Chronic Inflammation in People With HIV Linked to Pre-Treatment Immune System Damage
Chronic inflammation and immune activation (immune system activity) seen in people living with HIV is related to how much damage HIV causes before starting treatment, rather than HIV persistence while taking medications, a study published in PLOS Pathogens found.
Researchers analyzed blood samples of about 100 people living with HIV who had achieved undetectable viral loads for a median of seven years. The samples had been taken before starting antiretroviral therapy (ART), after one and four years on HIV treatment, and once after six to 15 years of ART. All participants had viral loads below 50 copies/mL from 48 weeks after starting treatment to the end of the study. Viral load measures the amount of HIV in a person's blood plasma.
"Our findings suggest that damage to the immune system that occurs before people are started on treatment leads to continued immune activation, even though the medicines are keeping the virus in check," said lead study author Rajesh Gandhi, M.D., in the study press release.
"This suggests that diagnosing HIV and starting antiretroviral therapy as soon as possible may prevent the elevated immune activation that can lead to health problems, such as heart disease," Gandhi added.
The study looked at levels of the virus, markers for inflammation and T-cell activation. T cells are important for the immune system's response to disease agents, such as viruses. For example, the number of CD4 cells, a type of T cell, indicates how well a person's immune system is working, which is why a CD4 test is one of the standard lab tests for people with HIV. Antiretroviral therapy lowers viral loads and increases CD4 counts in people living with HIV.
The researchers also measured the amount of HIV DNA and HIV RNA associated with blood cells. These cell-associated-DNA levels declined most steeply during the first four years on treatment, slowing to a decline of 5% per year after that. Cell-associated-RNA levels dropped even more steeply after one year on treatment, but then held steady. These measurements did not differ based on the treatment regimen that a participant took.
"It appears that different mechanisms are driving the stubborn persistence of HIV reservoirs and the harmful, chronic immune activation that are characteristic of HIV infection despite current treatments. This important finding is a first step towards identifying specific therapies for each problem," said senior author John Mellors, M.D., according to the study press release.
Participants with higher levels of inflammation before starting treatment continued to have more inflammation after starting treatment, even when their viral load was suppressed below 50 copies/mL. Chronic inflammation can cause heart disease and other health problems.
High levels of immune system activation before starting treatment were associated with greater numbers of activated T-cells for the first year of treatment, but that relationship became less significant by year four and disappeared altogether after six years of taking meds. Previous studies on the relationship between levels of HIV genetic material and immune activation during HIV treatment had reached different conclusions, study authors acknowledged. However, these studies had only looked at one time point, rather than following the course of HIV over time.
The ongoing inflammation and immune system activation experienced by people living with HIV, who are on treatment and have undetectable viral loads, thus appears to be linked to inflammation and immune activation levels before treatment is started. The virus causes damage that persists even after HIV itself is well-controlled by treatment.
One of the next steps is "to investigate viral and human genetic factors that affect HIV persistence and immune activation in people on ART and develop strategies to reduce HIV levels and inflammation that go beyond our current antiretroviral medications," concluded Gandhi.