Clinical trial NCT03070600: PrEP Implementation for Mothers in Antenatal Care
Official title: Delivering PrEP in Pregnancy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: HIV Infections
Pregnancy Related
Keywords: PrEP
Lead sponsor: University of Washington
Sponsor class: OTHER
Collaborators: name: Kenyatta National Hospital
name: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2017-03-03
Enrollment: 4447
Sex: FEMALE
Minimum age (years): 15
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
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).
Primary purpose: PREVENTION

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.

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

Primary outcomes:
measure: Maternal HIV Incidence
timeFrame: 6 weeks, 6 months, 9 months postpartum
measure: Appropriate PrEP Decision
timeFrame: Enrollment to 9 months postpartum, the median gestational age at enrollment was 24 weeks (IQR: 20, 30).
Secondary outcomes:
measure: PrEP Adherence
timeFrame: Enrollment to 9 months postpartum
measure: PrEP Duration
timeFrame: Enrollment to 9 months postpartum, the median gestational age at enrollment was 24 weeks (IQR: 20, 30).
measure: Partner With Known HIV Status
timeFrame: At 9 months postpartum
measure: Infant Birthweight
timeFrame: time of delivery
measure: Infant Growth
timeFrame: 9 months of age
measure: PrEP Use
timeFrame: Enrollment to 9 months postpartum, the median gestational age at enrollment was 24 weeks (IQR: 20, 30).
measure: PrEP Acceptance
timeFrame: Enrollment to 9 months postpartum, the median gestational age at enrollment was 24 weeks (IQR: 20, 30).
measure: Preterm Birth
timeFrame: At birth
Other outcomes:
measure: PrEP Adherence by Self-report
timeFrame: Enrollment to 9 months postpartum, the median gestational age at enrollment was 24 weeks (IQR: 20, 30).
measure: Partner on ART if HIV Positive
timeFrame: Enrollment to 9 months postpartum, the median gestational age at enrollment was 24 weeks (IQR: 20, 30).
Locations:
city: Ambira
country: Kenya
facility: Ambira Hospital
city: Bondo
country: Kenya
facility: Bondo Subcounty Hospital
city: Homa Bay
country: Kenya
facility: Homabay Teaching and Referral Hospital
city: Kandiege
country: Kenya
facility: Kandiege Subcounty Hospital
city: Kendu Bay
country: Kenya
facility: Kendu Bay Subcounty Hospital
city: Madiany
country: Kenya
facility: Madiany Subcounty Hospital
city: Malanga
country: Kenya
facility: Malanga Subcounty Hospital
city: Marindi
country: Kenya
facility: Marindi Subcounty Hospital
city: Mbita
country: Kenya
facility: Mbita Subcounty Hospital
city: Ndhiwa
country: Kenya
facility: Ndhiwa Subcounty Hospital
city: Ober
country: Kenya
facility: Ober Subcounty Hospital
city: Ongielo
country: Kenya
facility: Ongielo Subcounty Hospital
city: Rachuonyo South
country: Kenya
facility: Rachuonyo South Subcounty Hospital
city: Rangwe
country: Kenya
facility: Rangwe Subcounty Hospital
city: Rwambwa
country: Kenya
facility: Rwambwa Subcounty Hospital
city: Siaya
country: Kenya
facility: Siaya Teaching and Referral Hospital
city: Suba
country: Kenya
facility: Suba Subcounty Hospital
city: Usigu
country: Kenya
facility: Usigu Subcounty Hospital
city: Uyawi
country: Kenya
facility: Uyawi Subcounty Hospital
city: Yala
country: Kenya
facility: Yala Subcounty Hospital
Study officials:
affiliation: University of Washington
name: Grace John-Stewart, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Washington
name: Jared Baeten, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Kenyatta National Hospital
name: John Kinuthia, MBChB, MMed
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
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citation: 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.
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citation: 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.
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