable indicator of which individuals are likely to achieve a low viral load set point than the severity of primary HIV infection.”

They add, “our results suggest that early interactions between the HIV-1 virus and a new host, even before fully developed adaptive immune responses, are important in establishing viral load set point.”