PrEP Implementation for Mothers in Antenatal Care (PrIMA)

• 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: University of Washington
• Collaborators: Kenyatta National Hospital; National Institute of Allergy and Infectious Diseases (NIAID)
• Information provided by (Responsible Party): Grace John-Stewart, University of Washington

Study Description

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.

Study Design

• 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

Arms and Interventions

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: 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; participant declines partner self-tests regardless of partner HIV status, and/or; their partner declines self-testing or tests positive.

Outcome Measures

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

Eligibility Criteria

• 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

Contacts and Locations

Locations

Kenya

Ambira Hospital

Ambira, Kenya

Bondo Subcounty Hospital

Bondo, Kenya

Homabay Teaching and Referral Hospital

Homa Bay, Kenya

Kandiege Subcounty Hospital

Kandiege, Kenya

Kendu Bay Subcounty Hospital

Kendu Bay, Kenya

Madiany Subcounty Hospital

Madiany, Kenya

Malanga Subcounty Hospital

Malanga, Kenya

Marindi Subcounty Hospital

Marindi, Kenya

Mbita Subcounty Hospital

Mbita, Kenya

Ndhiwa Subcounty Hospital

Ndhiwa, Kenya

Ober Subcounty Hospital

Ober, Kenya

Ongielo Subcounty Hospital

Ongielo, Kenya

Rachuonyo South Subcounty Hospital

Rachuonyo South, Kenya

Rangwe Subcounty Hospital

Rangwe, Kenya

Rwambwa Subcounty Hospital

Rwambwa, Kenya

Siaya Teaching and Referral Hospital

Siaya, Kenya

Suba Subcounty Hospital

Suba, Kenya

Usigu Subcounty Hospital

Usigu, Kenya

Uyawi Subcounty Hospital

Uyawi, Kenya

Yala Subcounty Hospital

Yala, Kenya

Sponsors and Collaborators

University of Washington

Kenyatta National Hospital

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

• 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

More Information

Publications of Results:

Dettinger JC, Pintye J, Dollah A, Awuor M, Abuna F, Lagat H, Kohler P, John-Stewart G, O'Malley G, Kinuthia J, Beima-Sofie K. Brief Report: "What Is This PrEP?"-Sources and Accuracy of HIV Pre-Exposure Prophylaxis (PrEP) Awareness Among Adolescent Girls and Young Women Attending Family Planning and Maternal Child Health Clinics in Western Kenya. J Acquir Immune Defic Syndr. 2021 Dec 1;88(4):356-360. doi: 10.1097/QAI.0000000000002782.

Nganga N, Dettinger J, Kinuthia J, Baeten J, John-Stewart G, Gomez L, Marwa M, Ochieng B, Pintye J, Mugwanya K, Mugambi M. Prevalence and correlates of pregnancy self-testing among pregnant women attending antenatal care in western Kenya. PLoS One. 2021 Nov 12;16(11):e0258578. doi: 10.1371/journal.pone.0258578. eCollection 2021.

Escudero JN, Dettinger JC, Pintye J, Kinuthia J, Lagat H, Abuna F, Kohler P, Baeten JM, O'Malley G, John-Stewart GC, Beima-Sofie KM. Community Perceptions About Use of Pre-exposure Prophylaxis Among Adolescent Girls and Young Women in Kenya. J Assoc Nurses AIDS Care. 2020 Nov-Dec;31(6):669-677. doi: 10.1097/JNC.0000000000000191.

Pintye J, O'Malley G, Kinuthia J, Abuna F, Escudero JN, Mugambi M, Awuor M, Dollah A, Dettinger JC, Kohler P, John-Stewart G, Beima-Sofie K. Influences on Early Discontinuation and Persistence of Daily Oral PrEP Use Among Kenyan Adolescent Girls and Young Women: A Qualitative Evaluation From a PrEP Implementation Program. J Acquir Immune Defic Syndr. 2021 Apr 1;86(4):e83-e89. doi: 10.1097/QAI.0000000000002587.

Rogers Z, Pintye J, Kinuthia J, O'Malley G, Abuna F, Escudero J, Mugambi M, Awuor M, Dollah A, Dettinger JC, Kohler P, John-Stewart G, Beima-Sofie K. Key influences on the decision to initiate PrEP among adolescent girls and young women within routine maternal child health and family planning clinics in Western Kenya. AIDS Care. 2022 Mar;34(3):363-370. doi: 10.1080/09540121.2021.1981217. Epub 2021 Sep 20.

Other Publications:

Dettinger JC, Kinuthia J, Pintye J, Mwongeli N, Gomez L, Richardson BA, Barnabas R, Wagner AD, O'Malley G, Baeten JM, John-Stewart G. PrEP Implementation for Mothers in Antenatal Care (PrIMA): study protocol of a cluster randomised trial. BMJ Open. 2019 Mar 7;9(3):e025122. doi: 10.1136/bmjopen-2018-025122.

Wagner AD, Kinuthia J, Dettinger J, Mwongeli N, Gomez L, Watoyi S, Drake AL, Abuna F, Pintye J, Ochieng B, Odinga D, John-Stewart G, Baeten JM. Challenges of Discrepant HIV Tests in Pregnant Women in the PrEP era-to Treat or Not to Treat? J Infect Dis. 2021 Feb 3;223(2):234-237. doi: 10.1093/infdis/jiaa343.

Pintye J, Davey DLJ, Wagner AD, John-Stewart G, Baggaley R, Bekker LG, Celum C, Chi BH, Coates TJ, Groves AK, Haberer JE, Heffron R, Kinuthia J, Matthews LT, McIntyre JA, Moodley D, Mofenson LM, Mugo N, Mujugira A, Myer L, Shoptaw S, Stranix-Chibanda L, Baeten JM; PrEP in Pregnancy Working Group. Defining gaps in pre-exposure prophylaxis delivery for pregnant and post-partum women in high-burden settings using an implementation science framework. Lancet HIV. 2020 Aug;7(8):e582-e592. doi: 10.1016/S2352-3018(20)30102-8.

Joseph Davey DL, Pintye J, Baeten JM, Aldrovandi G, Baggaley R, Bekker LG, Celum C, Chi BH, Coates TJ, Haberer JE, Heffron R, Kinuthia J, Matthews LT, McIntyre J, Moodley D, Mofenson LM, Mugo N, Myer L, Mujugira A, Shoptaw S, Stranix-Chibanda L, John-Stewart G; PrEP in Pregnancy Working Group. Emerging evidence from a systematic review of safety of pre-exposure prophylaxis for pregnant and postpartum women: where are we now and where are we heading? J Int AIDS Soc. 2020 Jan;23(1):e25426. doi: 10.1002/jia2.25426.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Chen S, Pawelec G, Trompet S, Goldeck D, Mortensen LH, Slagboom PE, Christensen K, Gussekloo J, Kearney P, Buckley BM, Ford I, Jukema JW, Westendorp RGJ, Maier AB. Associations of Cytomegalovirus Infection With All-Cause and Cardiovascular Mortality in Multiple Observational Cohort Studies of Older Adults. J Infect Dis. 2021 Feb 3;223(2):238-246. doi: 10.1093/infdis/jiaa480.

• 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
• Results First Posted: May 10, 2022
• Last Update Posted: July 12, 2022
• Last Verified: July 2022

• 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:

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases