Trial Information

ARVs to Prevent Breastmilk HIV:Viral and Immune Responses

This will be a randomized study comparing breastfeeding women receiving
zidovudine/nevirapine (from 36 weeks to delivery/first day postpartum) to women receiving
HAART (zidovudine, nevirapine, lamivudine) initiated at 36 weeks and continuing throughout
lactation (recommended for 6 months, breastfeeding cessation prior to HAART cessation).

This a prospective cohort study that will follow HIV-1 seropositive women and their infants
to be conducted in Nairobi. Women with CD4 counts between 200 and 500 will be randomized
to one of the two regimens and compared.

The study procedures are outlined below:

1. Voluntary HIV-1 counseling and testing in a Nairobi City council antenatal clinic:
collection of blood using venipuncture following written informed consent.

2. Enrollment of HIV-1 infected women into new cohort before 32 wks gestation after
written informed consent

3. Routine antenatal care including STD screening and multivitamins/iron

4. Collection of maternal blood and genital specimens at 32 weeks for STD diagnosis, HIV-1
RNA levels, CD4 counts, liver function tests, and complete blood counts.

5. Assignment to treatment depending on CD4 count at 34 weeks:

1. CD4>500 zidovudine/nevirapine short-course treatment

2. CD4 200-500 randomization to zidovudine/nevirapine short-course or 3-drugs
(nevirapine, zidovudine, and 3TC) during pregnancy and breastfeeding, with
recommendation to stop breastfeeding at 6 months and the drugs to stop after
cessation of breastfeeding

3. CD4<200 3-drug regimen (nevirapine, zidovudine, and 3TC) through pregnancy and
breastfeeding continued after cessation of breastfeeding with referral to sites in
Nairobi providing long-term treatment

6. At delivery collection of maternal breastmilk (2-5 mls), cord blood (15 mls), maternal
blood (15 mls), and infant blood (3 mls) for HIV-1 RNA, CD4 counts, HIV-1 specific CTL
assays, complete blood counts, and liver function tests.

7. Collection of maternal breastmilk (2-5 mls) from home visits 3 times per week in the
first 2 weeks, then 2 times per week for the next two weeks. Filter paper blood
specimens will be collected weekly at the home visits.

8. Women receiving the 3-drug regimen who have expressible breastmilk after cessation of
breastfeeding and cessation of drugs will also have home collection (3-5 mls) of
specimens 3-times weekly for 2 weeks after cessation of breastfeeding.

9. Clinic visits at week 2, month 1, 3, and 6 with breastmilk and blood collection.
Higher volumes of breastmilk (~25 -50 mls) will be collected at the clinic visits (w2,
m1, 3, and 6) for HIV-1 RNA, DNA and HIV-1 specific immune assays. Collection of
maternal blood at week 2, month 1, 3, and 6 for HIV-1 RNA levels, CD4 counts, HIV-1 CTL
levels, liver function tests, and complete blood counts.

10. Collection of infant blood at m1, 3, and 6 for HIV-1 and HIV-1 specific immune
responses. Heel prick filter paper assays at months 9 and 12 for HIV-1 DNA PCR assays.