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

Abstract

Background: The 2-drug regimen dolutegravir plus lamivudine has demonstrated long-term noninferior efficacy vs 3-/4-drug regimens (3/4DRs) in phase 3 trials. This systematic literature review summarizes clinical trial and real-world evidence evaluating impact of dolutegravir plus lamivudine on inflammatory and atherogenesis biomarkers in people with human immunodeficiency virus type 1 (PWH).

Methods: Using Ovid MEDLINE, Embase, PubMed, and Cochrane library databases and conference proceedings, we searched for studies published from 1 January 2013 to 14 July 2021, reporting changes in inflammatory and atherogenesis biomarkers with dolutegravir plus lamivudine in antiretroviral therapy-experienced, virologically suppressed PWH aged ≥18 years.

Results: Four records representing 2 randomized controlled trials (RCTs) and 6 records of real-world evidence met eligibility criteria. All real-world studies evaluated CD4⁺/CD8⁺ ratio, while only 1 assessed inflammatory biomarkers. Across both RCTs, no consistent pattern of change in biomarkers was observed between dolutegravir/lamivudine and 3/4DR comparators. There were significant changes in soluble CD14 favoring dolutegravir/lamivudine in TANGO at weeks 48 and 144 and SALSA at week 48, and in interleukin-6 favoring the control group in TANGO at weeks 48 and 144. In the real-world study evaluating inflammatory biomarkers, median soluble CD14 significantly decreased 48 weeks postswitch to dolutegravir plus lamivudine (P < .001), while other biomarkers remained stable. In all 6 real-world studies, increases in CD4⁺/CD8⁺ ratio were reported after switch to dolutegravir plus lamivudine (follow-up, 12-60 months).

Conclusions: Results show that dolutegravir plus lamivudine has a comparable impact on inflammatory and atherogenesis biomarkers vs 3/4DRs, with no consistent pattern of change after switch in virologically suppressed PWH.

Keywords: 2-drug regimen; HIV-1; dolutegravir plus lamivudine; inflammation.

Figure 1.

Flow diagram of randomized controlled trial literature search for systematic review. 3TC, lamivudine; DTG, dolutegravir; IAS, International AIDS Society.

Figure 2.

Reported inflammatory and atherogenesis outcomes in people with human immunodeficiency virus receiving dolutegravir/lamivudine vs comparator in randomized controlled trials. P values are for treatment comparison. P values were not reported for SALSA 24-week data or for TANGO CD4⁺/CD8⁺ ratio data. Other P values that are not shown were not significant. ^aRatio is the estimated adjusted ratio in each group calculated using mixed-model repeated measures applied to change from baseline in log_e-transformed data adjusting for treatment, visit, baseline third agent class, CD4⁺ cell count (continuous), age (continuous), sex, race, body mass index (continuous), smoking status, hepatitis C virus coinfection status, log_e-transformed baseline biomarker value (continuous), treatment-by-visit interaction, and baseline value-by-visit interaction, with visit as the repeated factor. ^bParticipant numbers for individual inflammatory biomarkers vary. ^cMedian value at specified time point. Abbreviations: 3TC, lamivudine; CAR, current 3- or 4- drug antiretroviral therapy regimen; CRP, C-reactive protein; DTG, dolutegravir; IL-6, interleukin-6; sCD14, soluble CD14; sCD163, soluble CD163; TAF, tenofovir alafenamide.

Figure 3.

Flow diagram of real-world evidence literature search for systematic review. Abbreviations: 3TC, lamivudine; DTG, dolutegravir; IAS, International AIDS Society; PWH, people with human immunodeficiency virus type 1.

Figure 4.

Demographics, baseline (BL) characteristics, and change from BL in CD4⁺/CD8⁺ ratio in people with human immunodeficiency virus type 1 (PWH) receiving dolutegravir/lamivudine in studies of real-world evidence. ^aNumber of women calculated by subtracting originally reported data for men from total population. ^bMedian. ^cTriple ART was used by 66% of participants, but regimens were not specified; values listed in table reflect dual or monotherapies used by ≥5% of total PWH. ^dMean. ^eStudy also reported proportion of participants with CD4⁺/CD8⁺ ratio ≥1 at baseline vs week 96 (39/125 [31%] vs 51/125 [41%]; P < .001) and at baseline vs week 144 (13/53 [25%] vs 20/53 [38%]; P < .001). ^fSource only reported percentage (not number). ^gSource does not specify value as nadir CD4⁺ cell count. Abbreviations: 3TC, lamivudine; ART, antiretroviral therapy; ATV, atazanavir; BL, baseline; COBI, cobicistat; DRV, darunavir; DTG, dolutegravir; FTC, emtricitabine; IQR, interquartile range; LPV, lopinavir; NR, not reported; NS, not significant; PI, protease inhibitor; r, ritonavir; RAL, raltegravir; SD, standard deviation; TDF, tenofovir disoproxil fumarate.