Viral Load, “Leaky Guts,” and Inflammation: Connecting the Dots
A new study (albeit a pretty small one) suggests the answer is “yes.”
Reported in the February 1, 2013, issue of the Journal of Acquired Immune Deficiency Syndromes, research by Sergio Reus of the University of Alicante, Spain, and colleagues implies that tighter control of HIV viremia (ongoing viral replication) may help to address both microbial translocation and chronic inflammation—two key factors implicated in some of the illnesses experienced more commonly and at earlier ages by people with HIV.
Microbial translocation (MT for short; also known as “gut leakage”) occurs when bacteria and other pathogens escape from the gut and enter the bloodstream. Soon after HIV infection is established, immune system cells that line the gut are destroyed, making the gut more “leaky” and allowing microbial translocation to occur.
This, in turn, triggers inflammation, a normal immune response that summons disease-fighting cells to attack invading bacteria and other pathogens. However, chronic (ongoing) inflammation taxes the body and is associated with heart disease and non-AIDS-defining cancers.
“The aim of our study,” the authors write, “was to determine whether strict control of [HIV viral load] (<20 copies/mL) is associated with lower prevalence of MT,” as shown by the detection of genetic material (DNA) from bacteria and “biomarkers” of inflammation in blood samples.
The study included 52 participants, all of whom were on antiretroviral therapy. Of these, 65% were men, and the age range was 20–70 years; the median age—that is, the age at the midpoint of this range—was 45, and the median duration of HIV infection was 12 years. Participants started the study with CD4 cell counts between 126 and 1640 cells/mm3, with a median of 552 cells/mm3.
Thirteen participants had had low-level viremia (ongoing HIV replication), which the researchers identified as greater than 20 copies/mL. The remaining 39 participants had viral loads below 20 copies/mL, which was the limit of detection for the viral load test used in the study.
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The research team looked at various factors—including age, sex, CD4 count, smoking status, and HIV treatment regimen—to see which might be linked with evidence of microbial translocation.
Although participants with microbial DNA in their blood (indicating that microbial translocation had occurred) had lower baseline CD4 cell counts and lower nadir (lowest ever) CD4 counts than those without evidence of microbial translocation, “the values did not reach significance.”
The only factor that was statistically linked with presence of microbial DNA was viral load. Microbial DNA was found in blood samples from 46% of participants with low viral loads, compared with only 18% of those with fewer than 20 copies/mL.
Interestingly, individuals who had microbial DNA in their blood had higher levels of biomarkers of inflammation, regardless of their viral load. Those with higher viral loads but no microbial DNA had low levels of inflammation biomarkers.
Putting It All Together
So, to recap: In this study, higher viral load was linked with microbial translocation, but not necessarily with inflammation. Instead, microbial translocation appeared to be the key factor for inflammation—an intriguing result which, the researchers state, suggests “inflammation is caused by MT and not by HIV replication.”
What does all this mean for HIV treatment? As the researchers note, “undetectability (VL <50 copies/mL) is the recommended target in guidelines, but this goal has been defined according to the detection limits of commercial assays rather than according to clinical considerations.” (The term “undetectable viral load” refers to the sensitivity of the test used—that is, the smallest number of copies viral genetic material detectable in a milliliter of blood.)
The results of this study suggest that suppressing HIV to an even lower level of replication, measured by third-generation, ultra-sensitive viral load tests, could help curtail microbial translocation and thereby limit damaging inflammation and the illnesses it may cause.
“Currently, there are no therapies that specifically work against MT and inflammation markers,” the authors conclude; “hence, the fact that strict control of [HIV viral load] reduces these biomarkers supports that we should not focus just on low viremia but also on undetectability by the current third-generation techniques.”
Reilly O’Neal is a freelance writer and former editor of BETA.
Reus, S. and others. Low-level HIV viremia is associated with microbial translocation and inflammation. Journal of Acquired Immune Deficiency Syndromes 62(2):129-134. February 1, 2013.