CROI 2015: Inflammation and Gut Damage Persist in People with HIV Despite Early ART

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Inflammatory changes and damage to the gut begin very soon after initial HIV infection, and may not return to normal even when people start antiretroviral therapy (ART) very early, researchers reported at the recent 2015 Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle. Biomarkers of inflammation, coagulation and fibrosis increased early on, and while they generally decreased after starting ART, they did not fall to levels seen in HIV-negative people.

Netanya Sandler Utay of the University of Texas Medical Branch, Jintanat Ananworanich of the US Military HIV Research Program, and colleagues aimed to determine whether ART started during acute HIV infection would normalize biomarkers of gut damage, inflammation, and coagulation that predict morbidity and mortality during chronic HIV infection.

This analysis included 78 participants in the on-going SEARCH (RV254) study who were diagnosed during acute HIV infection and started ART within 0 to 5 days. The cohort is made up of people who sought HIV testing in Bangkok, Thailand, most of whom are men who have sex with men. More than 90% were male and the median age was 28 years. There was also a control group of 109 people without HIV infection; this group was matched for age but included more women (23%).

Among the HIV-positive participants, the median CD4 T-cell count at study entry was 384 cells/mm3 (range 293-525) and the median HIV viral load was 5.6 log10 copies/ml. Using Ananworanich's 4th generation staging system, 20 people were diagnosed during stage 1 of infection (HIV RNA positive; median 12 days after HIV acquisition), 15 during stage 2 (p24 antigen positive; median 16 days), and 43 during stage 3 (HIV antibody positive; median 18 days). About 40% started a standard ART regimen consisting of efavirenz (Sustiva) plus tenofovir/emtricitabine (the drugs in Truvada), while more than half started a more intensive regimen containing the same 3 drugs plus maraviroc (Selzentry) and raltegravir (Isentress).

The researchers assessed changes in biomarkers of microbial translocation (damage to the gut that allows leakage of intestinal bacteria), inflammation, coagulation (blood clotting) and fibrosis (accumulation of connective tissue). These processes are associated with complications and death among people with chronic HIV infection, but how soon they occur and how they might be affected by early treatment is not well understood.

Specifically, Utay and her team measured plasma levels of the following biomarkers at the time of HIV diagnosis or study entry (week 0) and again at weeks 2, 12, 24, 36, 48, and 96:

Prior studies have found that people with all stages of acute HIV infection have increased levels of hyaluronic acid, CRP and sCD14, while those with later stages of acute infection also have increased I-FABP and D-dimer, Utay noted as background.

Results

"Biomarkers of enterocyte death, microbial translocation, inflammation, coagulation, and fibrosis increase early in acute HIV infection," the researchers concluded. "I-FABP increases and remains elevated during infection despite suppressive ART, suggesting on-going enterocyte damage or turnover."

"[S]uppressive ART started during acute HIV infection does not eradicate the inflammation associated with increased morbidity and mortality in treated chronic HIV infection," they continued. However, they noted, most biomarkers decrease in people who start ART during acute infection to levels lower than those observed in patients who start ART during chronic HIV infection.

3/13/15

Reference

NS Utay, J Ananworanich, S Pinyakorn, et al. Inflammation Persists Despite Early Initiation of ART in Acute HIV Infection. 2015 Conference on Retroviruses and Opportunistic Infections. Seattle, February 23-24, 2015. Abstract 47.