BufferGel and PRO 2000/5: Vaginal Gels to Prevent HIV Infection in Women

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ClinicalTrials.gov Identifier: NCT00074425

Recruitment Status : Completed

First Posted : December 15, 2003

Last Update Posted : November 8, 2021

View this study on Beta.ClinicalTrials.gov

Sponsor:

Collaborators:

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

National Institute on Drug Abuse (NIDA)

National Institute of Mental Health (NIMH)

HIV Prevention Trials Network

Information provided by (Responsible Party):

National Institute of Allergy and Infectious Diseases (NIAID)

Study Description

Brief Summary:

The majority of HIV infected people worldwide became infected with the virus through heterosexual contact. BufferGel and PRO 2000 Gel are vaginal gels designed to prevent women from becoming infected with HIV during sexual intercourse with an HIV infected partner. This study will test the safety and effectiveness of these gels.

Condition or disease	Intervention/treatment	Phase
HIV Infections	Drug: BufferGel Drug: PRO 2000/5 Gel Drug: Placebo gel	Phase 2

Detailed Description:

Accessible, usable, and effective vaginal microbicides could significantly decrease the spread of HIV. Vaginal microbicides could be used with condoms to prevent HIV infection; they could also be used in situations in which an individual is unable to negotiate condom use. Vaginal microbicides are potentially bidirectional, preventing both male-to-female and female-to-male HIV transmission. This study will evaluate the safety and effectiveness of two vaginal microbicides, BufferGel and PRO 2000/5, in preventing the transmission of HIV. The study will also evaluate the effectiveness of these gels in preventing other common sexually transmitted infections (STIs).

BufferGel is a buffering agent designed to maintain normal vaginal acidity in the presence of ejaculate. Studies have shown that HIV is inactivated below a pH of 4 to 5.8. Carbopol 974, the major nonaqueous component of BufferGel, is commonly used as a gelling or tableting agent and has a well-documented safety record. BufferGel has proven safe and well tolerated in Phase I studies. PRO 2000/5 inhibits viral entry into susceptible cells. PRO 2000/5 has also been evaluated in Phase I studies and was found to be safe and well tolerated.

Participants in this study will be randomly assigned to receive one of four interventions: BufferGel, PRO 2000/5, placebo gel, or no gel. All participants will receive HIV risk reduction counseling, condoms, and diagnosis and treatment of sexually transmitted diseases. Participants in the three gel arms will be given single-use, prefilled applicators of gel and will be instructed to apply one dose of the product (BufferGel, PRO 2000/5, or placebo gel) intravaginally up to 60 minutes before each vaginal intercourse while in the study.

Participants will be enrolled for approximately 12 to 30 months, depending on when they enter the study. Participants will have two screening study visits and then monthly visits. Monthly study visits may take place at a clinic, the participant's home, or other community site. Monthly visits will include a medical interview; urine testing, including pregnancy testing; HIV and sexually transmitted infection risk reduction counseling; and distribution of study supplies (condoms and gel-filled applicators). Blood collection will occur at selected monthly visits. Four times a year, participants will be seen in the clinic for a more structured medical interview, pelvic exam, and HIV testing. At one of these visits, participants at particular sites who are willing will be asked to complete a behavioral risk assessment. At some visits vaginal fluid swabs will occur. Participants at non-US study sites will be asked for permission for these swabs to be stored for further testing. Assessment interviews will be both face to face and self-reporting.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	3101 participants
Allocation:	Randomized
Intervention Model:	Factorial Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Prevention
Official Title:	Phase II/IIb Safety and Effectiveness Study of the Vaginal Microbicides BufferGel and 0.5% PRO 2000/5 Gel (P) for the Prevention of HIV Infection in Women
Study Start Date :	January 2005
Actual Primary Completion Date :	September 2008
Actual Study Completion Date :	September 2008

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: 1 BufferGel	Drug: BufferGel Participants will be given single-use, prefilled applicators of gel and will be instructed to apply one dose of BufferGel intravaginally up to 60 minutes before each vaginal intercourse while in the study.
Experimental: 2 Pro 2000/5 Gel (P)	Drug: PRO 2000/5 Gel Participants will be given single-use, prefilled applicators of gel and will be instructed to apply one dose of PRO 2000/5 Gel intravaginally up to 60 minutes before each vaginal intercourse while in the study.
Placebo Comparator: 3 Placeo Gel	Drug: Placebo gel Participants will be given single-use, prefilled applicators of gel and will be instructed to apply one dose of PRO 2000/5 Gel intravaginally up to 60 minutes before each vaginal intercourse while in the study.
No Intervention: 4

Outcome Measures

Primary Outcome Measures :

Safety of BufferGel and 0.5% PRO 2000/5 Gel (P), as assessed by deep epithelial disruption, other genital symptoms, or other systemic symptoms [ Time Frame: Throughout study ]
HIV infection as measured by seroconversion [ Time Frame: Throughout study ]

Secondary Outcome Measures :

Bacterial vaginosis [ Time Frame: Throughout study ]
Chlamydia infection [ Time Frame: Throughout study ]
Genital ulcer disease [ Time Frame: Throughout study ]
Gonorrhea infection [ Time Frame: Throughout study ]
Herpes simplex virus-2 infection [ Time Frame: Throughout study ]
Pregnancy [ Time Frame: Throughout study ]
Syphilis infection [ Time Frame: Throughout study ]
Trichomoniasis [ Time Frame: Throughout study ]
Acceptability of study product [ Time Frame: At Month 3 and study exit ]
Number of behavioral risk assessment questions not answered in self-reported interviews [ Time Frame: Throughout study ]
Rates of condom use versus gel use [ Time Frame: Throughout study ]
Establishment of a repository of vaginal swab specimens for long-term storage and future research testing on biomarkers of microbicide safety and effectiveness [ Time Frame: Throughout study ]

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	Female
Accepts Healthy Volunteers:	Yes

Criteria

Note: Per the 12/15/06 amendment, all study participants will now enter the Phase IIb study.

Inclusion Criteria:

HIV uninfected
Have had sexual intercourse at least once in the 3 months prior to study entry
Able to provide adequate contact information to study officials for purposes of follow-up

Exclusion Criteria:

History of adverse reaction to latex
Nonmedical injection drug use in the 12 months prior to study entry
Vaginal intercourse more than an average of two times per day in the 2 weeks prior to study entry
Plan to become pregnant in the 30 months after study entry
Plan to travel away from the study site for more than 3 consecutive months in the 30 months after study entry
Plan to relocate away from the study site in the 30 months after study entry
Participation in another clinical trial of a vaginal product
Pregnant within 42 days of study entry
Have a sexually transmitted disease or other reproductive tract infection diagnosed by study staff
Abnormal pelvic exam indicating deep epithelial disruption
Condition that, in the opinion of the investigator, may interfere with the study
Liver or kidney function abnormality of Grade 3 or higher
Blood or blood clotting abnormality of Grade 4 or higher

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00074425

Locations

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United States, Pennsylvania
3535 Market Street CRS
Philadelphia, Pennsylvania, United States
Malawi
University of North Carolina Lilongwe CRS
Lilongwe, Central, Malawi
College of Med. JHU CRS
Blantyre, Southern, Malawi
South Africa
Chatsworth CRS
Chatsworth, KwaZulu-Natal, South Africa
Med. Research Council-Hlabisa
Durban, KwaZulu-Natal, South Africa
Zambia
Kamwala Clinic CRS
Lusaka, Zambia
Zimbabwe
Seke South CRS
Chitungwiza, Zimbabwe, 263
Spilhaus CRS
Harare, Zimbabwe, 263

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

National Institute on Drug Abuse (NIDA)

National Institute of Mental Health (NIMH)

HIV Prevention Trials Network

Investigators

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Study Chair:	Salim Abdool Karim, MBChB, PhD	University of KwaZulu-Natal, Centre for the AIDS Programme of Research in South Africa, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine
Study Chair:	Irving Hoffman, PA, MPH	School of Medicine, University of North Carolina
Study Chair:	Lisa Maslankowski, MD	University of Pennsylvania
Study Chair:	Groesbeck Parham, MD	Centre for Infectious Disease Research in Zambia
Study Chair:	Nancy Padian, PhD	Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco; AIDS Research Institute
Study Chair:	Gita Ramjee, PhD	Medical Research Council, HIV Prevention Research Unit
Study Chair:	Taha Taha, MD	Johns Hopkins Bloomberg School of Public Health

More Information

Publications of Results:

MacQueen KM, Namey E, Chilongozi DA, Mtweve SP, Mlingo M, Morar N, Reid C, Ristow A, Sahay S; HPTN 035 Standard of Care Assessment Team. Community perspectives on care options for HIV prevention trial participants. AIDS Care. 2007 Apr;19(4):554-60. doi: 10.1080/09540120601035284.

Minces LR, McGowan I. Advances in the Development of Microbicides for the Prevention of HIV Infection. Curr Infect Dis Rep. 2010 Jan;12(1):56-62. doi: 10.1007/s11908-009-0076-5.

Abdool Karim SS, Richardson BA, Ramjee G, Hoffman IF, Chirenje ZM, Taha T, Kapina M, Maslankowski L, Coletti A, Profy A, Moench TR, Piwowar-Manning E, Masse B, Hillier SL, Soto-Torres L; HIV Prevention Trials Network (HPTN) 035 Study Team. Safety and effectiveness of BufferGel and 0.5% PRO2000 gel for the prevention of HIV infection in women. AIDS. 2011 Apr 24;25(7):957-66. doi: 10.1097/QAD.0b013e32834541d9.

Other Publications:

Mayer KH, Peipert J, Fleming T, Fullem A, Moench T, Cu-Uvin S, Bentley M, Chesney M, Rosenberg Z. Safety and tolerability of BufferGel, a novel vaginal microbicide, in women in the United States. Clin Infect Dis. 2001 Feb 1;32(3):476-82. doi: 10.1086/318496. Epub 2001 Jan 26.

van De Wijgert J, Fullem A, Kelly C, Mehendale S, Rugpao S, Kumwenda N, Chirenje Z, Joshi S, Taha T, Padian N, Bollinger R, Nelson K. Phase 1 trial of the topical microbicide BufferGel: safety results from four international sites. J Acquir Immune Defic Syndr. 2001 Jan 1;26(1):21-7. doi: 10.1097/00126334-200101010-00003.

Clarke JG, Peipert JF, Hillier SL, Heber W, Boardman L, Moench TR, Mayer K. Microflora changes with the use of a vaginal microbicide. Sex Transm Dis. 2002 May;29(5):288-93. doi: 10.1097/00007435-200205000-00007.

Tabet SR, Callahan MM, Mauck CK, Gai F, Coletti AS, Profy AT, Moench TR, Soto-Torres LE, Poindexter III AN, Frezieres RG, Walsh TL, Kelly CW, Richardson BA, Van Damme L, Celum CL. Safety and acceptability of penile application of 2 candidate topical microbicides: BufferGel and PRO 2000 Gel: 3 randomized trials in healthy low-risk men and HIV-positive men. J Acquir Immune Defic Syndr. 2003 Aug 1;33(4):476-83. doi: 10.1097/00126334-200308010-00008. Erratum In: J Acquir Immune Defic Syndr. 2003 Sep 1;34(1):118.

Mayer KH, Karim SA, Kelly C, Maslankowski L, Rees H, Profy AT, Day J, Welch J, Rosenberg Z; HIV Prevention Trials Network (HPTN) 020 Protocol Team. Safety and tolerability of vaginal PRO 2000 gel in sexually active HIV-uninfected and abstinent HIV-infected women. AIDS. 2003 Feb 14;17(3):321-9. doi: 10.1097/00002030-200302140-00005.

D'Cruz OJ, Uckun FM. Clinical development of microbicides for the prevention of HIV infection. Curr Pharm Des. 2004;10(3):315-36. doi: 10.2174/1381612043386374.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Guffey MB, Richardson B, Husnik M, Makanani B, Chilongozi D, Yu E, Ramjee G, Mgodi N, Gomez K, Hillier SL, Karim SA; HIV Prevention Trials Network (HPTN) 035 Study Team. HPTN 035 phase II/IIb randomised safety and effectiveness study of the vaginal microbicides BufferGel and 0.5% PRO 2000 for the prevention of sexually transmitted infections in women. Sex Transm Infect. 2014 Aug;90(5):363-9. doi: 10.1136/sextrans-2014-051537. Epub 2014 Jun 4.

Richardson BA, Kelly C, Ramjee G, Fleming T, Makanani B, Roberts S, Musara P, Mkandawire N, Moench T, Coletti A, Soto-Torres L, Karim SA; HPTN 035 Study Team. Appropriateness of hydroxyethylcellulose gel as a placebo control in vaginal microbicide trials: a comparison of the two control arms of HPTN 035. J Acquir Immune Defic Syndr. 2013 May 1;63(1):120-5. doi: 10.1097/QAI.0b013e31828607c5.

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Responsible Party:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00074425
Obsolete Identifiers:	NCT00197665
Other Study ID Numbers:	HPTN 035 10065 ( Registry Identifier: DAIDS ES )
First Posted:	December 15, 2003 Key Record Dates
Last Update Posted:	November 8, 2021
Last Verified:	July 2013

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):


HIV Seronegativity Anti-Infective Agents, Local BufferGel	PRO 2000 Vagina Risk Factors

Additional relevant MeSH terms:

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Infections Communicable Diseases HIV Infections Acquired Immunodeficiency Syndrome Disease Attributes Pathologic Processes Blood-Borne Infections Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases	Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases Genital Diseases Urogenital Diseases Immunologic Deficiency Syndromes Immune System Diseases Slow Virus Diseases

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