HIV InfectionsPhase 2NCT03386578
Evaluating the Pharmacokinetics, Feasibility, Acceptability, and Safety of Oral Pre-Exposure Prophylaxis for HIV Prevention During Pregnancy and Postpartum
A Phase 2 study testing Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF), Behavioral HIV risk reduction package and Enhanced adherence support in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 7 sites in 4 countries.
Trial summary
The purpose of this study was to evaluate the pharmacokinetics, feasibility, acceptability, and safety of a fixed-dose combination of emtricitabine and tenofovir disoproxil fumarate (FTC/TDF) as oral daily pre-exposure prophylaxis (PrEP) to prevent HIV during pregnancy and postpartum in adolescents and young women and… Read more about this study
- Who is it for?
- Ages 16 to 24 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- HIV Infections
- What is being tested?
- Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF), Behavioral HIV risk reduction package and Enhanced adherence support
- Type of treatment
- Pill or oral medicine, Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 780 participants
- Where
- 7 sitesin 4 countries
- Study dates
- 3 Jul 2018to 24 Feb 2024
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 to 24 years
- Women only
- Healthy volunteers accepted
- Child, Adult
PK Component (Groups 1 and 2) Inclusion Criteria:
- At study entry, pregnant or recently delivered, in one of the following two enrollment windows:
- Group 1: Gestational age of 14 to 24 weeks.
- Group 2: 6 to 12 weeks postpartum.
- Willing to initiate daily PrEP for 12 weeks under directly observed therapy.
- HIV and Hepatitis B negative.
- At screening:
- Grade 1 or normal alanine transaminase (ALT), hemoglobin (HB), absolute neutrophil count (ANC) and normal creatinine clearance (CrCl).
- Negative or trace proteinuria (less than Grade 1).
- Normal dipstick urine for glucose (less than Grade 1).
- Mother weighs greater than 35 kg.
- Intention to stay within the study site's catchment area for at least 12 weeks (or through delivery).
Exclusion Criteria (PK Component and PrEP Comparison Component):
- Any current significant uncontrolled, active or chronic disease process.
- History of any of the following:
- Sickle cell anemia, chronic bleeding, blood transfusion within the past 120 days or other blood dyscrasias
- Bone fracture not explained by trauma
- Allergy/sensitivity to FTC/TDF or its components
- Fetus has a known or suspected major congenital anomaly
- Mother has confirmed renal insufficiency, a history of renal parenchymal disease or single kidney
- Current use of prohibited medications listed in the protocol
- Concurrent participation in any biomedical HIV prevention or investigational drug in an HIV vaccine or microbicide study
- Past participation in an HIV vaccine study
- Currently taking a PrEP regimen from non-study sources
- Any other condition or adverse social situation
- Past participation in IMPAACT 2009
PrEP Comparison Component (Cohorts 1 and 2) Inclusion Criteria:
- At screening, evidence of a viable singleton pregnancy with gestational age of 32 weeks or less.
- Within 14 days prior to study entry, negative HIV RNA test.
- HIV and Hepatitis B negative.
- At screening:
- Grade 1 or normal ALT, HB, ANC and normal CrCl.
- Negative or trace proteinuria (less than Grade 1).
- Normal dipstick urine for glucose (less than Grade 1).
- Intention to stay within the study site's catchment area through 26 weeks postpartum
- A cellular phone that is able to receive SMS messages, and for Cohort 1 only, is also able to send SMS messages.
- Cohort 1 only: Willingness to take PrEP from pregnancy up to 26 weeks postpartum
- Cohort 2 only: Unwillingness to take PrEP from pregnancy up to 26 weeks postpartum
- Mother weighs greater than 35 kg
- Mother is literate in one or more of the study languages
Trial locations and contacts
7 sites in 4 countries.
7 sites in 4 countries
Zimbabwe3 sites
Seke North CRS
Chitungwiza
Harare Family Care CRS
Harare
St Mary's CRS
Saint Mary's, Chitungwiza
South Africa1 site
Wits RHI Shandukani Research Centre CRS
Johannesburg, Gauteng, 2001
About this study
Official title: Pharmacokinetics, Feasibility, Acceptability, and Safety of Oral Pre-Exposure Prophylaxis for Primary HIV Prevention During Pregnancy and Postpartum in Adolescents and Young Women and Their Infants
The purpose of this study was to evaluate the pharmacokinetics, feasibility, acceptability, and safety of a fixed-dose combination of emtricitabine and tenofovir disoproxil fumarate (FTC/TDF) as oral daily pre-exposure prophylaxis (PrEP) to prevent HIV during pregnancy and postpartum in adolescents and young women and their infants.
Read the detailed description
This study evaluated the pharmacokinetics, feasibility, acceptability, and safety of FTC/TDF as oral daily PrEP to prevent HIV during pregnancy and postpartum in adolescents and young women and their infants. The study was conducted in two consecutive components: 1) Pharmacokinetics (PK) Component and 2) PrEP Comparison Component.
In the PK Component, women enrolled in one of two groups. Group 1 included pregnant women at 14 to 24 weeks' gestation and Group 2 included postpartum women who delivered 6 to 12 weeks prior to enrollment. Both groups received a fixed-dose combination of FTC/TDF administered once daily by direct observation from Day 0 through Week 12.
Mothers in the PK Component had weekly study visits through Week 12. Infants in Group 1, whose mothers enrolled during pregnancy, had study visits at birth and six weeks of life; infants in Group 2, who were enrolled with their mothers 6-12 weeks after birth, had study visits at Week 6 and Week 12. Study visits for mothers and infants in the PK Component included evaluation of drug levels and monitoring for adverse effects.
In the PrEP Comparison Component, pregnant women enrolled in one of two cohorts. Mothers in Cohort 1 chose to initiate PrEP at study entry, and mothers in Cohort 2 declined PrEP at entry. Participants in both Cohorts received a standard of care package of HIV prevention services, a study-specific behavioral risk reduction intervention, and periodic one-way short message service (SMS) messages to promote maternal and child health from Day 0 through Week 26. Cohort 1 opted to also receive daily oral FTC/TDF as PrEP and enhanced adherence support, including weekly two-way SMS messaging and feedback of drug levels with tailored adherence counseling. Participants who changed their mind about using PrEP during study participation were able to subsequently stop PrEP (Cohort 1) or initiate PrEP (Cohort 2/Step 2).
Mothers in the PrEP Comparison Component had regular study visits through delivery and Week 26 (postpartum). Infants in the PrEP Comparison Component had four study visits from birth through week 26 of life. For mothers, study visits included physical examinations, blood and urine collection, vaginal and (optional) rectal swab collection, vaginal secretions collection, ultrasounds, and dual-energy x-ray absorptiometry (DXA) scans. For infants, study visits included physical examinations, rectal swab and blood collection, and DXA scans.
In the PrEP Comparison Component analysis, maternal and infant participants were classified based on their PrEP exposure. The PrEP-exposed group included participants from Cohort 1 (throughout the entire study follow-up) and from Cohort 2/Step 2 (from Step 2 entry to the end of follow-up). The PrEP-unexposed group comprised participants from Cohort 2/Step 1 who did not enroll in Cohort 2/Step 2 (throughout the entire study follow-up) or who enrolled in Cohort 2/Step 2 (from study entry until enrolling in Cohort 2/Step 2).
- Conditions
- HIV Infections
- Being tested
- Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF), Behavioral HIV risk reduction package, Enhanced adherence support
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF)Drug
Also called Truvada
200 mg/300 mg of FTC/TDF administered orally as a fixed-dose combination tablet once daily
Behavioral HIV risk reduction packageBehavioural
Included cohort-appropriate SMS messages.
Enhanced adherence supportBehavioural
Included two-way SMS messaging and tailored counseling with drug level feedback.
| Study group | Role | What they receive |
|---|---|---|
| Maternal PK Component Group 1 | Experimental | Mothers enrolled during singleton pregnancy at 14-24 weeks' gestation received PrEP once daily under direct observation from day 0 through week 12. Receives: Drug: Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF) |
| Maternal PK Component Group 2 | Experimental | Mothers enrolled postpartum within 6-12 weeks after delivery received PrEP once daily under direct observation from day 0 through week 12. Receives: Drug: Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF) |
| Maternal PrEP Comparison Cohort 1 | Experimental | Mothers who initiated PrEP at study entry received daily oral PrEP, a behavioral HIV risk reduction package and enhanced adherence support from day 0 through postpartum week 26. Receives: Drug: Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF); Behavioral: Behavioral HIV risk reduction package; Behavioral: Enhanced adherence support |
| Maternal PrEP Comparison Cohort 2/Step 1 | Active comparator | Mothers who declined PrEP initiation at study entry received a behavioral HIV risk reduction package from day 0 through postpartum week 26. Receives: Behavioral: Behavioral HIV risk reduction package |
| Maternal PrEP Comparison Cohort 2/Step 2 | Experimental | Mothers from Cohort 2/Step 1 who subsequently chose to initiate PrEP during the study received daily oral PrEP and enhanced adherence support from Step 2 entry through postpartum week 26, along with the behavioral HIV risk reduction package. Receives: Drug: Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF); Behavioral: Behavioral HIV risk reduction package; Behavioral: Enhanced adherence support |
| Infant PK Component Group 1 | No intervention | Infants born to women in PK Component Group 1. Infants did not directly receive PrEP, but may have been exposed to PrEP through placental or breastmilk transfer. |
| Infant PK Component Group 2 | No intervention | Infants born to women in PK Component Group 2. Infants did not directly receive PrEP, but may have been exposed to PrEP through breastmilk transfer. |
| Infant PrEP Comparison Cohort 1 | No intervention | Infants born to women in PrEP Comparison Cohort 1. Infants did not directly receive PrEP, but may have been exposed to PrEP through placental or breastmilk transfer. |
| Infant PrEP Comparison Cohort 2/Step 1 | No intervention | Infants born to women in PrEP Comparison Cohort 2/Step 1. Infants were not exposed to PrEP during the study. |
| Infant PrEP Comparison Cohort 2/Step 2 | No intervention | Infants born to women in PrEP Comparison Cohort 2/Step 2. Infants did not directly receive PrEP, but may have been exposed to PrEP through placental or breastmilk transfer. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Estimated Threshold of Maternal Steady-state Tenofovir Diphosphate (TFV-DP) Concentration Levels Corresponding to Optimal Adherence in the PK Component
TFV-DP concentration levels were measured using dried blood spots (DBS) collected weekly during pregnancy and postpartum. These concentrations accumulated each week, and the plateau observed in the concentration-time curve represents the steady-state TFV-DP concentration, achieved at week 12. Predicted TFV-DP concentration levels for each maternal participant were obtained using a population PK model, and descriptive statistics were generated. The estimated steady-state TFV-DP concentration threshold for optimal adherence during pregnancy and postpartum is the 25th percentile when taking 7 doses per week. For more details, refer to the published paper (PubMed ID: 33341883).
Measured: Measured from study week 1 to study week 12 during pregnancy for Maternal PK Component Group 1 and from study week 1 to study week 12 during postpartum for Maternal PK Component Group 2
Proportion of Mothers With Optimal Adherence at Antepartum Study Week 4
TFV-DP concentration levels were measured using dried blood spots (DBS). Mothers with optimal adherence were identified based on TFV-DP concentration levels and the threshold established in the PK Component.
Measured: Antepartum study week 4
Proportion of Mothers With Optimal Adherence at Antepartum Study Week 8
TFV-DP concentration levels were measured using dried blood spots (DBS). Mothers with optimal adherence were identified based on TFV-DP concentration levels and the threshold established in the PK Component.
Measured: Antepartum study week 8
Proportion of Mothers With Optimal Adherence at Antepartum Study Week 12
TFV-DP concentration levels were measured using dried blood spots (DBS). Mothers with optimal adherence were identified based on TFV-DP concentration levels and the threshold established in the PK Component.
Measured: Antepartum study week 12
Proportion of Mothers With Optimal Adherence at Delivery
TFV-DP concentration levels were measured using dried blood spots (DBS). Mothers with optimal adherence were identified based on TFV-DP concentration levels and the threshold established in the PK Component.
Measured: Delivery
Proportion of Mothers With Optimal Adherence at Postpartum Week 6
TFV-DP concentration levels were measured using dried blood spots (DBS). Mothers with optimal adherence were identified based on TFV-DP concentration levels and the threshold established in the PK Component.
Measured: Postpartum Week 6
Proportion of Mothers With Optimal Adherence at Postpartum Week 14
TFV-DP concentration levels were measured using dried blood spots (DBS). Mothers with optimal adherence were identified based on TFV-DP concentration levels and the threshold established in the PK Component.
Measured: Postpartum week 14
Proportion of Mothers With Optimal Adherence at Postpartum Week 26
TFV-DP concentration levels were measured using dried blood spots (DBS). Mothers with optimal adherence were identified based on TFV-DP concentration levels and the threshold established in the PK Component.
Measured: Postpartum Week 26
Proportion of Maternal Visits With Optimal Adherence During Study Follow-up
TFV-DP concentration levels were measured using dried blood spots (DBS). Mothers with optimal adherence were identified based on TFV-DP concentration levels and the threshold established in the PK Component.
Measured: Study entry through 26 weeks postpartum, up to one year
Incidence Rate of Maternal Adverse Events Per 100 Person-years
Adverse events (AEs) were graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017. Maternal AEs were defined as the occurrence of at least one grade 2 (moderate) chemistry abnormality, or one grade 3 (severe), grade 4 (potentially life-threatening), or grade 5 (death) adverse event, during the study follow-up.
Measured: Study entry through 26 weeks postpartum, up to one year
Number of Composite Adverse Pregnancy Outcomes
Adverse outcomes are defined as at least one of the following: spontaneous abortion (less than 20 weeks gestation), stillbirth (greater than or equal to 20 weeks gestation), preterm delivery (less than 37 weeks), or small for gestational age (less than 10th percentile using INTERGROWTH-21 norms)
Measured: Measured at delivery
Incidence Rate of Infant Grade 3 or Higher Adverse Events Per 100 Person-years
Adverse events were assessed according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017. An infant grade 3 or higher adverse event was defined as a grade 3 (severe), grade 4 (potentially life-threatening), or grade 5 (death) adverse event.
Measured: From birth through week 26
Mean Infant Bone Mineral Content of Whole Body at Birth
Infant bone mineral content was measured by a dual-energy x-ray absorptiometry (DXA) scan of the whole body (WB-BMC)
Measured: Measured at birth
Mean Infant Bone Mineral Content of Lumbar Spine at Birth
Infant bone mineral content was measured by a dual-energy x-ray absorptiometry (DXA) scan of the lumbar spine (LS-BMC)
Measured: Measured at birth
Mean Infant Bone Mineral Content of Lumbar Spine at Week 26
Infant bone mineral content was measured by a dual-energy x-ray absorptiometry (DXA) scan of the lumbar spine (LS-BMC)
Measured: Measured at week 26 post-birth
Mean Infant Creatinine Levels at Birth in the PrEP Comparison Component
Infant creatinine levels were obtained from the chemistry/hematology test results at the birth visit
Measured: Measured at birth
Mean Infant Creatinine Levels at Week 26 in the PrEP Comparison Component
Infant creatinine levels were obtained from the chemistry/hematology test results at week 26 visit
Measured: Measured at week 26 post-birth
Mean Infant Creatinine Clearance (CrCl) Rate at Birth in the PrEP Comparison Component
The infant creatinine clearance (CrCl) rate was calculated using creatinine levels and length based on the Schwartz equation.
Measured: Measured at birth
Mean Infant Creatinine Clearance (CrCl) Rate at Week 26 in the PrEP Comparison Component
The infant creatinine clearance (CrCl) rate was calculated using creatinine levels and length based on the Schwartz equation.
Measured: Measured at week 26 post-birth
Mean Infant Length-for-age Z-score at Birth
The infant length-for-age Z-score was calculated based on the infant's sex, length, and age (in days) using WHO child growth standards. The Z-scores range from a minimum of -6 to a maximum of +6. Higher Z-scores indicate better outcomes, reflecting closer adherence to the WHO standards for infant length-for-age. A Z-score of 0 means that the infant's length is exactly at the mean length of the reference population. Z-score between -2 and +2 is considered normal or average. Infants within this range are typically seen as having an appropriate length for their age. Z-score < -3 is a threshold to identify severe stunting, indicating that the infant's length is significantly below the average and pointing to severe chronic undernutrition or other serious health concerns.
Measured: Measured at birth
Mean Infant Length-for-age Z-score at Week 26
The infant length-for-age z-score was calculated based on the infant's sex, length, and age (in days) using WHO child growth standards. The z-scores range from a minimum of -6 to a maximum of +6. Higher z-scores indicate better outcomes, reflecting closer adherence to the WHO standards for infant length-for-age. A Z-score of 0 means that the infant's length is exactly at the mean length of the reference population. Z-score between -2 and +2 is considered normal or average. Infants within this range are typically seen as having an appropriate length for their age. Z-score < -3 is a threshold to identify severe stunting, indicating that the infant's length is significantly below the average and pointing to severe chronic undernutrition or other serious health concerns.
Measured: Measured at week 26 post-birth
Secondary outcomes (1)
Maternal Median Steady State TFV-DP Concentration Levels at Study Week 12 During Pregnancy and Postpartum
TFV-DP concentration levels were measured using dried blood spots (DBS). Concentrations measured at week 12 represent the steady-state TFV-DP concentration.
Measured: Assessed at study Week 12 during pregnancy for Maternal PK Component Group 1 and at study Week 12 during postpartum for Maternal PK Component Group 2
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Dec 2017
- Study start3 Jul 2018
- Primary completion25 Oct 2023
- Study completion24 Feb 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 780 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- Gilead Sciences
- Responsible party
- Sponsor
- Investigators
- Benjamin Chi, MD, MSc, Study chair, University of North Carolina, Chapel HillLynda Stranix-Chibanda, MBChB, MMED, Study chair, University of Zimbabwe Faculty of Medicine and Health Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03386578
- Sponsor's protocol ID
- IMPAACT 2009
- Other IDs
- 30020
- Status last verified
- Jan 2025
- First submitted
- 18 Dec 2017
- Last updated
- 19 Feb 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data that underlie results in the publication, after deidentification.
Publications
Stranix-Chibanda L, Anderson PL, Kacanek D, Hosek S, Huang S, Nematadzira TG, Taulo F, Korutaro V, Nakabiito C, Masenya M, Lypen K, Brown E, Ibrahim ME, Yager J, Wiesner L, Johnston B, Amico KR, Rooney JF, Chakhtoura N, Spiegel HML, Chi BH; IMPAACT 2009 Team. Tenofovir Diphosphate Concentrations in Dried Blood Spots From Pregnant and Postpartum Adolescent and Young Women Receiving Daily Observed Pre-exposure Prophylaxis in Sub-Saharan Africa. Clin Infect Dis. 2021 Oct 5;73(7):e1893-e1900. doi: 10.1093/cid/ciaa1872.
PubMed 33341883