Safety Study of a Tenofovir-containing Drug Regimen for the Prevention of Mother-to-child Transmission of HIV and HBV
Information source: Centers for Disease Control and Prevention
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: HIV; Hepatitis B
Intervention: Tenofovir/lamivudine/lopinavir-ritonavir (Drug); Zidovudine/lamivudine/lopinavir-ritonavir (Drug)
Phase: Phase 2
Status: Recruiting
Sponsored by: Centers for Disease Control and Prevention Official(s) and/or principal investigator(s): Athena P Kourtis, MD, PhD, MPH, Principal Investigator, Affiliation: Centers for Disease Control and Prevention, Division of Reproductive Health
Overall contact: Sascha R Ellington, MSPH, Phone: 770-488-6037, Email: sellington@cdc.gov
Summary
The purpose of this study is to compare a regimen of
tenofovir/lamivudine/lopinavir-ritonavir to the WHO-recommended and locally practiced
standard of care regimen consisting of zidovudine/lamivudine/lopinavir-ritonavir during the
second and third trimesters of pregnancy in HIV and HBV co-infected women. This is a phase
II study evaluating the safety of the test regimen in pregnant women and their newborns.
While the study is not powered to examine efficacy, preliminary estimates of transmission of
HIV and HBV to the infants and of the rate of resistance development will be obtained.
Clinical Details
Official title: Maternal Tenofovir-containing Combination Drug Regimen During the Second and Third Trimesters of Pregnancy for Prevention of Mother-to-child Transmission of HIV and HBV in HIV-HBV Co-infected Mothers
Study design: Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention
Primary outcome: Tenofovir Safety for mothers measured by incidence of serious adverse events (SAEs)Dual Energy X-ray absorptiometry (DXA) scans of bone mineral density Maternal Tenofovir Pharmacokinetics Infant Tenofovir Pharmacokinetics Tenofovir safety for infants measured by incidence of serious adverse events (SAEs)
Secondary outcome: HBV viral load in mothersInfant HIV transmission rate Infant HBV transmission rate Prevalence of HIV resistance mutations Prevalence of HBV resistance mutations
Detailed description:
Great progress has been made in preventing mother-to-child transmission (MTCT) of HIV in
resource-rich settings with the use of combination antiretroviral regimens during pregnancy
and peripartum. In the resource-limited world simple inexpensive regimens administered
peripartum, such as single dose nevirapine to mothers and infants, have been effective in
reducing transmission but at the cost of development of resistance. Strategies that will
allow women to preserve their antiretroviral options when they will need therapy for their
own HIV disease and will improve efficacy are urgently needed. Moreover, co-infection with
hepatitis B virus (HBV) is a problem for a substantial proportion of HIV-infected pregnant
women. HIV alters the course of HBV disease by increasing levels of HBV DNA replication and
thus risk of transmission to the newborn. HBV immunization in the infant with the first dose
started soon after birth has decreased the bulk of such transmission, but the risk remains,
particularly for mothers with HBe antigen positivity. Ideally an antiviral regimen
administered during pregnancy with activity against both viruses would minimize transmission
of both HIV and HBV to the infant.
The investigators propose to study a combination of tenofovir/lamivudine/lopinavir-ritonavir
started between 14 and 28 weeks of pregnancy in HIV and HBV co-infected women. This regimen
provides potent antiviral activity for prevention of MTCT. In addition, tenofovir and
lamivudine both have activity against HBV, and could play a role in decreasing transmission
of HBV to the infant. This regimen will be compared to the WHO-recommended and locally
practiced standard of care, consisting of zidovudine/lamivudine/lopinavir-ritonavir, also
starting at 14-28 weeks of pregnancy. This will be a phase II study evaluating the safety of
the test regimen in pregnant women and their newborns, in particular renal, bone mineral
density and hepatic toxicity (including hepatic flares post discontinuation of therapy). The
study will recruit 80 pregnant women of at least 20 years of age in China and follow them
and their infants for 12 months post-delivery. The investigators will recruit from prenatal
clinics in some of the districts most heavily affected by HIV in the Guangxi province in
China. China is selected for this study as it is hyperendemic for hepatitis B and has a
rising HIV epidemic. Although not powered to examine efficacy, preliminary estimates of
transmission of HIV and HBV to the infants and of the rate of resistance development will be
obtained. The study will be done in collaboration with CDC-GAP China and the Chinese
Ministry of Health-National Center for AIDS, which will coordinate recruitment, study visits
and data collection through the local HIV/AIDS coordinators.
Eligibility
Minimum age: 20 Years.
Maximum age: N/A.
Gender(s): Female.
Criteria:
Inclusion Criteria:
- Serologically-confirmed HIV and HBV infection
- Gestational age less than 28 weeks
- Willingness to participate in a clinical trial
- Age 20 years or over on the day of inclusion
- Willingness to return for follow-up visits and to allow infant participation in the
trial
- Intent to remain in the clinic catchment area during the duration of the study
- No serious current complications of pregnancy
- No previous or current use of antiretrovirals including the HIVNET 012 regiment
- Hemoglobin over 8 g/dL
- Blood creatinine clearance greater than or equal to 60 mL/min estimated by the
Cockroft-Gault formula for women
Exclusion Criteria:
- Age less than 20
- Pregnant woman refuses to sign the consent to participate
- Unwillingness to adhere to visit schedule or maintain adherence with medications
- Illnesses so severe as to likely require maternal hospitalization
- Intend to breastfeed
Locations and Contacts
Sascha R Ellington, MSPH, Phone: 770-488-6037, Email: sellington@cdc.gov
Liuzhou MCH Hospital, Liuzhou, Guangxi, China; Recruiting
Guangxi MCH Hospital, Nanning, Guangxi, China; Recruiting Liu Wei, MD, Phone: 0771-2518308 Lili Chen, Professor, Phone: 0771-2826520
Additional Information
Starting date: May 2012
Last updated: February 2, 2015
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