IMPAACT 1077HS: Examining Benefits of HAART Continuation in Postpartum Women

This randomized strategy trial addressed therapeutic questions for women from regions where
antepartum HAART for PMTCT (for all CD4+ cell counts) and postpartum formula feeding is
standard of care, and who also had both a pre-HAART CD4+ cell count >400 cells/mm^3 and a
screening (on-HAART) CD4+ cell count > 400 cells/mm^3. For these women, the objectives
related to the relative efficacy and safety of continuing HAART (when it is no longer used
for PMTCT) versus discontinuing HAART.

Potential participants were identified/recruited and consented during pregnancy or after
delivery or other pregnancy outcome. Study-specific screening was initiated in the third
trimester or after pregnancy outcome. Women who were screened for the study were counseled to
continue their HAART until they were randomized.

Randomization would occur within 0-42 days after pregnancy outcome. Women who did not carry
their pregnancy to the third trimester but otherwise meet study eligibility criteria could be
enrolled.

Participants were randomized to one of the two study arms:

Arm A: Continuation of HAART Arm B: Discontinuation of HAART and resume HAART when
protocol-specified criteria were met

Participants were to be followed until 84 weeks after the last participant was randomized.

Key evaluations were conducted at Screening, Entry, post entry visits were scheduled to take
place 4 weeks after entry, 12 weeks after entry, and every 12 weeks thereafter. Key
evaluations included physical examinations, clinical assessments, and blood collection.

On 7 July 2015, the study sites received formal communications regarding the results of the
Strategic Timing of Antiretroviral Treatment (START) study and associated changes were
implemented to the 1077HS study in response to these results. All sites were instructed that
all women in the 1077HS study were to be informed of the START study results and that
antiretroviral therapy (ART) was recommended for all women based on the START study results.

Inclusion Criteria:

- Women age ≥ 18 years or who had attained the minimum age of independent consent, as
defined by the local Institutional Review Board (IRB), and were willing and able to
provide written informed consent Additionally, at sites with IRB approval to enroll
younger participants, women age 16-17 years who were willing and able to provide
written assent and whose parent or legal guardian was willing and able to provide
written informed consent

- Confirmed HIV infection, documented by positive results from two samples collected at
different time points prior to study entry, using protocol-specified tests (see
protocol for more details)

- Documentation of hepatitis B surface antibody (HBsAb) status and hepatitis B surface
antigen (HBsAg) status (if antibody was negative) within 12 months prior to study
entry

- Within 0-42 days after pregnancy outcome

- Antiretroviral treatment naïve, defined as < 14 days of one or more antiretroviral
agents, prior to therapy initiated during current pregnancy

- Receipt of at least four weeks of HAART prior to study entry, at least two weeks of
which must have been prior to pregnancy outcome (up to seven consecutive days of
missed therapy is permitted)

- CD4+ cell count ≥ 400 cells/mm^3 on a specimen obtained within 120 days prior to
initiation of HAART for current pregnancy

- CD4+ cell count ≥ 400 cells/mm^3 on a specimen obtained on HAART and within 45 days
prior to study entry

- The following laboratory values on a specimen obtained within 45 days prior to study
entry:

- Absolute neutrophil count ≥ 750/mm^3

- Hemoglobin ≥ 7.0 g/dL

- Platelet count ≥ 50,000/mm^3

- AST (SGOT), ALT (SGPT), and alkaline phosphatase ≤ 2.5 x ULN

- Estimated creatinine clearance of ≥ 60mL/min within 45 days prior to entry using the
Cockcroft-Gault formula

- Intent to remain in current geographical area of residence for the duration of the
study

- Willingness to attend study visits as required by the study

Exclusion Criteria:

- Previous participation in PROMISE (P1077BF - NCT01061151)

- Clinical indication for HAART including any World Health Organization (WHO) Clinical
Stage 3 or 4 condition, prior or current tuberculosis disease (a positive (Purified
protein Derivative) PPD test alone was not considered exclusionary), and/or any other
clinical indication per country-specific treatment guidelines

- Clinically significant illness or condition requiring systemic treatment and/or
hospitalization within 30 days prior to study entry

- Social or other circumstances which, in the opinion of the site investigator, would
hinder long-term follow up

- Use of any prohibited medications within 14 days prior to study entry (refer to the
study MOP for a list of prohibited medications)

- Current compulsory detention (involuntary incarceration) in a correctional facility,
prison, or jail for legal reasons or compulsory detention in a medical facility for
treatment of either a psychiatric or physical (e.g., infectious disease) illness

- Currently breastfeeding or planning to breastfeed

- Current documented conduction heart defect (specialized assessments to rule out this
condition were not required; a heart murmur alone and/or type 1 second-degree
atrioventricular block (also known as Mobitz I or Wenckebach) was not considered
exclusionary)

- Known evidence of HBV DNA levels >2000 IU/mL (approximately 10,000 copies/mL) in the
presence of elevated (grade 1 and higher) ALT (HBV DNA testing was not required for
study screening or enrollment but was considered to determine whether treatment for
HBV was indicated)