Eradication of minimal residual disease improves overall and progression‐free survival in patients with chronic lymphocytic leukaemia,evidence from NCRN CLL207: a phase II trial assessing alemtuzumab consolidation

With immunochemotherapy, remission duration and survival in patients with chronic lymphocytic leukaemia is dependent on the level of minimal residual disease (MRD ) after treatment. This phase II trial assessed alemtuzumab consolidation post‐chemotherapy in patients who responded with persistent low levels of detectable disease. Blood was screened for MRD using multi‐parameter flow cytometry, 6–24 months post‐chemotherapy. MRD ‐positive participants received alemtuzumab 30 mg subcutaneously 3 times weekly for 6 weeks. Following a marrow assessment, MRD ‐negative participants or non‐responders stopped therapy and MRD ‐positive participants with 1 + log reduction had 6 more weeks of alemtuzumab. Alemtuzumab consolidation was received by 47 participants. One death and 19 of 22 serious adverse events reported from 17 (36%) participants were alemtuzumab‐related. MRD eradication from blood and bone marrow was achieved in 39 (83%) participants at the end of consolidation, with 18 (38%) remaining MRD ‐negative in the blood 6 months later. Of the 18 participants who were MRD ‐negative at 6 months, the median time to MRD relapse was 46 months, which was similar to patients who were MRD ‐negative at baseline and were followed up. The 5‐year progression‐free survival (PFS ) and overall survival (OS ) of participants who were MRD ‐negative at 6 months was significantly better than MRD ‐positive participants [PFS : 78% vs. 39% (P  =  0·010), OS : 89% vs. 64% (P  =  0·029)].     

Minimal residual disease as biomarker for optimal biologic dosing of ARA‐C in patients with acute myeloid leukemia

We assessed by flow cytometry minimal residual disease (MRD) in patients with acute myeloid leukemia (AML) given standard‐dose (SDAC) and high‐dose ARA‐C (HDAC) regimens. Of 163 patients enrolled, 130 (median age, 45 years; range, 18–59 years) qualified for analysis, all achieving complete remission after treatment with SDAC (n = 78) or HDAC (n = 52) plus etoposide and daunorubicin. Consolidation consisted of intermediate‐dose ARA‐C and daunorubicin. MRD negativity was significantly more frequent in the SDAC vs. HDAC arm after both induction (37% vs. 15%, P = 0.007) and consolidation (44% vs. 18%, P = 0.002). Respective median residual leukemic cell counts with SDAC and HDAC use were 1.5 × 10^?3 and 4 × 10^?3 (P = 0.033) after induction and 5.7 × 10^?4 and 2.9 × 10^?3 (P = 0.008) after consolidation. Based on ARA‐C schedule and post‐consolidation MRD status, the four patient groups (SDAC‐MRD^?, HDAC‐MRD^?, SDAC‐MRD⁺, and HDAC‐MRD⁺) displayed 5‐year overall survival rates of 60%, 33%, 24%, and 42% (P = 0.007), respectively, with 24%, 35%, 74%, and 48% (P < 0.0001) respective cumulative incidence of relapse estimates. MRD may serve as a biomarker for optimal biologic dosing of ARA‐C, and SDAC regimen appears to yield more frequent MRD negativity. Am. J. Hematol. 90:125–131, 2015. © 2014 Wiley Periodicals, Inc.     

Salvage chemotherapy followed by granulocyte colony‐stimulating factor‐primed donor leukocyte infusion with graft‐vs.‐host disease control for minimal residual disease in acute leukemia/myelodysplastic syndrome after allogeneic hematopoietic stem cell transplantation: prognostic factors and clinical outcomes

This study investigated the prognostic factors and clinical outcomes of preemptive chemotherapy followed by granulocyte colony‐stimulating factor‐primed donor leukocyte infusion (Chemo‐DLI) according to minimal residual disease (MRD) status in patients with acute leukemia and myelodysplastic syndromes who received allogeneic hematopoietic stem cell transplantation (HSCT) (n = 101). Patients received immunosuppressive drugs to prevent graft‐vs.‐host disease (GVHD) after Chemo‐DLI. The 3‐yr cumulative incidences of relapse, non‐relapse mortality, and disease‐free survival (DFS) after HSCT were 39.5%, 9.6%, and 51.7%, respectively. The cumulative incidences of relapse and DFS were significantly poorer in patients who exhibited early‐onset MRD. Forty‐four patients turned MRD negative 1 month after Chemo‐DLI; their cumulative incidences of relapse and DFS were significantly better than those with persistent MRD 1 month after preemptive Chemo‐DLI (relapse: 19.8% vs. 46.8%, P = 0.001; DFS: 69.6% vs. 46.4%, P = 0.004). The cumulative incidences of relapse and DFS after HSCT were significantly better in patients with chronic GVHD (cGVHD) than those without cGVHD (relapse: 19.6% vs. 63.7%, P < 0.001; DFS: 74.4% vs. 23.8%, P < 0.001). Early‐onset MRD, persistent MRD after Chemo‐DLI, and non‐cGVHD after Chemo‐DLI, which were associated with increased relapse and impaired DFS, suggest unsatisfactory response to preemptive Chemo‐DLI.     

No impact of high‐dose cytarabine and asparaginase as early intensification with intermediate‐risk paediatric acute lymphoblastic leukaemia: results of randomized trial TCCSG study L99‐15

The Tokyo Children's Cancer Study Group conducted a randomized controlled study to evaluate the effect of experimental early intensification using high‐dose cytarabine and L‐asparaginase in paediatric intermediate‐risk (IR) acute lymphoblastic leukaemia (ALL). A total of 310 IR ALL patients were randomized to receive either experimental early intensification (n = 156) or standard early intensification including standard‐dose cytarabine arm (n = 154) after induction therapy. The experimental arm consisted of high‐dose cytarabine and L‐asparaginase, while the standard arm consisted of standard‐dose cytarabine, oral 6‐mercaptopurine and cyclophosphamide. The probabilities of event‐free survival at 8 years in the experimental and standard arms were 72·3 ± 3·7% and 77·5 ± 3·5%, respectively (P = 0·32). The 8‐year overall survival rates for these two arms were 85·0 ± 3·0% and 86·9 ± 2·8%, respectively (P = 0·72). The frequency of infectious events was significantly higher in the experimental arm (66·4%) than in the standard arm (24·6%) (P < 0·001). In conclusion, experimental early intensification including high‐dose cytarabine followed by L‐asparaginase had no advantage over standard early intensification in paediatric IR ALL patients.     

Pre‐ and post‐transplant minimal residual disease predicts relapse occurrence in children with acute lymphoblastic leukaemia

Relapse remains the leading cause of treatment failure in children with acute lymphoblastic leukaemia (ALL) undergoing allogeneic haematopoietic stem cell transplantation (HSCT). We retrospectively investigated the prognostic role of minimal residual disease (MRD) before and after HSCT in 119 children transplanted in complete remission (CR). MRD was measured by polymerase chain reaction in bone marrow samples collected pre‐HSCT and during the first and third trimesters after HSCT (post‐HSCT1 and post‐HSCT3). The overall event‐free survival (EFS) was 50%. The cumulative incidence of relapse and non‐relapse mortality was 41% and 9%. Any degree of detectable pre‐HSCT MRD was associated with poor outcome: EFS was 39% and 18% in patients with MRD positivity <1 × 10⁻³ and ≥1 × 10⁻³, respectively, versus 73% in MRD‐negative patients (P < 0·001). This effect was maintained in different disease remissions, but low‐level MRD had a very strong negative impact only in patients transplanted in second or further CR. Also, MRD after HSCT enabled patients to be stratified, with increasing MRD between post‐HSCT1 and post‐HSCT3 clearly defining cohorts with a different outcome. MRD is an important prognostic factor both before and after transplantation. Given that MRD persistence after HSCT is associated with dismal outcome, these patients could benefit from early discontinuation of immunosuppression, or pre‐emptive immuno‐therapy.     

Effective Response Metric: a novel tool to predict relapse in childhood acute lymphoblastic leukaemia using time‐series gene expression profiling

Accurate risk assignment in childhood acute lymphoblastic leukaemia is essential to avoid under‐ or over‐treatment. We hypothesized that time‐series gene expression profiles (GEPs) of bone marrow samples during remission‐induction therapy can measure the response and be used for relapse prediction. We computed the time‐series changes from diagnosis to Day 8 of remission‐induction, termed Effective Response Metric (ERM‐D8) and tested its ability to predict relapse against contemporary risk assignment methods, including National Cancer Institutes (NCI) criteria, genetics and minimal residual disease (MRD). ERM‐D8 was trained on a set of 131 patients and validated on an independent set of 79 patients. In the independent blinded test set, unfavourable ERM‐D8 patients had >3‐fold increased risk of relapse compared to favourable ERM‐D8 (5‐year cumulative incidence of relapse 38·1% vs. 10·6%; P = 2·5 × 10⁻³). ERM‐D8 remained predictive of relapse [P = 0·05; Hazard ratio 4·09, 95% confidence interval (CI) 1·03–16·23] after adjusting for NCI criteria, genetics, Day 8 peripheral response and Day 33 MRD. ERM‐D8 improved risk stratification in favourable genetics subgroups (P = 0·01) and Day 33 MRD positive patients (P = 1·7 × 10⁻³). We conclude that our novel metric – ERM‐D8 – based on time‐series GEP after 8 days of remission‐induction therapy can independently predict relapse even after adjusting for NCI risk, genetics, Day 8 peripheral blood response and MRD.     

Significance of recurrence of minimal residual disease detected by multi‐parameter flow cytometry in patients with acute lymphoblastic leukemia in morphological remission

We sought to determine the significance of minimal residual disease (MRD) relapse in patients with ALL after achieving MRD negative status following induction and consolidation therapy. Between January 2003 and September 2014, 647 newly diagnosed patients were treated [HyperCVAD‐based (n = 531); Augmented BFM (n = 116)]. Six hundred and one (93%) achieved complete remission (CR), and 546 (91%) became MRD negative. Fifty‐five patients [HyperCVAD‐based (n = 49); Augmented BFM (n = 6)] developed recurrence of MRD while still in morphological CR and are the subjects of this study. MRD was assessed by 6‐color (4‐color prior to 2009) multi‐parameter flow cytometry (MFC) at CR and multiple time points thereafter. Their median age was 44 years (range, 18–72 years), median WBC at initial presentation was 7.3 K/µL^?1 (range, 0.6–303.8 K/µL^?1) and median bone marrow blast percentage 88% (range, 26–98%). The median time to MRD relapse was 14 months (range 3–58 months). Forty‐four (80%) patients subsequently developed morphological relapse after median of 3 months (range, <1–33 months) from detection of MRD recurrence. Treatments received after MRD positivity and prior to morphological relapse: 16 continued maintenance chemotherapy; 15 received late intensification; 9 allogeneic stem cell transplant, 9 changed chemotherapy, 6 no further therapy. Only six remain alive and in CR1 and nine are alive after morphological relapse. MRD relapse detected by MFC at any time after achieving CR is associated with a high risk for morphological relapse. SCT can result in long‐term remission in some patients. Prospective studies of long‐term MRD assessments, together with less toxic treatment strategies to eradicate MRD, are warranted.     

Post‐transplant consolidation plus lenalidomide maintenance vs lenalidomide maintenance alone in multiple myeloma: A systematic review

Background

In newly diagnosed multiple myeloma (NDMM), autologous stem cell transplantation (ASCT) remains the standard approach for transplant‐eligible patients. To control the inevitable relapse, post‐transplant consolidation/maintenance strategies are commonly used. However, the benefit of post‐transplant consolidation is still uncertain

Method

We conducted a systematic review of phase II/III studies to compare the efficacy of post‐ASCT consolidation plus lenalidomide maintenance (CON+LEN) vs lenalidomide maintenance alone (LEN alone) in NDMM. A meta‐analysis using fixed and random effects models was performed.

Results

Fourteen studies were included with 2275 participants with NDMM treated with ASCT and lenalidomide maintenance. Two groups were identified: CON+LEN group (n = 1102) and LEN alone group (n = 1173). There was no statistically significant difference in the complete response rate between the two groups [RR = 1.1; 95% CI: 0.83‐1.44; P = .490]. Interestingly, we found that very good partial response or better rate is around 1.5‐fold significantly higher in the CON+LEN group compared to LEN alone group [RR: 1.46; 95% CI: 1.25‐1.70; P < .0001]. However, there was no significant difference between the two groups regarding PFS [RR: 1.0; 95% CI: 0.92‐1.08, P = .929] and OS [RR: 0.9; 95% CI: 0.92‐1.01; P = .148] at 3‐4 years follow‐up. The risk of secondary primary malignancy (SPM) was also similar between the two groups (RR: 1.2; 95% CI: 0.84‐1.92; P = .2). Data on adverse events were limited.

Conclusion

Our data suggest that, in NDMM patients treated with upfront ASCT, post‐transplant consolidation may improve depth of response, but does not add to OS or PFS, compared to lenalidomide maintenance alone. However, data in this context are still immature.     

Phosphodiesterase 5 inhibitor treatment and survival in interstitial lung disease pulmonary hypertension: A Bayesian retrospective observational cohort study

Background and Objective

Pulmonary hypertension is a life-limiting complication of interstitial lung disease (ILD-PH). We investigated whether treatment with phosphodiesterase 5 inhibitors (PDE5i) in patients with ILD-PH was associated with improved survival.

Methods

Consecutive incident patients with ILD-PH and right heart catheterisation, echocardiography and spirometry data were followed from diagnosis to death, transplantation or censoring with all follow-up and survival data modelled by Bayesian methods.

Results

The diagnoses in 128 patients were idiopathic pulmonary fibrosis (n = 74, 58%), hypersensitivity pneumonitis (n = 17, 13%), non-specific interstitial pneumonia (n = 12, 9%), undifferentiated ILD (n = 8, 6%) and other lung diseases (n = 17, 13%). Final outcomes were death (n = 106, 83%), transplantation (n = 9, 7%) and censoring (n = 13, 10%). Patients treated with PDE5i (n = 50, 39%) had higher mean pulmonary artery pressure (median 38 mm Hg [interquartile range, IQR: 34, 43] vs. 35 mm Hg [IQR: 31, 38], p = 0.07) and percentage predicted forced vital capacity (FVC; median 57% [IQR: 51, 73] vs. 52% [IQR: 45, 66], p=0.08) though differences did not reach significance. Patients treated with PDE5i survived longer than untreated patients (median 2.18 years [95% CI: 1.43, 3.04] vs. 0.94 years [0.69, 1.51], p = 0.003) independent of all other prognostic markers by Bayesian joint-modelling (HR 0.39, 95% CI: 0.23, 0.59, p < 0.001) and propensity-matched analyses (HR 0.38, 95% CI: 0.22, 0.58, p < 0.001). Survival difference with treatment was significantly larger if right ventricular function was normal, rather than abnormal, at presentation (+2.55 years, 95% CI: −0.03, +3.97 vs. +0.98 years, 95% CI: +0.47, +2.00, p = 0.04).

Conclusion

PDE5i treatment in ILD-PH should be investigated by a prospective randomized trial.     

Implications of delayed bone marrow aspirations at the end of treatment induction for risk stratification and outcome in children with acute lymphoblastic leukaemia

Minimal residual disease (MRD) at the end of induction therapy is important for risk stratification of acute lymphoblastic leukaemia (ALL), but bone marrow (BM) aspiration is often postponed or must be repeated to fulfil qualitative and quantitative criteria for morphological assessment of haematological remission and/or MRD analysis. The impact of BM aspiration delay on measured MRD levels and resulting risk stratification is currently unknown. We analysed paired MRD data of 289 paediatric ALL patients requiring a repeat BM aspiration. MRD levels differed in 108 patients (37%) with a decrease in the majority (85/108). This would have resulted in different risk group allocation in 64 of 289 patients (23%) when applying the ALL‐Berlin‐Frankfurt‐Münster 2000 criteria. MRD change was associated with the duration of delay; 40% of patients with delay ≥7 days had a shift to lower MRD levels compared to only 18% after a shorter delay. Patients MRD‐positive at the original but MRD‐negative at the repeat BM aspiration (n = 50) had a worse 5‐year event‐free survival than those already negative at first aspiration (n = 115) (86 ± 5% vs. 94 ± 2%; P = 0·024). We conclude that BM aspirations should be pursued as scheduled in the protocol because delayed MRD sampling at end of induction may result in false‐low MRD load and distort MRD‐based risk assessment.     

Insulin degludec improves health‐related quality of life (SF‐36®) compared with insulin glargine in people with Type 2 diabetes starting on basal insulin: a meta‐analysis of phase 3a trials

Aim

To compare the effect of insulin degludec and insulin glargine on health‐related quality of life in patients with Type 2 diabetes starting on insulin therapy.

Methods

Patient‐level data from three open‐label, randomized, treat‐to‐target trials of 26 or 52 weeks' duration were pooled using a weighted analysis in conjunction with a fixed‐effects model. Insulin‐naive patients received either insulin degludec (n = 1290) or insulin glargine (n = 632) once daily, in combination with oral anti‐diabetic drugs. Glycaemic control was assessed via HbA_1c and fasting plasma glucose concentrations. Rates of hypoglycaemia, defined as plasma glucose < 3.1 mmol/l (< 56 mg/dl), were recorded. Health‐related quality of life was evaluated using the 36‐item Short Form (SF‐36^®) version 2 questionnaire. Statistical analysis was performed using a generalized linear model with treatment, trial, anti‐diabetic therapy at baseline, gender, region and age as explanatory variables.

Results

Insulin degludec was confirmed as non‐inferior to insulin glargine based on HbA_1c concentrations. In each trial comprising the meta‐analysis, fasting plasma glucose and confirmed overall and nocturnal (00.01–05.59 h) hypoglycaemia were all numerically or significantly lower with insulin degludec vs. insulin glargine. At endpoint, the overall physical health component score was significantly higher (better) with insulin degludec vs. insulin glargine [+0.66 (95% CI 0.04–1.28)], largely attributable to a difference [+1.10 (95% CI 0.22–1.98)] in the bodily pain domain score. In the mental domains, vitality was significantly higher with insulin degludec vs. insulin glargine [+0.81 (95% CI 0.01–1.59)].

Conclusions

Compared with insulin glargine, insulin degludec leads to improvements in both mental and physical health status for patients with Type 2 diabetes initiating insulin therapy.

     

Randomized phase 2 study of otlertuzumab and bendamustine versus bendamustine in patients with relapsed chronic lymphocytic leukaemia

Otlertuzumab (TRU ‐016) is a humanized anti‐CD 37 protein therapeutic that triggers direct caspase‐independent apoptosis of malignant B cells and induces antibody‐dependent cell‐mediated cytotoxicity. Patients with relapsed chronic lymphocytic leukaemia (CLL ) received either otlertuzumab (20 mg/kg) weekly by IV infusion for two 28‐day cycles then every 14 days for four 28‐day cycles and IV bendamustine (70 mg/m²) on Days 1 and 2 of each cycle for up to six 28‐day cycles or bendamustine alone. Thirty‐two patients were treated with otlertuzumab and bendamustine and 33 with bendamustine alone. Overall response rate according to the International Workshop on Chronic Lymphocytic Leukaemia criteria was 69% in the otlertuzumab and bendamustine arm and 39% in the bendamustine alone arm (P  = 0·025). Median progression‐free survival (PFS ) was 15·9 months in the otlertuzumab and bendamustine arm and 10·2 months in the bendamustine alone arm (P  = 0·0192). There was a higher incidence of pyrexia (34% vs. 12%) and neutropenia (59% vs. 39%) with the combination but this did not result in a higher incidence of severe (grade 3/4) infections (13% vs. 27%). This combination significantly increased the response rate and prolonged the PFS over single agent bendamustine in patients with relapsed or refractory CLL .     

Effect of prandial treatment timing adjustment,based on continuous glucose monitoring,in patients with type 2 diabetes uncontrolled with once‐daily basal insulin: A randomized,phase IV study

Aims

To evaluate the glycaemic control achieved by prandial once‐daily insulin glulisine injection timing adjustment, based on a continuous glucose monitoring sensor, in comparison to once‐daily insulin glulisine injection before breakfast in patients with type 2 diabetes who are uncontrolled with once‐daily basal insulin glargine.

Materials and Methods

This was a 24‐week open‐label, randomized, controlled, multicentre trial. At the end of an 8‐week period of basal insulin optimization, patients with HbA1c ≥ 7.5% and FPG < 130 mg/dL were randomized (1:1) to either arm A (no sensor) or arm B (sensor) to receive 16‐week intensified prandial glulisine treatment. Patients in arm A received pre‐breakfast glulisine, and patients in arm B received glulisine before the meal with the highest glucose elevation based on sensor data. The primary outcome was mean HbA1c at week 24 and secondary outcomes included rates of hypoglycaemic events and insulin dosage.

Results

A total of 121 patients were randomized to arm A (n = 61) or arm B (n = 60). There was no difference in mean HbA1c at week 24 between arms A and B (8.5% ± 1.2% vs 8.4% ± 1.0%; P = .66). The prandial insulin glulisine dosage for arm A and arm B was 9.3 and 10.1 units, respectively (P = .39). The frequency of hypoglycaemic events did not differ between study arms (36.1% vs 51.7%; P = .08).

Conclusion

Using a CGM sensor to identify the meal with the highest glucose excursion and adjusting the timing of prandial insulin treatment did not show any advantage in terms of glycaemic control or safety in our patients.     

Low burden of minimal residual disease prior to transplantation in children with very high risk acute lymphoblastic leukaemia: The NOPHO ALL2008 experience

The population-based Nordic/Baltic acute lymphoblastic leukaemia (ALL) Nordic Society for Paediatric Haematology and Oncology (NOPHO) ALL2008 protocol combined minimal residual disease (MRD)-driven treatment stratification with very intense first line chemotherapy for patients with high risk ALL. Patients with MRD ≥5% at end of induction or ≥10⁻³ at end of consolidation or following two high risk blocks were eligible for haematopoietic cell transplantation (HCT) in first remission. After at least three high risk blocks a total of 71 children received HCT, of which 46 had MRD ≥5% at end of induction. Ten patients stratified to HCT were not transplanted; 12 received HCT without protocol indication. Among 69 patients with evaluable pre-HCT MRD results, 22 were MRD-positive, one with MRD ≥10⁻³. After a median follow-up of 5·5 years, the cumulative incidence of relapse was 23·5% (95% confidence interval [CI]: 10·5–47·7) for MRD-positive versus 5·1% (95% CI: 1·3–19·2), P = 0·02) for MRD-negative patients. MRD was the only variable significantly associated with relapse (hazard ratio 9·1, 95% CI: 1·6–51·0, P = 0·012). Non-relapse mortality did not differ between the two groups, resulting in disease-free survival of 85·6% (95% CI: 75·4–97·2) and 67·4% (95% CI: 50·2–90·5), respectively. In conclusion, NOPHO block treatment efficiently reduced residual leukaemia which, combined with modern transplant procedures, provided high survival rates, also among pre-HCT MRD-positive patients.     

Outcome of Down syndrome associated acute lymphoblastic leukaemia treated on a contemporary protocol

We report the outcome for children and young people with Down syndrome‐associated acute lymphoblastic leukaemia (DS‐ALL) treated on a contemporary protocol. Compared with non‐DS ALL, patients with DS‐ALL had an inferior event‐free survival (65·6% vs. 87·7% at 5 years; P < 0·00005) and overall survival (70·0% vs. 92·2%; P < 0·00005). Excess treatment‐related mortality – was primarily responsible for the worse outcomes for DS‐ALL (21·6% at 5 years, vs. 3·3%, P < 0·00005). Minimal residual disease (MRD) risk status was highly discriminant for relapse in DS patients with 0/28 relapses in the MRD low risk group.     

Dolutegravir in real life: Self-reported mental and physical health outcomes after transitioning from efavirenz- to dolutegravir-based antiretroviral therapy in a prospective cohort study in Lesotho

Introduction

HIV programmes across many countries in Africa have recently transitioned people living with HIV from efavirenz (EFV)- to dolutegravir (DTG)-containing antiretroviral therapy (ART). As both drugs are associated with neuropsychiatric adverse effects, this study assessed the mental health and HIV/ART-associated symptoms of people living with HIV before and after transition to DTG.

Methods

The prospective DO-REAL cohort enrolled people starting DTG-based ART in Lesotho from February to December 2020. For this analysis within DO-REAL, we included adults changing from tenofovir disoproxil fumarate (TDF)/lamivudine (3TC)/EFV to TDF/3TC/DTG within first-line therapy. At transition and 16 weeks thereafter, participants completed the Patient Health Questionnaire-9 (PHQ-9; depression screening), the 12-item Short-Form Health Survey (SF-12; mental and physical health), and a modified HIV Symptom Index (mHSI; HIV/ART-related symptoms). We also assessed weight change. We used McNemar tests with Bonferroni corrections to assess binary outcomes. ClinicalTrials.gov : NCT04238767.

Results

Among 1228 participants, 1131 completed follow-up. Of these, 60.0% were female, the median age was 46 years (interquartile range [IQR] 38–55), and the median time taking ART was 5.7 years (IQR 3.5–8.9). No change was observed for weight or overall PHQ-9 or SF-12 outcomes. However, three mHSI items decreased at follow-up: ‘feeling sad/down/depressed’ (bothered 6.0% vs. 3.3% of participants at least ‘a little’ before vs. after transition; adjusted p = 0.048); ‘feeling nervous/anxious’ (7.4% vs. 3.4%; adjusted p = 0.0009); and ‘nightmares, strange/vivid dreams’ (6.3% vs. 3.5%; adjusted p = 0.027). Individual PHQ-9 or SF-12 items also improved. Being symptom free across all measures increased from 5.1% to 11.4% (p < 0.0001).

Conclusions

We observed no negative impacts and potential moderate improvements with DTG, providing further support for the rollout of DTG.