Keeping viral load below 20,000 copies/ml still beneficial, even after HIV rebound

Individuals with persistent, but modest HIV viral load (between 400 copies/ml and 20,000 copies/ml) are no more likely to die or develop new AIDS-defining illnesses than patients with a viral load below 400 copies/ml, according to a United States study published in the September 1^st edition of the Journal of Acquired Immune Deficiency Syndromes. However, the study also found that patients whose viral load is above 20,000 copies/ml are significantly more likely to die or develop new AIDS-defining conditions.

The study’s investigators believe that their findings demonstrate that efforts to control viral load, even when an individual is unable to achieve undetectable levels, can still provide important clinical and immunologic benefits.

Investigators from the Collaborations in HIV Outcomes Research/United States (CHORUS) cohort stratified over 3000 HIV-positive patients into one of three groups according to their HIV viral load over a six-month period. Group one contained patients with a viral load below 400 copies/ml; group two's patients had viral loads between 400 and 20,000 copies/ml; and group three included individuals whose viral load was above 20,000 copies/ml.

A proportional hazard model was designed to determine the relationship between viral load and the risk of death or progression to new AIDS-defining events during a follow-up period.

Baseline characteristics

Compared to patients with a viral load below 400 copies/ml, individuals whose viral load was above 20,000 copies/ml were significantly more likely to be non-white (p = 0.001), have a lower baseline CD4 cell count (443 cells/mm³ versus 205 cells/mm³, p = 0.001), have a prior AIDS diagnosis (25% versus 44%, p = 0.001), and to have had less exposure to antiretroviral drugs (99% versus 93%, p = 0.001).

Results

Individuals were followed-up for a little over four years. Overall, 343 new deaths or AIDS-defining illnesses were recorded. The incidence of these events was similar for patients with a viral load below 400 copies/ml and between 400 copies/ml and 20,000 copies/ml (6% versus 7%, p = 0.5), but was significantly higher amongst patients with a viral load above 20,000 copies/ml (26%, p = 0.001 compared to patients with a viral load below 400 copies/ml).

In total 2% of individuals whose viral load was below 400 copies/ml or between 400 copies/ml and 20,000 copies/ml died, compared to 9% of patients with a viral load above 20,000 copies/ml (p

After adjusting for variables including CD4 cell count, prior AIDS events, use of antiretroviral drugs, age, gender and ethnicity, the investigators found that patients with a viral load above 20,000 copies/ml were at significantly greater risk of death or disease progression (hazard ratio 3.3, p

The investigators then looked at changes in CD4 cell count during the first year of follow-up amongst the three groups. They found that CD4 cell count increased by a median of 75 cells/mm³ for patients with a viral load below 400 copies/ml, and by a median of 13 cells/mm³ for patients with a viral load between 400 copies/ml and 20,000 copies/ml. By contrast, patients with a viral load above 20,000 copies/ml experienced a median fall in their CD4 cell count of 23 cells/mm³.

"The present study shows that patients who maintained an HIV [viral load] between 400 and 20,000 copies/ml…had no significantly higher risk for clinical disease progression over a three year period than patients with an HIV [viral load] below 400 copies/ml," write the investigators.

The investigators add, "this large observational study demonstrates the utility of efforts directed at controlling HIV [viral load] in patients who may not attain undetectable levels."

They conclude that their study has provided important information for doctors and patients attempting to develop a treatment strategy in the face of continued HIV replication as a "treatment regimen that only provides partial virologic suppression my still offer immunologic and clinical benefits."