Clinical trial NCT03902418: Evaluation of Pre-Exposure Prophylaxis (PrEP) in Pregnant and Breastfeeding Women
Official title: Evaluation of Pre-Exposure Prophylaxis (PrEP) Initiation, Retention, and Adherence in Pregnant and Breastfeeding Women
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: HIV-I Infection
Keywords: Prevention in Pregnant and Breastfeeding Women
HIV Pre-Exposure Prophylaxis (PrEP)
Lead sponsor: University of California, Los Angeles
Sponsor class: OTHER
Collaborators: name: University of Cape Town
First posted: 2019-04-04
Enrollment: 1195
Sex: FEMALE
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Study counselors will enroll consecutive eligible, consenting pregnant adolescent girls (\>16 years) and women in ANC (n=600 women per site; N=1200 pregnant women) and follow them up for 12-months postpartum or until censorship for a mean of 18-months' follow-up.

In a sub-study, STI and PrEP in Pregnancy Study (STIPPS), we will include n=268 women who recieve point of care STI results vs. those treated syndromically to evaluate PrEP initiation in pregnancy.

Brief summary: The investigators will conduct an observational cohort study in 1200 pregnant women who will be recruited at the first antenatal care (ANC) visit from the Gugulethu and one additional facility in the Klipfontein-Mitchell's Plain subdistrict of the Metro Region (to be identified in conjunction with provincial and local health authorities) Midwife Obstetric Units in Cape Town (n=600 pregnant women per site). The enrolled women will be followed through 12-months post-delivery.

Detailed description: The objectives of the study are to:

1. Determine the distribution of women across the PrEP cascade:

1. Evaluate the proportion of pregnant and breastfeeding women who initiate PrEP out of all women offered PrEP
2. Evaluate the proportion of pregnant and breastfeeding women who are retained in the PrEP cohort
3. Evaluate the proportion of pregnant and breastfeeding women who initiate PrEP who adhere to PrEP using objective dried blood spot measures and subjective measures of self-reported pill count and adherence
4. Evaluate the proportion of pregnant and breastfeeding women on PrEP (and not on PrEP) who acquire HIV, who transmit HIV to their infant, and who report adverse events 2. Evaluate patient and provider-level factors associated with the PrEP cascade using quantitative and qualitative approaches (including in-depth interviews) 3. Apply an established mathematical model to simulate the impact of improvement in the PrEP cascade on HIV infections averted (maternal and perinatal)

Eligibility criteria: Inclusion Criteria:

* \>16 years of age,
* confirmed HIV-negative (using 2 rapid tests,
* confirmed with a 4th generation antigen HIV test;
* lives within 20 km. of the clinic;
* confirmed to be pregnant;
* without psychiatric or medical contraindications to PrEP

Exclusion Criteria:

* Concurrent enrollment in another HIV-1 vaccine or prevention trial;
* medical hospitalization in the past year for any reason;
* receipt of TB treatment in the past 30 days; history of renal disease;
* exhibiting psychotic symptoms (including hallucinations, suicidal or homicidal ideation, or violent behavior),
* currently or history of taking anti-psychotic medications;
* positive Hepatitis B surface antigen test on screening;
* history of bone fracture not related to trauma;
* any other medical, psychiatric, or social condition which in the opinion of the investigators would affect the ability to consent and/or participate in the study.

Primary outcomes:
measure: Participants Initiating Pre-exposure Prophylaxis During Pregnancy
timeFrame: Percentage of participants initiating pre-exposure prophylaxis between first ante-natal clinic visit and birth of infant
measure: Adherence to TDF at 3-months on PrEP
timeFrame: Measured at 3 month follow up visit
measure: Women Initiating Pre-exposure Prophylaxis Post-partum
timeFrame: Percentage of participants initiating pre-exposure prophylaxis at first post-partum to final post-partum visit 12 months after birth
measure: Adherence to TDF at 6 Months Post-partum
timeFrame: Measured at 6-month post-partum visit
measure: Number of Participants With Adherence to TFV-DP at 6-month Visit
timeFrame: Measured at 6-month study visit
Secondary outcomes:
measure: PrEP Initiation Among Those With STI POC Testing vs Syndromic Management
timeFrame: Measured at enrollment and 1 month follow up
Other outcomes:
Locations:
city: Cape Town
country: South Africa
facility: University of Cape Town
state: Western Cape
Study officials:
affiliation: University of Cape Town
name: Landon Myer, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Joseph Davey DL, Daniels J, Beard C, Mashele N, Bekker LG, Dovel K, Ncayiyana J, Coates TJ, Myer L. Healthcare provider knowledge and attitudes about pre-exposure prophylaxis (PrEP) in pregnancy in Cape Town, South Africa. AIDS Care. 2020 Oct;32(10):1290-1294. doi: 10.1080/09540121.2020.1782328. Epub 2020 Jun 23.
citation: Joseph Davey DL, Wilkinson L, Grimsrud A, Nelson A, Gray A, Raphael Y, Wattrus C, Pillay Y, Bekker LG. Urgent appeal to allow all professional nurses and midwives to prescribe pre-exposure prophylaxis (PrEP) in South Africa. S Afr Med J. 2023 Aug 3;113(8):12-16. doi: 10.7196/SAMJ.2023.v113i8.1191. No abstract available.
citation: Khadka N, Gorbach PM, Nyemba DC, Mvududu R, Mashele N, Javanbakht M, Nianogo RA, Aldrovandi GM, Bekker LG, Coates TJ, Myer L, Joseph Davey DL. Evaluating the use of oral pre-exposure prophylaxis among pregnant and postpartum adolescent girls and young women in Cape Town, South Africa. Front Reprod Health. 2023 Sep 19;5:1224474. doi: 10.3389/frph.2023.1224474. eCollection 2023.
citation: Li KT, Li F, Jaspan H, Nyemba D, Myer L, Aldrovandi G, Joseph-Davey D. Changes in the Vaginal Microbiome During Pregnancy and the Postpartum Period in South African Women: a Longitudinal Study. Reprod Sci. 2024 Jan;31(1):275-287. doi: 10.1007/s43032-023-01351-4. Epub 2023 Sep 18.
citation: Haribhai S, Khadka N, Mvududu R, Mashele N, Bekker LG, Gorbach P, Coates TJ, Myer L, Joseph Davey DL. Psychosocial determinants of pre-exposure prophylaxis use among pregnant adolescent girls and young women in Cape Town, South Africa: A qualitative study. Int J STD AIDS. 2023 Jul;34(8):548-556. doi: 10.1177/09564624231152776. Epub 2023 Mar 22.
citation: Joseph Davey D, Nyemba DC, Castillo-Mancilla J, Wiesner L, Norman J, Mvududu R, Mashele N, Johnson LF, Bekker LG, Gorbach P, Coates TJ, Myer L. Adherence challenges with daily oral pre-exposure prophylaxis during pregnancy and the postpartum period in South African women: a cohort study. J Int AIDS Soc. 2022 Dec;25(12):e26044. doi: 10.1002/jia2.26044.
citation: Joseph Davey D, Hsiao NY, Wendy Spearman C, Sonderup M, Hu NC, Mashele N, Mvududu R, Myer L. Low prevalence of hepatitis B virus infection in HIV-uninfected pregnant women in Cape Town, South Africa: implications for oral pre-exposure prophylaxis roll out. BMC Infect Dis. 2022 Sep 1;22(1):719. doi: 10.1186/s12879-022-07697-5.
citation: Beesham I, Mansoor LE, Joseph Davey DL, Palanee-Phillips T, Smit J, Ahmed K, Selepe P, Louw C, Singata-Madliki M, Kotze P, Heffron R, Parikh UM, Wiesner L, Rees H, Baeten JM, Beksinska M. Brief Report: Quantifiable Plasma Tenofovir Among South African Women Using Daily Oral Pre-exposure Prophylaxis During the ECHO Trial. J Acquir Immune Defic Syndr. 2022 Sep 1;91(1):26-30. doi: 10.1097/QAI.0000000000003023. Epub 2022 Jun 9.
citation: Miller AP, Shoptaw S, Mvududu R, Mashele N, Coates TJ, Bekker LG, Essack Z, Groenewald C, Petersen Z, Gorbach PM, Myer L, Joseph Davey DL. Sexual Risk among Pregnant Women at Risk of HIV Infection in Cape Town, South Africa: What Does Alcohol Have to Do with It? AIDS Behav. 2023 Jan;27(1):37-50. doi: 10.1007/s10461-022-03742-1. Epub 2022 Jun 23.
citation: Beesham I, Dovel K, Mashele N, Bekker LG, Gorbach P, Coates TJ, Myer L, Joseph Davey DL. Barriers to Oral HIV Pre-exposure Prophylaxis (PrEP) Adherence Among Pregnant and Post-partum Women from Cape Town, South Africa. AIDS Behav. 2022 Sep;26(9):3079-3087. doi: 10.1007/s10461-022-03652-2. Epub 2022 Mar 22.
citation: Joseph Davey DL, Mvududu R, Mashele N, Lesosky M, Khadka N, Bekker LG, Gorbach P, Coates TJ, Myer L. Early pre-exposure prophylaxis (PrEP) initiation and continuation among pregnant and postpartum women in antenatal care in Cape Town, South Africa. J Int AIDS Soc. 2022 Feb;25(2):e25866. doi: 10.1002/jia2.25866.
citation: Joseph Davey DL, Dovel K, Mvududu R, Nyemba D, Mashele N, Bekker LG, Gorbach PM, Coates TJ, Myer L. Pre-exposure Prophylaxis Recent Adherence With Real-Time Adherence Feedback and Partner Human Immunodeficiency Virus Self-Testing: A Pilot Trial Among Postpartum Women. Open Forum Infect Dis. 2021 Dec 23;9(2):ofab609. doi: 10.1093/ofid/ofab609. eCollection 2022 Feb.
citation: Joseph Davey DL, Bekker LG, Bukusi EA, Chi BH, Delany-Moretlwe S, Goga A, Lyerly AD, Mgodi NM, Mugo N, Myer L, Noguchi LM, Stranix-Chibanda L, Slack C, Pintye J. Where are the pregnant and breastfeeding women in new pre-exposure prophylaxis trials? The imperative to overcome the evidence gap. Lancet HIV. 2022 Mar;9(3):e214-e222. doi: 10.1016/S2352-3018(21)00280-0. Epub 2022 Jan 25.
citation: Moran A, Mashele N, Mvududu R, Gorbach P, Bekker LG, Coates TJ, Myer L, Joseph Davey D. Maternal PrEP Use in HIV-Uninfected Pregnant Women in South Africa: Role of Stigma in PrEP Initiation, Retention and Adherence. AIDS Behav. 2022 Jan;26(1):205-217. doi: 10.1007/s10461-021-03374-x. Epub 2021 Jul 21.
citation: Joseph Davey DL, Knight L, Markt-Maloney J, Tsawe N, Gomba Y, Mashele N, Dovel K, Gorbach P, Bekker LG, Coates TJ, Myer L. "I had Made the Decision, and No One was Going to Stop Me" -Facilitators of PrEP Adherence During Pregnancy and Postpartum in Cape Town, South Africa. AIDS Behav. 2021 Dec;25(12):3978-3986. doi: 10.1007/s10461-021-03320-x. Epub 2021 Jun 3.