Effect of Dolutegravir/Lamivudine on Inflammatory Biomarkers in People With HIV

3d illustration of HIV virus
3d illustration of HIV virus. Medical concept.
Researchers conducted a systematic review to assess the effect of dolutegravir plus lamivudine on inflammatory and atherogenesis biomarkers in people with HIV infection.

Among virologically suppressed people with HIV infection (PWH), switching to dolutegravir plus lamivudine resulted in similar inflammatory and atherogenesis biomarkers compared with remaining on 3- or 4-drug regimens (3/4-DR). These findings, from a systematic literature review, were published in Open Forum Infectious Diseases.

Publication databases were searched through July 2021 for randomized controlled trials of combinatorial therapies for PWH with inflammatory and atherogenesis outcomes. One publication met the inclusion criteria and an additional 3 abstracts presented at conferences in 2021 were also included in the review. In addition, a review of studies using real-world data identified 6 other studies that met the inclusion criteria.

The 4 trials included in the review were from the TANGO and SALSA trials. The TANGO trial was a phase 3, open-label trial that enrolled PWH who had an HIV RNA viral load of less than 50 copies/mL for at least 6 months. Participants were randomly assigned to either switch to dolutegravir plus lamivudine (n=369) or remain on tenofovir alafenamide-based 3/4-DRs (n=372). The SALSA trial was an open-label, phase 3 trial that enrolled PWH with a similar profile of virologic suppression. Participants were randomly assigned to either switch to dolutegravir plus lamivudine (n=247) or remain on their current 3/4-DRs (n=247).

Results of the TANGO trial found that switching to dolutegravir plus lamivudine was noninferior compared with remaining on 3/4-DRs for maintaining virologic suppression through the conclusion of the study at week 144. At week 144, there were small changes to inflammatory biomarkers, with significant differences to soluble CD14 that favored dolutegravir plus lamivudine (P =.044) and interleukin (IL)-6 that favored 3/4-DRs (P =.039).

Results of the SALSA trial found that switching to dolutegravir plus lamivudine was noninferior compared with 3/4-DRs for maintaining virologic suppression through the conclusion of the study at week 48. At week 48, small changes to soluble CD14 favored dolutegravir plus lamivudine (P =.002).

For the studies that used real-world data, the ratio of CD4+ to CD8+ was found to significantly increase compared with baseline after switching to dolutegravir plus lamivudine (all P <.05). For the remaining 2 studies, results of a retrospective, case-crossover study found a trend toward improvement from baseline compared with week 48 (P =.060), and results of a single-center cohort study found that the ratio of CD4+ to CD8+ from baseline to month 48 increased by a median of 0.14 (IQR, -0.02 to 0.30).

This review was limited by the small number of included studies, and the researchers noted that further investigation via additional controlled trials is likely needed.

These data indicated that switching to dolutegravir plus lamivudine from 3/4-DRs likely allows PWH to maintain viral suppression without significantly affecting inflammatory and atherogenesis biomarkers.

Disclosure: Multiple authors declared affiliations with industry. Please see to the original reference for a full list of disclosures.

Reference

Llibre JM, Cahn PE, Lo J, et al. Changes in inflammatory and atherogenesis biomarkers with the 2-drug regimen dolutegravir plus lamivudine in antiretroviral therapy–experienced, virologically suppressed people with HIV-1: a systematic literature review.Open Forum Infect Dis. 2022;9(4):ofac068. doi:10.1093/ofid/ofac068