Uncontrolled viral load increases risk of AIDS for patients with a CD4 cell count above 350

Uncontrolled HIV replication is associated with an increased risk of AIDS for patients with a CD4 cell count above 350 cells/mm³, European investigators report in the online edition of AIDS. The researchers also found patients with a viral load above 500 copies/ml had an increased risk of serious non-AIDS related illnesses, but only after they had adjusted their results to take account of confounding factors.

“In HIV-positive individuals with a CD4 cell count > 350 cells/mm³ we observed an association with uncontrolled viral replication and a higher incidence of fatal and non-fatal AIDS events and a slightly increased incidence of fatal and non-fatal non-AIDS events,” comment the investigators. “The higher incidence of AIDS events was observed in…both crude and adjusted analysis. However, the increased incidence of non-AIDS events was only apparent after adjustment.”

European HIV treatment guidelines currently recommend that patients should initiate antiretroviral therapy when their CD4 cell count is in the region of 350 cells/mm³. Initiating treatment at this time, rather than waiting until later, reduces the risk of developing AIDS-related illnesses as well as some serious non-HIV-related illnesses such as cardiovascular disease.

Uncontrolled HIV replication is known to cause immune stimulation and inflammation. However, the impact of viral load on disease progression in patients with higher CD4 cell counts has received little attention.

Therefore investigators from the EuroSIDA cohort study analysed the risk of developing an AIDS-defining illness or a serious non-AIDS-defining event in patients with a CD4 cell count above 350 cells/mm³ according to their viral load.

The patients were divided into three viral load strata:

• Low – below 500 copies/ml.

• Intermediate – between 500 copies/ml and 9999 copies/ml.

• High – above 10,000 copies/ml.

A total of 11,492 patients who received care after 1997 were included in the analysis investigating the relationship between viral load and the risk of AIDS-related events. For the non-AIDS event analysis, 10,869 patients who were seen after 2001 were included.

Most of the patients (82%) had a viral load below 500 copies/ml, with 11% having an intermediate viral load and 7% a viral load above 10,000 copies/ml. A total of 90% of patients with a low viral load were taking HIV therapy, compared to 61% of individuals with an intermediate viral load and 36% of those with a high viral load.

Overall, 354 AIDS events were reported, and the overall incidence was 0.68 events per 100 person years of follow-up.

Initial analysis showed that the incidence of AIDS-related illnesses was 0.53 per 100 person years for patients with a low viral load, increasing to 0.90 per 100 person years for those with an intermediate viral load and 2.12 per 100 person years for individuals with a high viral load.

The relationship between both an intermediate and a high viral load and an increased risk of progression to AIDS remained significant after results were adjusted for potentially confounding factors (p = 0.03 and p < 0.001 respectively).

“The association we found between viral replication and the incidence of AIDS events appears to be almost linear and was independent of current CD4 cell count,” comment the investigators.

There were 572 non-AIDS-related events. These included 208 (36%) cardiovascular events and 204 (36%) non-AIDS-related malignancies. The overall incidence of serious non-AIDS-related illnesses was 1.31 per 100 person years of follow-up.

Incidence was 1.28 per 100 person years of follow-up for patients with a viral load below 500 copies/ml, compared to 1.52 per 100 person years for individuals with an intermediate viral load and 1.38 per 100 person years for those with a higher viral load.

The investigators adjusted these results to take account of factors such as HIV risk group, region, hepatitis co-infection, diabetes, high blood pressure, a previous  AIDS diagnosis and use of HIV therapy.

These adjusted results showed that compared to individuals with a low viral load, patients with intermediate viraemia were 61% more likely to develop a serious non-HIV-related illness (IRR = 1.61; 95% CI, 1.21-2.14; 0 = 0.001), and those with a viral load above 10,000 copies were 66% more likely to experience such an event (IRR = 1.66; 95% CI, 1.17-2.34; p = 0.004).

Further analysis showed that a viral load between 500 and 9999 copies/ml was associated with a significant increase in the risk of cardiovascular disease (p = 0.03).

However, the investigators comment: “A larger study with longer follow-up would be needed to analyse the association between each specific non-AIDS events and viral replication further.”

The investigators then looked at the risk of AIDS and non-AIDS events according to CD4 cell count. Compared to individuals with a CD4 cell count between 350 and 499 cells/mm³, patients with a CD4 cell count above 500 cells/mm³ had a non-significant reduction in their risk of both AIDS-related and non-AIDS-related events.

  “In conclusion,” write the investigators, “in HIV-positive individuals with a CD4 cell count > 350 cells/mm³, an increased incidence of AIDS and a slightly increased incidence of non-AIDS was found in those with uncontrolled viral replication.”