Antiretroviral therapy cuts mortality risk for people diagnosed with HIV-related lymphoma

Higher cumulative viral load in the six months after diagnosis with HIV-related lymphoma is associated with a subsequent increase in mortality risk, results of a large observational study published in the online edition of AIDS show.

Investigators from the United States monitored people who were alive six months after their lymphoma diagnosis for up to five years. Each 1 log₁₀ increase in cumulative viral load during the first six months after diagnosis was associated with a 35% increase in subsequent mortality risk.

The investigators believe their findings “support treatment strategies incorporating early ART [antiretroviral therapy] with maximal HIV suppression, concurrently with chemotherapy for patients with HIV-associated lymphoma”.

Cancers, including lymphomas, remain an important cause of death among people with HIV. Early antiretroviral therapy has been shown to improve outcomes for people diagnosed with several HIV-related opportunistic infections and is therefore recommended in disease management guidelines.

However, consensus guidelines for the treatment of HIV-related lymphomas make no strong recommendation for or against the use of antiretroviral therapy during chemotherapy for cancer. There are some concerns that the beneficial effects of HIV treatment could be offset by an increased risk of interactions or drug-related toxicities.

A team of investigators from the United States wanted to get a clearer understanding of the benefits of early HIV therapy for people with HIV who are diagnosed with lymphoma.

They therefore reviewed the medical records of over 25,000 people who received care between 1996 and the end of 2011.

Analysis was limited to the 224 people (1%) diagnosed with a lymphoma. All were alive six months after their diagnosis and had two or more viral load measurements in this period. The investigators looked at the impact of cumulative viral load in the six months after lymphoma diagnosis on survival over five years. Cumulative viral load was selected as a marker of early and effective HIV therapy.

The people in this group had a median age of 43 years, 92% were male and 52% were white. Overall, 183 (82%) were diagnosed with non-Hodgkin's lymphoma and 18% had Hodgkin's lymphoma.

At the lymphoma diagnosis, the patients had a median CD4 cell count of 148 cells/mm³ and the median nadir CD4 cell count was 73 cells/mm³. Some 47% were taking HIV treatment at the time of diagnosis. The median overall viral load was approximately 10,000 copies/ml but was undetectable (below 400 copies/ml) in a third of patients.

Each patient contributed an average of three viral load measures during the six months after their diagnosis.

Median cumulative viral load for the entire study population over this period was 2.68 log₁₀ copies x 6-months/ml. There were 64 people (29%) who maintained an undetectable viral load throughout these six months.

The proportion of people in the group taking antiretroviral therapy increased from 47% at baseline to 58% three months after lymphoma diagnosis and 71% six months after diagnosis.

There were 82 deaths during 851 person-years of follow-up, a mortality rate of 9.6 per 100 person-years.

Almost two-thirds of patients were still alive five years after their diagnosis with lymphoma.

However, survival rates differed according to cumulative viral load during the first six months after diagnosis.

After five years, 54% of patients with a cumulative six-month viral load above the median value were alive, compared to 70% of patients with a cumulative six-month viral load below the median. This difference was statistically significant (p = 0.014).

The investigators calculated that each 1 log₁₀ increase in cumulative viral load during the first six months after diagnosis was associated with a 35% increase (95% CI, 1.11-1.65) in subsequent mortality risk between month six and year five.

Older age and lower CD4 cell count at the time of diagnosis were also associated with an elevated mortality risk.

Further analysis showed that viral load at the time of diagnosis was not associated with the subsequent risk of death. However, viral load six months after diagnosis was. Each 1 log₁₀ increase was associated with a 32% (95% CI, 1.12-1.56) increase in mortality risk.

People with an unsuppressed viral load during the first six months after cancer diagnosis were 64% (95% CI, 1.03-2.63) more likely to die during the study period than people with an undetectable viral load during this six-month period.

“Increased viremia during the six months after lymphoma diagnosis is associated with an increased risk of death between six months and five years after diagnosis,” comment the investigators. They believe the consistent relationship between viral load and increased mortality risk shows that “effective ART during chemotherapy may improve overall survival”.