Early Infant HIV Treatment in Botswana

• Status: Active, not recruiting
• Trial end date: 2022-05-01
• Target enrollment: 0
• Participant gender: All

Summary

The overall objective of this study is to determine whether very early antiretroviral treatment (ART) initiation in HIV-infected infants limits the seeding of viral reservoirs and maintains immune responses, potentially allowing future periods off ART.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Harvard School of Public Health; Harvard School of Public Health (HSPH)
• Collaborators: Brigham and Women's Hospital; Ragon Institute of MGH, MIT and Harvard; University of California, San Diego
• Treatments: Lamivudine; Lopinavir; Nevirapine; Zidovudine

Criteria

Inclusion Criteria (antepartum infection cohort):

1. Mother/guardian ≥18 years of age and able to provide informed consent

2. Gestational age at birth ≥35 weeks

3. Birth weight ≥2000 grams

4. Age is less than 7 days*

5. HIV-infection identified by testing conducted within 96 hours after birth NOTE:

HIV-infection is defined as DNA PCR positive on at least one specimen, with confirmation specimen either positive or pending**

6. Ability to initiate ART within 7 days after birth

7. Eligible for ART through the Botswana government program

8. Ability to be followed in BHP clinic for up to 192 weeks from enrollment**

9. Blood samples collected and submitted for real-time safety lab evaluations; results may be pending at the time of entry.

• At least half of infants in the antepartum cohort must be < 3 days at enrollment, including 3 of the first 6 infants enrolled.

Inclusion Criteria (peripartum infection cohort):

1. Mother/guardian ≥18 years of age and able to provide informed consent

2. Age is greater than 4 days and less than 57 days

3. HIV-negative within 96 hours after birth NOTE: HIV-negative is defined as HIV-negative by DNA PCR on a single specimen or HIV-negative on 2 separate confirmatory specimens following a re-test of an HIV-positive sample

4. HIV-positive between 96 hours and 56 days after birth NOTE: DNA PCR positive on at least one specimen between 96 hour and 42 days after birth, with confirmation either positive or pending**

5. Ability to initiate ART at enrollment

6. Eligible for ART through the Botswana government program

7. Ability to be followed in BHP clinic for ART for up to 192 weeks after enrollment

8. Blood samples collected and submitted for real-time safety lab evaluations (results may be pending at the time of entry).

• An enrolled infant later determined to be HIV uninfected by confirmatory testing will end participation in the study and this enrollment will not be counted against the total number of enrollments planned.

Inclusion Criteria (control group):

1. Mother/guardian ≥18 years of age and able to provide informed consent

2. 24-36 months of age

3. HIV-infection documented within 365 days after birth

4. ART initiated within the following timeframe based on timing of HIV-infection diagnosis > 30-365 days after birth if HIV-infection diagnosed within 96 hours after birth OR > 57-365 days after birth if infant was HIV-negative based on testing performed within 96 hours after birth (or if unknown HIV status < 96 hours from birth) and then found to be HIV-positive based on testing performed between 96 hours and 365 days after birth.

5. After 6 months of ART, no more than one HIV RNA measurement > 400 copies/mL

Exclusion Criteria (for antepartum and peripartum infection cohort):

1. Hospitalization for life-threatening medical illness

2. Medical condition making it unlikely that the infant will survive to 96 weeks

3. If lab values are available prior to enrollment, the following Division of AIDS 2014 graded results, from samples collected within 7 days prior to entry without subsequent testing, will exclude an infant:

• Grade ≥3 ALT

• Grade ≥3 AST

• Grade ≥4 hemoglobin

Note: Baseline lab values may not be available at the time of ART start. However, as soon as these values are available (occasionally within <24 hours), they will be used to make rapid treatment decisions. Neonates with baseline Grade 4 hemoglobin will be called immediately to have ZDV discontinued if the value is confirmed. Neonates with baseline Grade 3 or 4 ALT or AST will be called immediately to stop either NVP or LPV/r if the value is confirmed. Neonates who remain on ART may remain on study. Neonates who discontinue all ART for pre-ART laboratory abnormalities will not be counted against total enrollments.

Exclusion Criteria (control group):

1) < 85% reported adherence to prescribed doses or interruption of ART for more than 7 consecutive days since its initiation.