Evaluating HIV-1 Neutralization Antibody Breadth in Response to HIV gp120 Protein Vaccine in HIV-uninfected Adults With Quiescent Systemic Lupus Erythematosus

Inclusion Criteria: General and Demographic Criteria * Age of 18 to 50 years * Weight greater than 110 pounds * Meets American College of Rheumatology (ACR) criteria for the classification of SLE with serologic evidence of disease including a positive test for antinuclear antibodies at a titer of 1:640 or greater, or the presence of a positive test for antibodies to double-strand DNA (dsDNA), or the presence of anti-Sm, anti-RNP, or anti-Ro antibodies, as documented by medical records and as assessed by a rheumatologist or designee. * Currently taking hydroxychloroquine for SLE and for at least 6 months prior to enrollment * Access to a participating HIV Vaccine Trials Network (HVTN) clinical research site (CRS) and willingness to be followed for the planned duration of the study * Ability and willingness to provide informed consent * Allows ongoing access to medical records pertaining to their rheumatologic disease * Assessment of understanding: volunteer demonstrates understanding of this study; completes a questionnaire prior to first vaccination with verbal demonstration of understanding of all questionnaire items answered incorrectly * Agrees not to enroll in another study of an investigational research agent before the last required protocol clinic visit HIV-Related Criteria: * Willingness to receive HIV test results * Willingness to discuss HIV infection risks and amenable to HIV risk reduction counseling. * Assessed by the clinic staff as being at "low risk" for HIV infection and committed to maintaining behavior consistent with low risk of HIV exposure through the last required protocol clinic visit (see protocol for more information) Laboratory Inclusion Values Hemogram/Complete blood count (CBC) * Hemoglobin greater than or equal to 11.0 g/dL for volunteers who were assigned female sex at birth, greater than or equal to 12.0 g/dL for volunteers who were assigned male sex at birth. * White blood cell count equal to 2,500 to 12,000 cells/mm\^3 * Total lymphocyte count greater than or equal to 800 cells/mm\^3 * Remaining differential either within institutional normal range or with site physician approval * Platelets equal to 100,000 to 550,000/mm\^3 Chemistry * Chemistry panel: alanine amino transferase (ALT) and aspartate aminotransferase (AST) less than 1.25 times the institutional upper limit of normal; creatinine less than or equal to institutional upper limit of normal. Virology * Negative HIV-1 and -2 blood test: volunteers must have a negative US Food and Drug Administration (FDA)-approved enzyme immunoassay (EIA) within 56 days prior to enrollment. * Negative Hepatitis B surface antigen (HBsAg) within 56 days prior to enrollment * Negative anti-Hepatitis C virus antibodies (anti-HCV), or negative HCV polymerase chain reaction (PCR) if the anti-HCV is positive within 56 days prior to enrollment Urine * Normal urine by urinalysis: * Negative urine glucose, and * Negative or trace urine protein, and * Red blood cell (RBC) levels within institutional normal range, and * No RBC casts Reproductive Status * Volunteers who were assigned female sex at birth: negative serum or urine beta human chorionic gonadotropin (β-HCG) pregnancy test in accordance with local regulatory requirements, performed prior to vaccination on the day of initial vaccination. Persons who are NOT of reproductive potential due to having undergone total hysterectomy or bilateral oophorectomy (verified by medical records), are not required to undergo pregnancy testing. * Reproductive status: A volunteer who was assigned female sex at birth must: * Agree to use effective contraception for sexual activity that could lead to pregnancy from at least 21 days prior to enrollment through the last required protocol clinic visit. Effective contraception is defined as using the following methods: * Condoms (male or female) with or without a spermicide, * Diaphragm or cervical cap with spermicide, * Intrauterine device (IUD), * Hormonal contraception, or * Any other contraceptive method approved by the HVTN 121 Protocol Safety Review Team (PSRT) * Successful vasectomy in any partner assigned male sex at birth (considered successful if a volunteer reports that a male partner has \[1\] documentation of azoospermia by microscopy, or \[2\] a vasectomy more than 2 years ago with no resultant pregnancy despite sexual activity postvasectomy); * Or not be of reproductive potential, such as having reached menopause (no menses for 1 year) or having undergone hysterectomy, bilateral oophorectomy, or tubal ligation; * Or be sexually abstinent. * Volunteers who were assigned female sex at birth must also agree not to seek pregnancy through alternative methods, such as artificial insemination or in vitro fertilization until after the last required protocol clinic visit Exclusion Criteria: General * Blood products received within 120 days before first vaccination * Investigational research agents not used to treat SLE received within 30 days before first vaccination (additional exclusions may apply, see criteria below) * Intent to participate in another study of an investigational research agent or any other study that requires non-HVTN HIV antibody testing during the planned duration of the HVTN 121 study * Pregnant or breastfeeding * Active duty and reserve US military personnel SLE status. The following criteria must be verified by a rheumatologist or designee * Currently with active lupus as defined by a Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) greater than 4 (see protocol for more information). * Documented SLEDAI score of greater than 20 in medical record at any time indicating severe activity, or evidence of moderate disease activity (SELENA-SLEDAI greater than 6) within the last six months, (see protocol for more information). * Has had a condition listed on the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACR DI) or has had an increase in the SLICC/ACR D1 score within the last 12 months other than cataracts, premature ovarian failure or diabetes mellitus with approval of the PSRT http://www.clinexprheumatol.org/article.asp?a=2697 * A history of central nervous system (CNS) disease * Thrombotic event within the past 12 months in association with confirmed antiphospholipid antibody * A history of renal disease (SLE-related renal injury) confirmed by prior biopsy, active urine sediment, or proteinuria * Prednisone dose greater than 10 mg/day for more than 6 months within the past year * Administration of anti-B-cell therapy (rituximab or belimumab) or any investigational research agents used to treat SLE within the preceding 2 years * Administration of cyclophosphamide within the preceding year; or administration of mycophenolate mofetil within the last 6 months; or administration of methotrexate, leflunomide, or azathioprine within the last 3 months * Administration of any investigational immunosuppressant medication within the last year * Administration of other immunosuppressive medications not listed above, with the exception of topical steroids, topical immunosuppressives (eg, cyclosporine, FK506), or ophthalmic immunosuppressives (eg, steroids, cyclosporine), within 6 months before first vaccination, unless approved by the HVTN 121 PSRT Vaccines and other Injections * HIV vaccine(s) received in a prior HIV vaccine trial. For volunteers who have received control/placebo in an HIV vaccine trial, the HVTN 121 PSRT will determine eligibility on a case-by-case basis. * Non-HIV experimental vaccine(s) received within the last 5 years in a prior vaccine trial. Exceptions may be made by the HVTN 121 PSRT for vaccines that have subsequently undergone licensure by the FDA. For volunteers who have received control/placebo in an experimental vaccine trial, the HVTN 121 PSRT will determine eligibility on a case-by-case basis. For volunteers who have received an experimental vaccine(s) greater than 5 years ago, eligibility for enrollment will be determined by the HVTN 121 PSRT on a case-by-case basis. * Vaccines received within 30 days before first study vaccination or scheduled within 30 days after injection (eg, influenza, tetanus, pneumococcal, Hepatitis A or B, measles, mumps, and rubella \[MMR\]; oral polio vaccine \[OPV\]; varicella; yellow fever) * Allergy treatment with antigen injections within 30 days before first vaccination or that are scheduled within 14 days after first vaccination Immune System * Serious adverse reactions to vaccines or to vaccine components (such as yeast protein, amorphous aluminum hydroxyphosphate sulfate, L-histidine, polysorbate 80, sodium borate), including history of anaphylaxis and related symptoms such as hives, respiratory difficulty, angioedema, and/or abdominal pain. (Not excluded from participation: a volunteer who had a nonanaphylactic adverse reaction to pertussis vaccine as a child.) * Immunoglobulin received within 60 days before first vaccination * Immunodeficiency, such as common variable immunodeficiency Clinically significant medical conditions * Ongoing bleeding or hemorrhage (excluding menstruation), or any subject on anticoagulant therapy * Clinically significant medical condition, physical examination findings, clinically significant abnormal laboratory results, or past medical history with clinically significant implications for current health, other than SLE and its manifestations. A clinically significant condition or process includes but is not limited to: * A process that would affect the immune response, * A process that would require medication that affects the immune response, * Any contraindication to repeated injections or blood draws, * A condition that requires active medical intervention or monitoring to avert grave danger to the volunteer's health or well-being during the study period, * A condition or process for which signs or symptoms could be confused with reactions to vaccine, or * Any condition specifically listed among the exclusion criteria below. * Any medical, psychiatric, occupational, or other condition that, in the judgment of the investigator, would interfere with, or serve as a contraindication to, protocol adherence, assessment of safety or reactogenicity, or a volunteer's ability to give informed consent * Psychiatric condition that precludes compliance with the protocol. Specifically excluded are persons with psychoses within the past 3 years, ongoing risk for suicide, or history of suicide attempt or gesture within the past 3 years. * Current anti-tuberculosis (TB) prophylaxis or therapy * Asthma exclusion criteria: Asthma other than mild, well-controlled asthma. (Symptoms of asthma severity as defined in the most recent National Asthma Education and Prevention Program (NAEPP) Expert Panel report). Exclude a volunteer who: * Uses a short-acting rescue inhaler (typically a beta 2 agonist) daily, or * Uses moderate/high dose inhaled corticosteroids, or * In the past year has either of the following: * Greater than 1 exacerbation of symptoms treated with oral/parenteral corticosteroids; * Needed emergency care, urgent care, hospitalization, or intubation for asthma. * Uncontrolled diabetes mellitus, Hb A1C greater than 7.0. (not excluded: history of isolated gestational diabetes.) * Uncontrolled hypertension: * If a person has a history of hypertension, or is found to have elevated blood pressure or hypertension during screening, exclude for blood pressure that is not well controlled. Well-controlled blood pressure is defined as consistently less than or equal to 140 mm Hg systolic and less than or equal to 90 mm Hg diastolic, with only isolated, brief instances of higher readings, which must be less than or equal to 150 mm Hg systolic and less than or equal to 100 mm Hg diastolic. For these volunteers, blood pressure must be less than or equal to 140 mm Hg systolic and less than or equal to 90 mm Hg diastolic at enrollment. * If a person has NOT been found to have elevated blood pressure or hypertension during screening or previously, exclude for systolic blood pressure greater than or equal to 150 mm Hg at enrollment or diastolic blood pressure greater than or equal to 100 mm Hg at enrollment. * Bleeding disorder diagnosed by a doctor (eg, factor deficiency, coagulopathy, or platelet disorder requiring special precautions) * Malignancy (not excluded from participation: Volunteer who has had malignancy excised surgically and who, in the investigator's estimation, has a reasonable assurance of sustained cure, or who is unlikely to experience recurrence of malignancy during the period of the study) * Seizure disorder: History of seizure(s) within past three years. Also exclude if volunteer has used medications in order to prevent or treat seizure(s) at any time within the past 3 years. * Asplenia: any condition resulting in the absence of a functional spleen (not excluded: splenectomy for splenic trauma) * History of hereditary angioedema, acquired angioedema, or idiopathic angioedema.