Ignite Creation Date:
2024-05-05 @ 11:53 AM
Last Modification Date:
2024-10-26 @ 9:15 AM
Study NCT ID:
NCT00167674
Status:
COMPLETED
Last Update Posted:
2012-06-18
First Post:
2005-09-09
Brief Title:
ARVs to Prevent Breastmilk HIVViral and Immune Responses
Sponsor:
University of Washington
Organization:
University of Washington
Study Overview
Official Title:
ARVs to Prevent Breastmilk HIVViral and Immune Responses
Status:
COMPLETED
Status Verified Date:
2012-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Identifying new approaches for preventing breastmilk transmission of HIV-1 is an important research priority To this end clinical trials are underway to evaluate the efficacy of HAART zidovudine lamivudine nevirapine during late pregnancylactation versus zidovudinenevirapine peripartum for prevention of breastmilk HIV-1 transmission It is important to understand the mechanism of effect of these antiretroviral ARV strategies on prevention of breastmilk HIV-1 transmission
This phase II trial will compare HAART vs peripartum zidovudinenevirapine for effect on breastmilk HIV-1 breastmilk HIV-1 specific immune responses and infant HIV-1 specific immune responses
100 pregnant HIV-1 seropositive women in Nairobi with CD4 counts between 200 to 500 who have chosen to breastfeed will receive either ARV regimen Mother-infant pairs will be followed for 1 year after delivery Home visits will be conducted in the first month 10 visits to collect 2-5 mls of breastmilk per visit Mother-infant pairs will be seen in the study clinic with maternal blood and breastmilk and infant blood collected at months 1 3 and 6 for HIV-1 and HIV-1 Elispot assays Breastmilk HIV-1 RNA and DNA levels will be quantified in Dr Overbaughs laboratory in Seattle and Elispot assays conducted in Nairobi with validation of a subset in Dr Rowland-Jones laboratory in Oxford Viral loads decay curves half-life and re-population following ARV cessation will be estimated for each regimen and regimens compared These studies will provide insight into the viral and immune responses to ARV regimens proposed for prevention of breastfeeding HIV-1 transmission and will be important for rational design of future interventions After taking into account estimated loss to follow-up the targeted sample size with outcome data was 80 women 40 in each trial arm estimating undetectable breast milk HIV-1 RNA levels in the HAART arm and median breast milk HIV-1 RNA levels of 30 log10 in women receiving ZDVNVP
This phase II trial will compare HAART vs peripartum zidovudinenevirapine for effect on breastmilk HIV-1 breastmilk HIV-1 specific immune responses and infant HIV-1 specific immune responses
100 pregnant HIV-1 seropositive women in Nairobi with CD4 counts between 200 to 500 who have chosen to breastfeed will receive either ARV regimen Mother-infant pairs will be followed for 1 year after delivery Home visits will be conducted in the first month 10 visits to collect 2-5 mls of breastmilk per visit Mother-infant pairs will be seen in the study clinic with maternal blood and breastmilk and infant blood collected at months 1 3 and 6 for HIV-1 and HIV-1 Elispot assays Breastmilk HIV-1 RNA and DNA levels will be quantified in Dr Overbaughs laboratory in Seattle and Elispot assays conducted in Nairobi with validation of a subset in Dr Rowland-Jones laboratory in Oxford Viral loads decay curves half-life and re-population following ARV cessation will be estimated for each regimen and regimens compared These studies will provide insight into the viral and immune responses to ARV regimens proposed for prevention of breastfeeding HIV-1 transmission and will be important for rational design of future interventions After taking into account estimated loss to follow-up the targeted sample size with outcome data was 80 women 40 in each trial arm estimating undetectable breast milk HIV-1 RNA levels in the HAART arm and median breast milk HIV-1 RNA levels of 30 log10 in women receiving ZDVNVP
Detailed Description:
This will be a randomized study comparing breastfeeding women receiving zidovudinenevirapine from 36 weeks to deliveryfirst 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 multivitaminsiron
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 CD4500 zidovudinenevirapine short-course treatment
2 CD4 200-500 randomization to zidovudinenevirapine 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 CD4200 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
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 multivitaminsiron
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 CD4500 zidovudinenevirapine short-course treatment
2 CD4 200-500 randomization to zidovudinenevirapine 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 CD4200 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| Elizabeth Glaser | OTHER_GRANT | Scientist Award 11-03 | None |