PrEP Implementation for Mothers in Antenatal Care

HIV Infections Clinical Trial

— PrIMA  

Official title:

Delivering PrEP in Pregnancy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03070600
• Other study ID #: STUDY00000438
• Secondary ID: 1R01AI125498
• Status: Completed
• Phase: Phase 4
• Start date: January 15, 2018
• Est. completion date: January 15, 2021

Study information

• Verified date: July 2022
• Source: University of Washington
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 4447
• Est. completion date: January 15, 2021
• Est. primary completion date: January 15, 2021
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 15 Years and older

Eligibility

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

Related Conditions & MeSH terms

• HIV Infections
• Pregnancy Related

Intervention

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.
• 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.

Locations

Country	Name	City	State
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

Sponsors (3)

Lead Sponsor	Collaborator
University of Washington	Kenyatta National Hospital, National Institute of Allergy and Infectious Diseases (NIAID)

Country where clinical trial is conducted

Kenya, 

References & Publications (9)

Dettinger JC, Kinuthia J, Pintye J, Mwongeli N, Gómez 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. — View Citation

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 a — View 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 Nurse — View Citation

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. — View Citation

Nganga N, Dettinger J, Kinuthia J, Baeten J, John-Stewart G, Gómez 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 N — View 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. — View Citation

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 — View 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 mat — View Citation

Wagner AD, Kinuthia J, Dettinger J, Mwongeli N, Gómez 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	PrEP Adherence by Self-report	Any missed doses in the last month reported by participants	Enrollment to 9 months postpartum, the median gestational age at enrollment was 24 weeks (IQR: 20, 30).
Other	Partner on ART if HIV Positive	Participant report of partner ART use if partner is HIV positive	Enrollment to 9 months postpartum, the median gestational age at enrollment was 24 weeks (IQR: 20, 30).
Primary	Maternal HIV Incidence	Maternal HIV Incidence	6 weeks, 6 months, 9 months postpartum
Primary	Appropriate PrEP Decision	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	Enrollment to 9 months postpartum, the median gestational age at enrollment was 24 weeks (IQR: 20, 30).
Secondary	PrEP Adherence	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.	Enrollment to 9 months postpartum
Secondary	PrEP Duration	Number of months on PrEP	Enrollment to 9 months postpartum, the median gestational age at enrollment was 24 weeks (IQR: 20, 30).
Secondary	Partner With Known HIV Status	Participants report of partner's HIV status	At 9 months postpartum
Secondary	Infant Birthweight	Infant Birthweight	time of delivery
Secondary	Infant Growth	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.	9 months of age
Secondary	PrEP Use	PrEP Utilization by participants	Enrollment to 9 months postpartum, the median gestational age at enrollment was 24 weeks (IQR: 20, 30).
Secondary	PrEP Acceptance	PrEP accepted by participants	Enrollment to 9 months postpartum, the median gestational age at enrollment was 24 weeks (IQR: 20, 30).
Secondary	Preterm Birth	Birth <37 weeks gestation	At birth