HIV PrEP Priming of Immune Effectors

HIV-1 Infections Clinical Trial

— PREPPIE  

Official title:

HIV Pre-Exposure Prophylaxis Priming of Immune Effectors

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02593409
• Other study ID #: PREPPIE001
• Status: Recruiting
• Phase: Phase 4
• First received: October 21, 2015
• Last updated: September 18, 2017
• Start date: May 25, 2017
• Est. completion date: June 2018

Study information

• Verified date: September 2017
• Source: MRC/UVRI Uganda Research Unit on Aids
• Contact: Berna Kalanzi
• Phone: +256417704000
• Email: berna.kalanzi[@]mrcuganda.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Can HIV-specific immunity develop in HIV uninfected humans exposed to HIV whilst receiving antiretroviral pre-exposure prophylaxis (PrEP)? Investigators will investigate this possibility in commercial sex workers in Kampala who will be receiving Truvada PrEP for one year.

Description:

Design This will be a single centre open label longitudinal observational trial. Women attending the "Good Health for Women" clinic will be informed about the objectives of the trial and volunteers able to provide informed consent and with high risk of exposure to HIV-1 determined by a sexual history questionnaire will be screened by Rapid antibody test. Seronegatives will be checked for eligibility by clinical examination and laboratory tests. The endpoint for enrolment will be 220 uninfected high risk participants.

Baseline blood samples will be obtained from participants at month 0. A monthly diary card will be provided for self documenting sexual exposure, alcohol use and pill taking. Participants will receive provisions of PrEP (tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) sufficient for one month, will be instructed on the daily prophylaxis and on how to record adherence on the diary card. Participants will be asked to return each month for treatment re-provisioning and a new card. The content of the diary card will be discussed in a short interview each month.

At month 6 and 12 blood samples will be collected for evaluating immune responses to HIV-1. Additional tests will be done for monitoring HIV-1 status, pregnancy and sexually transmitted infections (STIs). After month 12 PrEP will be discontinued (unless participants opt to continue PrEP until the end of the follow up) and all participants will provide blood samples at month 18.

Baseline and follow-up peripheral blood mononuclear cells (PBMC) samples will be compared for T cell responses to HIV by interferon-γ (IFN-γ) enzyme-linked immunospot (ELISPOT). In case of a positive immune response, plasma collected at the same time point will be nucleic acid test (NAT) tested to verify absence of HIV infection.

HIV infected participants will be evaluated for cluster of differentiation 4 (CD4) T cells and viral load and referred to a Care Program (PEPFAR).

At month 6, 12 and 18 in-depth interviews will be conducted with a randomly selected sample of 44 women (20 percent) to discuss facilitators and barriers to adherence. The diary answers will be tabulated to look for patterns and trends. A framework approach to analysis will be used for the analysis of the qualitative data from interviews.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 220
• Est. completion date: June 2018
• Est. primary completion date: April 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• age =18 at screening

• not intending to move away from the clinic's catchment area for the next 2 years

• HIV-1 antibody negative

• reports commercial sex work

• contact information is provided

• written informed consent

Exclusion Criteria:

• HIV infection at screening

• participation in previous or concurrent HIV vaccine trials

• lactating, pregnant or planning pregnancy

• renal function impairment (serum creatinine >1.5 mg/dl), Fanconi syndrome

• abnormal liver function tests (AST/ALT > 43 U/L), liver disease, viral hepatitis, hepatitis B virus (HBV) infection

• serum phosphorus <2.2mg/dl, osteoporosis

• known sensitivity to components of the Truvada® formulation

• any immunosuppressive treatment, such as systemic corticosteroids

• assumption of medication that interacts with Truvada®

• high likelihood of poor adherence to PREP and clinic attendance

• any condition that in the opinion of the attending physician could endanger the health of the participant or render her unsuitable to participate in the trial

Related Conditions & MeSH terms

• HIV-1 Infections

Intervention

Drug:
• TDF/FTC
All participants receive pre-exposure prophylaxis in the form of a daily tablet containing 300 mg of tenofovir disoproxil fumarate and 200 mg emtricitabine (Truvada®, Gilead) for one year, with an optional extension for 6 months.

Locations

Country	Name	City	State
Uganda	MRC/UVRI Uganda Research Unit on Aids - Good Health for Women Project	Kampala

Sponsors (1)

Lead Sponsor	Collaborator
MRC/UVRI Uganda Research Unit on Aids

Country where clinical trial is conducted

Uganda, 

References & Publications (1)

Cranage M, Sharpe S, Herrera C, Cope A, Dennis M, Berry N, Ham C, Heeney J, Rezk N, Kashuba A, Anton P, McGowan I, Shattock R. Prevention of SIV rectal transmission and priming of T cell responses in macaques after local pre-exposure application of tenofovir gel. PLoS Med. 2008 Aug 5;5(8):e157; discussion e157. doi: 10.1371/journal.pmed.0050157. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	HIV-1 incidence.		0-18 months
Other	Viral load among participants who become infected with HIV-1 despite PREP.		0-18 months
Other	Adherence to PREP as measured by plasma sampling.		0-18 months
Other	Adherence to PREP as measured by pill counts.		0-18 months
Other	Adherence to PREP as measured by participant self-report.		0-18 months
Primary	Change in IFN-? ELISPOT response to HIV-1 peptides in persistently uninfected individuals between baseline and 12 months on PREP		0-12 months
Secondary	Change in IFN-? ELISPOT response to HIV-1 peptides in persistently uninfected individuals between baseline and 6 months on PREP		0-6 months
Secondary	Change in IFN-? ELISPOT response to HIV-1 peptides in persistently uninfected individuals between 12 months on PREP and at 18 months after PREP cessation		12-18 months