Evaluating the Response to Two Antiretroviral Medication Regimens in HIV-Infected Pregnant Women, Who Begin Antiretroviral Therapy Between 20 and 36 Weeks of Pregnancy, for the Prevention of Mother-to-Child Transmission

While there are many ARV medications and combination regimens available to treat HIV-infected
people, the number of ARV medications studied in HIV-infected pregnant women for the
prevention of mother-to-child transmission remains limited. HIV-infected pregnant women who
begin taking ARV medications late in their pregnancies require effective therapy to reduce
the risk of transmitting HIV to their children. Currently, there is no data available that
compares the effects of non-nucleoside reverse transcriptase inhibitors (NNRTI) and integrase
inhibitors (which are two classes of ARV medications) in pregnant women. The purpose of this
study is to compare the safety, tolerance, and virologic and pharmacologic responses to two
different medication regimens, each including an NNRTI or integrase inhibitor, in pregnant
HIV-infected women who begin ARV therapy late in their pregnancies (i.e., a gestational age
between 20 and 36 weeks).

Participants in this study will be randomly assigned to one of two arms. Participants in Arm
A will receive lamivudine 150 mg/zidovudine 300 mg twice a day and efavirenz 600 mg each
night. Participants in Arm B will receive lamivudine 150 mg/zidovudine 300 mg twice a day and
raltegravir 400 mg twice a day. All participants will receive their assigned medications from
study entry through delivery. Participants will attend study visits at entry and Weeks 1, 2,
and 4; and thereafter, every two weeks until labor and delivery. Study visits will include a
medical history review, physical examination, questionnaires, blood collection, and a vaginal
swab procedure.

While participants are in labor, they will continue to receive their study medications. Some
participants may receive additional or alternate medications according to local standard of
care/guidelines. Participants will have a physical examination and blood collection. After
delivery, some women will continue to receive ARV medications according to the local
guidelines. Participants will attend study visits following the delivery at Weeks 2 to 4, 6,
16, and 24, which will include a medical history review, physical examination, and blood
collection. One study visit will include a vaginal swab procedure. Some participants may have
vaginal specimens stored for future research.

Participants' babies will receive ARV medications as prescribed by the babies' doctors. Study
visits for babies will occur at birth; Weeks 2 to 4, 6, 16, and 24. Each study visit will
include a medical history review, physical examination, and blood collection. Select visits
will include oral and nasopharyngeal swab collection.

Inclusion Criteria:

- Naive to antiretroviral therapy (ART) or have received ART with short course
zidovudine (maximum of 8 weeks) for prevention of mother-to-child transmission in
previous pregnancies

- Willing and able to sign informed consent. Participant must be of an age to provide
legal informed consent as defined by the country in which the participant resides. If
not, the informed consent must be signed by a legal guardian/parent, as per country
guidelines.

- Documentation of HIV-1 infection defined as positive results from two samples
collected at different time points. The same method may be used at both time points.
All samples tested must be whole blood, serum, or plasma. Documentation may be
abstracted from medical records to satisfy these criteria for infection. More
information on this criterion can be found in the protocol.

- Viable pregnancy with gestational age of greater than or equal to 20 weeks to less
than or equal to 36 weeks based upon menstrual history and/or ultrasound. Note: If
menstrual history is unknown or if there is a discrepancy between menstrual history
and ultrasound, determination of gestational age should be based upon best available
methodology at each site.

- Intends to continue pregnancy

- Willingness and intent to deliver at the participating clinical site and to be
followed for the duration of the study at the site or associated outpatient facility

- Willing to comply with the study regimen

- Agrees to use two reliable methods of contraception after delivery if randomized to
the efavirenz arm and is sexually active. A barrier method of contraception (condoms,
diaphragm, or cervical cap) together with another reliable form of contraception must
be used for 4 weeks after stopping efavirenz.

Exclusion Criteria:

- Active labor defined as onset of regular contractions or cervical dilatation greater
than 2 cm

- Use of ART during current pregnancy

- Chemotherapy for active malignancy

- HIV genotypic resistance, as defined in the protocol, to efavirenz or raltegravir or
to NRTIs that will be included in the ART regimen. Note: A lack of HIV drug resistance
test results at the time of enrollment is not exclusionary.

- Serious active opportunistic infection and/or serious bacterial infection including
active tuberculosis (TB) or unstable or severe medical condition within 14 days of
study entry

- Active drug or alcohol use or dependence that, in the opinion of the site
investigator, would interfere with adherence to study requirements

- 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 the outcome of this study

- Vomiting or inability to swallow medications due to an active, pre-existing condition
that prevents adequate swallowing and absorption of study medication

- Known allergy/sensitivity to any study drugs or their formulations or sulfonamide
allergy

- The following laboratory values (within 30 days of enrollment):

1. Hemoglobin greater than or equal to Grade 3

2. Absolute neutrophil count greater than or equal to Grade 2

3. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than
or equal to Grade 2

4. Serum creatinine greater than or equal to Grade 1

5. Platelet count greater than or equal to Grade 3

- Evidence of pre-eclampsia (such as persistent diastolic blood pressure greater than 90
mm Hg)

- Receipt of disallowed medications as described in the protocol