The Tatelo Plus Study

Inclusion Criteria, Step 1

• Previously enrolled in the EIT/Tatelo, or Moso Cohort Study

• Receiving prescribed ART for at least 24 weeks prior to study entry as determined bythe site investigator based on participant/parent/guardian report and availablemedical records

• 24 weeks to 12 years of age at enrollment, inclusive

• If entering Step 1a: HIV-1 RNA <40 copies/mL for at least 24 weeks prior to entry,including documented suppression to <40 copies/mL within 30 days of Step 1 entry

• If entering Step 1b: HIV-1 RNA <200 copies/mL for at least 24 weeks prior to entry,including documented suppression to <40 copies/mL within 30 days of Step 1 entry.

• Normal temperature (<37.4°C axillary, or <38°C non-axillary) and no signs orsymptoms of acute illness at entry as determined by the site investigator based onparticipant/parent/guardian report and available medical records

• Normal, grade 1 or grade 2 results for all of the following laboratory tests atscreening, based on testing of specimens collected within 30 days prior to entry andgrading per protocol:

• Hemoglobin

• Absolute neutrophil count

• Platelet count

• Alanine aminotransferase

• Aspartate aminotransferase

• Creatinine

• For female participants who are able to become pregnant (defined as having reachedmenarche and not having undergone surgical sterilization), not pregnant based ontesting performed from a specimen collected within 5 days prior to enrollment).Note: Pregnancy is not expected in Step 1 given the age range of eligibleparticipants.

• Expected to be available for the duration of participation and expected to complywith the visit schedule and other requirements as determined by the siteinvestigator based on participant/parent/guardian report at entry

• Not currently participating in another study of an investigational agent and is notexpected to participate in any such study for the duration of participation, asdetermined by the site investigator based on participant/parent/guardian report atentry. Prior or current participation in the EIT/Tatelo or Moso cohort studies ispermitted.

• Parental/legal guardian is willing and able to provide written permission forchild's participation and, child is willing and able to provide written assent forparticipation if 7- 17 years of age

Inclusion Criteria, Step 2

• At or beyond the Week 24 visit in Step 1

• Susceptible to at least 2 of the 3 bNAbs under study at or prior to Step 1 entry ORNegative EIA and negative qualitative DNA result at last available evaluation inStep 1 in the absence of available susceptibility data

• No confirmed HIV-1 RNA ≥40 copies/mL throughout Step 1 and for at least 24 weeksprior to Step 1 entry

Inclusion Criteria, Step 3

• If entering from Step 1:

1. At or beyond the Week 24 visit in Step 1, with no confirmed HIV-1 RNA ≥40copies/mL throughout Step 1

2. Not eligible for Step 2

3. No confirmed HIV-1 RNA ≥40 copies/mL for at least 96 weeks prior to Step 3entry (or since 24 weeks of age if 96-120 weeks of age)

4. Detection of >80% of intact proviruses in heterochromatin DNA regions (i.e.non-genic DNA, satellite DNA, ZNF genes) from any PBMC sample analyzed byMIP-seq, and no recorded viremia (>40 copies/mL) after this evaluation ORNegative EIA and negative Qualitative HIV DNA result within 12 weeks prior toStep 3 entry

5. Approved for entry by Clinical Management Committee (CMC)

6. Willingness and ability to provide independent written informed consent forparticipation or parental/legal guardian is willing and able to provide writtenpermission for child's participation and, child is willing and able to providewritten assent for participation if 7-17 years of age

• If entering from Step 2:

1. At or beyond the Week 24 visit of Step 2, with HIV-1 RNA <40 copies/mLthroughout Steps 1 and 2

2. No confirmed HIV-1 RNA ≥40 copies/mL for at least 96 weeks prior to Step 3entry (or since 24 weeks of age if 96-120 weeks of age)

3. Negative EIA and negative qualitative DNA result within 12 weeks prior to Step 3 entry OR Detection of >80% of intact proviruses in heterochromatin DNAregions (i.e. non-genic DNA, satellite DNA, ZNF genes) from any PBMC sampleanalyzed by MIP-seq, and no recorded viremia (>40 copies/mL) after thisevaluation entry AND approved for entry by CMC

4. For Moso participants, not currently being breastfed

5. Willingness and ability to provide independent written informed consent forparticipation or parental/legal guardian is willing and able to provide writtenpermission for child's participation and, child is willing and able to providewritten assent for participation if 7-17 years of age

• If entering Step 3 directly upon enrollment:

1. Previously enrolled in the EIT/Tatelo, Moso, or BHP Adolescent Cohort Study

2. 96 weeks to 25 years of age at enrollment, inclusive

3. "Non-encoding" virus: Detection of >80% of intact proviruses in heterochromatinDNA regions (i.e. non-genic DNA, satellite DNA, ZNF genes) from any PBMC sampleanalyzed by MIP-seq, and no recorded viremia (>40 copies/mL) after thisevaluation OR "No intact virus": adolescent (13-25 years) with no intact HIVdetected in at least 20 million PBMCs sampled within the prior 4 years

4. For "non-encoding" virus: Receiving prescribed ART prior to Step 3 entry, withHIV-1 RNA <40 copies/mL for at least 96 weeks prior to entry (or since 24 weeksof age if 96-120 weeks of age), including documented suppression to <40copies/mL within 30 days of Step 3 entry

5. For "no intact virus": Receiving prescribed ART prior to Step 3 entry, withHIV-1 RNA <40 copies/mL for at least 10 years prior to entry, includingdocumented suppression to <40 copies/mL within 30 days of Step 3 entry

6. Approved for entry by CMC

7. For Moso participants, not currently being breastfed

8. For female participants who are able to become pregnant (defined as havingexperienced menarche and not having undergone surgical sterilization), notpregnant based on testing performed from a specimen collected within 5 daysprior to enrollment)

9. For female participants who are able to become pregnant (defined as havingreached menarche and not having undergone surgical sterilization) and reportsexual activity that could lead to pregnancy, willing to use two methods ofcontraception while on study. One of the two methods must be highly effective;highly effective methods include the following:

• Contraceptive intrauterine device or intrauterine system
• Subdermal contraceptive implant
• Progestogen injections
• Combined estrogen and progestogen oral contraceptive pills
• Percutaneous contraceptive patch
• Contraceptive vaginal ring The highly effective method must be initiatedprior to enrollment. The second method must be a barrier method for dualprotection against pregnancy and to avoid transmission of HIV during theATI and other sexually transmitted infections.

10. For female participants who are able to become pregnant, not currentlybreastfeeding an infant, and not intending to breastfeed an infant for theduration of the study, based on participant/parent/guardian report at entry

11. For participants who report sexual activity, willing to receive counseling andto use condoms to avoid transmission of HIV

12. Expected to be available for the duration of participation and expected tocomply with the visit schedule and other requirements as determined by the siteinvestigator based on participant/parent/guardian report at entry

13. Not currently participating in another study of an investigational agent and isnot expected to participate in any such study for the duration ofparticipation, as determined by the site investigator based onparticipant/parent/guardian report at entry. Prior or current participation inthe EIT/Tatelo, Moso, or BHP Adolescent cohort studies is permitted.

14. Willingness and ability to provide independent written informed consent forparticipation or parental/legal guardian is willing and able to provide writtenpermission for child's participation and, child is willing and able to providewritten assent for participation if 7-17 years of age

Inclusion Criteria, Step 4

• Previously entered the study in Step 1 or Step 3. All participants will enter Step 4upon completing a prior study step. Participants ending Step 1a or Step 1b who, forany reason, do not proceed to Step 2 or to Step 3 will be eligible to proceed toStep 4. Participants ending Step 2 who, for any reason, do not proceed to Step 3will be eligible to proceed to Step 4. Participants ending Step 3 for any reasonwill be eligible to proceed to Step 4.

Exclusion Criteria:

• Active tuberculosis (either suspected or proven) or malignancy.

• Hepatitis B surface antigen (HBsAg) positive

• Received within 30 days prior to study entry, or is identified as requiring, any ofthe following:

• Any immunoglobulin-based treatment

• Chronic (more than 14 days) systemic steroid treatment

• Has any other documented or suspected clinically significant medical condition orany other condition that, in the opinion of the site investigator, would makeparticipation in the study unsafe, complicate interpretation of study outcome data,or otherwise interfere with achieving the study objectives.

• For participants entering Step 1 and Step 2: <5 kg or >115kg.

• For participants entering Step 3 directly: Received NNRTI-based ART (includingefavirenz, nevirapine, rilpivirine) within 14 days of Step 3 entry