Expanded Use PK of Dapivirine Vaginal Ring

Key Inclusion Criteria:

• Women 18 and ≤ 40 years of age who can give written informed consent
• Available for all visits and consent to follow all procedures scheduled for the trial
• Healthy, based on medical history, vital signs, physical examination, urinalysis, laboratory evaluations for genital infections, and laboratory evaluations for haematology and chemistry
• HIV-negative as determined by an HIV test at the time of enrolment
• On a stable form of contraception, defined as:

• A stable oral contraceptive regimen for at least 2 months prior to enrolment, OR
• Transdermal contraceptive patch for at least 3 months prior to enrolment, OR
• Long-acting progestins for at least 6 months prior to enrolment, OR
• An IUD inserted at least 3 months prior to enrolment, OR
• Have undergone surgical sterilisation at least 3 months prior to enrolment AND willing to use oral contraceptives if necessary to delay menstruation during the vaginal sampling period
• Upon pelvic examination at the time of enrolment, the cervix and vagina appear normal as determined by the Investigator/Physician
• Asymptomatic for genital infections at the time of enrolment
• Willing to refrain from the use of topical vaginal medications, vaginal products or objects
• Documentation of no abnormality on cervical cytology, including grossly bloody smear, within 90 days prior to screening
• Willing to refrain from participation in any other research trial for the duration of this trial
• 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
• Willing to agree to abstain from all the following for a total of 2 days (48 hours) prior to each trial visit:

• Penile-vaginal intercourse
• Oral contact with her genitalia
• Hepatitis B and C negative at the time of enrolment.

Key Exclusion Criteria:

• Currently pregnant or had their last pregnancy outcome within 3 months prior to screening
• Currently breast-feeding
• Currently or within two months of participation in any other clinical research trial involving investigational or marketed products prior to screening
• Untreated symptomatic urogenital infections, e.g. urinary tract or other sexually transmitted infections, or other gynaecological conditions such as vaginal itching, pain, or discharge, within 2 weeks prior to enrolment
• Have a Grade 2 or higher pelvic examination finding, according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events;
• History of significant urogenital or uterine prolapse, undiagnosed vaginal bleeding, urethral obstruction, incontinence or urge incontinence
• Current vulvar or vaginal symptoms/abnormalities that could influence the trial results
• Cervical cytology at screening that requires cryotherapy, biopsy, treatment (other than for infection), or further evaluation
• Symptomatic genital herpes simplex virus (HSV) infection or a history of genital herpetic infection
• Any Grade 2, 3 or 4 haematology, biochemistry or urinalysis laboratory abnormality at baseline (screening) according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events;
• Unexplained, abnormal bleeding per vagina during or following vaginal intercourse, or gynaecologic surgery within 90 days prior to enrolment
• Any history of anaphylaxis or severe allergy resulting in angioedema; or a history of sensitivity/allergy to latex or silicone
• Any serious acute, chronic or progressive or signs of cardiac disease, renal failure, or severe malnutrition
• Have undergone a hysterectomy
• Any condition(s) that, in the opinion of the Investigator, might interfere with adherence to trial requirements or evaluation of the trial objectives.