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PrEP Implementation for Mothers in Antenatal Care (PrIMA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03070600
Recruitment Status : Completed
First Posted : March 3, 2017
Results First Posted : May 10, 2022
Last Update Posted : July 12, 2022
Sponsor:
Collaborators:
Kenyatta National Hospital
National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by (Responsible Party):
Grace John-Stewart, University of Washington

Brief Summary:
In a region with 15-20% HIV prevalence, an estimated 20% of HIV-uninfected women could have HIV exposures in pregnancy. In a theoretical scenario of perfect PrEP coverage, all women at risk receive PrEP while no women not at HIV risk receive PrEP (Figure 4). With mandatory PrEP given to all women (similar to the approaches used for malaria prophylaxis), all women at risk would be covered but many women not at risk receive unnecessary PrEP. Our premise is that a targeted PrEP model may be closer to perfect coverage than a universal offer/self-select model. Implementing targeted PrEP through strategies that include facilitation of partner testing with self-tests could add HIV prevention benefit by increasing partner HIV diagnosis and treatment similar to the initiation of PrEP among pregnant women. By implementing these strategies and measuring uptake, use, and HIV incidence, we can inform the best health systems model for PrEP delivery in pregnancy.

Condition or disease Intervention/treatment Phase
HIV Infections Pregnancy Related Other: Universal PrEP Counseling Other: Targeted PrEP Counseling Phase 4

Detailed Description:

Women living in regions with high HIV prevalence are at high risk of HIV acquisition in pregnancy and postpartum because they infrequently use condoms, do not know their partner's HIV status, and have biologic changes or changes in their partner's sexual partnerships that increase susceptibility. Oral pre-exposure antiretroviral prophylaxis (PrEP) may be an attractive strategy for HIV prevention in pregnancy/postpartum; however, it is important to ensure PrEP reaches women who are at risk for acquiring HIV during pregnancy while avoiding unnecessary PrEP use during pregnancy. Clinicians and women are using PrEP in pregnancy; in qualitative studies, women, health workers and policy-makers support use of PrEP in pregnancy but advocate for models of PrEP delivery that ensure women at risk receive PrEP while minimizing unnecessary PrEP use in women not at risk. Targeting PrEP to women at greatest risk of HIV may maximize benefits, minimize potential risks, and optimize cost-effectiveness. This cluster-randomized clinical trial (RCT) in 20 Maternal Child Health (MCH) clinics in western Kenya (10 clinics per arm, up to 250 women per clinic, up to 5000 women overall), will compare 2 models of PrEP delivery in pregnancy. Clinics will offer universal availability of PrEP (and women self-select whether to use) or targeted offer of PrEP (i.e., offer to women identified as high risk through a standardized risk assessment and partner self-testing, and then women identified as high-risk select whether to use). Leveraging the pre-existing MCH clinic visit schedule will enable programmatically relevant assessment of PrEP uptake, use, and HIV incidence. The outcome of the study will be a model of PrEP delivery in pregnancy that optimizes effectiveness, safety, and cost-effectiveness. Our team has expertise in maternal-child HIV (John-Stewart, Kinuthia), PrEP clinical trials and implementation science (Baeten, Richardson), partner self-testing (Thirumurthy), economics and qualitative research (Barnabas, O'Malley).

AIM 1a. In a cluster-RCT, compare universal PrEP (offer to all; women self-select PrEP) to targeted PrEP (limit the offer to women identified as high risk through a standardized risk assessment and partner self-testing) for outcomes reflecting the balance of PrEP effectiveness and avoiding unnecessary PrEP exposure to women at low or no risk of HIV: HIV incidence at 9 months postpartum among all women (including those who did and did not receive PrEP) and proportion of women exposed to PrEP.

AIM 1b. To compare trial arms for proportion of women 'appropriately' on PrEP (risk factors), PrEP adherence (drug levels) and duration, partners with known HIV status, partners on ART; infant outcomes (growth, birth outcomes, HIV status).

AIM 2. To estimate the incremental cost-effectiveness of targeted PrEP compared to universal PrEP for women during pregnancy and postpartum, per HIV infection and disability-adjusted life-year (DALY) averted.

AIM 3. To qualitatively assess barriers and facilitators to uptake, adherence, acceptability, and feasibility in universal and targeted PrEP models at the organizational, provider, and individual woman level.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 4447 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: We will select 20 clinics from Western Kenya. Ten clinics will be randomized to universal PrEP and ten to targeted PrEP (Table 2). To ensure balance between study arms in terms of key site characteristics, sites will be categorized on HIV prevalence and ANC volume, and restricted randomization will be used for site (cluster) allocation to intervention and control arms (68).
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Delivering PrEP in Pregnancy
Actual Study Start Date : January 15, 2018
Actual Primary Completion Date : January 15, 2021
Actual Study Completion Date : January 15, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Universal PrEP Counselling
All enrolled women receiving antenatal care at facilities assigned to Universal PrEP arm will receive standardized HIV risk counseling and then self-select whether they want to use PrEP.
Other: Universal PrEP Counseling
Counseling at universal sites, will use a standardized counseling script to state that PrEP is available for women at risk for HIV, explain that HIV prevalence in the region is high, and will note that women with HIV positive partners or who don't know their partner's status may be at risk. Counseling will specify that women may have their own reasons to feel at risk or to want PrEP. Following standardized counseling, women will select PrEP at the same visit or will be allowed to deliberate on the decision and come back at the next visit with a decision. Women will be informed that it is advisable to use PrEP if they know their partner is HIV positive or if they do not know their partner's status and will be encouraged to bring untested partners to clinic if status is unknown.

Experimental: Targeted PrEP Clinics
All enrolled women receiving antenatal care at facilities assigned to the Targeted PrEP arm will be assessed for HIV-risk prior to receiving targeted PrEP counseling.
Other: Targeted PrEP Counseling

Following enrollment, the targeted PrEP clinics will provide two inter-related innovations over two ANC visits. In the targeted PrEP clinics, any of the following three criteria can trigger enhanced PrEP counseling. A participant that meets any one of these criteria will receive PrEP counseling during the study visit where the criteria is met:

  1. Risk Score >6 (Risk score includes male partner status known/unknown, syphilis infection, and lifetime number of male partners) or any National AIDS and STI Control Programme (NASCOP) risk factors
  2. participant declines partner self-tests regardless of partner HIV status, and/or
  3. their partner declines self-testing or tests positive.




Primary Outcome Measures :
  1. Maternal HIV Incidence [ Time Frame: 6 weeks, 6 months, 9 months postpartum ]
    Maternal HIV Incidence

  2. Appropriate PrEP Decision [ Time Frame: Enrollment to 9 months postpartum, the median gestational age at enrollment was 24 weeks (IQR: 20, 30). ]
    Scored 1 for high risk women using PrEP and low risk women not using PrEP; 0 for high risk women NOT on PrEP and low risk women using PrEP


Secondary Outcome Measures :
  1. PrEP Adherence [ Time Frame: Enrollment to 9 months postpartum ]
    Sequential dried blood spots, PrEP adherence by DBS dichotomous by pregnancy or postpartum thresholds equivalent to ~7 doses per week (≥650 fmol/punch during pregnancy or ≥950 fmol/punch postpartum) based on the thresholds established by the 2009 IMPAACT directly observed PrEP PK study.

  2. PrEP Duration [ Time Frame: Enrollment to 9 months postpartum, the median gestational age at enrollment was 24 weeks (IQR: 20, 30). ]
    Number of months on PrEP

  3. Partner With Known HIV Status [ Time Frame: At 9 months postpartum ]
    Participants report of partner's HIV status

  4. Infant Birthweight [ Time Frame: time of delivery ]
    Infant Birthweight

  5. Infant Growth [ Time Frame: 9 months of age ]
    Infant height, weight, and age (Weight-for-Age [WAZ], Height-for-Age [HAZ], Weight-for-Height [WHZ] Z-scores). A Z-score of 0 represents the population mean. Indicators of infant malnutrition are defined as Underweight- WAZ Z-score<-2; Stunting-HAZ Z-Score <-2; Wasting- WHZ Z-Score <-2.

  6. PrEP Use [ Time Frame: Enrollment to 9 months postpartum, the median gestational age at enrollment was 24 weeks (IQR: 20, 30). ]
    PrEP Utilization by participants

  7. PrEP Acceptance [ Time Frame: Enrollment to 9 months postpartum, the median gestational age at enrollment was 24 weeks (IQR: 20, 30). ]
    PrEP accepted by participants

  8. Preterm Birth [ Time Frame: At birth ]
    Birth <37 weeks gestation


Other Outcome Measures:
  1. PrEP Adherence by Self-report [ Time Frame: Enrollment to 9 months postpartum, the median gestational age at enrollment was 24 weeks (IQR: 20, 30). ]
    Any missed doses in the last month reported by participants

  2. Partner on ART if HIV Positive [ Time Frame: Enrollment to 9 months postpartum, the median gestational age at enrollment was 24 weeks (IQR: 20, 30). ]
    Participant report of partner ART use if partner is HIV positive



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   15 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Gender Eligibility Description:   All participants must be pregnant at time of enrollment.
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Eligibility for enrollment will include age ≥15 years
  • Pregnant at any gestational age
  • Tuberculosis negative
  • Plans to reside in area for at least one year postpartum
  • Plans to receive postnatal and infant care at the study facility
  • Not currently enrolled in any other studies.

Exclusion Criteria:

  • HIV+ at time of enrollment

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03070600


Locations
Show Show 20 study locations
Sponsors and Collaborators
University of Washington
Kenyatta National Hospital
National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
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Principal Investigator: Grace John-Stewart, MD, PhD University of Washington
Principal Investigator: Jared Baeten, MD, PhD University of Washington
Study Director: John Kinuthia, MBChB, MMed Kenyatta National Hospital
  Study Documents (Full-Text)

Documents provided by Grace John-Stewart, University of Washington:
Study Protocol  [PDF] May 13, 2019
Statistical Analysis Plan  [PDF] January 5, 2021

Publications of Results:

Other Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Grace John-Stewart, Professor, Global Health, University of Washington
ClinicalTrials.gov Identifier: NCT03070600    
Other Study ID Numbers: STUDY00000438
1R01AI125498 ( U.S. NIH Grant/Contract )
First Posted: March 3, 2017    Key Record Dates
Results First Posted: May 10, 2022
Last Update Posted: July 12, 2022
Last Verified: July 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Grace John-Stewart, University of Washington:
PrEP
Additional relevant MeSH terms:
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HIV Infections
Blood-Borne Infections
Communicable Diseases
Infections
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Immunologic Deficiency Syndromes
Immune System Diseases