PrEP Implementation for Mothers in Antenatal Care

NCT ID: NCT03070600

Last Updated: 2022-07-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 4447 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-01-15
• Study Completion Date: 2021-01-15

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.

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.

Conditions

HIV Infections; Pregnancy Related

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Universal PrEP Counseling

Intervention Type: OTHER

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.

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.

Group Type: EXPERIMENTAL

Targeted PrEP Counseling

Intervention Type: OTHER

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: OTHER

Eligibility 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

• Minimum Eligible Age: 15 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Kenyatta National Hospital

OTHER_GOV

Sponsor Role: collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: collaborator

University of Washington

OTHER

Sponsor Role: lead

Responsible Party

Grace John-Stewart

Professor, Global Health

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Grace John-Stewart, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Washington

Jared Baeten, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Washington

John Kinuthia, MBChB, MMed

Role: STUDY_DIRECTOR

Kenyatta National Hospital

Locations

Ambira Hospital

Ambira, , Kenya

Bondo Subcounty Hospital

Bondo, , Kenya

Homabay Teaching and Referral Hospital

Homa Bay, , Kenya

Kandiege Subcounty Hospital

Kandege, , Kenya

Kendu Bay Subcounty Hospital

Kendu Bay, , Kenya

Madiany Subcounty Hospital

Madiany, , Kenya

Malanga Subcounty Hospital

Malanga, , Kenya

Marindi Subcounty Hospital

Marinde, , 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

Countries

Kenya

References

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.

Reference Type: BACKGROUND

PMID: 30850409 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 32561928 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 32763221 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 31912985 (View on PubMed)

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.

Reference Type: RESULT

PMID: 34379606 (View on PubMed)

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.

Reference Type: RESULT

PMID: 34767573 (View on PubMed)

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.

Reference Type: RESULT

PMID: 32675642 (View on PubMed)

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.

Reference Type: RESULT

PMID: 33273211 (View on PubMed)

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.

Reference Type: RESULT

PMID: 34543077 (View on PubMed)

Gomez L, Kinuthia J, Abuna F, Baeten JM, Dettinger J, Larsen A, Marwa M, Ngumbau N, Odhiambo B, Omondi P, Stern J, Richardson BA, Watoyi S, John-Stewart G, Pintye J; PrEP Implementation for Mothers in Antenatal Care (PrIMA) Study Team. Prenatal exposure to HIV pre-exposure prophylaxis and birth, growth, and social-emotional developmental outcomes throughout early childhood in Kenya: a prospective cohort study. Lancet Glob Health. 2025 Mar;13(3):e467-e478. doi: 10.1016/S2214-109X(24)00471-6.

Reference Type: DERIVED

PMID: 40021305 (View on PubMed)

Marwa MM, Larsen A, Abuna F, Dettinger J, Odhiambo B, Watoyi S, Omondi P, Ngumbau N, Gomez L, John-Stewart G, Kinuthia J, Pintye J. Brief Report: HIV Risk Perception and Pre-Exposure Prophylaxis Uptake Among Pregnant Women Offered Pre-Exposure Prophylaxis During Antenatal Care in Kenya. J Acquir Immune Defic Syndr. 2025 Jun 1;99(2):116-122. doi: 10.1097/QAI.0000000000003641.

Reference Type: DERIVED

PMID: 39885623 (View on PubMed)

Ngumbau NM, Neary J, Wagner AD, Abuna F, Ochieng B, Dettinger JC, Gomez L, Marwa MM, Watoyi S, Nzove E, Pintye J, Baeten JM, Kinuthia J, John-Stewart G. Cofactors of Partner HIV Self-testing and Oral PrEP Acceptance Among Pregnant Women at High Risk of HIV in Kenya. J Acquir Immune Defic Syndr. 2024 Mar 1;95(3):238-245. doi: 10.1097/QAI.0000000000003355.

Reference Type: DERIVED

PMID: 38408215 (View on PubMed)

Pintye J, Kinuthia J, Abuna F, Anderson PL, Dettinger JC, Gomez L, Haberer JE, Marwa MM, Ngumbau N, Omondi P, Odhiambo B, Stern J, Watoyi S, Baeten JM, John-Stewart G; PrEP Implementation for Mothers in Antenatal Care (PrIMA) Study Team. HIV pre-exposure prophylaxis initiation, persistence, and adherence during pregnancy through the postpartum period. AIDS. 2023 Sep 1;37(11):1725-1737. doi: 10.1097/QAD.0000000000003617. Epub 2023 Jun 6.

Reference Type: DERIVED

PMID: 37289583 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 32909605 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

1R01AI125498

Identifier Type: NIH

Identifier Source: secondary_id

View Link

STUDY00000438

Identifier Type: -

Identifier Source: org_study_id