Patients with HIV show durable viral suppression after switch to DTG/3TC

Results of a study published in Open Forum Infectious Diseases suggests that inflammatory biomarker levels among patients with HIV infection are similar between those who switch to dolutegravir (DTG) plus lamivudine (3TC) and those who remain on tenofovir alafenamide (TAF)-based antiretroviral (ART) regimens.

Treatment-naive patients with HIV infection tend to show high levels of inflammation and immune activation. Following ART initiation, inflammatory biomarker levels in HIV-positive patients also remain higher than that of the general population.

In this post hoc analysis, researchers assessed inflammatory biomarkers among patients with HIV infection who were enrolled in a multicenter, open-label, randomized, noninferiority, phase 3 trial (ClinicalTrials.gov Identifier: NCT03446573). Eligible patients (N=743) included virologically suppressed adults who had received uninterrupted TAF-based ART for more than 6 months. Patients were randomly assigned 1:1 to either switch to DTG/3TC once daily (n=371) or continue their TAF-based regimen (n=372) for 144 weeks.

The researchers evaluated interleukin (IL)-6, D-dimer, high-sensitivity C-reactive protein (CRP), soluble CD14, and soluble CD163 levels at baseline and at week 144. They also evaluated the frequency of viral “blips” (HIV viral load, 50-200 copies/mL with <50 copies/mL adjacent load), as well as the percentage of patients with very-low-level (<40 copies/mL) or low-level (≥40 to <50 and ≥50 copies/mL) viremia.

Among patients who switched to DTG/3TC and those who continued TAF-based ART, the median ages were 40 (range, 20-74) and 39 (range, 18-73) years, 93% and 91% were men, and 80% and 78% were White, respectively.

At every follow-up visit through 144 weeks, 33% of patients in the DTG/3TC group and 27% in the TAF group had very-low-level viremia. In both groups, the majority patients never reached a postbaseline HIV viral load of 40 copies/mL or more (92% and 86%, respectively).

Further analysis showed that viral blips occurred among 5% of patients who switched ART regimens and 7% of those who continued their current regimen.

At week 144, no between-group differences were observed in IL-6, D-dimer, high-sensitivity CRP, or soluble CD163 levels. However, patients who switched to DTG/3TC had lower levels of soluble CD14 (ratio, 0.92; 95% CI, 0.85-1.00; P =.040).

The researchers performed subgroup analyses to determine predictors of increased inflammatory biomarker levels. These included obesity, active smoking status, and older age for increased IL-6 levels; obesity, low-level baseline viremia, and older age for increased D-dimer levels; and female sex, obesity, and high baseline triglycerides for increased high-sensitivity CRP levels. Moreover, advanced HIV disease was associated with increased soluble CD14 levels, and older age was associated with increased soluble CD163 levels.

For all 4 inflammatory biomarkers assessed, increased baseline levels were associated with increased levels at 144 weeks.

Limitations of this study include the inability to adjust for certain pre-ART disease characteristics, the use of a single discrete sample to quantify and assess biomarkers, and a small patient population for certain subgroups.

“Long-term inflammatory biomarker levels were low and comparable between treatment groups and were independently associated with multiple demographic, lifestyle, and baseline HIV disease characteristics,” the researchers concluded.

Disclosures: This research was supported by ViiV Healthcare, and multiple study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

By Jessica Nye, PhD

References:

Wang R, Underwood M, Llibre JM, et al. Very-low-level viremia, inflammatory biomarkers, and associated baseline variables: 3-year results of the randomized TANGO study. Open Forum Infect Dis. Published online December 9, 2023. doi:10.1093/ofid/ofad626