1. IMPAACT P1078 Eligibility Criteria
Changes from Version 1.0 to Version 2.0

2. * Important Note *
All references to “Version 1.0” in this presentation reflect protocol Version 1.0 and subsequent protocol Letter of Amendment and Clarification Memoranda

3. Note that there were minor changes to the eligibility criteria numbering.
For example, became

4. P1078
Inclusion Criteria

5. P1078 Inclusion Criterion 4.1.1 Version 1.0 Version 2.0
Documentation of HIV-1 infection is defined as positive results from two samples collected at different timepoints. All samples tested must be whole blood, serum or plasma. For studies conducted under an IND, all test methods should be FDA-approved if available. If FDA-approved methods are not available, test methods should be verified according to GCLP and approved by the IMPAACT central laboratory…
Documentation of HIV-1 infection is defined as positive results from two samples collected at different time points. All samples tested must be whole blood, serum, or plasma. As this study is being conducted under an IND, all test methods should be FDA-approved if available. If FDA-approved methods are not available, test methods should be verified according to GCLP and approved by the IMPAACT Laboratory Center...

6. Confirming Maternal HIV Infection
Q: Can study site staff collect Sample #1 and Sample #2 on the same day (if non-study test results are not available or not adequate for Sample #1)?
A: YES, but the two samples MUST be collected in two different tubes and at two different times.

7. P1078 Inclusion Criterion 4.1.1 (cont.)
Version 1.0
Version 2.0
Sample #1 may be tested by non-study public or PEPFAR programs. However, both the result and the assay date must be recorded in subject’s chart. Source documentation {subject’s medical record/chart, Ministry of Health (MOH) registers, laboratory results, etc.} must be available if requested.
Sample #2 must be performed in a CAP/CLIA-approved laboratory (for US sites) or in a laboratory that operates according to GCLP guidelines and participates in appropriate external quality assurance programs (for international sites).
Sample #1 may be tested by non-study public or PEPFAR programs. However, both the result and the assay date must be recorded in participant’s charts. Source documentation (participant’s medical record/chart, Ministry of Health (MOH) registers, laboratory results, etc.) must be available if requested.
Sample #2 must be performed in a CAP/CLIA-approved laboratory or in a laboratory that operates according to GCLP guidelines, participates in appropriate external quality assurance program, and is approved by the IMPAACT Laboratory Center.

8. P1078 Inclusion Criterion 4.1.1 (cont.)
Version 1.0
Version 2.0
Sample #1 may be tested using any of the following:
Two rapid antibody tests from two different manufacturers or based on different principles and epitopes
One EIA OR Western Blot OR immunofluorescence OR chemiluminescence
One HIV DNA PCR
One quantitative HIV RNA PCR (> 5,000 copies/mL)
One qualitative HIV RNA PCR
One HIV culture (prior to August 2009)
One total HIV nucleic acid test
If Sample #1 is positive, then collect and test Sample #2.
Two rapid antibody tests from different manufacturers or based on different principles and epitopes
One quantitative HIV RNA PCR (above the limit of detection)
(HIV culture removed)

9. Confirming Maternal HIV Infection
Adequate documentation for Sample #1 if using non-study tests:
Participant Name/Identifier
Sample/Test Date
Name of Test(s) Performed
Result(s)
If two Rapid Tests were performed at the non-study clinic, you would need the above information for both tests – NOT just the overall result/diagnosis.

10. P1078 Inclusion Criterion 4.1.1 (cont.)
Version 1.0
Version 2.0
Sample #2 may be tested using any of the following:
One EIA confirmed by Western Blot OR immunofluorescence OR chemiluminescence
One HIV DNA PCR
One quantitative HIV RNA PCR (> 5,000 copies/mL)
One qualitative HIV RNA PCR
One total HIV nucleic acid test
Rapid antibody tests are not allowed for Sample #2.
Rapid antibody test. If this option is used in combination with two rapid tests for Sample #1, at least one of the three rapid tests must be FDA-approved and the third rapid test must be from a third manufacturer or based on a third principle or epitope.
One EIA OR Western Blot OR immunofluorescence OR chemiluminescence
One quantitative HIV RNA PCR (above the limit of detection)
(removed)

11. Example #1
A potential participant comes from the ANC clinic with this information recorded on a result slip or in her health passport book:
Khayelitsha Clinic
Participant Name: Margaret Bamba
MR#
Sample/Test Date: 17 June 2015
Result: Positive
Question: Does this information meet the requirements for adequate documentation for Sample #1?
Answer: NO!

12. Example #2
A potential participant comes from the ANC clinic with this information recorded on a result slip or in her health passport book:
Khayelitsha Clinic
Participant Name: Ruth Bakonjo
MR#
Sample/Test Date: 15 June 2015
Determine Result: Positive
Unigold Result: Positive
Question: Does this information meet the requirements for adequate documentation for Sample #1?
Answer: YES!

13. P1078 Inclusion Criteria 4.1.2 – 4.1.4 Version 1.0 Version 2.0
4.1.2 Documented HIV treatment, according to WHO guidelines, for PMTCT and standard of care for HIV infection
4.1.3 Pregnant females age ≥ 18 years
4.1.4 Pregnant females between ≥ 13 and < 18 years who are able and willing to provide signed informed consent under local law, or pregnant females unable to consent under local law whose parents/legal guardians provide consent or “minimum age of consent according to locally applicable laws or regulations.”
No change

14. P1078 Inclusion Criteria 4.1.5 and 4.1.6
Version 1.0
Version 2.0
4.1.5 Pregancy gestational age confirmed by best available method at site to be ≥ 14 weeks through ≤ 34 weeks (34 weeks, 6 days)
4.1.6 Weight ≥ 35 kg at screening
No change

15. P1078 Inclusion Criterion 4.1.7 Version 1.0 Version 2.0
4.1.7 The following laboratory values obtained within 30 days prior to study entry:
ANC > 750 cells/mm3
Hemoglobin > 7.5 g/dL
Platelet count > 50,000 cells/mm3
AST (SGOT), ALT (SGPT), and total bilirubin < 1.25 times upper limit of normal (ULN)
AST (SGOT), ALT (SGPT), and total bilirubin < 1.25 times upper limit of normal (ULN) (Note: If participant is taking atazanavir, direct bilirubin may be used to determine eligibility.)

16. P1078 Inclusion Criterion 4.1.8 Version 1.0 Version 2.0
4.1.8 Intent to remain in current geographical area of residence for the duration of the study
No change

17. P1078
Exclusion Criteria

18. P1078 Exclusion Criterion 4.2.1 Version 1.0 Version 2.0
Any woman with a positive TB symptom screen per WHO guidelines, including any one or more of the following: any cough, fever, self- reported weight loss, or night sweats.
Note: If a potential subject is found to be negative for TB upon further testing, the subject may be re- screened for the study.
Any woman with a positive TB symptom screen per WHO guidelines, including any one or more of the following: any cough, fever, self- reported weight loss, or night sweats
(Note: If a potential participant is found to be negative for TB upon further testing, the participant may be re-screened for the study.)

19. P1078 Exclusion Criterion 4.2.2 Version 1.0 Version 2.0
Any positive AFB smear or culture from any- body site within the past 12 weeks, or chest radiograph (x-ray) with findings suggestive of active TB, or clinician suspects active TB
Any positive AFB smear, Xpert, or any other rapid TB screening test or culture from any site within the past 12 weeks, or chest radiograph (x- ray) with findings suggestive of active TB, or clinician suspects active TB

20. P1078 Exclusion Criteria 4.2.3 – 4.2.5 Version 1.0 Version 2.0
4.2.3 Known exposure to AFB smear- positive active TB case within past 12 weeks prior to study entry
4.2.4 Reported INH exposure (> 30 days) in the past year prior to study entry
4.2.5 Receipt of any TB or atypical mycobacteria therapy for > 30 days in the past year
No change

21. P1078 Exclusion Criterion 4.2.6 Version 1.0 Version 2.0
Evidence of acute hepatitis, such as jaundice, dark urine (not concentrated urine), and/or acholic stools sustained for > 3 days within 90 days prior to entry.
Note: A positive HBsAg and/or HCV do not exclude a subject from participating in the study.
Evidence of acute hepatitis, such as jaundice, dark urine (not concentrated urine), and/or acholic stools sustained for > 3 days within 90 days prior to entry
(Note: A positive HBsAg and/or HCV does not exclude a participant from joining the study.)

22. P1078 Exclusion Criteria 4.2.7 – 4.2.8 Version 1.0 Version 2.0
4.2.7 ≥ Grade 1 peripheral neuropathy.
Note: Grading of peripheral neuropathy will be determined using the Brief Neuropathy Screen (BPNS), discussed in section 6.13, Appendix II and the P1078 MOP.
4.2.8 History of acute systemic adverse reaction or allergy to INH
No change

23. P1078 Exclusion Criteria 4.2.9 – 4.2.10 Version 1.0 Version 2.0
4.2.9 Known current heavy alcohol use (> 2 drinks per week) or alcohol exposure that, in the investigator’s opinion, would compromise participation and the outcome of this study
Presence of new AIDS-defining opportunistic infection that has been treated less than 30 days prior to study entry
No change

24. P1078 Exclusion Criteria 4.2.11 – 4.2.12 Version 1.0 Version 2.0
Receipt of an investigational agent or chemotherapy for active malignancy within 30 days prior to study entry
Any clinically significant diseases (other than HIV infection) or clinically significant findings during the screening medical history or physical examination that, in the investigator’s opinion, would compromise participation and the outcome of this study
No change