This study will enrol sexually active, healthy girls aged 16-17 to assess and compare the acceptability and preference for a monthly vaginal ring, bi-monthly injectable contraception or daily dose oral contraception, as proxy for female-controlled ARV-based HIV prevention methods.

The family planning field has shown the importance of providing sufficient choice to meet individuals' changing needs and preferences, and has demonstrated that diversifying delivery modes and dosing options is key to expanding acceptability, use and continuation of contraceptive products. It is not yet clear to what extent choice and preference of modes of delivery will play in the biomedical HIV prevention world. It may be possible that closely associated with the behavioural components of decision to use, uptake, and consistent adherence to prevention products will hinge on a sense that a particular modality is preferred or suits an individual compared to other modalities. Vaginal rings, pills, and injectables have already proven successful in the field of contraception, and therefore may act as surrogates for a range of HIV prevention delivery options that may help to meet the different sexual and reproductive health concerns of women.

A better understanding of the population of adolescents seeking contraception can also help researchers understand the acceptability and feasibility of, as well as adherence to similar modes of delivery for HIV prevention options. By using contraceptive methods as a proxy for available female-controlled HIV prevention delivery methods, such as microbicides and PrEP, we propose to examine in detail, the acceptability of these surrogates to adolescent women; their preferences for mode of delivery; and their adherence barriers and facilitators thereof to such products. Three contraceptive options will be used in this study to emulate the modes of delivery currently being developed for HIV prevention options: (1) monthly vaginal ring (NuvaRing), (2) bi-monthly injectable contraception (Nuristerate) and (3) daily dose oral contraception (Triphasil or Nordette).

This is an open-label, randomized crossover study of 150 sexually active female adolescents (>16 and <18 years) to be recruited, with parental consent, and randomly assigned to a monthly vaginal ring, bi-monthly injectable contraception, or daily dose oral contraception at baseline. After 4 months, participants will crossover, ensuring that all participants use the vaginal ring, and either the oral contraceptive or the bi-monthly injectable contraceptive throughout the course of the study. Participants will be followed for a total of 8 months.

Upon enrollment participants will be randomly assigned in a 1:1:1 ratio to one of three study arms (50 participants per arm):

Arm 1/Group A: Participants will receive an injectable contraceptive once every 8 weeks for a 4 month period.

Arm 2/Group B: Participants will receive the contraceptive intravaginal NuvaRing to be inserted once every 28 days (and removed after 21 days of each 28 day insertion) for a 4 month period

Arm 3/Group C: Participants will be supplied with oral contraceptives and will be required to take a daily tablet for 21 days each month and a placebo tablet for days 22 to 28 each month, for a 4 month period.

After 4 months, participants in Group A and Group C will be assigned to Group B; participants in Group B will be allowed to select either Groups A or Group C, ensuring that all participants use the vaginal ring, and most either the oral contraceptive or the bi-monthly injectable contraceptive.

Participants will attend follow-up visits every 8 weeks throughout the duration of the study. Those participants receiving the oral contraceptive or intravaginal ring will therefore receive 8 weeks' product supply at each visit. At each visit preference / acceptability, sexual behaviour and adherence to study product will be assessed using mainly quantitative measures and general attitudes and experiences of use will be assessed in focus group discussions at the end of the study.

Inclusion Criteria:

1. Age 16 to 17 years (inclusive) at screening, verified per study site SOPs.
2. Able and willing to provide written informed consent and has a guardian who is able and willing to provide written informed consent to be screened for and to take part in the study.
3. Report being sexually active, as defined by penetrative vaginal sex in the last 90 days.
4. (For those potential participants who are currently using a method of hormonal contraception) Reports being within 30 days or less of needing a new supply of contraception; agrees to terminate her current method of contraception; and indicates willingness to use the contraceptive options as assigned in the study.
5. Able and willing to provide adequate locator information, as defined in site SOPs.
6. HIV-uninfected based on testing performed by study staff at screening and enrollment.
7. Has negative pregnancy test at screening and enrollment and per participant report, does not intend to become pregnant in the next 8 months.
8. Agrees to use condoms, in addition to the assigned contraception options, for the duration of the study
9. Does not report intention to relocate out of the study area during the course of the study.
10. At Screening/ Enrollment, participant states a willingness to refrain from inserting any non-study vaginal products or objects into the vagina, including but not limited to, spermicides, diaphragms, contraceptive vaginal rings (besides the Nuvaring), vaginal medications, menstrual cups, cervical caps (or any other vaginal barrier method), douches, lubricants, sex toys (vibrators, dildos, etc) throughout the duration of study participation.
11. Does not have job or other obligations that would require long absences from the area (> 8 weeks at a time).
12. Willing to undergo all study-required procedures.
13. At screening and enrollment, agrees not to participate in other research studies involving medical devices or vaginal products for the next 32 weeks

Exclusion Criteria:

1. Diagnosed with pelvic inflammatory disease, a sexually transmitted infection (STI) or reproductive tract infection (RTI) requiring treatment per current WHO guidelines.

   Note: Otherwise eligible participants diagnosed with STI or RTI during screening will be offered treatment and may be enrolled after completing treatment and all symptoms have resolved.

2. Urine dipstick for protein and glucose, of more than > 1+.

3. Any Grade > 2 toxicity on screening tests and assessments.

4. Has any other condition that, in the opinion of the investigator, would preclude informed consent, make study participation unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving study objectives.

5. Known allergy or sensitivity to the study products.

6. Demonstrates intent or desire to conceive in the next 32 weeks.

7. Appears psychologically unstable, intoxicated or under the influence of alcohol or other drugs at the time of informed consent.

8. Has any other condition that, in the opinion of the investigator/designee, would preclude informed consent, make study participation unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives.

9. Has hormonal contraceptive implant device or an intrauterine contraceptive device.