Inflammatory biomarkers in HIV support the safety of switching to two-drug antiretroviral therapy

In patients with HIV infection, the switch from 3-agent antiretroviral therapy (ART) to 2-agent antiretroviral therapy (ART) of dolutegravir plus lamivudine showed a favorable trend for 2 soluble inflammatory biomarkers, according to the results of a study published in has been published HIV research and clinical practice.

Researchers conducted a longitudinal study in patients with virologically suppressed HIV infection receiving a 3-agent ART regimen between August 2019 and May 2021. Investigators compared inflammatory biomarkers between patients who switched to a 2-agent ART regimen of dolutegravir plus lamivudine at baseline and those who continued on a 3-agent ART regimen (controls). Patients in the 2-drug and control groups were matched based on age, sex, and anchor drug type. At baseline and at week 48, plasma concentrations of interleukin-6 (IL-6), intestinal fatty acid-binding protein (I-FABP), D-dimer, and C-reactive protein (CRP) were quantified via microfluidic ultrasensitive enzyme-linked immunosorbent assay performed and compared between the 2 groups.

A total of 208 patients were included in the analysis, 101 in the 2-drug group and 107 in the control group. The mean age of all patients was 55.4 (IQR, 47.7-61.3) years, 63% were male, 89.9% were white, and the median duration of ART was 13.0 (IQR, 6.4-61.3) 20.6) years.

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At baseline, the mean plasma concentrations of IL-6, I-FABP, D-dimer and CRP were similar in the two patient groups. The mean CD4+ cell count (cells/mm³) was significantly increased in patients in the 2-drug group compared to those in the control group (746 vs. 624; P =.006).

A significant decrease in the mean plasma concentration of I-FABP (log₁₀ pg/mL) occurred in patients in the 2-drug group (-0.088; 95% CI, -0.14 to -0.041) compared to those in the control group (0.033; 95% CI, -0.007 to 0.072). Baseline and week to 48 (P <.001). There were also significant differences in the mean plasma concentrations of CRP (log₁₀ pg/mL) between patients in the 2-drug group (-0.028; 95% CI, -0.118 to 0.063) versus those in the control group (0.118; 95% CI, 0.024-0.211) at this time point (P =.028). The mean plasma concentrations of IL-6 and D-dimer between baseline and week 48 did not differ significantly in the patients of both groups.

Similar results were noted after the analysis was restricted to patients receiving integrase strand-transfer inhibitor-based ART at baseline (70.7%), with the exception of a favorable trend in mean plasma concentrations of IL-6 seen in Patients treated with the 2 drug group was observed versus those in the control group.

Although virologic suppression was maintained in most patients through week 48, a single HIV viral rebound occurred in 2 patients in the 2-drug group during the study period.

This study was potentially limited by unmeasured and uncontrolled bias due to its longitudinal design.

According to the researchers, “Further studies with a longer follow-up period are warranted to further elucidate the inflammatory consequences of switching to the dolutegravir plus lamivudine regimen in patients with sustained virologic suppression, and [to] better clarify whether it could be an advantage over triple therapy.”

Disclosure: Some authors declared their affiliation with biotech, pharmaceutical, and/or device companies. For a full list of disclosures, see the original reference.

Relation

Lombardi F, Belmonti S, Moschese D, et al. Inflammatory markers in virologically suppressed HIV-infected patients after switching to dolutegravir plus lamivudine vs. continued triple therapy: 48-week real-world results. HIV Res clinic practice. 2022;23(1):28-36. doi:10.1080/25787489.2022.2080625