A Pilot Study on Raltegravir, Tenofovir and Emtricitabine for Peri-exposure Prophylaxis for HIV Infection

NCT ID: NCT01697046

Last Updated: 2012-10-02

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 65 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-11-30
• Study Completion Date: 2014-03-31

Brief Summary

This will be a pilot, open label study involving 65 participants. All participants will be followed until seroconversion or until the last enrolled participant completes one year of follow-up, whichever happens first. Participant study number will be given at the screening visit, prior to inclusion in the study.

The chosen intervention and study regimen are based on the dynamics of viral infection and the pharmacokinetics of the study drugs. In order to inhibit reverse transcription nucleoside and nucleotide analogues need to be phosphorylated intracellularly. On the other hand, available data indicate that it takes approximately 10 hours between exposure and HIV viral integration, offering a window of opportunity for Raltegravir to block integration and thus prevent infection, given that this drug does not need to be metabolized to exert its effect. The intervention will be maintained for 4 weeks following exposure, in accordance with Brazilian and CDC guidelines for PEP.

Detailed Description

Subjects with reported high-risk behavior (and anticipated future high-risk behavior) but no exposure in the immediate past will be the focus of this study.

Participants will be prescribed raltegravir 400 mg BID + Truvada once daily. All study participants will receive a 4-days starter pack. Study participants will be instructed to start study drugs if they expect or experience an exposure of any mucous membrane (oral, urethral, anal) to semen. Subjects who expect or experience these exposures will be instructed to take 1 pill of Raltegravir 400mg and one pill of truvada, followed by a second dose of Raltegravir 12 hours later. From the second day onward, participants will be instructed to take Raltegravir 400 mg BID + Truvada once daily. The first dose should be taken no more than 6 hours before or 6 hours after the expected or actual exposure and continued for 28 days.

Enrolled subjects will also be instructed to report to the study site within 4 days of beginning study drugs to respond to a CASI questionnaire and to have blood taken. They will be instructed to return at the end of the 4-week chemoprophylaxis course for reevaluation and to be given another 4-day supply of medication. Under no circumstances will any participant be given a greater than 4 week supply of medication; all will be evaluated for toxicity and adherence following each course of chemoprophylaxis.

The study participants will be monitored closely for safety after each course of chemoprophylaxis and at the end of the trial. In addition, subjects will be instructed to immediately contact the site if they experience certain symptoms consistent with severe toxicity. At each evaluation a careful clinical history, physical examination, and laboratory assessment, including HIV serology, will be completed. Adherence will be estimated based on self-report and the use of pill counts. During each visit, subjects will be reminded of the need to not increase high-risk sexual behavior. HIV serology and response to a CASI questionnaire will be conducted monthly.

Conditions

Infection; HIV

Keywords

peri-exposure; chemoprophylaxis

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Isentress+Truvada

All participants will receive the intervention

Group Type: EXPERIMENTAL

Truvada and Isentress

Intervention Type: DRUG

Subjects with reported high-risk behavior (and anticipated future high-risk behavior) but no exposure in the immediate past will be the focus of this study.

Participants will be prescribed raltegravir 400 mg BID + Truvada once daily. All study participants will receive a 4-days starter pack. Study participants will be instructed to start study drugs if they expect or experience an exposure of any mucous membrane (oral, urethral, anal) to semen. Subjects who expect or experience these exposures will be instructed to take 1 pill of Raltegravir 400mg and one pill of truvada, followed by a second dose of Raltegravir 12 hours later. From the second day onward, participants will be instructed to take Raltegravir 400 mg BID + Truvada once daily. The first dose should be taken no more than 6 hours before or 6 hours after the expected or actual exposure and continued for 28 days.

Interventions

Truvada and Isentress

Subjects with reported high-risk behavior (and anticipated future high-risk behavior) but no exposure in the immediate past will be the focus of this study.

Participants will be prescribed raltegravir 400 mg BID + Truvada once daily. All study participants will receive a 4-days starter pack. Study participants will be instructed to start study drugs if they expect or experience an exposure of any mucous membrane (oral, urethral, anal) to semen. Subjects who expect or experience these exposures will be instructed to take 1 pill of Raltegravir 400mg and one pill of truvada, followed by a second dose of Raltegravir 12 hours later. From the second day onward, participants will be instructed to take Raltegravir 400 mg BID + Truvada once daily. The first dose should be taken no more than 6 hours before or 6 hours after the expected or actual exposure and continued for 28 days.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

Individuals will be included in the clinical trial if they meet ALL of the following criteria:

• Male sex (at birth);
• Willing and able to provide written informed consent;
• Age 18 years or older;
• HIV-1-uninfected;
• Absence of signs or symptoms compatible with an acute viral disease
• Evidence of high risk for acquiring HIV-1 infection including any one of the following: 1) No condom use during the last receptive and/or insertive anal intercourse with a male HIV-positive partner or a male partner of unknown HIV status during the last 6 months; (2) anal intercourse with more than 4 male sex partners during the last 6 months; (3) exchange of money, gifts, shelter, or drugs for anal sex with a male partner during the last 6 months; (4) sex with a male partner and STI diagnosis during the last 6 months or at screening, or (5) sexual partner of an HIV-infected man with whom condoms are not consistently used.
• Adequate renal function
• Adequate hepatic function

Exclusion Criteria

• Glycosuria or proteinuria
• Acute hepatitis B infection
• History of pathological bone fractures not related to trauma
• Active alcohol or drug use considered sufficient to hinder compliance with any study procedures
• At enrollment, has any other condition that, based on the opinion of the investigator or designee, would preclude provision of informed consent; make participation in the study unsafe; complicate interpretation of study outcome data; or otherwise interfere with achieving the study objectives

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

Projeto Praça Onze

OTHER

Sponsor Role: lead

Responsible Party

Mauro Schechter

MD, PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Mauro Schechter, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Projeto Praça Onze

Locations

Monica Barbosa de Souza

Rio de Janeiro, Rio de Janeiro, Brazil

Countries

Brazil

Central Contacts

Monica Barbosa de Souza, BA

Role: CONTACT

Phone: +55 21 22739073

Email: monica@ponze.ufrj.br

Carina Beppu Yoshida, RN

Role: CONTACT

Phone: +55 21 22739073

Email: carina@ponze.ufrj.br

Facility Contacts

Carina Beppu Yoshida, RN

Role: primary

References

Centers for Disease Control and Prevention (CDC). Update: provisional Public Health Service recommendations for chemoprophylaxis after occupational exposure to HIV. MMWR Morb Mortal Wkly Rep. 1996 Jun 7;45(22):468-80.

Reference Type: BACKGROUND

PMID: 8622618 (View on PubMed)

Cardo DM, Culver DH, Ciesielski CA, Srivastava PU, Marcus R, Abiteboul D, Heptonstall J, Ippolito G, Lot F, McKibben PS, Bell DM. A case-control study of HIV seroconversion in health care workers after percutaneous exposure. Centers for Disease Control and Prevention Needlestick Surveillance Group. N Engl J Med. 1997 Nov 20;337(21):1485-90. doi: 10.1056/NEJM199711203372101.

Reference Type: BACKGROUND

PMID: 9366579 (View on PubMed)

Schechter M, do Lago RF, Mendelsohn AB, Moreira RI, Moulton LH, Harrison LH; Praca Onze Study Team. Behavioral impact, acceptability, and HIV incidence among homosexual men with access to postexposure chemoprophylaxis for HIV. J Acquir Immune Defic Syndr. 2004 Apr 15;35(5):519-25. doi: 10.1097/00126334-200404150-00010.

Reference Type: BACKGROUND

PMID: 15021317 (View on PubMed)

Grant, RM; Lama, JR; Anderson, PL; McMahan, V; Liu, AY; Vargas, L; Goicochea, P; Casapía, M; Guanira-Carranza, JV; Ramirez-Cardich, ME; Montoya-Herrera,O; Fernandez, T; Veloso, VG; Buchbinder, SP; Chariyalertsak, S; Schechter, M; Gail -Bekker, L; Mayer, KM; Kallas, EG; Amico, KR; Mulligan, K; Bushman, LR; Hance, TJ; Ganoza, C; Defechereux, P; Brian, P; Wang, F; McConnell, JJ; Zheng, JH; Lee, J; Rooney, JF; Jaffe, HS; Martinez, AI; Burns, DN; Glidden, DV. Pre-Exposure Chemoprophylaxis for HIV Prevention in Men who Have Sex with Men. New Eng J Med 2010; 363:2587-99.

Reference Type: BACKGROUND

Other Identifiers

IIS# 39550

Identifier Type: -

Identifier Source: org_study_id