Please select the eligibility criteria that correspond to the clinical trial below.
Title: Phase 2B Safety and Effectiveness Study of Tenofovir 1% Gel, Tenofovir Disproxil Fumarate Tablet and Emtricitabine/Tenofovir Disoproxil Fumarate Tablet for the Prevention of HIV Infection in Women
Brief Summary: A new approach to HIV prevention currently being studied includes the use of microbicides, substances that kill microbes. Tenofovir disoproxil fumarate (TDF) and emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) are oral, FDA-approved, anti-HIV drugs, and tenofovir gel is an experimental microbicide. The purpose of this study is to determine the safety and effectiveness of daily tenofovir 1% gel compared to a vaginal placebo gel, and the safety and effectiveness of oral TDF and oral FTC/TDF compared to an oral placebo in preventing HIV infection among women at risk for sexually transmitted infections.


Options:
A: Inclusion Criteria:

* Willing to provide adequate locator information
* Sexually active, defined as having vaginal intercourse at least once in the 3 months prior to screening
* Agree to not participate in other research studies involving drugs, medical devices, or vaginal products for duration of study.
* Agree to use effective method of contraception. More information on this criterion can be found in the protocol.

Exclusion Criteria:

* HIV infected
* Known adverse reaction to any of the study products
* Known adverse reaction to latex
* Pathologic bone fracture not related to trauma
* Non-therapeutic injection drug use in the 12 months prior to screening
* Post-exposure prophylaxis for HIV exposure within 6 months prior to enrollment
* Last pregnancy outcome 42 days or less prior to enrollment
* Gynecologic or genital procedure 42 days or less prior to enrollment
* Participation in any other research study involving drugs, medical devices, or vaginal products 30 days or less prior to enrollment
* Currently using spermicide, interferon or interleukin therapy, or certain medications. More information on this criterion can be found in the protocol.
* Any significant uncontrolled active or chronic disease. More information on this criterion can be found in the protocol.
* Certain abnormal laboratory values. More information on this criterion can be found in the protocol.
* Intends to become pregnant in the 24 months after enrollment
* Plans to relocate or travel away from the study site for more than 8 consecutive weeks in the 24 months after enrollment
* Urinary tract infection
* Pelvic inflammatory disease, an STI, or reproductive tract infection requiring treatment
* Grade 2 or higher pelvic exam finding
* Any condition that, in the opinion of the investigator, would interfere with the study
* Pregnant or breastfeeding
B: Inclusion Criteria:

* Normal menstrual history with regular cycles and with a minimum of 21 days between menses
* Low risk for HIV/STI infection. More information on this criterion can be found in the protocol.
* Agree to abstain from vaginal and anal intercourse and to not use vaginal products within 48 hours prior to study entry and for the duration of the study

Exclusion Criteria:

* HIV-infected
* Menopausal
* Currently using hormonal contraception or have used hormonal contraception within 2 months of study entry
* Menstruating at screening or enrollment visits
* Urinary tract infection at screening
* Positive chlamydia, gonorrhea, or trichomonas result at screening
* Abnormal Pap smear
* Clinically detectable genital abnormality. More information on this criterion can be found in the protocol.
* Currently participating in a research study of other vaginal products
* History of intermenstrual bleeding within 3 months prior to study entry
* Previous gynecologic surgery or have received treatment for syphilis, genital herpes, chlamydia, gonorrhea, trichomonas, or genital warts within 6 months prior to study entry
* Received treatment for Candida, bacterial vaginosis, or urinary tract infection within 1 month prior to study entry
* Have douched or used vaginal products, including lubricants, feminine hygiene products, vaginal drying agents, and sex toys within 48 hours prior to study entry
* Vaginal or anal intercourse during the 48 hours prior to study entry
* Oral antibiotics within 7 days of study entry
* Pregnant, less than 6 months postpartum, or breastfeeding
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:

* 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.

Answer: A