This is a Phase 1/2 study to evaluate the safety, tolerability, and pharmacokinetics of two broadly neutralizing monoclonal human antibodies (bNAbs), 3BNC117-LS-J, which targets the CD4 binding site on HIV-1 envelope protein, and 10-1074-LS-J which targets the V3 loop of HIV-1 envelope protein. The hypothesis is that the two antibodies will be safe for healthy HIV-1 uninfected adults when co-administered subcutaneously or intravenously and, after subcutaneous administration in the optimal ratio, each antibody will maintain serum levels >10 µg/ml for at least 3 months in HIV-uninfected participants.

Inclusion Criteria:

• Healthy male and female individuals, as assessed by a medical history, physical exam, and laboratory tests
• At least 18 years of age on the day of screening and have not reached their 46th birthday on the day of the first administration
• Willing to undergo HIV testing, risk reduction counseling and receive HIV test results; committed to maintaining low-risk behavior for the trial duration
• Willing to comply with the requirements of the protocol and available for follow-up for the planned duration of the study
• All male and female participants of reproductive potential who are engaging in sexual activity that could lead to pregnancy must commit to use an effective method of contraception from enrollment until 9 months after the last administration
• Willing to forgo donations of blood, or any other tissues during the study following confirmation of study eligibility and, for those who test HIV-positive due to antibody-induced seropositivity, until the anti-HIV antibody titers become undetectable on HIV tests used in the community

Exclusion Criteria:

• Confirmed HIV infection
• Reported risk for HIV infection within 6 months prior to investigational product administration, as defined by: Unprotected sexual intercourse with a known HIV-infected person, a partner known to be at high risk for HIV infection and/or a casual partner (i.e. no continuing established relationship), engaged in sex work, frequent excessive daily alcohol use or frequent binge drinking or any other use of illicit drugs, history of newly-acquired syphilis, gonorrhea, non-gonococcal urethritis, HSV-2, chlamydia, pelvic inflammatory disease (PID), trichomonas, mucopurulent cervicitis, epididymitis, proctitis, lymphogranuloma venereum, chancroid, or hepatitis B or hepatitis C, three or more sexual partners
• Any clinically significant acute or chronic medical condition that is considered progressive or in the opinion of the investigator makes the participant unsuitable for participation in the study
• Infectious disease diagnosis: Hepatitis B infection as measured by HbsAg and/or PCR, Hepatitis C infection (US: HCV RNA positive, or interferon-alpha treatment for hepatitis C infection in the past year, or interferon-alpha-free treatment for hepatitis C infection completed in the past 6 months; Africa: HCV Ab positive and/or PCR positive), active syphilis (positive RPR confirmed by TPHA)
• Receipt of blood transfusion or blood-derived products within the previous 3 months
• Participation in another clinical trial of an investigational product currently, within the previous 3 months or expected participation during this study (Concurrent participation in an observational trial not requiring blood or tissue sample collection is not an exclusion)
• Psychiatric condition that compromises safety of the participant and 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
• Body mass index (BMI) >40
• Active tuberculosis