bHIV per 100 PY in the Incidence Phase was calculated using RITA. The RITA incorporated HIV-1 testing results and recency assay testing results to estimate the bHIV. Recency assay testing was performed for participants in the All Screened Set found to have HIV-1 infection at the Incidence Phase Screening Visit as defined below. Participants were considered to have recent HIV-1 infection if the normalized optical density (ODn) was below 1.5 threshold using the Sedia limiting antigen avidity enzyme immunoassay (LAg-EIA) and the HIV-1 RNA (viral load) was > 75 copies/mL of blood.

HIV-1 infection was defined as participants having at least one of the following central lab results at the Incidence Phase screening visit:

• Positive HIV-1/2 differentiation Ab, OR
• Positive HIV-1 ribonucleic acid (RNA) qualitative test, OR
• HIV-1 RNA quantitative test ≥200 copies/mL.

Participants in the All Screened Set were analyzed. The All Screened Set included all participants who were screened for HIV-1 in the Incidence Phase and had a non-missing HIV-1 diagnosis based on HIV test results at Incidence Phase screening. As the outcome measure was assessed prior to Randomized Blinded Phase, the data is reported in one arm consisting of all participants screened in Incidence Phase.

HIV-1 incidence per 100 PY for LEN was calculated as the number of participants who acquired HIV-1 divided by the total of a) for participants not diagnosed with HIV-1, sum of all duration of follow-up time in years, while at risk of HIV-1 infection (where a year is 365.25 days) and b) for participants diagnosed with HIV-1, sum of all duration of follow-up time up to confirmed HIV-1 diagnoses. HIV-1 diagnosis was determined by an HIV adjudication committee who reviewed potential HIV-1 infection events in the randomized participants. The committee, in a blinded, consistent, and unbiased manner, determined whether HIV test results confirmed HIV-1 infection and determined the date of diagnosis for each case, defined as the date of the earliest study visit with evidence of HIV infection considering both prospective HIV testing and back-testing of archived samples. bHIV incidence per 100 PY in All Screened Set was estimated as described in outcome measure#1.

Participants in the LEN group in the Full Analysis Set (FAS) were analyzed. The FAS included all randomized participants who received at least 1 dose of any study drug and had not been diagnosed with HIV-1 on or prior to the first dose date. Per prespecified analysis, HIV-1 incidence for this outcome measure was reported only for participants who received LEN. The HIV-1 incidence was compared with participants in the All Screened Set.

HIV-1 incidence per 100 PY was calculated as the number of participants who acquired HIV-1 divided by the total of a) for participants not diagnosed with HIV-1, sum of all duration of follow-up time in years, while at risk of HIV-1 infection (where a year is 365.25 days) and b) for participants diagnosed with HIV-1, sum of all duration of follow-up time up to confirmed HIV-1 diagnoses. HIV-1 diagnosis was determined by an HIV adjudication committee who reviewed potential HIV-1 infection events in the randomized participants. The committee, in a blinded, consistent, and unbiased manner, determined whether HIV test results confirmed HIV-1 infection and determined the date of diagnosis for each case, defined as the date of the earliest study visit with evidence of HIV infection considering both prospective HIV testing and back-testing of archived samples.

Participants in the Full Analysis Set were analyzed.

A participant was defined as adherent to LEN if they have received all per-protocol administrations of LEN within 28 weeks since the previous administration. The incidence of HIV-1 infection per 100 PY calculation is defined in outcome measure #2.

Participants in the Full Analysis Set who were adherent to LEN were analyzed.

TEAEs were defined as 1 or both of the following:

Any adverse events (AEs) leading to premature discontinuation of study drug, or Any AEs with an onset date on or after the study drug start date and no later than the last exposure date after permanent discontinuation of the study drug.

An AE was any untoward medical occurrence in a clinical study participant administered a study drug that did not necessarily have a causal relationship with the treatment.

Treatment-emergent laboratory abnormalities were defined as values that increased at least 1 toxicity grade from baseline at any post-baseline visit, up to and including the last exposure date for participants who permanently discontinued study drug, or the last available date in the database snapshot for participants who were still on treatment at the time of an analysis.