Please select the eligibility criteria that correspond to the clinical trial below.
Title: Phase 3, Multi-center, Double-blind, Randomized, Placebo-controlled Effectiveness and Safety Study to Assess the Role of Truvada® in Preventing HIV Acquisition in Women
Brief Summary: This Phase III, double-blind, randomized, placebo-controlled trial enrolled HIV-negative women from 4 sites in 3 countries (Kenya, Tanzania, South Africa). The study's purpose was to investigate the safety and effectiveness of a once-daily Truvada® pill (compared with placebo) in preventing HIV among HIV-uninfected women at risk of becoming infected through sexual intercourse.

The study population included HIV-antibody-negative women between the ages of 18-35 who were at risk of HIV acquisition through sexual intercourse. Each participant was randomized to take either a daily single oral tablet of Truvada®, which is a fixed-dose combination of emtricitabine (FTC; 200 mg) and tenofovir disoproxil fumarate (TDF; 300 mg), or an identical placebo.

After enrollment, each participant was followed every four weeks. All participants were followed for an additional eight weeks after study drug was stopped. Incidence rates of HIV infection were compared between the two groups (active drug and placebo) using the intent-to-treat principle.


Options:
A: Inclusion Criteria:

* Male sex (at birth)
* HIV uninfected
* Age having reached the local age of consent
* High risk for HIV infection including any of the following: 1) No condom use during anal intercourse with a male HIV-positive partner or a male partner of unknown HIV status during the last 6 months; (2) anal intercourse with more than 3 male sex partners during the last 6 months; (3) exchange of money, gifts, shelter, or drugs for anal sex with a male partner during the last 6 months; (4) sex with a male partner and STI diagnosis during the last 6 months or at screening, or (5) sexual partner of an HIV-infected man with whom condoms are not consistently used in the last 6 months.
* Able to provide a street address of residence for themselves and one personal contact who would know their whereabouts during the study period
* Healthy enough to work, as indicated by score of 80 or greater on the Karnofsky scale
* Certain laboratory values
* A urine dipstick with a negative or trace result for both glucose and protein within 28 days of enrollment.
* Ability to understand and local language for which an informed consent form has been approved by a local IRB and registered with the study sponsor.

Inclusion Criteria for Open-Label Extension:

* Participated in a randomized, placebo-controlled, PrEP trail
* Has been unblinded
* Has provided informed consent

Exclusion Criteria:

* Previously diagnosed active and serious infections, including tuberculosis infection, osteomyelitis, or infections requiring parenteral antibiotic therapy
* Active clinically significant medical problems including heart disease (e.g., symptoms of ischemia, congestive heart failure, arrhythmia), lung disease (steroid-dependent chronic obstructive pulmonary disease), diabetes requiring hypoglycemic medication, or previously diagnosed cancer expected to require further treatment
* Acute HBV infection at the screening visit or presence of treatment indications for hepatitis B based on local practice standards; or clinical signs of hepatic cirrhosis
* History of pathological bone fractures not related to trauma
* Receiving ongoing therapy with certain HIV/AIDS-related medications or other medications as determined by the investigator
* Definitely or possibly received an anti-HIV vaccine while participating in a blinded clinical trial
* Current alcohol or drug use that, in the opinion of the investigator, may interfere with the study
* Current participation in a clinical trial or cohort study other than sub-studies of this protocol
* Any condition at enrollment that, in the opinion of the investigator, would make participation in the study unsafe or would interfere with the study
* Sites may utilize additional criteria that restrict enrollment to a subset of people who meet the protocol-defined enrollment criteria.

Exclusion Criteria for Open-Label Extension:

- Site leadership believes participant will have difficulty completing requirements
B: Inclusion Criteria for HIV-1 uninfected partner:

* Partner within an HIV-1 discordant heterosexual relationship
* One partner meets study eligibility for HIV-1 uninfected study participant and the other partner meets study eligibility criteria for HIV-1 infected participant
* Plan to remain in the relationship for the duration of the study period
* Adequate renal, hepatic \& hematologic function
* Negative Hepatitis B surface antigen test
* Willing and able to provide written informed consent \& locator information

Exclusion Criteria for HIV-1 uninfected partner:

* Current pregnancy, or planning to become pregnant during the study period
* Currently breastfeeding
* Concurrent enrollment in another HIV-1 vaccine or prevention trial
* Receiving ongoing antiretroviral therapy
* Repeated positive urine dipstick tests for glycosuria or proteinuria
* Active and serious infections
* History of pathological bone fractures not related to trauma

Inclusion Criteria for HIV-1 infected partner:

* Partner within an HIV-1 discordant heterosexual relationship
* One partner meets study eligibility for HIV-1 uninfected study participant and the other partner meets study eligibility criteria for HIV-1 infected participant
* HIV-1 infected based on positive EIA
* No history of any clinical AIDS-defining diagnoses
* Plan to remain in the relationship for the duration of the study period
* Willing and able to provide written informed consent \& locator information

Exclusion Criteria for HIV-1 infected partner:

* Current use of antiretroviral therapy
* Concurrent enrollment in another HIV-1 treatment trial
C: Inclusion Criteria:

* citizen of Botswana 18-39 years old
* sexually active
* HIV uninfected
* Hepatitis B and C uninfected
* Calculated creatinine clearance \>= 60 mL/min
* hemoglobin \>= 8 gm/dL
* ALT and AST \<= 2x ULN
* total bilirubin \<= 1.5 mg/dL
* total serum amylase \<= 1.5x ULN
* Serum phosphorus \>= 2.2 mg/dL
* willing to use hormonal contraception (females)
* living within 1 hours travel of study clinic
* pass comprehension test
* willing and able to give informed consent

Exclusion Criteria:

* 18-20 without parent/guardian consent
* history of significant renal or bone disease
* any chronic illness requiring ongoing prescription medication
* pregnant or breastfeeding
* planning to move away from site in the next year
* participating in another HIV prevention or vaccine safety trial
* any other clinical condition or prior therapy that, in the opinion of the study physician, would make the volunteer unsuitable for the study or unable to comply with the dosing requirements
D: Inclusion Criteria:

1. Willing and able (see criterion 2) to provide written informed consent to be screened for and to participate in the trial
2. Able to answer a percentage of informed consent screening (75%) and enrollment (100%) comprehension quiz questions correctly
3. Between 18-35 years old, inclusive
4. At higher risk of becoming HIV infected
5. Have a final negative result according to the site-specific screening HIV testing algorithm and a final negative result at enrollment according to the study HIV testing algorithm
6. Willing to participate in all aspects of the study and to comply with study procedures, for up to 60 weeks, including:

   * Be randomized
   * Use study product as directed
   * Adhere to follow-up schedule and willing to be contacted by site staff between study visits (by phone and/or in person)
   * Use a study-approved effective non-barrier method of contraception for the duration of the study
   * Take study product, as evidenced by swallowing a vitamin tablet that is similar in size to the study product at enrollment
   * Provide contact information and agrees to some form of contact method throughout the study
7. Not intending to relocate out of the area for the duration of the study participation and does not have a job or other obligations that may require long absences from the area ( \> 1 month at a time)
8. In general good health and have no condition (social or medical) which, in the opinion of the Site Investigator, would make study participation unsafe or complicate data interpretation
9. Not pregnant or breastfeeding, and does not anticipate a desire for pregnancy during the 52 weeks of on-product participation
10. Medically eligible at screening including:

    * Adequate renal function (serum creatinine ≤ upper limit of normal (ULN) of local range and creatinine clearance ≥ 60ml/min estimated by the Cockcroft-Gault Creatinine Clearance Formula
    * Adequate hepatic function (hepatic transaminases ALT and AST \< 2x ULN \[according to local normal ranges\])
    * HBsAg negative
    * Serum phosphorus levels above the lower limit of the local normal range (according to local normal ranges - grade 3 \& 4 hypophosphatemia will be excluded even if within normal local ranges)
11. Not received or receiving an experimental HIV vaccine, participating in another HIV prevention study or participating in any other clinical trial with a biomedical intervention
12. No clinical signs of liver disease (e.g., ascites, spider angiomata, hepatomegaly, jaundice)
13. No definite evidence of glycosuria or proteinuria (i.e., no repeated positive \[ ≥ + 1 \] urine dipstick). If a urine dipstick is positive for either glucose and/or protein at the first test, a second urine sample will be tested.
14. No history of pathological bone fractures
15. No history of adverse reaction to latex
16. Not taking any of the following medications: nephrotoxic agents; aminoglycoside antibiotics (including gentamicin); intravenous (IV) amphotericin B; cidofovir; cisplatin; foscarnet; IV pentamidine; oral or IV vancomycin; oral or IV gancyclovir; other agents with significant nephrotoxic potential; drugs that slow renal excretion; probenecid; immune system modulators; systemic chemotherapeutic agents (i.e. cancer treatment medications); systemic corticosteroids; interleukin-2 (IL-2); immunomodulators; interferon (alpha, beta, or gamma); other antiretrovirals (including nucleoside analogs, non-nucleoside reverse transcriptase inhibitors, protease inhibitors or investigational antiretroviral agents)

Answer: D