ARVs to Prevent Breastmilk HIV:Viral and Immune Responses

NCT00167674 | Completed Phase 2 Results

• 2 other identifiers: 02-5529-A03Elizabeth Glaser
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 1

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 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.

Conditions

HIV Infections

Keywords

breastmilk; HIV-1; antiretroviral; mother-to-child; transmission

Outcome Measures

Primary Outcomes (1)

• Outcome 1: Serial HIV-1 RNA Levels in Breastmilk.

  Weeks 0, 1, 2, 3 and 4

Study Arms (2)

B

ACTIVE COMPARATOR

Combined short-course Zidovudine/Nevirapine

Drug: Combined short-course zidovudine/nevirapine

A

EXPERIMENTAL

HAART during pregnancy and 6 months postpartum

Drug: HAART

Interventions

Combined short-course zidovudine/nevirapine DRUG

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.

B

HAART DRUG

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.

A

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

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

Sponsors & Collaborators

• University of Washington: lead
• Elizabeth Glaser Pediatric AIDS Foundation: collaborator

Study Sites (1)

University of Nairobi

Nairobi, Kenya

Location

Related Publications (5)

• Chung MH, Kiarie JN, Richardson BA, Lehman DA, Overbaugh J, Njiri F, John-Stewart GC. Independent effects of nevirapine prophylaxis and HIV-1 RNA suppression in breast milk on early perinatal HIV-1 transmission. J Acquir Immune Defic Syndr. 2007 Dec 1;46(4):472-8. doi: 10.1097/qai.0b013e3181594c1c.

  PMID: 18077838 BACKGROUND

• Lehman DA, Chung MH, John-Stewart GC, Richardson BA, Kiarie J, Kinuthia J, Overbaugh J. HIV-1 persists in breast milk cells despite antiretroviral treatment to prevent mother-to-child transmission. AIDS. 2008 Jul 31;22(12):1475-85. doi: 10.1097/QAD.0b013e328302cc11.

  PMID: 18614871 RESULT

• 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.

  PMID: 18839781 RESULT

• Lehman DA, Chung MH, Mabuka JM, John-Stewart GC, Kiarie J, Kinuthia J, Overbaugh J. Lower risk of resistance after short-course HAART compared with zidovudine/single-dose nevirapine used for prevention of HIV-1 mother-to-child transmission. J Acquir Immune Defic Syndr. 2009 Aug 15;51(5):522-9. doi: 10.1097/QAI.0b013e3181aa8a22.

  PMID: 19502990 RESULT

• Slyker JA, Richardson B, Chung MH, Atkinson C, Asbjornsdottir KH, Lehman DA, Boeckh M, Emery V, Kiarie J, John-Stewart G. Maternal Highly Active Antiretroviral Therapy Reduces Vertical Cytomegalovirus Transmission But Does Not Reduce Breast Milk Cytomegalovirus Levels. AIDS Res Hum Retroviruses. 2017 Apr;33(4):332-338. doi: 10.1089/AID.2016.0121. Epub 2016 Dec 6.

  PMID: 27796131 DERIVED

MeSH Terms

Conditions

HIV Infections

Interventions

Nevirapine; Antiretroviral Therapy, Highly Active

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Drug Therapy, Combination; Drug Therapy; Therapeutics

Results Point of Contact

• Title: Grace John-Stewart
• Organization: University of Washington

gjohn@uw.edu

206 948 9357

Study Officials

• Grace C. John-Stewart, MD, PhD

  University of Washington

  PRINCIPAL INVESTIGATOR

• 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 Center

  STUDY DIRECTOR

• John Kinuthia, MBChB, MMed

  University of Nairobi

  STUDY DIRECTOR

• Barbra Richardson, PhD

  University of Washington

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor: School of Medicine

Study Record Dates

• First Submitted: September 9, 2005
• First Posted: September 14, 2005
• Study Start: November 3, 2003
• Primary Completion: March 1, 2005
• Study Completion: April 1, 2006
• Last Updated: January 15, 2025
• Results First Posted: January 15, 2025

Record last verified: 2024-12

Locations

KE (1)