Reasons, Efficacy and Safety of Switching to Dolutegravir-Based Regimens Among Virologically Suppressed PLWH: A Retrospective Cohort Study of 96 Weeks

Abstract

Purpose: The study aimed to explore the reasons, efficacy, and safety of switching to dolutegravir (DTG) based regimens in virologically suppressed people living with HIV (PLWH) in tertiary hospitals in China. Therefore, the study could provide a valuable reference for the rational clinical use of DTG.

Methods: PLWH's basic information, treatment details, and reasons for switching were collected, through the electrical clinical medical record system and telephone follow-up. Data included the proportion of PLWH with HIV RNA <50 copies/mL, changes in immunological indicators, and metabolic metrics at week 48 and week 96.

Results: 319 PLWH were included in the analysis. The three major reasons for switching were neurological toxicity (16.30%), simplification (13.79%), and renal toxicity (11.29%). Our study showed high rates of virologic suppression in the per-protocol analysis (week 48: 99.69%; week 96: 99.29%) after switching to DTG-based regimens. The median CD4+ T cell count increased from 579 cells/μL (IQR 420.5-758) to 642 cells/μL (IQR 466.5-854) at week 96 (p<0.0001). An improvement was observed in liver function (ALT: p<0.0001; AST: p<0.0001) and fasting glucose (p<0.0001). However, there was an elevation in creatinine (Cr) (p<0.0001) and a slight decrease in the estimated glomerular filtration rate (eGFR) (p<0.0001). Regarding lipid profile, triglyceride (TG) levels declined, while total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels increased. Further analysis revealed that the increase in TC and LDL-C was associated with the withdrawal of tenofovir disoproxil fumarate (TDF). This observed increase in lipid parameters only concerned the PLWH who switched from a TDF-containing regimen to a non-TDF regimen.

Conclusion: This study confirmed the virologic efficacy of switching to DTG-based regimens in virologically suppressed PLWH over a 96-week period. The findings also expanded the evidence of immune reconstitution and metabolic safety associated with this switch.

Keywords: HIV; dolutegravir; lipids profile; switching; virologically suppressed.

Figure 1

Study profile.

Figure 2

The reasons for switching. Unknown (n=64), neurological toxicity (n=52), renal toxicity (n=36), simplification (n=35), dyslipidemia (n=30), osteoporosis (n=24) and convenience (n=21), avoidance of long-term toxicities (n=13), liver toxicity (n=11), other toxicities (n=10), gastrointestinal toxicity (n=8), poor immune reconstitution (n=6), resistance/limited treatment options (n=4), pill burden (n=2), clinical trial (n=2) and drug-drug interactions (n=11).

Figure 3

Virologic and immunologic response. (A) Virologic control (HIV-RNA < 50 copies/mL), virologic failure (HIV-RNA ≥ 50 copies /mL), and missing virologic data at week 48 and week 96. ITT: intention-to-treat analysis—missing equal failure; PP: per-protocol analysis— missing equal excluded. No missing data were recorded at week 48, thus the ITT and the PP analyses are equal (yellow bar). At week 96 missing data were recorded; thus, the figure shows bars for both the ITT analysis (blue bar) and the PP analysis (light blue bar). (B) Changes of CD4+ T cell count, CD8+ T cell count, and CD4/CD8 ratio at week 48 and week 96 (week 0: n = 317; week 48: n = 283; week 96: n = 257).

Figure 4

Metabolic profile during the follow-up. The bars show the median relative difference from week 0 for the considered metabolic parameters at both week 48 and week 96. The p-value shown under each bar comes from the paired Wilcoxon test between week 0 and the considered time-point; the p-value above between the week 48 bar and the week 96 bar comes from the paired Wilcoxon test between week 48 and week 96. Vertical lines show the 95% CI. (A) Changes in liver function and fasting glucose from week 0 to week 48 and 96 (week 0: n = 314; week 48: n = 288; week 96: n = 259). (B) Changes in renal function from week 0 to week 48 and 96 (week 0: n = 315; week 48: n = 287; week 96: n = 257). (C) Changes in lipids from week 0 to week 48 and 96 (week 0: n = 311; week 48: n = 283; week 96: n = 253).

Figure 5

The reason for the increase of TC and LDL-C. (A) Changes in TC and LDL-C from week 0 to week 48 and week 96 (Group 1, week 0: n=198; week 48: n=174; week 96: n=159; Group 2, week 0: n=56; week 48: n=55; week 96: n=47; Group 3: week 0: n=53; week 48: n=50; week 96: n=43). (B) Changes with non-missing fasting lipid data in TC and LDL-C from week 0 to week 48 and week 96 by the Chinese Guidelines for Lipid Management (2023).