iprex fact sheet: about the iprex study

iPrEx Fact Sheet: About the iPrEx Study 1

EMBARGOED UNTIL RELEASE CONTACT Tuesday, 23 November 2010, 8 a.m. EST Mark Aurigemma; 646-270-9451; [email protected] Pedro Goicochea; 415-490-8350 [email protected]

iPrEx Fact Sheet: About the iPrEx Study

Study name: iPrEx, which derives from the Spanish 'Iniciativa Profilaxis Preexposicion” (Prexposure Prophylaxis Initiative) Study sponsor: iPrEx is funded by the U.S. National Institutes of Health (NIH) through a grant to the J. David Gladstone Institutes, a non-profit independent research organization affiliated with the University of California at San Francisco (UCSF). Additional funding is provided by the Bill & Melinda Gates Foundation. Sites: iPrEx was conducted at 11 sites in nine cities in six countries on four continents:

PERU: Asociación Civil Impacta Salud y Educación (Lima); Investigaciones Médicas en Salud (Lima); Asociación Civil Selva Amazónica (Iquitos) ECUADOR: Fundación Ecuatoriana Equidad (Guayaquil) BRAZIL: Instituto de Pesquisa Clinica Evandro Chagas -- FIOCRUZ (Rio de Janeiro); Projeto Praça Onze, Universidade Federal de Rio de Janeiro (Rio de Janeiro); Universidade de São Paulo (São Paulo) UNITED STATES: Fenway Community Health (Boston); San Francisco Department of Public Health (San Francisco) SOUTH AFRICA: Desmond Tutu HIV Foundation, University of Cape Town (Cape Town) THAILAND: Research Institute for Health Sciences, University of Chiang Mai (Chiang Mai) Participants: iPrEx enrolled 2,499 participants; 56% of iPrEx participants were in Peru, 15% in Brazil, 12% in Ecuador, 9% in the USA, 5% in Thailand and 3% in South Africa. Of the 2,499 participants in the study, 1,251 were randomized to the FTC/TDF PrEP arm; 1,248 were randomized to the placebo arm. Duration: After 3 years of preparation, iPrEx began on June 14th, 2007, enrolled the first participant on July 10th, 2007, and enrolled its last participant on December 18th, 2009. Starting in August 2010, participants discontinued study medication and continued in follow-up to assure safety after medication was stopped. The final study follow-up visit is expected to occur in March of 2011. The primary analysis considered visits through May 1st, 2010.

Design: iPrEx is a randomized, double-blind, placebo-controlled event-driven study to evaluate the safety and efficacy of once daily oral co-formulated emtricitabine 200 mg/tenofovir 300 mg (FTC/TDF) for prevention of HIV acquisition among men who are highly exposed to HIV who also receive a comprehensive package of prevention services, including HIV testing and risk reduction counseling, condoms and STI management. The project aimed to determine if PrEP is a) safe and acceptable; and b) reduces HIV-1 seroincidence. Primary endpoints for the study are adverse events and HIV seroconversion.


Study agent: Emtricitabine (FTC 200 mg) and tenofovir (TDF 300 mg), are reverse transcriptase inhibitors licensed for the treatment of HIV-1 by the U.S. FDA

Study Expansion: iPrEx was originally initiated at four sites in Peru and Ecuador. Prior to enrolling the first participant, plans were finalized for expanding the study to new sites in Brazil, South Africa, Thailand and the United States using co-funding from the Bill & Melinda Gates Foundation. The expansion sites began enrollment on June 24th, 2008. The expansion of the study aimed to increase the power and generalizabilty of the study results. Protocol Development and Review: iPrEx was designed and implemented according to rigorous international ethical standards. Work on the iPrEx study protocol began in February 2004 through extensive consultation with community leaders, prospective research participants, sponsors, funders and government officials, using methods that later became called “Good Participatory Practices” or GPP. The protocol was sponsored by the Division of AIDS of the NIH and registered with the US FDA under Investigational New Drug (IND) 71,859. The iPrEx protocol was approved by Ethical Committees at each of the 11 study sites; by national authorities at each country: the Instituto Nacional de Salud (Peru), Ministerio de Salud Pública (Ecuador), Medical Research Council (South Africa), Ministério da Saúde, Conselho Nacional de Saúde and the Comissão Nacional de Ética em Pesquisa (CONEP, Brazil) and Ministry of Public Health (Thailand). Inclusion criteria: iPrEx participants are men and transgendered women who have sex with men, a population at extremely high risk for HIV infection worldwide that is often overlooked in HIV prevention studies and services; age 18 and over at time of enrollment; in good health; HIV-1 uninfected; not acutely infected with hepatitis B; willing and able to provide informed consent, physically capable of providing blood and urine for safety assessments; and at high-risk for sexual acquisition of HIV.

Risk criteria: The evidence of risk for HIV acquisition included any of the following in the 6 months prior to screening: anal sex with 3 or more male partners; a diagnosis of a sexually transmitted disease; history of transactional sex activity; or condomless anal sex with a partner who was HIV infected or of unknown infection status. Exclusion criteria: Exclusion criteria included serious and active illness including diabetes requiring hypoglycemic agents, active tuberculosis and cancer requiring further therapy; substance use sufficient to impair compliance with visits; use of nephrotoxic agents. Serum creatinine and platelet count had to be within normal limits and an absolute neutrophil count of at least 1500 cells /mm3 was required. Persons with active hepatitis B infection could be enrolled provided they were informed of the special risks and benefits of FTC/TDF use and consented to undergo 24 weeks of follow-up after stopping study drug. Study Visits: Study visits were scheduled every 4 weeks following enrollment. Every 4 week visit included drug dispensation, adherence counseling, HIV antibody testing with rapid tests, pre- and post-test risk reduction counseling and a medical history. Every 12-week visit also involved a sexual behavior interview by interviewers and a computer assisted self interview (CASI) and plasma and serum storage. Persons who had reactive HIV rapid tests were followed every 2 weeks until their HIV-1 infection status was confirmed, and then at week 4, 8,


12 and every 12 weeks thereafter. Evaluation and Follow-up: All participants were evaluated at four-week intervals throughout the study. All participants were followed up for at least 8 weeks after stopping study medication, until the end of October of 2010. In addition:

• Participants reactive to hepatitis antigens are followed for hepatitis flares for 16 additional weeks, for a total of 24 weeks after stopping the study medication.

• Participants enrolled in the optional sub study of bone mineral density, fat distribution and fasting lipids are asked to return for one additional visit 24 weeks after stopping the study drug.

• Participants who became HIV infected during their participation in the study are followed up for at least 24 weeks after they stop taking the study drug.

Prevention Interventions: All participants received standard prevention interventions including HIV testing and risk reduction counseling, condoms and diagnosis and treatment of sexually transmitted infections including gonorrhea and chlamydia urethritis and syphilis. Serological testing for herpes simplex and asymptomatic sexually transmitted infections was performed every 24 weeks. All participants were instructed to protect themselves from HIV using methods other than PrEP, because the pill they were receiving could be a placebo or an active drug which may have no protective power. Participants reporting a recent unprotected exposure to an HIV-1 infected partner were referred for Post Exposure Prophylaxis (PEP), at sites where PEP is available and considered to be the standard prevention care, and study medication was temporarily stopped. Data collection: Data was collected on case report forms (CRF) and faxed to a Datafax server at DFNet a data management organization based in Seattle, Washington state in the United States. Optical character recognition was followed by two rounds of entry checking. Discrepancies were resolved by the sites using source documents. A computer assisted self interview (CASI) was used to collect information about educational status, social identity, alcohol and substance use and sexual behavior. Laboratory Testing: HIV antibody testing was performed with two rapid tests at every visit (Bioline and Determine outside the United States; Oraquick and Clearview in the United States). All reactive rapid tests were tested using a Western Blot (BioRad). HIV plasma RNA testing (Abbott and Roche) was performed at enrollment, if seroconversion was detected within 12 weeks of enrollment or if there were missed visits before the first seropositive visit. In addition, plasma HIV RNA level testing was performed to evaluate infection status at enrollment or among those with indeterminant Western Blot tests on three specimens. HIV plasma viral RNA level monitoring and CD4 T cell counts were measured among those with confirmed HIV infection. Drug resistance genotyping was conducted using the Trugene test (Siemens), a population genotyping assay, and phenotyping was conducted using the PhenoSense assay (Monogram).


Sexually Transmitted Infections (STI) testing included evaluation for urethritis using a urine dipstick for leukocyte esterase test (LE), an RPR, and HSV-2 serology. Positive LE tests were followed up with nucleic acid testing for gonorrhea and chlamydia. Reactive RPRs were followed up with confirmatory treponemal syphilis tests. Other laboratory testing was performed by local laboratories who participate in external quality assurance from the College of American Pathologists as managed by the NIH SMILE program. Laboratory audits were conducted annually or more frequently. DSMB Monitoring: The study was monitored by the NIH/NIAID/DAIDS Multinational Data Safety Monitoring Board (DSMB) in November 2007 (safety), November 2008 (safety), May 2009 (safety), November 2009 (safety and efficacy) and May 2010 (safety). Study Termination: The protocol sample size was targeted to observe 85 seroconversion events for the modified intention to treat analysis. In November 2009 the DSMB recommended that iPrEx enrollment should end in December 2009 because enrollment was sufficient to meet the goals of the study. Without access to any unblinded information, the sponsor decided in October 2010 that the primary analysis should be performed shortly after 85 seroconversions were observed. In December 2009, the sponsor decided that visits through May 1st, 2010 should be included. The date was chosen to allow lessons learned from the study to be analyzed and reported as promptly as possible. Other statistics: iPrEx involved:

• 43,248 participant visits • 39,754 visits for HIV testing and counseling • 650,000 pages of data faxed to the data management center • 1,184,400 tablets of study drug dispensed • 4,533 HBV vaccination doses given • 1,019 syphilis cases diagnosed and treated • ~500,000 condoms distributed to participants

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iprex fact sheet: about the iprex study

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