'Intimate' link between viral load increases and CD4 cell loss in patients not on HIV therapy

There is a strong link between increases in viral load and CD4 cell count loss in HIV-infected patients who are not taking antiretroviral therapy, UK investigators report in the online edition of AIDS.

The researchers from London’s Royal Free Hospital comment that they observed “an intimate link between HIV RNA [viral load] increases and CD4 cell count depletion.”

A wide variability in the rate of CD4 cell count decline has been observed in antiretroviral-naïve HIV-positive patients. Although a higher viral “set point” – viral load after primary HIV infection – has been associated with a faster decline in CD4 cell count, the exact interplay between changes in viral load over time and the loss of CD4 cells is not fully understood.

Therefore investigators undertook a prospective study involving 1169 patients receiving their HIV care at the Royal Free Hospital in north London between 1996 and 2007. These patients were broadly representative of the wider demographics of the UK HIV population.

Both CD4 cell count and viral load were measured on average every three months. The investigators paired consecutive CD4 cell counts, and these were matched with viral load measurements obtained at the same time.

A total of 5940 CD4 cell count pairs and matching viral load measurements were available for analysis.

Overall, CD4 cell counts fell by a mean of 66 cells/mm³ each year. The mean annual increase in viral load was 0.091 log₁₀/ copies/ml, representing a 23% increase in viral load each year, and a doubling every 3.3 years.

The rate of CD4 cell count decline was greater for patients with higher baseline viral loads.

Each 1 log₁₀ copies/ml increase in baseline viral load was associated with the loss of an additional 46 CD4 cells/mm³ per year.

A relationship was also found between current CD4 cell count and viral load.

Compared to patients with a current viral load of 3 log₁₀ copies/ml (1,000 copies/ml), those with a viral load of at least 5.7 log₁₀ copies/ml (501,000 copies/ml) lost 106 CD4 cells/mm³ more per year.

After adjusting for the current level, higher baseline viral load was not associated with the loss of CD4 cells. Rather, the more viral load increased from baseline to the current time, the greater the subsequent loss of CD4 cells.

The investigators also found that 96% of patients with a CD4 cell count below 200 cells/mm³ had previously had a viral load above 4 log₁₀ copies/ml (10,000 copies/ml). In addition, 86% of those whose CD4 cell count fell to the dangerously low level of 50 cells/mm³ had had a viral load above 4.7 log₁₀ copies/ml (50,100 copies/ml).

This suggested to the investigators that “CD4 cell count depletion can generally only continue below a certain level if the HIV RNA level is sufficiently high.”

Furthermore, the investigators found that current CD4 cell count could predict subsequent changes in viral load. Each 100 cell/mm³ reduction in CD4 cell count was associated with a 0.04 log₁₀ copies/ml greater annual increase in viral load. (p < 0.0001).

Annual viral load increases were 0.14 log₁₀ copies/ml lower in women than men (p < 0.0001). However, no association was found between age and changes in viral load.

“We show here that variability in CD4 cell count decline is linked more closely to viral replication than has previously been documented. Further study of predictors of increases in HIV RNA levels may help us understand the cause of CD4 cell count depletion.”