Evaluating the Safety, Tolerability, and Pharmacokinetics of an Investigational, Injectable HIV Medicine (GSK1265744) in HIV-Uninfected Adults

Inclusion Criteria: * Men and women, 18 to 65 years old at the time of screening * Willing to provide informed consent for the study * In the last 12 months (at the time of screening): * No self-reported unprotected anal or vaginal intercourse with someone known to be HIV-infected or of unknown HIV infection status * No self-reported stimulant use (cocaine \[including crack\], methamphetamine, or non-physician-prescribed pharmaceutical-grade stimulants) or inhaled nitrate * No self-reported illicit injection drug use of any kind * No self-reported diagnosis of gonorrhea (GC), chlamydia (CT), incident syphilis, bacterial vaginosis, or trichomoniasis * Not reporting five or more different sexual partners, regardless of use of protection or knowledge of HIV status. More information on this criterion is available in the protocol. * In general good health, as evidenced by the following laboratory values, which must be from specimens obtained within 45 days prior to study enrollment: * Non-reactive/negative HIV test results. More information on this criterion is available in the protocol. * Hemoglobin greater than 11 g/dL * Absolute neutrophil count greater than 750 cells/mm\^3 * Platelet count greater than or equal to 100,000/mm\^3 * 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 or equal to the upper limit of normal (ULN) * Total bilirubin less than or equal to Grade 1 and direct bilirubin less than or equal to ULN * Hepatitis B surface antigen (HBsAg) negative * Hepatitis C Ab negative * Note: Chemistry and hematology parameters which do not meet the inclusion criteria above may be repeated once during screening. * 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). More information on this criterion is available in the protocol. * 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 Additional requirements for all women: * If of reproductive potential (defined as pre-menopausal women who have not had a sterilization procedure per self-report, such as hysterectomy, bilateral oophorectomy, tubal ligation, or salpingectomy), must have a negative urine pregnancy test performed (and results known) within 48 hours before initiating the protocol-specified medication(s) at enrollment. Women are considered menopausal if they have not had a menses for at least 12 months and have a follicle stimulating hormone (FSH) level of greater than 40 IU/L; if FSH testing is not available, they must have had amenorrhea for 24 or more consecutive months. (FSH testing is not a protocol requirement.) * If of reproductive potential and participating in sexual activity that could lead to pregnancy, women must agree to use a form of contraception during the trial and for 30 days after stopping the oral study medication or for 52 weeks after stopping the long acting injectable from the list below: * Intrauterine device (IUD) or intrauterine system (IUS) that meets less than 1% failure rate as stated in the product label * Hormone-based contraceptive Exclusion Criteria: * One or more reactive or positive HIV test result at Screening or Enrollment, even if HIV infection is not confirmed * Any active sexually transmitted infection detected by laboratory testing at Screening * Co-enrollment in any other HIV interventional research study or other concurrent studies which may interfere with this study (as provided by self-report or other available documentation; exceptions may be made if appropriate after consultation with the Clinical Management Committee \[CMC\].) * Past or current participation in HIV vaccine trial. An exception will be made for participants that can provide documentation of receipt of placebo (not active arm). * Use of antiretroviral therapy (ART) (e.g., for non-occupational post-exposure prophylaxis \[PEP\] or PrEP) in the 90 days prior to study entry * Clinically significant cardiovascular disease, including: * ECG (one repeat ECG is allowed during screening; may be performed on the same day) with: * heart rate less than 45 or greater than 100 beats per minute for men, and less than 50 or greater than 100 beats per minute for women * interval from the beginning of the Q wave to the end of the S wave (QRS) duration greater than 120 msec * corrected QT (QTc) interval (B or F) greater than 450 msec * evidence of previous myocardial infarction (pathologic Q waves, S-T segment changes) (except early repolarization) * any clinically significant conduction abnormality (including but not specific to left or right complete bundle branch block, atrioventricular \[AV\] block \[2nd degree (type II) or higher\], Wolf Parkinson White \[WPW\] syndrome) (any question of clinical significance should be referred to the CMC for adjudication) * sinus pauses greater than 3 seconds * any clinically significant arrhythmia that, in the opinion of the Investigator of Record (IoR) or designee, will interfere with the safety for the individual participant (any question of clinical significance should be referred to the CMC for adjudication) * or history of non-sustained (greater than or equal to 3 consecutive ventricular ectopic beats on ECG at screening or entry) or sustained ventricular tachycardia * History/evidence of symptomatic arrhythmia, angina/ischemia, coronary artery bypass grafting (CABG) surgery or percutaneous transluminal coronary angioplasty (PTCA) or any clinically significant cardiac disease * Systolic blood pressure at screening outside the range of 90 to 140 mm Hg or diastolic blood pressure outside the range of 45 to 90 mm Hg (confirmed on repeat measurement) * Underlying skin disease or currently active skin disorder (e.g., infection, inflammation, dermatitis, eczema, psoriasis, urticaria). Mild cases of localized acne or folliculitis or other mild skin condition may not be exclusionary at the discretion of the IoR or designee in consultation with the CMC. * Has a tattoo or other dermatological condition overlying the buttock region that in the opinion of the IoR or designee, in consultation with the CMC, may interfere with interpretation of injection site reactions * Current or chronic history of liver disease (e.g., non-alcoholic or alcoholic steatohepatitis) or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome, asymptomatic gallstones, or cholecystectomy) * Coagulopathy (primary or iatrogenic) that would contraindicate IM injection (concomitant anticoagulant or anti-platelet therapy use should be discussed with the CMC) * Active or planned use of prohibited medications as described in the Investigator's Brochure or listed in the Study Specific Procedures (SSP) Manual (provided by self-report, or obtained from medical history or medical records) * A score of greater than or equal to 8 on the WHO Alcohol Use Disorders Identification Test (AUDIT) at screening. Note: A score of greater than or equal to 8 indicates a medium to high level of problem alcohol use. * For women: pregnant or currently breastfeeding, or intends to become pregnant and/or breastfeed during the study * A history of seizure disorder, by self-report