ARVs to Prevent Breastmilk HIV:Viral and Immune Responses - Full Text View

Sponsors and Collaborators:	University of Washington Elizabeth Glaser Pediatric AIDS Foundation
Information provided by:	University of Washington
ClinicalTrials.gov Identifier:	NCT00167674

Purpose

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 pregnancy/lactation versus zidovudine/nevirapine 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 zidovudine/nevirapine 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. Overbaugh's 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 3.0 log10 in women receiving ZDV/NVP.

Condition	Intervention	Phase
HIV Infections	Drug: Combined short-course zidovudine/nevirapine Drug: HAART	Phase II

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study
Official Title:	ARVs to Prevent Breastmilk HIV:Viral and Immune Responses

Resource links provided by NLM:

MedlinePlus related topics: AIDS

Drug Information available for: Zidovudine Nevirapine

U.S. FDA Resources

Further study details as provided by University of Washington:

Primary Outcome Measures:

Outcome 1: Serial HIV-1 RNA and DNA levels in breastmilk. [ Time Frame: 1 month to 6 months ] [ Designated as safety issue: No ]
Outcome 2: Infant HIV-1 specific cellular responses during the first 6 months in uninfected and infected infants. [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Breastmilk HIV-1 specific CTLs [ Time Frame: 1 to 6 months ] [ Designated as safety issue: No ]

Enrollment:	58
Study Start Date:	May 2003
Study Completion Date:	April 2006
Primary Completion Date:	March 2005 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
B: Active Comparator Combined short-course Zidovudine/Nevirapine	Drug: Combined short-course zidovudine/nevirapine 300 mg of ZDV was given twice daily from 34 weeks gestation until labor then every 3 hours until delivery; 200 mg of NVP was given as a single oral dose at the onset of labor; and a single 2 mg/kg (6 mg if birthweight > 2.5 kg) oral dose of NVP suspension was administered to the infant within 72 hours of delivery.
A: Experimental HAART during pregnancy and 6 months postpartum	Drug: HAART 300 mg of zidovudine (ZDV), 150 mg of lamivudine, and 200 mg nevirapine (NVP) was given twice daily from 34 weeks gestation until six months after delivery.

Detailed Description:

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:

Voluntary HIV-1 counseling and testing in a Nairobi City council antenatal clinic: collection of blood using venipuncture following written informed consent.
Enrollment of HIV-1 infected women into new cohort before 32 wks gestation after written informed consent
Routine antenatal care including STD screening and multivitamins/iron
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.
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
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.
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.
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.
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.
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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

The subject population is recruited from Mathare North Clinic in Nairobi, Kenya where voluntary HIV-1 counseling and testing is offered to pregnant women
Pregnant women who test positive for HIV-1 antibody are eligible for the study if they are over 18 years of age
At less than 32 weeks' gestation
Have never previously been exposed to antiretroviral medications
Agree to serial maternal blood
Breast milk
Infant blood draws
Plan to live in Nairobi for at least a year after delivery.

Exclusion Criteria:

CD4 >500 or <200
Not planning to live in Nairobi after delivery
Not planning to breastfeed.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00167674

Locations

Kenya
University of Nairobi
Nairobi, Kenya

Sponsors and Collaborators

University of Washington

Elizabeth Glaser Pediatric AIDS Foundation

Investigators

Principal Investigator:	Grace C. John-Stewart, MD, PhD	University of Washington
Study Director:	Carey Farquhar, MD, MPH	University of Washington
Study Director:	Dorothy Mbori-Ngacha, MBChB,MPH	University of Nairobi
Study Director:	Ruth Nduati, MBChB,MPH	University of Nairobi
Study Director:	James Kiarie, MBChB, MPH	University of Nairobi
Study Director:	Michael Chung, MD, MPH	University of Washington
Study Director:	Julie Overbaugh, PhD	Fred Hutchinson Cancer Research Center
Study Director:	John Kinuthia, MBChB, MMed	University of Nairobi
Study Director:	Barbra Richardson, PhD	University of Washington

More Information

No publications provided by University of Washington

Additional publications automatically indexed to this study by National Clinical Trials Identifier (NCT ID):

Chung MH, Kiarie JN, Richardson BA, Lehman DA, Overbaugh J, Kinuthia J, Njiri F, John-Stewart GC. Highly active antiretroviral therapy versus zidovudine/nevirapine effects on early breast milk HIV type-1 Rna: a phase II randomized clinical trial. Antivir Ther. 2008;13(6):799-807.

Responsible Party:	University of Washington ( Grace John-Stewart )
Study ID Numbers:	02-5529-A03, Glaser Scientist Award #11-03
Study First Received:	September 9, 2005
Last Updated:	March 13, 2008
ClinicalTrials.gov Identifier:	NCT00167674 History of Changes
Health Authority:	United States: Institutional Review Board

Keywords provided by University of Washington:

breastmilk
HIV-1
antiretroviral
mother-to-child
transmission

Study placed in the following topic categories:

Antimetabolites
Sexually Transmitted Diseases, Viral
Anti-HIV Agents
Acquired Immunodeficiency Syndrome
Zidovudine
Lamivudine
Antiviral Agents
Immunologic Deficiency Syndromes

Reverse Transcriptase Inhibitors
Virus Diseases
Nevirapine
Anti-Retroviral Agents
HIV Infections
Sexually Transmitted Diseases
Retroviridae Infections

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Molecular Mechanisms of Pharmacological Action
Zidovudine
Infection
Reverse Transcriptase Inhibitors
Anti-Retroviral Agents
Therapeutic Uses
Retroviridae Infections
Nucleic Acid Synthesis Inhibitors
RNA Virus Infections

Anti-HIV Agents
Immune System Diseases
Acquired Immunodeficiency Syndrome
Enzyme Inhibitors
Antiviral Agents
Immunologic Deficiency Syndromes
Pharmacologic Actions
Virus Diseases
Nevirapine
HIV Infections
Sexually Transmitted Diseases
Lentivirus Infections

ClinicalTrials.gov processed this record on July 06, 2009