Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Multi-Centre, Randomised, Double-Blind, Placebo-Controlled Safety and Efficacy Trial of a Dapivirine Vaginal Matrix Ring in Healthy HIV-Negative Women
Brief Summary: This is a double-blind, randomised, placebo-controlled study to assess the safety and efficacy of a silicone elastomer vaginal matrix ring.


Options:
A: 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.
B: Inclusion Criteria:

* 18 to 35 year old women
* HIV negative
* More than one sexual partner in past 3 months
* Average of 3 coital acts per week
* Willing to use vaginal gel and condoms for 12 months

Exclusion Criteria:

* HIV positive
* Pregnant
C: Inclusion Criteria:

* Sexually active

Exclusion Criteria:

* Never been sexually active
* Tested for chlamydia in past 3 months and no new sexual partner since then
* Pregnant
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: D