Viral Suppression, Viral Failure, and Safety Outcomes in Children and Adolescents With HIV on Dolutegravir in Europe and Thailand

Abstract

Background: Dolutegravir (DTG) is a preferred anchor antiretroviral therapy (ART) for children and adolescents with HIV (CAWH).

Methods: We assessed the effectiveness and safety of DTG in CAWH aged 0-18 years at DTG start in routine care in Europe and Thailand, evaluating viral suppression (viral load [VL] <50 copies/mL), cumulative incidence and associated factors of viral failure (VF; confirmed VL ≥400 copies/mL) and safety outcomes.

Results: Of 1230 CAWH on DTG, 49% were female. At DTG start, median (IQR) age was 14 (11-16) years, 10% were ART-naive, 49% ART-experienced/suppressed (VL <200 copies/mL), 13% ART-experienced/viremic (VL ≥200 copies/mL), and 28% ART-experienced/unknown VL. Median duration on DTG was 93 (49-163) weeks. Virall suppression was 88%-91% throughout follow-up. Cumulative incidence (95% CI) of VF at weeks 96 and 144 was 4.3% (3.1%-6.1%) and 8.3% (6.2%-11.1%). Increased risk of VF was associated with female sex, ART-experienced/viremic, advanced/severe immunosuppression, previous treatment failure, and region (P < .05, adjusting for age, sex and ART/VL status). The risk of VF was lower on DTG than CAWH on protease-inhibitor-based regimens (P < .001). Among 1146 with clinical data, 26 (2%) experienced 52 DTG-related adverse events, including 5 serious adverse events. Of 849 with laboratory data, 44 (5%) had 54 grade ≥3 events (<1 per 100 person-years). DTG discontinuation by weeks 96 and 144 was 5.0% (3.8%-6.7%) and 9.5% (7.5%-12.0%).

Conclusions: DTG was well tolerated, with ∼90% virally suppressed <50 copies/mL. VF was low overall but was significantly higher in children/adolescents ART-experienced and viraemic at DTG start, requiring close monitoring.

Keywords: ART; HIV; children/adolescents; dolutegravir; effectiveness.

Graphical Abstract

This graphical abstract is also available at Tidbit: https://tidbitapp.io/institutional-portal/clinical-infectious-diseases/tidbits/viral-suppression-viral-failure-and-safety-outcomes-in-children-and-adolescents-living-with-hiv-on-dolutegravir-in-europe-and-thailand-e2134500-ec6e-45cc-a103-6e224edab3d1/update

Figure 1.

Viral suppression (<50 c/mL) over time, overall, and by ART experience/viral suppression at DTG start. Abbreviations: ART, antiretroviral therapy; c/mL, copies/mL; exp, experienced; DTG, dolutegravir; VL, viral load.

Figure 2.

Time to viral failure on DTG (A) overall and by (B) ART and VL status, (C) sex, and (D) age group. Viral failure was defined as 2 consecutive VLs ≥400 c/mL after 24 weeks of treatment or 1 VL ≥400 c/mL after 24 weeks of treatment followed by discontinuation of DTG within 4 months. Incidence of failure was estimated using Kaplan-Meier methods. Follow-up was censored at the earliest of last suppressed VL or discontinuation of DTG in patients who did not experience viral failure. Analysis was restricted to patients with at least 24 weeks of follow-up after DTG start. Patients who initiated DTG in a trial are excluded. Abbreviations: ART, antiretroviral therapy; c/mL, copies/mL; DTG, dolutegravir; exp, experienced; VL, viral load.

Figure 3.

Rates of first grade 1, grade 2, and grade ≥3 laboratory events while on a DTG-based regimen stratified by laboratory marker. Event rates were calculated for episodes on DTG (CAWH could have >1 episode if they discontinued DTG for >30 days and then restarted DTG). Abbreviations: ALT, alanine aminotransferase; AMY, amylase; ANC, absolute neutrophil count; APT, alkaline phosphatase; AST, aspartate aminotransferase; CAWH, children and adolescents with HIV; CHOL, total cholesterol; DAIDS, Division of AIDS; DTG, dolutegravir; FPG_H, high fasting blood glucose; FPG_L, low fasting blood glucose; GGT, gamma-glutamyl transferase; Hb, hemoglobin; HDL, high-density lipoprotein; LDL, low-density lipoprotein cholesterol; LIP, lipase; N-FPG_H, high nonfasting blood glucose; N-FPG_L, low nonfasting blood glucose; PHOS, serum phosphate; PLT, platelets; S-Ca_H, high serum calcium; S-Ca_L, low serum calcium; S-CREAT, serum creatinine; TBIL, total bilirubin; TRIG, triglycerides.^† There are no DAIDS definitions for HDL abnormalities, instead the guidelines from the US Agency for Healthcare Research and Quality were used. “Borderline low” is presented as grade 1 and “low” as grade 2. There is no grade 3 or 4 category for HDL.