Risk of disease progression linked to CD4 cell count and HIV DNA level during primary infection

Patients with a low CD4 cell count during primary infection or a high level of HIV DNA within their blood cells are at an increased risk of disease progression after infection with HIV, according to an analysis of data from the French PRIMO Cohort. The study was published in the 1^st March edition of Clinical Infectious Diseases.

The study’s authors suggest that people with low CD4 cell counts or high HIV DNA levels during primary infection should be closely monitored and may benefit from early HIV treatment to prevent them becoming ill.

It is unclear whether treatment soon after HIV infection is beneficial for HIV-positive people. Early treatment is thought to improve outcomes by reducing the spread of HIV through the body, limiting the activation of T-cells and preserving the anti-HIV activity of the immune system. However, it puts patients at risk of side-effects and the development of resistance to anti-HIV drugs.

To work out which patients may be at the greatest risk of becoming ill after infection, investigators examined the rates of disease progression in the 163 patients from the PRIMO Cohort who did not receive antiretroviral treatment. This cohort recruits patients within six months of HIV seroconversion, and collects information on their disease progression.

Over a median follow-up of 24 months, 56 (34%) of the patients experienced a fall in their CD4 cell count to below 350 cells/mm³. CD4 cell counts fell to this level a median of 6.7 months after enrolment, with a median viral load of 100,000 copies/ml.

The investigators calculated that the risk of CD4 cell counts falling to below 350 cells/mm³ was 25% at one year after enrolment. This rose to 34% after two years and 42% after three years.

In a multivariate analysis, they found that a lower CD4 cell count (p

“The HIV DNA level in peripheral blood mononuclear cells provides an estimate of the cellular HIV reservoir, which is established soon after infection,” the investigators write. “We found that HIV DNA level was predictive of the risk of progression … This is consistent with previous studies”.

In contrast, viral load was not associated with the risk of disease progression. “This apparent discrepancy may be because of the strong variability of HIV RNA levels, a phenomenon that may undermine their predictive value,” the investigators explain.

The investigators only saw one AIDS-defining event during their study, which was a case of recurrent bacterial pneumonia in a patient with a CD4 cell count of 222 cells/mm³. They explain that this low incidence is due to the study only including patients who did not receive antiretroviral therapy. These patients had less severe symptoms of acute infection than the remaining 389 patients, who did receive anti-HIV therapy.

However, the researchers were surprised at the high rate of CD4 cell count decline in their study. “This study underlines the fact that immunological status can worsen rapidly in the absence of early treatment during primary infection, even in a selected population of patients with relatively mild acute symptoms,” they write.

“Such patients must receive close clinical and laboratory monitoring if it is decided to postpone treatment. In addition to the CD4 cell count, the HIV DNA level may be a useful tool for making decisions regarding the optimal time to prescribe treatment to a patient with primary HIV-1 infection,” they add.