Trial Outcomes & Findings for Safety and Pharmacokinetics of Dolutegravir in Pregnant HIV Mothers and Their Neonates: A Pilot Study (NCT NCT02245022)

Results Overview

Rich PK with sampling at t0, 1, 2, 4, 6, 8 and 24 hours relative to drug dose

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

60 participants

Primary outcome timeframe

In 3rd trimester and 2 weeks postpartum

Results posted on

2025-09-04

Participant Flow

Participant milestones

Participant milestones
Measure	Dolutegravir 50mg od Patients who will receive dolutegravir 50mg once daily plus the same NRTI backbone as the active comparator group (lamivudine and tenofovir) Dolutegravir 50mg once daily: Patients randomised to receive either Dolutegravir 50mg once daily or standard of care (Efavirenz 600mg once daily) plus Lamivudine 300mg once daily/ Tenofovir 300mg once daily	Standard of Care Patients randomised to receive antiretroviral therapy as per Uganda national guidelines (Efavirenz 600mg once daily based plus Tenofovir 300mg once daily and Lamivudine 300mg once daily) Standard of Care: Patients are randomised 1:1 to receive either Dolutegravir 50mg once daily in combination with Lamivudine 300mg once daily and tenofovir 300mg once daily or standard of care (Efavirenz 600mg plus Lamivudine 300mg once daily and tenofovir 300mg once daily)
Overall Study STARTED	29	31
Overall Study COMPLETED	29	31
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Safety and Pharmacokinetics of Dolutegravir in Pregnant HIV Mothers and Their Neonates: A Pilot Study

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dolutegravir 50mg od n=29 Participants 30 patients who will receive dolutegravir 50mg once daily plus the same NRTI backbone as the active comparator group (lamivudine and tenofovir) Dolutegravir 50mg od: Patients randomised to receive either Dolutegravir 50mg od or standard of care (Efavirenz 600mg od) plus Lamivudine 300mg od/ Tenofovir 300mg od	Standard of Care n=31 Participants Patients randomised to receive antiretroviral therapy as per Uganda national guidelines (Efavirenz 600mg od based plus Tenofovir 300mg od and Lamivudine 300mg od) Standard of Care: Patients are randomised 1:1 to receive either Dolutegravir 50mg once daily in combination with Lamivudine 300mg od and tenofovir 300mg od or standard of care (Efavirenz 600mg plus Lamivudine 300mg od and tenofovir 300mg od)	Total n=60 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Age, Categorical Between 18 and 65 years	29 Participants n=99 Participants	31 Participants n=107 Participants	60 Participants n=206 Participants
Age, Categorical >=65 years	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Sex: Female, Male Female	29 Participants n=99 Participants	31 Participants n=107 Participants	60 Participants n=206 Participants
Sex: Female, Male Male	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Asian	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Black or African American	29 Participants n=99 Participants	31 Participants n=107 Participants	60 Participants n=206 Participants
Race (NIH/OMB) White	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Region of Enrollment Uganda	14 participants n=99 Participants	16 participants n=107 Participants	30 participants n=206 Participants
Region of Enrollment South Africa	15 participants n=99 Participants	15 participants n=107 Participants	30 participants n=206 Participants

PRIMARY outcome

Timeframe: In 3rd trimester and 2 weeks postpartum

Population: Not all participants on dolutegravir underwent the intensive pharmacokinetic sampling - hence the discrepancy in numbers. This related to the challenges of doing such a study in pregnancy and postpartum

Rich PK with sampling at t0, 1, 2, 4, 6, 8 and 24 hours relative to drug dose

Outcome measures

Outcome measures
Measure	Dolutegravir 50mg od n=28 Participants 30 patients who will receive dolutegravir 50mg once daily plus the same NRTI backbone as the active comparator group (lamivudine and tenofovir) Dolutegravir 50mg od: Patients randomised to receive either Dolutegravir 50mg od or standard of care (Efavirenz 600mg od) plus Lamivudine 300mg od/ Tenofovir 300mg od	Postpartum n=17 Participants Same patients as in arm 1, but with the pharmacokinetic parameters measured postpartum.
AUC0-24 of DTG in Pregnant Women in Third Trimester and 2 Weeks Postpartum	35322 ng*h/mL Interval 19196.0 to 67922.0	40127 ng*h/mL Interval 22795.0 to 59633.0

PRIMARY outcome

Timeframe: After 2 weeks of starting dolutegravir, and again 2 weeks after delivery

Population: Not all participants on dolutegravir underwent the intensive pharmacokinetic sampling - hence the discrepancy in numbers. This related to the challenges of doing such a study in pregnancy and postpartum

Maximum plasma concentration of dolutegravir in pregnancy vs postpartum

Outcome measures

Outcome measures
Measure	Dolutegravir 50mg od n=28 Participants 30 patients who will receive dolutegravir 50mg once daily plus the same NRTI backbone as the active comparator group (lamivudine and tenofovir) Dolutegravir 50mg od: Patients randomised to receive either Dolutegravir 50mg od or standard of care (Efavirenz 600mg od) plus Lamivudine 300mg od/ Tenofovir 300mg od	Postpartum n=17 Participants Same patients as in arm 1, but with the pharmacokinetic parameters measured postpartum.
Cmax of Dolutegravir	2534 ng/mL Interval 1462.0 to 3986.0	2899 ng/mL Interval 1397.0 to 4224.0

PRIMARY outcome

Timeframe: At 2 weeks after starting dolutegravir and again 2 weeks after delivery

Population: Not all participants on dolutegravir underwent the intensive pharmacokinetic sampling - hence the discrepancy in numbers. This related to the challenges of doing such a study in pregnancy and postpartum

Concentration at 24 hours after dose, immediately prior to next dose) of dolutegravir

Outcome measures

Outcome measures
Measure	Dolutegravir 50mg od n=28 Participants 30 patients who will receive dolutegravir 50mg once daily plus the same NRTI backbone as the active comparator group (lamivudine and tenofovir) Dolutegravir 50mg od: Patients randomised to receive either Dolutegravir 50mg od or standard of care (Efavirenz 600mg od) plus Lamivudine 300mg od/ Tenofovir 300mg od	Postpartum n=17 Participants Same patients as in arm 1, but with the pharmacokinetic parameters measured postpartum.
Trough Concentration	642 ng/mL Interval 188.0 to 3088.0	777 ng/mL Interval 348.0 to 1210.0

SECONDARY outcome

Timeframe: From 7 days after start of treatment to 6 months postpartum

Population: Analysis of participants experiencing a pre-defined Severe Adverse Event

Safety questionnaires at every scheduled and unscheduled study visit Infant safety questionnaires at all post-partum visits Self-reporting Participants were reviewed for safety and tolerability after 7, 14 and 28 days on treatment, and after 56 days if delivery had not taken place. Following delivery, safety assessments were

Outcome measures

Outcome measures
Measure	Dolutegravir 50mg od n=29 Participants 30 patients who will receive dolutegravir 50mg once daily plus the same NRTI backbone as the active comparator group (lamivudine and tenofovir) Dolutegravir 50mg od: Patients randomised to receive either Dolutegravir 50mg od or standard of care (Efavirenz 600mg od) plus Lamivudine 300mg od/ Tenofovir 300mg od	Postpartum n=31 Participants Same patients as in arm 1, but with the pharmacokinetic parameters measured postpartum.
Number of Participants Reporting Severe Adverse Events During Study Period	2 participants	1 participants

SECONDARY outcome

Timeframe: At delivery

Population: Number with HIV viral load \< 50 copies/ mL at delivery

HIV viral load will be measured at enrollment into the study and at delivery

Outcome measures

Outcome measures
Measure	Dolutegravir 50mg od n=29 Participants 30 patients who will receive dolutegravir 50mg once daily plus the same NRTI backbone as the active comparator group (lamivudine and tenofovir) Dolutegravir 50mg od: Patients randomised to receive either Dolutegravir 50mg od or standard of care (Efavirenz 600mg od) plus Lamivudine 300mg od/ Tenofovir 300mg od	Postpartum n=31 Participants Same patients as in arm 1, but with the pharmacokinetic parameters measured postpartum.
Percentage of Women in Each Arm With VL < 50 Copies/mL, and <400 Copies/mL at Delivery	21 Participants	12 Participants

SECONDARY outcome

Timeframe: At delivery

Population: Participants in DTG arm who had cord and maternal blood sampling at delivery This is calculated by the ratio of drug in the cord blood to the maternal plasma - both samples were taken simultaneously

A maternal blood sample and a cord blood sample will be taken at delivery to calculate the transplacental transfer of Dolutegravir

Outcome measures

Outcome measures
Measure	Dolutegravir 50mg od n=16 Participants 30 patients who will receive dolutegravir 50mg once daily plus the same NRTI backbone as the active comparator group (lamivudine and tenofovir) Dolutegravir 50mg od: Patients randomised to receive either Dolutegravir 50mg od or standard of care (Efavirenz 600mg od) plus Lamivudine 300mg od/ Tenofovir 300mg od	Postpartum Same patients as in arm 1, but with the pharmacokinetic parameters measured postpartum.
Cord:Maternal Plasma DTG Ratio	1.21 Cord: Maternal blood ratio Interval 0.51 to 2.11	—

SECONDARY outcome

Timeframe: At 2 weeks postpartum, and 24 hours after final maternal dose

Population: Participants in DTG arm who underwent breastmilk pharmacokinetic sampling The ratio is calculated by comparing the concentration in breastmilk to that in maternal blood, so giving the milk: plasma ratio which is a standard measure of this outcome.

At the timepoints indicated, a single maternal blood sample and a sample of breast milk will be taken to measure Dolutegravir levels in both matrices and allow estimation of transmammary drug exposure

Outcome measures

Outcome measures
Measure	Dolutegravir 50mg od n=17 Participants 30 patients who will receive dolutegravir 50mg once daily plus the same NRTI backbone as the active comparator group (lamivudine and tenofovir) Dolutegravir 50mg od: Patients randomised to receive either Dolutegravir 50mg od or standard of care (Efavirenz 600mg od) plus Lamivudine 300mg od/ Tenofovir 300mg od	Postpartum Same patients as in arm 1, but with the pharmacokinetic parameters measured postpartum.
Maternal Plasma: Breastmilk DTG Ratio	0.03 Milk to plasma ratio Interval 0.03 to 0.04	—

SECONDARY outcome

Timeframe: At maternal steady state (2 weeks postpartum) and at 1, 2 and 3 days after transfer to standard of care

Population: Infants of mothers in DTG arm who underwent pharmacokinetic sampling

Infants from the Dolutegravir arm (N=30) will be randomised 1:1:1 to return for PK sampling 1, 2 or 3 days after the mother has discontinued Dolutegravir and changed to Standard of Care treatment. All infants will have a single capillary blood sample (heel prick) taken at 2 weeks postpartum, and then at the time point they have been randomised to.

Outcome measures

Outcome measures
Measure	Dolutegravir 50mg od n=17 Participants 30 patients who will receive dolutegravir 50mg once daily plus the same NRTI backbone as the active comparator group (lamivudine and tenofovir) Dolutegravir 50mg od: Patients randomised to receive either Dolutegravir 50mg od or standard of care (Efavirenz 600mg od) plus Lamivudine 300mg od/ Tenofovir 300mg od	Postpartum Same patients as in arm 1, but with the pharmacokinetic parameters measured postpartum.
Infant DTG Levels	66.7 ng/mL Interval 21.0 to 654.0	—

SECONDARY outcome

Timeframe: Up to 3 days after change to standard of care, approximately 2 weeks after delivery

Population: Number of participants with abnormal biochemical or haematological parameters

Laboratory test measured routinely up until 3 days after change to standard of care. In addition, patients will remain under follow-up until 6 months postpartum, and laboratory tests will be performed if clinically indicated at any point. The routinely measured 'safety bloods' in this study are Full Blood Count, Urea and Electrolytes including eGFR, Liver Function Tests including Alanine Aminotransferase and Bilirubin

Outcome measures

Outcome measures
Measure	Dolutegravir 50mg od n=29 Participants 30 patients who will receive dolutegravir 50mg once daily plus the same NRTI backbone as the active comparator group (lamivudine and tenofovir) Dolutegravir 50mg od: Patients randomised to receive either Dolutegravir 50mg od or standard of care (Efavirenz 600mg od) plus Lamivudine 300mg od/ Tenofovir 300mg od	Postpartum n=31 Participants Same patients as in arm 1, but with the pharmacokinetic parameters measured postpartum.
Number and Severity of Adverse Events and Laboratory Abnormalities	2 Participants	0 Participants

SECONDARY outcome

Timeframe: Until 2 weeks postpartum

Mothers will be switched to standard of care at 2 weeks postpartum

Outcome measures

Outcome measures
Measure	Dolutegravir 50mg od n=29 Participants 30 patients who will receive dolutegravir 50mg once daily plus the same NRTI backbone as the active comparator group (lamivudine and tenofovir) Dolutegravir 50mg od: Patients randomised to receive either Dolutegravir 50mg od or standard of care (Efavirenz 600mg od) plus Lamivudine 300mg od/ Tenofovir 300mg od	Postpartum n=31 Participants Same patients as in arm 1, but with the pharmacokinetic parameters measured postpartum.
Percentage of Subjects Who Discontinue Treatment Due to Adverse Events	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 6 months postpartum

Population: Number with mother to child transmission of HIV

Infant HIV testing by PCR will be undertaken at six weeks and six months of age, as per Uganda National Policy

Outcome measures

Outcome measures
Measure	Dolutegravir 50mg od n=28 Participants 30 patients who will receive dolutegravir 50mg once daily plus the same NRTI backbone as the active comparator group (lamivudine and tenofovir) Dolutegravir 50mg od: Patients randomised to receive either Dolutegravir 50mg od or standard of care (Efavirenz 600mg od) plus Lamivudine 300mg od/ Tenofovir 300mg od	Postpartum n=31 Participants Same patients as in arm 1, but with the pharmacokinetic parameters measured postpartum.
Percentage of Mother to Child Transmission of HIV	0 Participants	0 Participants

SECONDARY outcome

Timeframe: End of study

Population: This analysis was not undertaken for the following reason. DolPHIN-1 was designed as a pilot study to inform the design of a larger study with longer follow up. We obtained funding for DolPHIN-2 before DolPHIN-1 was complete, and in this we have included genome wide association survey of 250 mothers (125 per arm). Because this study has higher power to explore the pharmacogenomics, it was felt that undertaking this analysis in DolPHIN-1 would not add further useful information.

Frequency of relevant polymorphisms and association with drug concentrations

Outcome measures

Outcome data not reported

Adverse Events

Dolutegravir 50mg od

Serious events: 2 serious events

Other events: 2 other events

Deaths: 0 deaths

Standard of Care

Serious events: 1 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Dolutegravir 50mg od n=29 participants at risk 30 patients who will receive dolutegravir 50mg once daily plus the same NRTI backbone as the active comparator group (lamivudine and tenofovir) Dolutegravir 50mg od: Patients randomised to receive either Dolutegravir 50mg od or standard of care (Efavirenz 600mg od) plus Lamivudine 300mg od/ Tenofovir 300mg od	Standard of Care n=31 participants at risk Patients randomised to receive antiretroviral therapy as per Uganda national guidelines (Efavirenz 600mg od based plus Tenofovir 300mg od and Lamivudine 300mg od) Standard of Care: Patients are randomised 1:1 to receive either Dolutegravir 50mg once daily in combination with Lamivudine 300mg od and tenofovir 300mg od or standard of care (Efavirenz 600mg plus Lamivudine 300mg od and tenofovir 300mg od)
Blood and lymphatic system disorders Low haemoglobin	3.4% 1/29 • Number of events 1 • Until 6 months postpartum Causality assessments were undertaken by a dedicated clinical pharmacist using the Liverpool Causality Assessment Tool. Grade \>3 AEs summarised	0.00% 0/31 • Until 6 months postpartum Causality assessments were undertaken by a dedicated clinical pharmacist using the Liverpool Causality Assessment Tool. Grade \>3 AEs summarised
Infections and infestations Maternal malaria	3.4% 1/29 • Number of events 1 • Until 6 months postpartum Causality assessments were undertaken by a dedicated clinical pharmacist using the Liverpool Causality Assessment Tool. Grade \>3 AEs summarised	0.00% 0/31 • Until 6 months postpartum Causality assessments were undertaken by a dedicated clinical pharmacist using the Liverpool Causality Assessment Tool. Grade \>3 AEs summarised
Pregnancy, puerperium and perinatal conditions Pre-eclampsia	0.00% 0/29 • Until 6 months postpartum Causality assessments were undertaken by a dedicated clinical pharmacist using the Liverpool Causality Assessment Tool. Grade \>3 AEs summarised	3.2% 1/31 • Number of events 1 • Until 6 months postpartum Causality assessments were undertaken by a dedicated clinical pharmacist using the Liverpool Causality Assessment Tool. Grade \>3 AEs summarised
Pregnancy, puerperium and perinatal conditions Stillbirth	0.00% 0/29 • Until 6 months postpartum Causality assessments were undertaken by a dedicated clinical pharmacist using the Liverpool Causality Assessment Tool. Grade \>3 AEs summarised	3.2% 1/31 • Number of events 1 • Until 6 months postpartum Causality assessments were undertaken by a dedicated clinical pharmacist using the Liverpool Causality Assessment Tool. Grade \>3 AEs summarised

Other adverse events

Other adverse events
Measure	Dolutegravir 50mg od n=29 participants at risk 30 patients who will receive dolutegravir 50mg once daily plus the same NRTI backbone as the active comparator group (lamivudine and tenofovir) Dolutegravir 50mg od: Patients randomised to receive either Dolutegravir 50mg od or standard of care (Efavirenz 600mg od) plus Lamivudine 300mg od/ Tenofovir 300mg od	Standard of Care n=31 participants at risk Patients randomised to receive antiretroviral therapy as per Uganda national guidelines (Efavirenz 600mg od based plus Tenofovir 300mg od and Lamivudine 300mg od) Standard of Care: Patients are randomised 1:1 to receive either Dolutegravir 50mg once daily in combination with Lamivudine 300mg od and tenofovir 300mg od or standard of care (Efavirenz 600mg plus Lamivudine 300mg od and tenofovir 300mg od)
Blood and lymphatic system disorders Low haemoglobin	6.9% 2/29 • Number of events 2 • Until 6 months postpartum Causality assessments were undertaken by a dedicated clinical pharmacist using the Liverpool Causality Assessment Tool. Grade \>3 AEs summarised	6.5% 2/31 • Number of events 2 • Until 6 months postpartum Causality assessments were undertaken by a dedicated clinical pharmacist using the Liverpool Causality Assessment Tool. Grade \>3 AEs summarised

Additional Information

Catriona Waitt

University of Liverpool

Phone: 0778288217

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place