Acute HIV-1 infection is the phase of HIV-1 disease immediately after infection that is characterized by an initial burst of viremia; although anti-HIV-1 antibodies are undetectable, HIV-1 RNA or p24 antigen are present. Acute human immunodeficiency virus type 1 (HIV-1) infection is a major contributor to transmission of HIV-1. Therefore, an understanding of acute HIV-1 infection may be important in the development of treatment strategies to eradicate HIV-1 or achieve a functional cure. Now, researchers from the Walter Reed Army Institute of Research have enrolled and intensively followed a cohort of high-risk individuals, tracking their HIV status and characterizing the disease through the acute stages of HIV infection. The team state that RV217, or the Early Capture HIV Cohort Study (ECHO), is a prospective study that has captured samples from some of the earliest stages of HIV infection, in some cases within days, along with blood samples before infection. The study is published in The New England Journal of Medicine.
Previous studies show that an estimated 40% to 90% of patients with acute HIV-1 infection will experience symptoms of acute retroviral syndrome, such as fever, lymphadenopathy, pharyngitis, skin rash, myalgia, arthralgia, and other symptoms. However, because the self-limiting symptoms are similar to those of many other viral infections, such as influenza and infectious mononucleosis, primary care clinicians often do not recognize acute HIV-1 infection. It has been shown that the amount of HIV virus in blood increases rapidly during acute infection and then decreases over time. The exact duration and type of human immune responses for controlling the viremia have not been not well-defined. The current study shows that it is possible to define the symptoms and signs during the acute interval.
The current study investigates individuals from East Africa and Thailand at high risk for HIV infection, who had blood drawn twice weekly for qualitative plasma HIV RNA nucleic-acid testing, a highly sensitive assay that allows for early detection of the virus. Results capture people with HIV infection before they have symptoms and before they have antibodies, which is how a diagnosis of HIV is usually made, and while their viral loads were actually very low.
The lab state that events which occur in the first 30-days or so of infection are critical, which they refer to as the acute phase. Data findings show a correlation between peak viremia, which is the point during acute infection when the amount of virus in the blood is highest, and set-point viremia, which dictates the risk of transmission and long-term disease course. Results show that the viral load set-point is established at resolution of acute viremia, within 18-42 days after infection.
The team explain that this indicates that events during acute infection are abrupt and decisive, meaning they play a role in later disease outcomes over many years of HIV infection in the absence of treatment. They go on to add that their cohort also demonstrated that clinical presentation of HIV infections was less symptomatic than previously believed; the duration and number of symptoms being briefer, milder and fewer than reported previously.
The researchers hypothesize that most of the patients would not have come into a clinic with complaints and would not have been identified as acutely HIV infected, which changes the way the global medical community need to think about identifying people with acute infection. The lab state that, to their knowledge, this is the first study to characterize the evolution of symptoms and signs prospectively in a large number of persons with acute infection.
The team surmise that their findings suggest interventions during acute HIV-1 infection may influence the long-term course of the disease. They go on to add that their study demonstrates identifying infected individuals during the observed brief acute HIV-1 infection interval is possible, although not yet feasible on a large-scale, as it would require scalable diagnostic approaches. For the future, the researchers state that the study is now being re-purposed to allow promising new interventions at the very earliest period possible of HIV infection, with a view to develop approaches to HIV cure.