Please select the eligibility criteria that correspond to the clinical trial below.
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
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.


Options:
A: 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
B: Inclusion Criteria:

* Women \> 18 and \< 45 years of age, at screening, who can provide informed consent;
* Available for all visits and consent to follow all procedures scheduled for the trial;
* Self-reported sexually active (defined as an average of at least one penetrative penile-vaginal coital act per month for the last 3 months prior to screening);
* HIV-negative as determined by the HIV algorithm applied at screening and enrolment;
* On a stable form of contraception as defined within section 5.4 and willing to continue on stable contraception for the duration of the clinical trial, unless post-menopausal or surgically sterilised;
* Asymptomatic for genital infections at the time of enrolment (if a woman is diagnosed with any clinically significant curable STI, she must have initiated treatment at least 1 week prior to enrolment and have completed the full course of treatment);
* Willing to provide adequate locator information for trial retention purposes and be reachable per local standard procedures (e.g., by home visit or telephone; or via family or close neighbour contacts); confidentiality to be maintained;
* Willing to refrain from participation in another research trial using drugs, vaccines, medical devices, microbicides or oral pre-exposure prophylaxis investigational drugs for the duration of the IPM 027 trial.

Exclusion Criteria:

* Currently pregnant or last pregnancy within 3 months prior to screening or intends to become pregnant during trial participation;
* Currently breast-feeding;
* Non-therapeutic injection drug use in the 12 months prior to screening;
* Participated in another research trial using drugs, medical devices, microbicides or oral pre-exposure prophylaxis agents within 60 days prior to screening;
* Previously participated or currently participating in any HIV vaccine trial;
* Untreated, clinically significant urogenital infections , e.g., urinary tract, or other sexually transmitted infections, or other gynaecological symptoms within 1 week prior to enrolment;
* Has a Grade 2 or higher pelvic examination finding, according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events; Addendum 1 Female Genital Grading Table for Use in Microbicide Studies;
* History of significant urogenital or uterine prolapse, undiagnosed vaginal bleeding, diagnosed chronic and/or recurrent vulvovaginal candidiasis, urethral obstruction, incontinence or urge incontinence;
* Any gynaecological surgery within 90 days prior to screening;
* Any Grade 1 or higher baseline aspartate aminotransferase (AST), alanine transaminase (ALT), or platelet count, and any Grade 2 or higher baseline haematology, chemistry or urinalysis laboratory value according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events;
* Any history of anaphylaxis or severe allergy resulting in angioedema; or a history of sensitivity/allergy to latex or a silicone elastomer;
* Any history of diabetes mellitus and chronic use of oral corticosteroid therapy; and any uncontrolled serious chronic or progressive disease;
* Cervical cytology at screening that requires cryotherapy, biopsy or treatment (other than for infection). Women with Grade 1 cervical cytology findings can be enrolled upon completion of the initial phase of evaluation if no current treatment is indicated (based on local standard of care for management of abnormal cervical cytology);
* Any condition(s) that, in the opinion of the investigator, might put the participant at risk, or interfere with the trial objectives or the participant's adherence to trial requirements.
C: Inclusion Criteria:

* Confirmed age 18-40 years (inclusive)
* Able and willing to provide written informed consent
* Able and willing to provide adequate locator information for study retention and safety purposes
* Sexually active, defined as having had vaginal intercourse at least twice in the past 30 days prior to screening
* HIV negative on two rapid tests performed by study staff within 30 days of enrolment (see algorithm in Appendix 3).
* No evidence of glycosuria
* No evidence of proteinuria greater than trace\*
* No history of pathological bone fractures
* Have a negative pregnancy test
* Women currently breastfeeding may be enrolled in the study
* Agree to use a study-approved effective non-barrier form of contraception
* Agree to adhere to study visits and procedures
* Willing to use study gel as advised
* Not using or taking any of the following groups of medications:

  * Nephrotoxic agents
  * Drugs that slow renal excretion
  * Immune system modulators
  * Other antiretrovirals

Exclusion Criteria:

* History of adverse reaction to latex.
* Plans any of the following during the study period

  * To travel away from the study site for more than 30 consecutive days.
  * To relocate away from the study site.
  * To become pregnant.
  * To enrol in any other study of an investigational product or behaviour modification related to HIV prevention.
* If in the opinion of the examining clinician, is not sexually active
* Inadequate renal function (serum creatinine greater than 1.5mg/dl and creatinine clearance less than 50ml/min, as estimated using the method of Cockcroft and Gault96 )
* Grade 3 and above ALT and AST at screening or any clinical sign of liver disease ( e.g. ascites, hepatomegaly, jaundice)
* Abnormal serum phosphate levels (Grade 3 and above)
* Has a clinically apparent finding on speculum pelvic examination (observed by study staff) involving deep epithelial disruption. Otherwise eligible participants with speculum pelvic examination findings involving deep epithelial disruption may proceed with enrolment after the findings have resolved and the inclusion/exclusion are met.
* Received previously or receiving an experimental HIV vaccine
* Currently participating in another HIV prevention intervention study or participation in any other clinical trial with a biomedical intervention in the last six months
* Has current STI symptoms and/or other reproductive tract infection requiring treatment, as assessed by study staff. Otherwise eligible participants diagnosed during screening with infection(s) requiring treatment may be enrolled provided that treatment has been completed.
* Any clinical evidence of untreated cervical abnormalities
* 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.
D: Inclusion Criteria:

* Age 18 through 45 years (inclusive) at screening, verified per site SOPs; within this range, sites may restrict the upper age limit per site SOPs, to target women at high risk of HIV infection
* Able and willing to provide written informed consent to be screened for and to take part in the study
* Able and willing to provide adequate locator information, as defined in site SOPs
* HIV-uninfected based on testing performed by study staff at screening and enrollment (per applicable algorithm in Appendix II)
* Per participant report, sexually active, defined as having vaginal intercourse at least once in the 3 months prior to screening
* Using an effective method of contraception at enrollment, and intending to use an effective method for the duration of study participation; effective methods include hormonal methods (except contraceptive ring); intrauterine device (IUD); and sterilization (of participant, as defined in site SOPs)
* At screening and enrollment, agrees not to participate in other research studies involving drugs, medical devices, vaginal products, or vaccines for the duration of study participation -- Note: Tampons may be used for the duration of the trial.

Exclusion Criteria:

* Per participant report at screening:

  * Intends to become pregnant during study participation
  * Plans to relocate away from the study site during study participation
  * Plans to travel away from the study site for more than 8 consecutive weeks during study participation
* Is pregnant

  -- Note: A documented negative pregnancy test performed by study staff is required for inclusion; however a self-reported pregnancy is adequate for exclusion from the study.
* Currently breastfeeding
* Diagnosed with urinary tract infection (UTI)

  -- Note: Otherwise eligible participants diagnosed with UTI during screening are offered treatment and may be enrolled after completing treatment and all symptoms have resolved. If treatment is completed and symptoms have resolved within 28 days of obtaining informed consent for screening, the participant may be enrolled.
* Diagnosed with pelvic inflammatory disease, an STI or reproductive tract infection (RTI) requiring treatment per current WHO guidelines

  -- Note: Otherwise eligible participants diagnosed during screening with pelvic inflammatory disease or STI/RTI requiring treatment per WHO guidelines - other than asymptomatic BV and asymptomatic candidiasis - are offered treatment and may be enrolled after completing treatment and all symptoms have resolved. If treatment is completed and symptoms have resolved within 28 days of obtaining informed consent for screening, the participant may be enrolled. Genital warts requiring treatment also must be treated prior to enrollment. Genital warts requiring therapy are defined as those that cause undue burden or discomfort to the participant, including bulky size, unacceptable appearance, or physical discomfort.
* Has a clinically apparent Grade 2 or higher pelvic exam finding (observed by study staff) as per the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events Version 1.0, December, 2004 (Clarification dated August 2009), Addendum 1-Female Genital Grading Table for Use in Microbicide Studies

  * Note: Cervical bleeding associated with speculum insertion and/or specimen collection judged to be within the range of normal according to the clinical judgment of the Investigator of Record (IoR)/designee is considered expected non-menstrual bleeding and is not exclusionary.
  * Note: Otherwise eligible participants with exclusionary pelvic exam findings may be enrolled/randomized after the findings have improved to a non-exclusionary severity grading or resolved. If improvement to a non-exclusionary grade or resolution is documented within 28 days of providing informed consent for screening, the participant may be enrolled.
* Participant report and/or clinical evidence of any of the following:

  * Known adverse reaction to any of the study products (ever)
  * Known adverse reaction to latex (ever)
  * Chronic vaginal candidiasis
  * Non-therapeutic injection drug use in the 12 months prior to Screening
  * Post-exposure prophylaxis (PEP) for HIV exposure within 6 months prior to enrollment
  * Last pregnancy outcome 90 days or less prior to enrollment
  * Gynecologic or genital procedure (e.g., tubal ligation, dilation and curettage, piercing) 90 days or less prior to enrollment
  * Recent participation in any other research study involving drugs, medical devices, vaginal products, or vaccines, within 60 days of enrollment
  * Participation in the MTN-003, Vaginal and Oral Interventions to Control the Epidemic (VOICE) clinical trial, or any other HIV prevention study using systemic or topical antiretroviral medications, within 12 months of enrollment
  * As determined by the IoR/designee, any significant uncontrolled active or chronic cardiovascular, renal, liver, hematologic, neurologic, gastrointestinal, psychiatric, endocrine, respiratory, immunologic disorder or infectious disease, including active tuberculosis
* Has any of the following laboratory abnormalities at Screening Visit:

  * Aspartate aminotransferase (AST) or alanine transaminase (ALT) Grade 1 or higher as per the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events Version 1.0, December, 2004 (Clarification dated August 2009)
  * Creatinine Grade 2 or higher as per the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events Version 1.0, December, 2004 (Clarification dated August 2009)
  * Hemoglobin Grade 2 or higher as per the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events Version 1.0, December, 2004 (Clarification dated August 2009)
  * Platelet count Grade 1 or higher as per the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events Version 1.0, December, 2004 (Clarification dated August 2009)
  * Pap result Grade 2 or higher according to the Female Genital Grading Table for Use in Microbicide Studies Addendum 1 to the DAIDS Table for Grading Adult and Pediatric Adverse Events, Version 1.0, December 2004 (Clarification dated August 2009)

    * Note: Otherwise eligible participants with an exclusionary test may be re-tested during the screening process.
    * Note: Women with a documented normal result within the 12 months prior to enrollment need not have Pap smear during the screening period. Women with a Grade 1 abnormal Pap smear can be enrolled upon completion of the initial phase of evaluation if no current treatment is indicated (based on local standard of care for management of abnormal cervical cytology). Need for a repeat Pap within 6 months does not preclude enrollment prior to that result becoming available.
* Has any other condition that, in the opinion of the IoR/designee, would preclude informed consent, make study participation unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives

Answer: A