Evaluating the Safety and Tolerability of Antiretroviral Drug Regimens Used as Pre-Exposure Prophylaxis to Prevent HIV Infection in At-Risk Men Who Have Sex With Men and in At-Risk Women

Inclusion Criteria: * For participants in the men's component of the study, born male. For participants in the women's component of the study, born female. * 18 years or older at the time of screening * Willing to provide informed consent for the study * Able to read at a level required for the study components (e.g., computer-assisted self-interview \[CASI\] and short message service \[SMS\], per the judgment of the study investigator) * For men, a history of receptive or insertive anal intercourse without use of condoms with at least one HIV-infected male partner or male partner of unknown HIV serostatus within 90 days of study entry (provided by self-report) * For women, a history of vaginal intercourse or receptive anal intercourse without use of condoms with at least one HIV-infected male partner or male partner of unknown HIV serostatus within 90 days of study entry (provided by self-report) * The following laboratory values must be from specimens obtained within 45 days prior to study enrollment: Nonreactive HIV test results (more information on this criterion can be found in the protocol); hemoglobin (men) greater than 11 g/dL; hemoglobin (women) greater than or equal to 10.5 g/dL; absolute neutrophil count greater than 750 cells/mm\^3; platelet count greater than or equal to 100,000/mm\^3; for men and women, calculated creatinine clearance greater than or equal to 70 mL/minute using the Cockcroft-Gault equation; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than 3 times the upper limit of normal (ULN); total bilirubin less than 2.5 ULN; urine protein less than 2+; and hepatitis B surface antigen (HBsAg) negative. * No alcohol or substance use that, in the opinion of the study investigator, would interfere with the conduct of the study (e.g., provided by self-report or found upon medical history and examination or in available medical records) * No medical condition that, in the opinion of the study investigator, would interfere with the conduct of the study (e.g., provided by self-report or found upon medical history and examination or in available medical records) * Willing to undergo all required study procedures (including sexual assessment by CASI, use of the drug monitoring device, and SMS \[i.e., texting\]) * For all women participants: If of reproductive potential (defined as girls who have reached menarche and pre-menopausal women who have not had a sterilization procedure per self-report (e.g., hysterectomy, bilateral oophorectomy, tubal ligation or salpingectomy), must have a negative serum or urine pregnancy test performed within 48 hours before initiating the protocol-specified medication(s). More information on this criterion can be found in the protocol. * For all women participants: If participating in sexual activity that could lead to pregnancy, must agree to use a form of contraception from the following list during the trial and for 30 days after stopping the study medication: condoms (male or female) with or without a spermicidal agent, diaphragm or cervical cap with spermicide, IUD, or hormone-base contraceptive. Inclusion Criteria for the Tissue Subset: * For men and women participating in the rectal component, willing to abstain from receptive anal intercourse and practices involving insertion of anything in the rectum (drug, enema, penis, or sex toy) for 3 days prior to rectal biopsy and for 7 days post-biopsy, to minimize risk of HIV-1 infection and bleeding complications after each procedure * For women participating in the vaginal component, willing to abstain from vaginal intercourse and practices involving insertion of anything in the vagina (drug, douche, penis, or sex toy) for 3 days prior to cervical biopsy and for 7 days post-biopsy, to minimize risk of HIV-1 infection and bleeding complications after each procedure * For women only, per participant report at screening, usual menstrual cycle with at least 21 days between menses (does not apply to participants who report using a progestin-only method of contraception at screening, e.g., Depo-Provera) * For women, satisfactory Pap results in the 12 calendar months prior to enrollment consistent with Grade 0 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), or satisfactory evaluation with no treatment required of Grade 1 or higher Pap result per American Society for Colposcopy and Cervical Pathology (ASCCP) guidelines in the 12 calendar months prior to enrollment. If there is no document of satisfactory Pap results, the participant should be offered to have the test performed by the site prior to the enrollment visit. If they refuse, they are not eligible. Exclusion Criteria: * One or more reactive HIV test results at screening or enrollment, even if HIV infection is not confirmed * Coenrollment in any other HIV interventional research study (provided by self-report or other available documentation) or prior enrollment and receipt of active arm (i.e., NOT a placebo) of an HIV vaccine trial (provided by available documentation) * Use of ARV therapy (e.g., for post-exposure prophylaxis \[PEP\] or PrEP) in the 90 days prior to study entry * Prior history of a gastrectomy, colostomy, ileostomy, or any other procedure altering the gastrointestinal tract or drug absorption (provided by self-report or obtained from medical history or records) * Receipt of prohibited medications as described in the study drug package inserts or listed in the Study-Specific Populations (SSP) Manual (provided by self-report or obtained from medical history or medical records) * Ongoing intravenous drug use: episodic use or any use in the past 90 days (as assessed by the study investigator) * Known medical history of allergy to soy (soya or soybeans) or peanuts * Weight exceeding 300 pounds (exceeds weight limit of DXA scanners) * For women, pregnancy or currently breastfeeding Exclusion Criteria for the Tissue Subset: For Men and Women: * The following applies to men, and only to women who opt for rectal sampling: Abnormalities of the colorectal mucosa or significant colorectal symptom(s), which in the opinion of the study investigator represent a contraindication to biopsy (including but not limited to presence of any unresolved injury, infectious or inflammatory condition of the local mucosa, and presence of symptomatic external hemorrhoids) * Per participant report at screening, anticipated use and/or unwillingness to abstain from the following medications during the period of study participation: Heparin, including Lovenox®, Warfarin, Plavix® (clopidogrel bisulfate), or any other drugs that are associated with increased risk of bleeding following biopsy procedures in the opinion of the study investigator * The following applies to men, and only to women who opt for rectal sampling: Per participant report at screening, anticipated use and/or unwillingness to abstain from rectally administered medications (including over-the-counter products) for 3 days prior to rectal biopsies and for 7 days after biopsies * Per participant report at screening, anticipated use and/or unwillingness to abstain from the following medications for a period of 10 days before a biopsy procedure: aspirin (daily use of low-dose aspirin \[no more than 81 mg\] is allowed at the discretion of the Investigator of Record) or non-steroidal anti-inflammatory drugs (NSAIDS) * Abnormal laboratory results for coagulation tests that may indicate an increased risk of bleeding (in the opinion of the investigators) * Active untreated syphilis, gonorrhea, or chlamydia infection For Women Only: * Carcinoma in situ of the cervix or invasive cervical cancer. Abnormalities of the vaginal mucosa or significant vaginal symptom(s), which in the opinion of the study investigator represent a contraindication to biopsy (including but not limited to presence of any unresolved injury, and infectious or inflammatory condition of the local mucosa). * Hysterectomy * Per participant report at screening, anticipated use and/or unwillingness to abstain from vaginally administered medications (including over-the-counter products) and vaginal douching for 3 days prior to cervical biopsies and for 7 days after biopsies