Please select the eligibility criteria that correspond to the clinical trial below.
Title: Safety of Acidform Lubricant (Amphora) in Women at Low Risk for HIV-1 Infection
Brief Summary: Topical microbicides, substances that kill microbes, are being studied to prevent sexual transmission of HIV and other disease pathogens. In the future, topical microbicides may be applied vaginally to prevent both acquisition and transmission of HIV and other sexually transmitted infections (STIs). The purpose of this study is to compare the safety of daily applications of Acidform lubricant and HEC gel in healthy women at low risk for HIV infection and assess the effect of a microbicide candidate on the natural immunity women have to STI pathogens.


Options:
A: 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
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:

* 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:

* 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

Answer: D