Early Infant HIV Treatment in Botswana

• Register: ClinicalTrials.gov
• Last refreshed on: 20 November 2023
• Main ID: NCT02369406
• Date of registration: 12/02/2015
• Prospective Registration: Yes
• Primary sponsor: Harvard School of Public Health (HSPH)
• Public title: Early Infant HIV Treatment in Botswana EIT
• Scientific title: BHP Early Infant Treatment Study: A Clinical Treatment Trial of HIV+ Infants in Botswana
• Date of first enrolment: May 4, 2015
• Target sample size: 67
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT02369406
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2/Phase 3

Countries of recruitment

Botswana, United States

Contacts

• Name: Daniel R. Kuritzkes, MD
• Affiliation: Brigham and Women's Hospital

• Name: Mathias Lichterfeld, MD, PhD
• Affiliation: Ragon Institute of MGH, MIT and Harvard

• Name: Roger L Shapiro, MD, MPH
• Affiliation: Harvard School of Public Health (HSPH)

Key inclusion & exclusion 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 240 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.

- Participants will be offered extended follow-up for up to 576 weeks.
However, willingness to participate in optional extended follow-up is not an
inclusion criterion.

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 with confirmation specimen either positive or pending repeat draw
or result**

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 240 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.

- Participants will be offered extended follow-up for up to 576 weeks.
However, willingness to participate in optional extended follow-up is not an
inclusion criterion.

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.



Age minimum: 0 Days
Age maximum: 3 Years
Gender: All

Health Condition(s) or Problem(s) studied

Pediatric AIDS

HIV

Intervention(s)

Drug: Lamivudine

Drug: Kaletra

Drug: Nevirapine

Drug: Zidovudine

Primary Outcome(s)

To determine the proportion of infants who have treatment-limiting adverse events within the first 14 days of treatment [Time Frame: 14 days]

To evaluate virologic and immunologic outcomes of very early ART in infancy [Time Frame: 84-96 weeks]

To determine the proportion of infants in the antepartum cohort with trough drug concentrations below defined therapeutic ranges at 7 and 14 days of treatment (trough concentrations will be evaluated for NVP, ZDV, 3TC) [Time Frame: 14 days]

To determine the proportion of infants who fail to achieve at least a 1.5 log10 copies/mL reduction in HIV-1 RNA by the 14th day of treatment [Time Frame: 14 days]

Secondary Outcome(s)

Median CD4 cell count (cells/mm3) and 95% confidence intervals among participants [Time Frame: up to 576 weeks]

Number of participants with HIV-1 RNA levels <40 copies/mL [Time Frame: up to 576 weeks]

Number of participants with reservoir HIV-1 DNA (in copies/million peripheral blood mononuclear cells, PBMCs) below the level of detection for total virus [Time Frame: up to 576 weeks]

Secondary ID(s)

U01AI114235

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Brigham and Women's Hospital

Ragon Institute of MGH, MIT and Harvard

University of California, San Diego