Trial Outcomes & Findings for Analytical Treatment Interruption in HIV Positive Patients (NCT NCT02590354)

Last Updated: 2019-09-24

Results Overview

The number of post treatment controllers (PTC - i.e. patients under ART at baseline that show low peripheral blood proviral DNA and still will show sustained viral suppression at 48 weeks after treatment interruption) will be determined. The assessment will be based on the plasma viral load (expressed in copies/ml) measured two-weekly (or four-weekly after W12) until W48 after treatment interruption. Patients below the lower limit of detection (\<50 HIV RNA copies/ml plasma) at 48 weeks after treatment interruption will be considered as PTC.

Recruitment status

COMPLETED

Study phase

Target enrollment

114 participants

Primary outcome timeframe

48 weeks after treatment interruption

Results posted on

2019-09-24

Participant Flow

Participant milestones

Participant milestones
Measure	Treatment Interruption The ART treatment in patients with a very low viral reservoir will be interrupted. Phase 1: Screening visit for HIV patients. During this visit a blood sample is taken for HIV reservoir analysis. Patients in which the reservoir is below a certain treshold will continue to phase 2 and will have their ART treatment interrupted (treatment interruption period).
Phase 1 STARTED	114
Phase 1 COMPLETED	16
Phase 1 NOT COMPLETED	98
Phase 2 - Treatment Interruption STARTED	16
Phase 2 - Treatment Interruption COMPLETED	14
Phase 2 - Treatment Interruption NOT COMPLETED	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Treatment Interruption The ART treatment in patients with a very low viral reservoir will be interrupted. Phase 1: Screening visit for HIV patients. During this visit a blood sample is taken for HIV reservoir analysis. Patients in which the reservoir is below a certain treshold will continue to phase 2 and will have their ART treatment interrupted (treatment interruption period).
Phase 1 Active hepatitis B or C infection	1
Phase 1 Confirmed neutrophil count <1200/µl	1
Phase 1 Detectable level of HIV DNA or caRNA	75
Phase 1 Subject does not want to participate	20
Phase 1 Lost to Follow-up	1
Phase 2 - Treatment Interruption Lost to Follow-up	2

Baseline Characteristics

114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Participants (Both Phase 1 and 2) n=114 Participants 114 subjects were screened in phase 1. Only those with a low viral reservoir continued to phase 2 (16 subjects).
Age, Continuous Phase 1	45.5 years n=114 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
Age, Continuous Phase 2	43.5 years n=16 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
Sex: Female, Male Phase 1 · Female	6 Participants n=114 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
Sex: Female, Male Phase 1 · Male	108 Participants n=114 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
Sex: Female, Male Phase 2 · Female	1 Participants n=16 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
Sex: Female, Male Phase 2 · Male	15 Participants n=16 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
Race/Ethnicity, Customized Phase 1 · Asian	1 Participants n=114 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
Race/Ethnicity, Customized Phase 1 · Black African	1 Participants n=114 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
Race/Ethnicity, Customized Phase 1 · White	111 Participants n=114 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
Race/Ethnicity, Customized Phase 1 · Other: Colombian	1 Participants n=114 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
Race/Ethnicity, Customized Phase 2 · Asian	0 Participants n=16 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
Race/Ethnicity, Customized Phase 2 · Black African	0 Participants n=16 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
Race/Ethnicity, Customized Phase 2 · White	16 Participants n=16 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
Race/Ethnicity, Customized Phase 2 · Other: Colombian	0 Participants n=16 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
Risk group Phase 1 · Heterosexual contact	14 Participants n=114 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
Risk group Phase 1 · Homo/Bisexual contact	95 Participants n=114 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
Risk group Phase 1 · Transfusion, non-haemophilia related	1 Participants n=114 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
Risk group Phase 1 · Other: unknown	4 Participants n=114 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
Risk group Phase 2 · Heterosexual contact	3 Participants n=16 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
Risk group Phase 2 · Homo/Bisexual contact	12 Participants n=16 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
Risk group Phase 2 · Transfusion, non-haemophilia related	0 Participants n=16 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
Risk group Phase 2 · Other: unknown	1 Participants n=16 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
Duration of HIV infection (months) Phase 1	70.9 months n=114 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
Duration of HIV infection (months) Phase 2	47.2 months n=16 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
Duration of HIV infection (years) Phase 1	5.9 years n=114 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
Duration of HIV infection (years) Phase 2	3.9 years n=16 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
Duration of ART (months) Phase 1	51.2 months n=114 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
Duration of ART (months) Phase 2	47.3 months n=16 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
Duration of ART (years) Phase 1	4.3 years n=114 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
Duration of ART (years) Phase 2	4.0 years n=16 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
Last used ART Phase 1 · II + NRTI	49 Participants n=114 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
Last used ART Phase 1 · NNRTI + NRTI	51 Participants n=114 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
Last used ART Phase 1 · PI + NRTI	10 Participants n=114 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
Last used ART Phase 1 · Other	4 Participants n=114 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
Last used ART Phase 2 · II + NRTI	11 Participants n=16 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
Last used ART Phase 2 · NNRTI + NRTI	4 Participants n=16 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
Last used ART Phase 2 · PI + NRTI	1 Participants n=16 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
Last used ART Phase 2 · Other	0 Participants n=16 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
HIV type Phase 1 · A	3 Participants n=114 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
HIV type Phase 1 · B	106 Participants n=114 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
HIV type Phase 1 · C	1 Participants n=114 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
HIV type Phase 1 · CRF02_AG	4 Participants n=114 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
HIV type Phase 2 · A	1 Participants n=16 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
HIV type Phase 2 · B	15 Participants n=16 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
HIV type Phase 2 · C	0 Participants n=16 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
HIV type Phase 2 · CRF02_AG	0 Participants n=16 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
Nadir CD4 count Phase 1	379.0 cells/µl n=114 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
Nadir CD4 count Phase 2	440.5 cells/µl n=16 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
ALT Phase 1	31.0 IU/L n=114 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
ALT Phase 2	21.5 IU/L n=16 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
AST Phase 1	27.0 IU/L n=114 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
AST Phase 2	21.5 IU/L n=16 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
Neutrophil count Phase 1	3.1 cells/µL n=114 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
Neutrophil count Phase 2	2.8 cells/µL n=16 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
CD4 count Phase 1	733.0 cells/µL n=114 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
CD4 count Phase 2	758.0 cells/µL n=16 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
Creatin Phase 1	1.0 mg/dL n=114 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
Creatin Phase 2	1.0 mg/dL n=16 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
Hemoglobin Phase 1	15.0 g/dL n=114 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
Hemoglobin Phase 2	15.1 g/dL n=16 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
HCVAb Phase 1	1.0 IU/mL n=114 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
HCVAb Phase 2	1.0 IU/mL n=16 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
HBsAb Phase 1 · >1000mIU/mL	32 Participants n=114 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
HBsAb Phase 1 · Negative	74 Participants n=114 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
HBsAb Phase 1 · No result	8 Participants n=114 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
HBsAb Phase 2 · >1000mIU/mL	3 Participants n=16 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
HBsAb Phase 2 · Negative	11 Participants n=16 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
HBsAb Phase 2 · No result	2 Participants n=16 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
HBcAb Phase 1 · Negative (<0.8 IU/mL)	61 Participants n=114 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
HBcAb Phase 1 · Positive (1.0 IU/mL or more)	38 Participants n=114 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
HBcAb Phase 1 · Grey Zone (0.8-0.99 IU/mL)	3 Participants n=114 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
HBcAb Phase 1 · No result	12 Participants n=114 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
HBcAb Phase 2 · Negative (<0.8 IU/mL)	7 Participants n=16 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
HBcAb Phase 2 · Positive (1.0 IU/mL or more)	7 Participants n=16 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
HBcAb Phase 2 · Grey Zone (0.8-0.99 IU/mL)	1 Participants n=16 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
HBcAb Phase 2 · No result	1 Participants n=16 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
HBsAg Phase 1 · Negative	100 Participants n=114 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
HBsAg Phase 1 · Positive	2 Participants n=114 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
HBsAg Phase 1 · No results	12 Participants n=114 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
HBsAg Phase 2 · Negative	15 Participants n=16 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
HBsAg Phase 2 · Positive	0 Participants n=16 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
HBsAg Phase 2 · No results	1 Participants n=16 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
Plasma viral load Phase 1	19.0 copies/mL n=114 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
Plasma viral load Phase 2	19.0 copies/mL n=16 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
Platelets Phase 1	232.0 10^9 cells/L n=114 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
Platelets Phase 2	239.5 10^9 cells/L n=16 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
Reservoir CD4 caRNA	105.5 copies/million CD4+ T-cells n=16 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption). This variable was only tested in those subjects that continued to phase 2 (treatment interruption).
Ultra-sensitive plasma viral load	0.3 copies/mL n=16 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption). This variable was only tested in those subjects that continued to phase 2 (treatment interruption).
Viral reservoir assay DNA Phase 1	107.0 copies/10^6PBMCs n=114 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
Viral reservoir assay DNA Phase 2	37.5 copies/10^6PBMCs n=16 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
Viral reservoir assay RNA Phase 1	3.0 copies/10^6PBMCs n=16 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
Viral reservoir assay RNA Phase 2	2.0 copies/10^6PBMCs n=16 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption).
Spontaneous VRA CD4	1.0 copies/mL n=16 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption). This variable was only tested in those subjects that continued to phase 2 (treatment interruption).
Stimulated VRA CD4	1.6 copies/mL n=16 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption). This variable was only tested in those subjects that continued to phase 2 (treatment interruption).
Spontaneous VRA PBMC	0.7 copies/mL n=16 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption). This variable was only tested in those subjects that continued to phase 2 (treatment interruption).
Stimulated VRA PBMC	2.2 copies/mL n=16 Participants • 114 participants were included in phase 1 of the study. 16 of those continued to phase 2 (treatment interruption). This variable was only tested in those subjects that continued to phase 2 (treatment interruption).

PRIMARY outcome

Timeframe: 48 weeks after treatment interruption

Population: Analysis population contains all subjects enrolled in phase 2 (treatment interruption phase)

Outcome measures

Outcome measures
Measure	Treatment Interruption n=16 Participants The ART treatment in patients with a very low viral reservoir will be interrupted. ART interruption
Assessment of the Number of Participants With a HIV Plasma Viral Load Below the Lower Limit of Detection 48 Weeks Following Interruption of Antiretroviral Treatment	0 Participants

SECONDARY outcome

Timeframe: 23 months

Population: Population analyzed are the subject enrolled in het treatment interruption phase.

Confirmation of the safety of a treatment interruption strategy in selected patients will be based on the number and intensity of AEs graded according to the NCI Common Terminology Criteria for Adverse Events v4.0 (CTCAE) on a five-point scale (Grade 1 to 5: Mild, Moderate, Severe, Life-threatening and Death).

Outcome measures

Outcome measures
Measure	Treatment Interruption n=16 Participants The ART treatment in patients with a very low viral reservoir will be interrupted. ART interruption
Number of Patients With and the Severity of Adverse Events That Are Related to the Study Intervention, Graded According to NCI CTCAE Version 4.0 Fatigue · Mild	1 Participants
Number of Patients With and the Severity of Adverse Events That Are Related to the Study Intervention, Graded According to NCI CTCAE Version 4.0 Fatigue · Moderate	0 Participants
Number of Patients With and the Severity of Adverse Events That Are Related to the Study Intervention, Graded According to NCI CTCAE Version 4.0 Fatigue · Severe	0 Participants
Number of Patients With and the Severity of Adverse Events That Are Related to the Study Intervention, Graded According to NCI CTCAE Version 4.0 Fatigue · Life-threatening	0 Participants
Number of Patients With and the Severity of Adverse Events That Are Related to the Study Intervention, Graded According to NCI CTCAE Version 4.0 Fatigue · No AE	15 Participants
Number of Patients With and the Severity of Adverse Events That Are Related to the Study Intervention, Graded According to NCI CTCAE Version 4.0 Influenza-like illness · Mild	1 Participants
Number of Patients With and the Severity of Adverse Events That Are Related to the Study Intervention, Graded According to NCI CTCAE Version 4.0 Influenza-like illness · Moderate	0 Participants
Number of Patients With and the Severity of Adverse Events That Are Related to the Study Intervention, Graded According to NCI CTCAE Version 4.0 Influenza-like illness · Severe	0 Participants
Number of Patients With and the Severity of Adverse Events That Are Related to the Study Intervention, Graded According to NCI CTCAE Version 4.0 Influenza-like illness · Life-threatening	0 Participants
Number of Patients With and the Severity of Adverse Events That Are Related to the Study Intervention, Graded According to NCI CTCAE Version 4.0 Influenza-like illness · No AE	15 Participants
Number of Patients With and the Severity of Adverse Events That Are Related to the Study Intervention, Graded According to NCI CTCAE Version 4.0 Oropharyngeal pain · Mild	1 Participants
Number of Patients With and the Severity of Adverse Events That Are Related to the Study Intervention, Graded According to NCI CTCAE Version 4.0 Oropharyngeal pain · Moderate	0 Participants
Number of Patients With and the Severity of Adverse Events That Are Related to the Study Intervention, Graded According to NCI CTCAE Version 4.0 Oropharyngeal pain · Severe	0 Participants
Number of Patients With and the Severity of Adverse Events That Are Related to the Study Intervention, Graded According to NCI CTCAE Version 4.0 Oropharyngeal pain · Life-threatening	0 Participants
Number of Patients With and the Severity of Adverse Events That Are Related to the Study Intervention, Graded According to NCI CTCAE Version 4.0 Oropharyngeal pain · No AE	15 Participants

SECONDARY outcome

Timeframe: At screening, baseline, week 2, week 4, week 6, week 8 and at 12 weeks after relapse

Population: Population analyzed are the subjects enrolled in phase 2 (treatment interruption).

Assessment of the viral reservoir magnitude on cryopreserved Peripheral Blood Mononuclear Cells (PBMCs) prior and after treatment interruption by means of Total HIV DNA.

Outcome measures

Outcome measures
Measure	Treatment Interruption n=16 Participants The ART treatment in patients with a very low viral reservoir will be interrupted. ART interruption
Evaluation of the Reservoir Replenishment Upon Interruption of Antiretroviral Treatment (TI) by Quantifying the Viral Reservoir at Baseline (i.e. Just Before TI) and at Viral Rebound (Total HIV DNA). Screening	37.5 copies/10^6PBMCs Interval 11.5 to 55.5
Evaluation of the Reservoir Replenishment Upon Interruption of Antiretroviral Treatment (TI) by Quantifying the Viral Reservoir at Baseline (i.e. Just Before TI) and at Viral Rebound (Total HIV DNA). Baseline	22.5 copies/10^6PBMCs Interval 4.0 to 53.5
Evaluation of the Reservoir Replenishment Upon Interruption of Antiretroviral Treatment (TI) by Quantifying the Viral Reservoir at Baseline (i.e. Just Before TI) and at Viral Rebound (Total HIV DNA). Week 2	27.5 copies/10^6PBMCs Interval 11.0 to 69.0
Evaluation of the Reservoir Replenishment Upon Interruption of Antiretroviral Treatment (TI) by Quantifying the Viral Reservoir at Baseline (i.e. Just Before TI) and at Viral Rebound (Total HIV DNA). Week 4	46.5 copies/10^6PBMCs Interval 18.0 to 127.0
Evaluation of the Reservoir Replenishment Upon Interruption of Antiretroviral Treatment (TI) by Quantifying the Viral Reservoir at Baseline (i.e. Just Before TI) and at Viral Rebound (Total HIV DNA). Week 6	38.0 copies/10^6PBMCs Interval 22.0 to 141.5
Evaluation of the Reservoir Replenishment Upon Interruption of Antiretroviral Treatment (TI) by Quantifying the Viral Reservoir at Baseline (i.e. Just Before TI) and at Viral Rebound (Total HIV DNA). Week 8	83.5 copies/10^6PBMCs Interval 82.0 to 85.0
Evaluation of the Reservoir Replenishment Upon Interruption of Antiretroviral Treatment (TI) by Quantifying the Viral Reservoir at Baseline (i.e. Just Before TI) and at Viral Rebound (Total HIV DNA). Post week 12	42.5 copies/10^6PBMCs Interval 29.0 to 117.0

SECONDARY outcome

Timeframe: At screening, baseline, week 2, week 4, week 6, week 8 and at 12 weeks after relapse

Population: Population analyzed are the subjects enrolled in phase 2 (treatment interruption).

Assessment of the viral reservoir magnitude on cryopreserved Peripheral Blood Mononuclear Cells (PBMCs) prior and after treatment interruption by means of unspliced RNA.

Outcome measures

Outcome measures
Measure	Treatment Interruption n=16 Participants The ART treatment in patients with a very low viral reservoir will be interrupted. ART interruption
Evaluation of the Reservoir Replenishment Upon Interruption of Antiretroviral Treatment (TI) by Quantifying the Viral Reservoir at Baseline (i.e. Just Before TI) and at Viral Rebound (Unspliced RNA). Screening	2 copies/10^6PBMCs Interval 0.0 to 3.5
Evaluation of the Reservoir Replenishment Upon Interruption of Antiretroviral Treatment (TI) by Quantifying the Viral Reservoir at Baseline (i.e. Just Before TI) and at Viral Rebound (Unspliced RNA). Baseline	7.0 copies/10^6PBMCs Interval 4.0 to 16.5
Evaluation of the Reservoir Replenishment Upon Interruption of Antiretroviral Treatment (TI) by Quantifying the Viral Reservoir at Baseline (i.e. Just Before TI) and at Viral Rebound (Unspliced RNA). Week 2	7.5 copies/10^6PBMCs Interval 5.0 to 19.5
Evaluation of the Reservoir Replenishment Upon Interruption of Antiretroviral Treatment (TI) by Quantifying the Viral Reservoir at Baseline (i.e. Just Before TI) and at Viral Rebound (Unspliced RNA). Week 4	23.5 copies/10^6PBMCs Interval 5.0 to 179.0
Evaluation of the Reservoir Replenishment Upon Interruption of Antiretroviral Treatment (TI) by Quantifying the Viral Reservoir at Baseline (i.e. Just Before TI) and at Viral Rebound (Unspliced RNA). Week 6	30.5 copies/10^6PBMCs Interval 10.5 to 177.0
Evaluation of the Reservoir Replenishment Upon Interruption of Antiretroviral Treatment (TI) by Quantifying the Viral Reservoir at Baseline (i.e. Just Before TI) and at Viral Rebound (Unspliced RNA). Week 8	34.5 copies/10^6PBMCs Interval 31.0 to 38.0
Evaluation of the Reservoir Replenishment Upon Interruption of Antiretroviral Treatment (TI) by Quantifying the Viral Reservoir at Baseline (i.e. Just Before TI) and at Viral Rebound (Unspliced RNA). Post week 12	12 copies/10^6PBMCs Interval 5.0 to 15.0

SECONDARY outcome

Timeframe: At screening, baseline, week 2, week 4, week 6, week 8, End of Intervention (relapse), 4 weeks after relapse and 12 weeks after relapse

Population: The population analyzed are the subjects enrolled in phase 2 (treatment interruption).

The kinetics will be on the plasma viral load (expressed in copies/ml) measured two-weekly (or four-weekly after W12) until W48 after treatment interruption. A viral load of 19 means \<20 copies/mL (lower limit of detection).

Outcome measures

Outcome measures
Measure	Treatment Interruption n=16 Participants The ART treatment in patients with a very low viral reservoir will be interrupted. ART interruption
Assessment of the Kinetics of HIV Viral Load Rebound After Treatment Interruption Based on the Repetitive Plasma Viral Load Measurements. Screening	19 copies/mL Interval 19.0 to 19.0
Assessment of the Kinetics of HIV Viral Load Rebound After Treatment Interruption Based on the Repetitive Plasma Viral Load Measurements. Baseline	19 copies/mL Interval 19.0 to 19.0
Assessment of the Kinetics of HIV Viral Load Rebound After Treatment Interruption Based on the Repetitive Plasma Viral Load Measurements. Week 2	19 copies/mL Interval 19.0 to 55.5
Assessment of the Kinetics of HIV Viral Load Rebound After Treatment Interruption Based on the Repetitive Plasma Viral Load Measurements. Week 4	1223 copies/mL Interval 26.0 to 40600.0
Assessment of the Kinetics of HIV Viral Load Rebound After Treatment Interruption Based on the Repetitive Plasma Viral Load Measurements. Week 6	4020 copies/mL Interval 2110.0 to 21100.0
Assessment of the Kinetics of HIV Viral Load Rebound After Treatment Interruption Based on the Repetitive Plasma Viral Load Measurements. Week 8	3480 copies/mL Interval 3480.0 to 3480.0
Assessment of the Kinetics of HIV Viral Load Rebound After Treatment Interruption Based on the Repetitive Plasma Viral Load Measurements. En of Intervention (moment of relapse)	28000 copies/mL Interval 2330.0 to 44900.0
Assessment of the Kinetics of HIV Viral Load Rebound After Treatment Interruption Based on the Repetitive Plasma Viral Load Measurements. Post week 4	22 copies/mL Interval 19.0 to 165.0
Assessment of the Kinetics of HIV Viral Load Rebound After Treatment Interruption Based on the Repetitive Plasma Viral Load Measurements. Post week 12	19 copies/mL Interval 19.0 to 26.0

Adverse Events

Treatment Interruption

Serious events: 0 serious events

Other events: 13 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Treatment Interruption n=16 participants at risk Subjects enrolled in phase 2 (treatment interruption). There was no AE collection during phase 1.
Gastrointestinal disorders Abdominal pain	6.2% 1/16 • Number of events 1 • Adverse events were collected over the whole study period (from start of treatment interruption until end of follow-up period which was 12 weeks after relapse and treatment restart).
Gastrointestinal disorders Faeces soft	6.2% 1/16 • Number of events 1 • Adverse events were collected over the whole study period (from start of treatment interruption until end of follow-up period which was 12 weeks after relapse and treatment restart).
Gastrointestinal disorders Stomatitis	6.2% 1/16 • Number of events 1 • Adverse events were collected over the whole study period (from start of treatment interruption until end of follow-up period which was 12 weeks after relapse and treatment restart).
Gastrointestinal disorders Vomiting	6.2% 1/16 • Number of events 1 • Adverse events were collected over the whole study period (from start of treatment interruption until end of follow-up period which was 12 weeks after relapse and treatment restart).
General disorders Fatigue	18.8% 3/16 • Number of events 3 • Adverse events were collected over the whole study period (from start of treatment interruption until end of follow-up period which was 12 weeks after relapse and treatment restart).
General disorders Influenza-like illness	25.0% 4/16 • Number of events 4 • Adverse events were collected over the whole study period (from start of treatment interruption until end of follow-up period which was 12 weeks after relapse and treatment restart).
Infections and infestations Bronchitis	6.2% 1/16 • Number of events 1 • Adverse events were collected over the whole study period (from start of treatment interruption until end of follow-up period which was 12 weeks after relapse and treatment restart).
Infections and infestations Ear infection	6.2% 1/16 • Number of events 1 • Adverse events were collected over the whole study period (from start of treatment interruption until end of follow-up period which was 12 weeks after relapse and treatment restart).
Infections and infestations Fungal infection	6.2% 1/16 • Number of events 1 • Adverse events were collected over the whole study period (from start of treatment interruption until end of follow-up period which was 12 weeks after relapse and treatment restart).
Infections and infestations Influenza	6.2% 1/16 • Number of events 1 • Adverse events were collected over the whole study period (from start of treatment interruption until end of follow-up period which was 12 weeks after relapse and treatment restart).
Infections and infestations Nasopharyngitis	25.0% 4/16 • Number of events 4 • Adverse events were collected over the whole study period (from start of treatment interruption until end of follow-up period which was 12 weeks after relapse and treatment restart).
Infections and infestations Oral herpes	6.2% 1/16 • Number of events 1 • Adverse events were collected over the whole study period (from start of treatment interruption until end of follow-up period which was 12 weeks after relapse and treatment restart).
Infections and infestations Pyelonephritis	6.2% 1/16 • Number of events 1 • Adverse events were collected over the whole study period (from start of treatment interruption until end of follow-up period which was 12 weeks after relapse and treatment restart).
Infections and infestations Rhinitis	6.2% 1/16 • Number of events 1 • Adverse events were collected over the whole study period (from start of treatment interruption until end of follow-up period which was 12 weeks after relapse and treatment restart).
Infections and infestations Tracheitis	6.2% 1/16 • Number of events 1 • Adverse events were collected over the whole study period (from start of treatment interruption until end of follow-up period which was 12 weeks after relapse and treatment restart).
Metabolism and nutrition disorders Vit D deficiency	6.2% 1/16 • Number of events 1 • Adverse events were collected over the whole study period (from start of treatment interruption until end of follow-up period which was 12 weeks after relapse and treatment restart).
Musculoskeletal and connective tissue disorders Arthralgia	6.2% 1/16 • Number of events 1 • Adverse events were collected over the whole study period (from start of treatment interruption until end of follow-up period which was 12 weeks after relapse and treatment restart).
Musculoskeletal and connective tissue disorders Back pain	6.2% 1/16 • Number of events 1 • Adverse events were collected over the whole study period (from start of treatment interruption until end of follow-up period which was 12 weeks after relapse and treatment restart).
Musculoskeletal and connective tissue disorders Fasciitis	6.2% 1/16 • Number of events 1 • Adverse events were collected over the whole study period (from start of treatment interruption until end of follow-up period which was 12 weeks after relapse and treatment restart).
Psychiatric disorders Insomnia	6.2% 1/16 • Number of events 1 • Adverse events were collected over the whole study period (from start of treatment interruption until end of follow-up period which was 12 weeks after relapse and treatment restart).
Renal and urinary disorders Dysuria	6.2% 1/16 • Number of events 1 • Adverse events were collected over the whole study period (from start of treatment interruption until end of follow-up period which was 12 weeks after relapse and treatment restart).
Respiratory, thoracic and mediastinal disorders Cough	12.5% 2/16 • Number of events 2 • Adverse events were collected over the whole study period (from start of treatment interruption until end of follow-up period which was 12 weeks after relapse and treatment restart).
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	6.2% 1/16 • Number of events 1 • Adverse events were collected over the whole study period (from start of treatment interruption until end of follow-up period which was 12 weeks after relapse and treatment restart).

Additional Information

Dr. Eric Florence

Institute of Tropical Medicine Antwerp

Phone: +32 3 247 66 42

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place