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Ensayos clínicos

Evaluating Strategies to Reduce Mother-to-Child Transmission of HIV Infection in Resource-Limited Countries

Patrocinador(es) del estudio: National Institute of Allergy and Infectious Diseases (NIAID)
Números de identificación: NCT01061151, 1077BF (PROMISE)
  • Inscripciones abiertas

Propósito del estudio

The purpose of this study is to examine effective methods of preventing the transmission of HIV from mother to child during pregnancy, labor and delivery, and breastfeeding. Study researchers will also evaluate ways to promote positive health outcomes in mothers and their children. This is one part of the four-part PROMISE study and will be conducted at locations in Africa and other parts of the world where women typically receive a short course of highly active antiretroviral therapy (HAART) during pregnancy and breastfeeding is common.

Afección:
Infecciones por el VIH

Detalles del estudio

The incidence of mother-to-child transmission of HIV has improved in recent years in the

United States, Europe, and other resource-advantaged countries. Several factors have

contributed to this improvement, including the administration of HAART during pregnancy,

caesarean section delivery methods, and the use of formula to feed infants, instead of

breastfeeding. However, in resource-limited countries, the incidence of pediatric HIV

infection remains high. Many pregnant women in these countries do not receive an adequate

course of HAART and the majority breastfeed their children. The PROMISE study is evaluating

effective methods of preventing the transmission of HIV from a mother to her baby during

pregnancy, labor and delivery, and breastfeeding, in addition to examining ways to ensure

that both the HIV-infected mother and HIV-exposed baby stay as healthy as possible. This

version of the PROMISE study will be conducted at research sites in east and southern Africa

and other parts of the world where the standard of care for the prevention of

mother-to-child transmission (PMTCT) is a short course HAART regimen and breastfeeding is

common.



This study is divided into four parts:



1. Antepartum Component: This part of the study will compare the safety and effectiveness

of different HAART regimens at preventing the transmission of HIV during pregnancy,

labor, and delivery.



Pregnant HIV-infected women will be randomly assigned to one of the following two

groups:



Arm A: Participants will receive zidovudine (ZDV) + single dose nevirapine (sdNVP) +

emtricitabine-tenofovir disoproxil fumarate (Truvada [TRV]) tail.



Arm B: Participants will receive lamivudine (3TC)-zidovudine (ZDV) + lopinavir

(LPV)-ritonavir (RTV).



If women are co-infected with HIV and hepatitis B (HBV), they may also be assigned to

Arm C: TRV/LPV-RTV.



Participants will take their assigned medications through 1 week postpartum. All

infants will receive NVP once a day through 6 weeks of age, regardless of which study

arm their mother is enrolled in. Should women need HAART or to switch HAART regimens

for their own health they will be moved into Step 2 or Step 3 of this part of the

study.



Women and infants will be monitored during labor and delivery and will attend a study

visit 7 to 12 days after delivery. Study staff will discuss the other three parts of

the study with participants and decide if they are eligible to enroll. While

participants are breastfeeding, follow up visits will occur at Weeks 1, 3, 6, 10, and

14. Thereafter, they will be once a month for infants and every 3 months for women.

Each study visit will include a medical history review, questionnaires, interviews,

physical exam, blood collection, and a breast milk collection.



2. Postpartum Component: This part of the study will compare the safety and effectiveness

of different HAART regimens at preventing HIV infection in infants who are being

breastfed by an HIV-infected mother.



Participants will be randomly assigned to one of two arms:



Arm A: Women will receive LPV-RTV plus TRV from 7 (up to 12) days postpartum through

the end of breastfeeding or through 18 months postpartum, whichever comes first.

Infants will receive NVP once a day through 6 weeks (42 days) of age.



Arm B: Infants will receive NVP once a day from 7 (up to 12) days of age through the

end of breastfeeding or through 18 months postpartum, whichever comes first.



While women are breastfeeding, study visits will occur once a month. After

breastfeeding stops, study visits will occur once every 3 months. Study visits will

include a medical history review, questionnaires, interviews, physical exam, blood

collection, and a breast milk collection. Should women need HAART or to switch HAART

regimens for their own health they will be moved into Step 2 or Step 3 of this part of

the study.



3. Maternal Health Component: This part of the study will examine if women who received a

triple ARV regimen during pregnancy and while breastfeeding have better health outcomes

than women who discontinue a triple ARV regimen.



Participants will include women who were receiving the triple ARV regimen in the

Postpartum Component or receiving the triple ARV regimen in the Antepartum Component

and were ineligible for the Postpartum Component.



Participants will be randomly assigned to one of two study arms:



Arm A: Participants will continue to receive the triple ARV regimen (TRV and LPV-RTV).



Arm B: Participants will discontinue the triple ARV regimen.



Study visits will occur at Weeks 4 and 12, and every 3 months thereafter. Study visits

will include a medical history review, questionnaires, physical exam, and blood

collection. Should women need a triple ARV regimen or to switch triple ARV regimens for

their own health they will be moved into Step 2 or Step 3 of this part of the study.



4. Infant Health Component: This part of the study will examine the safety and

effectiveness of the medication cotrimoxazole (CTX) at preventing common illnesses in

infants who have stopped breastfeeding. Infants in the Postpartum Component of the

study will be eligible to enroll in this part of the study.



Infants will be randomly assigned to one of two study arms:



Arm A: Infants will receive CTX until they are 18 months of age.



Arm B: Infants will receive placebo until they are 18 months of age.



Study visits will occur monthly until the infant is 18 months old, and then at 21 and 24

months of age. Study visits will include a medical history review, questionnaires, physical

exam, and blood collection (every 3 months). Some infants will have stool samples taken at

study entry and at the 18 and 24 month study visits.



The total duration of the four study components is 5 years. Women will remain in the study

for follow up for 2 to 5 years, depending on when they enroll. Infants will remain in the

study through 104 weeks of age.The incidence of mother-to-child transmission of HIV has improved in recent years in the

United States, Europe, and other resource-advantaged countries. Several factors have

contributed to this improvement, including the administration of HAART during pregnancy,

caesarean section delivery methods, and the use of formula to feed infants, instead of

breastfeeding. However, in resource-limited countries, the incidence of pediatric HIV

infection remains high. Many pregnant women in these countries do not receive an adequate

course of HAART and the majority breastfeed their children. The PROMISE study is evaluating

effective methods of preventing the transmission of HIV from a mother to her baby during

pregnancy, labor and delivery, and breastfeeding, in addition to examining ways to ensure

that both the HIV-infected mother and HIV-exposed baby stay as healthy as possible. This

version of the PROMISE study will be conducted at research sites in east and southern Africa

and other parts of the world where the standard of care for the prevention of

mother-to-child transmission (PMTCT) is a short course HAART regimen and breastfeeding is

common.



This study is divided into four parts:



1. Antepartum Component: This part of the study will compare the safety and effectiveness

of different HAART regimens at preventing the transmission of HIV during pregnancy,

labor, and delivery.



Pregnant HIV-infected women will be randomly assigned to one of the following two

groups:



Arm A: Participants will receive zidovudine (ZDV) + single dose nevirapine (sdNVP) +

emtricitabine-tenofovir disoproxil fumarate (Truvada [TRV]) tail.



Arm B: Participants will receive lamivudine (3TC)-zidovudine (ZDV) + lopinavir

(LPV)-ritonavir (RTV).



If women are co-infected with HIV and hepatitis B (HBV), they may also be assigned to

Arm C: TRV/LPV-RTV.



Participants will take their assigned medications through 1 week postpartum. All

infants will receive NVP once a day through 6 weeks of age, regardless of which study

arm their mother is enrolled in. Should women need HAART or to switch HAART regimens

for their own health they will be moved into Step 2 or Step 3 of this part of the

study.



Women and infants will be monitored during labor and delivery and will attend a study

visit 7 to 12 days after delivery. Study staff will discuss the other three parts of

the study with participants and decide if they are eligible to enroll. While

participants are breastfeeding, follow up visits will occur at Weeks 1, 3, 6, 10, and

14. Thereafter, they will be once a month for infants and every 3 months for women.

Each study visit will include a medical history review, questionnaires, interviews,

physical exam, blood collection, and a breast milk collection.



2. Postpartum Component: This part of the study will compare the safety and effectiveness

of different HAART regimens at preventing HIV infection in infants who are being

breastfed by an HIV-infected mother.



Participants will be randomly assigned to one of two arms:



Arm A: Women will receive LPV-RTV plus TRV from 7 (up to 12) days postpartum through

the end of breastfeeding or through 18 months postpartum, whichever comes first.

Infants will receive NVP once a day through 6 weeks (42 days) of age.



Arm B: Infants will receive NVP once a day from 7 (up to 12) days of age through the

end of breastfeeding or through 18 months postpartum, whichever comes first.



While women are breastfeeding, study visits will occur once a month. After

breastfeeding stops, study visits will occur once every 3 months. Study visits will

include a medical history review, questionnaires, interviews, physical exam, blood

collection, and a breast milk collection. Should women need HAART or to switch HAART

regimens for their own health they will be moved into Step 2 or Step 3 of this part of

the study.



3. Maternal Health Component: This part of the study will examine if women who received a

triple ARV regimen during pregnancy and while breastfeeding have better health outcomes

than women who discontinue a triple ARV regimen.



Participants will include women who were receiving the triple ARV regimen in the

Postpartum Component or receiving the triple ARV regimen in the Antepartum Component

and were ineligible for the Postpartum Component.



Participants will be randomly assigned to one of two study arms:



Arm A: Participants will continue to receive the triple ARV regimen (TRV and LPV-RTV).



Arm B: Participants will discontinue the triple ARV regimen.



Study visits will occur at Weeks 4 and 12, and every 3 months thereafter. Study visits

will include a medical history review, questionnaires, physical exam, and blood

collection. Should women need a triple ARV regimen or to switch triple ARV regimens for

their own health they will be moved into Step 2 or Step 3 of this part of the study.



4. Infant Health Component: This part of the study will examine the safety and

effectiveness of the medication cotrimoxazole (CTX) at preventing common illnesses in

infants who have stopped breastfeeding. Infants in the Postpartum Component of the

study will be eligible to enroll in this part of the study.



Infants will be randomly assigned to one of two study arms:



Arm A: Infants will receive CTX until they are 18 months of age.



Arm B: Infants will receive placebo until they are 18 months of age.



Study visits will occur monthly until the infant is 18 months old, and then at 21 and 24

months of age. Study visits will include a medical history review, questionnaires, physical

exam, and blood collection (every 3 months). Some infants will have stool samples taken at

study entry and at the 18 and 24 month study visits.



The total duration of the four study components is 5 years. Women will remain in the study

for follow up for 2 to 5 years, depending on when they enroll. Infants will remain in the

study through 104 weeks of age.

Criterios de inclusión

    Antepartum Component (Step 1):
    • Confirmed HIV infection, documented by the results of testing performed on two
    separate specimens at any time prior to study entry. More information on this criterion can be found in the protocol.
    • Currently pregnant and greater than 14 weeks gestation based on clinical or other
    obstetrical measurements
    • CD4 count higher than 350 cells/mm3 on specimen obtained within 30 days prior to
    study entry
    • Results of HBV screening (HBsAg testing) available from specimen obtained within 30
    days prior to study entry
    • The following laboratory values from a specimen obtained within 30 days prior to
    study entry: 1. Hemoglobin greater than 7.5 g/dL 2. White blood cell count (WBC) greater than 1500 cells/mm3 3. Absolute neutrophil count (ANC) greater than 750 cells/mm3 4. Platelets greater than 50,000 cells/mm3 5. Alanine aminotransferase (ALT) less than or equal to 2.5 times the upper limit of normal (ULN) 6. Estimated creatinine clearance of greater than 60 mL/min using the Cockroft-Gault equation for women
    • Plans to deliver in the study-affiliated clinic or hospital
    • Has no plans to move outside of the study site area during the 24 months following
    delivery
    • Age of legal majority for the respective country and willing and able to provide
    written informed consent
    • Intends to breastfeed
    Antepartum Component

Criterios de exclusión

    (Step 1):
    • Participation in PROMISE for a prior pregnancy
    • Receipt of any antiretroviral therapy (including solely for PMTCT) during current
    pregnancy according to self report or available medical records
    • Requires triple ARV therapy (HAART) for own health based on local standard guidelines
    • World Health Organization (WHO) stage 4 disease
    • Prior receipt of HAART for maternal treatment indications (e.g., CD4 less than 350
    cells/mm3 or clinical indications); however, could have received ARVs for the sole purpose of PMTCT in previous pregnancies (prior PMTCT regimens could have included a triple ARV regimen, ZDV, 3TC-ZDV, and/or sdNVP for PMTCT, as well as use of a short dual nucleoside reverse transcriptase inhibitor [NRTI] "tail" to reduce risk of NVP resistance.)
    • In labor
    • at onset or beyond (will be eligible for the Late Presenter registration)
    • Serious illness (including tuberculosis [TB]) and/or hospitalization until
    participant either completes therapy or is clinically stable on therapy in the opinion of the investigator for at least 30 days prior to study entry
    • Receipt of TB treatment within 30 days prior to study entry
    • Use of prohibited medications within 14 days prior to study entry (refer to the
    protocol for a list of prohibited medications)
    • Fetus detected to have serious congenital malformation (ultrasound not required to
    rule out this condition)
    • History of documented structural or conduction heart defect (specialized assessments
    to rule out this condition are not required, and a heart murmur alone is not considered exclusionary)
    • Known to meet the local standard criteria for treatment of HBV (Note: HBV DNA testing
    or other specialized assessments are not expected to be performed as part of this study. A woman would be excluded only if this information is documented from other sources and she meets the local standard criteria for HBV treatment based on those assessments.)
    • Social or other circumstances which would hinder long-term follow-up, in the opinion
    of the site investigator
    • Currently incarcerated
    Antepartum Component Inclusion Criteria (Step 2):
    • Randomized to Antepartum Step 1 Arm A or to Step 1 Arm B or C but not currently on
    triple ARV (stopped the regimen), including mothers who were not enrolled in the Postpartum Component or Maternal Health Component but remain in follow-up
    • Reached an indication for initiation of triple ARV therapy (HAART) as specified in
    the protocol
    • Willing and able to initiate HAART
    Antepartum Component

Centros de estudio/contactos

Maharashtra

    Byramjee Jeejeebhoy Medical College (BJMC) CRS, Pune, Maharashtra, 411001, India

             Nishi Suryavanshi, PhD, 91-98-23248979, nishi@jhumitpune.com

Inscripciones abiertas

    Blantyre CRS, Blantyre, Maharashtra, 411001, Malawi

             Leslie Degnan, 265-1874885, ldegnan@jhsph.edu

Inscripciones abiertas

    Malawi CRS, Lilongwe, Maharashtra, 411001, Malawi

             Deborah D. Kamwendo, 265-888-251778, kamwendo@email.unc.edu

Inscripciones abiertas

Gauteng

    Shandukani CRS, Johannesburg, Gauteng, 2001, South Africa

             Hermien Gous, PharmD, 27-11-3585503, hgous@wrhi.ac.za

Inscripciones abiertas

    Soweto IMPAACT CRS, Johannesburg, Gauteng, 1864, South Africa

             Nasreen Abrahams, 27-11-9899700, abrahamsn@phru.co.za

Inscripciones abiertas

KwaZulu-Natal

    Durban Paediatric HIV CRS, Durban, KwaZulu-Natal, 4001, South Africa

             Rosie Mngqibisa, MBBS, 27-31-2604669, mngqibisa@ecarefoundation.com

Inscripciones abiertas

    Umlazi CRS, Durban, KwaZulu-Natal, 4001, South Africa

             Vani Chetty, 27-31-2601998, Chettyv1@ukzn.ac.za

Inscripciones abiertas

Western Cape Province

    Family Clinical Research Unit (FAM-CRU) CRS, Tygerberg, Western Cape Province, 7505, South Africa

             Joan Coetzee, 27-21-9384157, joan@sun.ac.za

Inscripciones abiertas

    Kilimanjaro Christian Medical Center CRS, Moshi, Western Cape Province, 7505, Tanzania

             Cynthia A. Asiyo, 255-27-2754086, casiyo@gmail.com

Inscripciones pendientes

    Kilimanjaro Christian Medical Centre (KCMC), Moshi, Western Cape Province, 7505, Tanzania

             Cynthia A. Asiyo, 255-753698484, casiyo@gmail.com

Inscripciones abiertas

Mpigi

    MU-JHU Research Collaboration CRS, Kampala, Mpigi, 7505, Uganda

             Carolyne Onyango, MD, 256-414-541044, carolonyango@mujhu.org

Inscripciones abiertas

    George CRS, Lusaka, Mpigi, 7505, Zambia

             Bethany L. Freeman, 260-966-673134, bethany.freeman@cidrz.org

Inscripciones abiertas

    Seke North CRS, Chitungwiza, Mpigi, 7505, Zimbabwe

             Suzen Maonera, 263-772-268521, suzen@uz-ucsf.co.zw

Inscripciones abiertas

    St. Mary's CRS, Chitungwiza, Mpigi, 7505, Zimbabwe

             Emmie Marote, R.N., B.A., 263-772-268519, emarote@uz-ucsf.co.zw

Inscripciones abiertas

    Parirenyatwa CRS, Harare, Mpigi, 7505, Zimbabwe

             Rachel Mahachi, 263-4-701356, rmahachi@uzcrc.co.zw

Inscripciones abiertas

Actualizado: 25 de marzo del 2014

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