Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase III, Multi-Centre, Randomized Controlled Trial to Assess the Safety and Effectiveness of the Vaginal Microbicide 1% Tenofovir Gel in the Prevention of Human Immunodeficiency Virus Type 1 Infection in Women, and to Examine Effects of the Microbicide on the Incidence of Herpes Simplex Virus Type 2 Infection
Brief Summary: The purpose of the study is to assess the safety and effectiveness of intravaginal 1% tenofovir gel in preventing Human Immunodeficiency Virus (HIV-1) infection and Herpes Simplex Virus (HSV-2) infection in sexually active women.


Options:
A: 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.
B: Inclusion Criteria:

* Willing and able to give informed consent
* At least 18 years old and not more than 35 years old
* Average of three vaginal coital acts per week with a male partner
* More than one male sexual partner in the last 3 months
* Willing to use study product as directed
* Willing to adhere to follow-up schedule
* Willing to participate in the study for 12 months
* Willing to report self-medication during study participation
* Willing to give urine for pregnancy testing; self-administered vaginal swabs for GC/CT testing; OMT for HIV monthly; finger prick for HIV confirmation if required; and blood draw for syphilis and HIV at baseline, and for HIV at the final visit
* Willing to not use a spermicide, other vaginal contraceptive, or vaginal lubricant during the study
* At least 3 months since end of the last pregnancy

Exclusion Criteria:

* History of adverse reactions to the study products, including latex
* Pregnant or desire a pregnancy during the 12 months of participation
* Injection drug user
* Gynecological abnormality that may have an impact on the safety and/or response to the study gel according to the investigator
* HIV positive as diagnosed by OraQuick® rapid test
* Participation in any other microbicide research
* Discontinued from the CS study previously
* Any condition (social or medical) which, in the opinion of the investigator, would make study participation unsafe or complicate data interpretation
C: 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
D: Inclusion Criteria:

* Age 18-40 years (inclusive)
* Able and willing to provide written informed consent to be screened for, and to enrol in, the study.
* Able and willing to provide adequate locator information for study retention purposes.
* Sexually active, defined as having had vaginal intercourse at least twice in the past 30 days prior to screening.
* HIV negative on testing performed by study staff within 30 days of enrolment.
* Have a negative pregnancy test which was performed by study staff within 21 days of enrolment
* Agree to use a non-barrier form of contraceptive
* Agree to adhere to study visits and procedures

Exclusion Criteria:

* History of adverse reaction to latex.
* Plans any of the following during the next 16 to 30 months (depending the anticipated date of study completion):

  * 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.
* Has a creatinine clearance \<50ml/min, as estimated using the method of Cockcroft and Gault(33).
* Has active Hepatitis B infection (since January 2009)
* Has a clinically apparent pelvic examination finding (observed by study staff) involving deep epithelial disruption. Otherwise eligible participants with pelvic examination findings involving deep epithelial disruption may proceed with enrolment after the findings have resolved and the inclusion/exclusion are met.
* Has in the past year participated in any research related to any vaginally applied product/s.
* 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 commenced.
* 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.

Answer: A