HIV Diagnosis and Treatment at Birth for Newborn With High Risk HIV Exposure (DIAVINA)

• ClinicalTrials.gov Identifier: NCT03642704
• Recruitment Status: Completed
• First Posted: August 22, 2018
• Last Update Posted: October 22, 2019
• Sponsor: ANRS, Emerging Infectious Diseases
• Information provided by (Responsible Party): ANRS, Emerging Infectious Diseases

Study Description

Brief Summary:

Principal objective Assess the operational efficacy of a strategy combining early diagnosis and preventive antiretroviral treatment systematically reinforced from the birth* among infants at high risk of infection with HIV** .

• in a maximum of 48 hours after delivery

  • born from HIV infected mothers who received less than 4 weeks of antiretroviral therapy prior delivery and / or HIV infection diagnosed at delivery

Intervention, a combined strategy :

After positive HIV infection screening from mother in the delivery room and put on antiretroviral treatment of mothers with post partum according to national guidelines , newborns benefit :

• Early detection of HIV infection at birth
• Without awaiting the outcome of early detection result, a preventive reinforced antiretroviral treatment (zidovudine, lamivudine, nevirapine or zidovudine, lamivudine if their mother is infected with HIV-2), from birth for 12 weeks.
• Regular HIV screening until the end of breastfeeding or later to 18 months.
• In case of positive results of an HIV test, an antiretroviral treatment with zidovudine, lamivudine, lopinavir, ritonavir whatever serology HIV 1 or 2.

Condition or disease	Intervention/treatment	Phase
Mother to Child HIV Transmission	Drug: Reinforced preventive ARV therapy	Phase 4

Detailed Description:

Objectives Principal objective Assess the operational efficacy of a strategy combining early diagnosis and preventive antiretroviral treatment systematically reinforced from the birth* among infants at high risk of infection with HIV** .

* in a maximum of 48 hours after delivery

**born from HIV infected mothers who received less than 4 weeks of antiretroviral therapy prior delivery and / or HIV infection diagnosed at delivery Secondary objectives

• Measure the cascade management of HIV infected mothers and HIV infected infants
• Measure the tolerance of reinforced preventive antiretroviral treatment
• Describe the rate of mother to child transmission of HIV and its risk factors
• Describe the clinical and immuno-virologic outcomes in mothers, in HIV infected children and in HIV-non-infected children
• Evaluate the acceptability of the strategy by mothers and caregivers.
• Compare the early diagnosis of HIV infection with Abbott and Biocentric HIV RNA tests

Methodology Prospective non-comparative study of mother-child pairs whose mother is HIV-infected and received less than 4 weeks of antiretroviral therapy before birth or whose HIV infection has been diagnosed at birth.

Estimated enrolment: 300 mother-child pairs

Eligibility:

Inclusion criteria:

Mother-child pairs whose mother is HIV-infected and received less than 4 weeks of antiretroviral therapy before delivery or whose HIV infection has been diagnosed at delivery Mother who signed the informed consent form to participate in the study.

non-inclusion criteria: Mother treated with antiretrovirals during the month preceding delivery No inclusion for precautionary reason : clinical symptoms suggesting an opportunistic infection of the central nervous system.

No inclusion for monitoring difficulties History or presence of allergy to the study drugs or their components Contra-indications to the study drugs Symptoms, physical signs or laboratory values suggestive of systemic disorders, (including renal, hepatic, cardiovascular, pulmonary, skin, or psychiatric and other conditions, which could interfere with the interpretation of the trial results

Intervention, a combined strategy :

After positive HIV infection screening from mother in the delivery room and put on antiretroviral treatment of mothers with post partum according to national guidelines , newborns benefit :

• Early detection of HIV infection at birth
• Without awaiting the outcome of early detection result, a preventive reinforced antiretroviral treatment (AZT / 3TC / NVP or AZT / 3TC if their mother is infected with HIV -2), from birth for 12 weeks.
• Regular HIV screening until the end of breastfeeding or later to 18 months.
• In case of positive results of an HIV test, an antiretroviral treatment with AZT / 3TC / LPV whatever serology HIV 1 or 2.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 56 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: Prospective non-comparative study of mother-child pairs whose mother is HIV-infected and received less than 4 weeks of antiretroviral therapy before birth or whose HIV infection has been diagnosed at birth. Assess the operational efficacy of a strategy combining early diagnosis and preventive antiretroviral treatment systematically reinforced from the birth among infants at high risk of infection with HIV.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: HIV Diagnosis and Treatment at Birth for HIV Exposed Newborn Whose Mother Was Not Treated With Antiretroviral Therapy (ART) During Last Month Before Delivery : Strategy Evaluation in Guinea.
• Actual Study Start Date: February 22, 2017
• Actual Primary Completion Date: September 17, 2019
• Actual Study Completion Date: September 17, 2019

Arms and Interventions

Arm

Intervention/treatment

Experimental: Reinforced preventive ARV therapy; The proposed reinforced preventive ARV Therapy will be administrated to all newborns exposed to HIV (zidovudine+lamivudine+nevirapine if the newborn is exposed to HIV-1 or HIV-1/2, zidovudine+lamivudine if the newborns exposed to HIV-2)

Drug: Reinforced preventive ARV therapy; If the mother is HIV-1 or HIV 1/2 infected: zidovudine / laminvudine (60/30 mg), ¼ cp morning and evening orally for 12 weeks.; nevirapine: 15mg/OD if weight ≥ 2500g / 10mg/OD if weight = 2000-2499g / 2mg/kg/OD if weight < 2000g for 12 weeks in case of HIV-1 infection. After 6 weeks, nevirapine will increase at 20mg/OD If the mother is HIV-2 infected: - zidovudine / laminvudine (60/30 mg), ¼ cp morning and evening orally for 12 weeks.; Other Name: Early diagnosis in children exposed to HIV

Outcome Measures

Primary Outcome Measures :

1. Proportion of newborns who have received an HIV diagnosis and reinforced preventive antiretroviral treatment at birth. [ Time Frame: Day 2 ]
   Proportion of newborns who have received both HIV test and reinforced preventive antiretroviral treatment in a maximum of 48 hours after birth.

Secondary Outcome Measures :

1. Proportion of mothers diagnosed with HIV who will initiate an antiretroviral therapy [ Time Frame: Week 72 ]
   • Proportion of mothers diagnosed with HIV at Day 0 who will initiate an antiretroviral therapy
2. Proportion of children diagnosed with HIV who will initiate an antiretroviral therapy [ Time Frame: Week 72 ]
   • Proportion of children diagnosed with HIV from Day 0 to Week 72 who will initiate an antiretroviral therapy
3. Proportion of mother-child pairs retained in the study with child having 2 PCR performed after stopping reinforced preventive antiretroviral treatment [ Time Frame: Week 24 ]
   • Proportion of mother-child pairs retained in the study from Day 0 to Week 24 with child having 2 PCR performed after stopping reinforced preventive antiretroviral treatment
4. Proportion of mother-child pairs retained in the study [ Time Frame: Week 72 ]
   • Proportion of mother-child pairs retained in the study from Day 0 to Week 72.

Other Outcome Measures:

1. Measure the clinical tolerance of reinforced preventive antiretroviral treatment in children [ Time Frame: Week 12 ]
   • Nature of clinical adverse events
2. Measure the biological tolerance of reinforced preventive antiretroviral treatment in children [ Time Frame: Week 12 ]
   • Nature of biological adverse events
3. Measure the proportion of children on reinforced preventive antiretroviral treatment with anemia [ Time Frame: Week 12 ]
   • Proportion of children with anemia superior or equal to grade 2
4. Measure the proportion of children who change antiretroviral therapy for grade 4 adverse event [ Time Frame: Week 12 ]
   • Proportion of children who change antiretroviral therapy for grade 4 adverse event
5. Measure the proportion of children with preventive antiretroviral treatment interruption [ Time Frame: Week 12 ]
   • Proportion of children with preventive antiretroviral treatment interruption
6. Describe the clinical events occurring in mothers [ Time Frame: Week 72 ]
   • Description of clinical events occurring in mothers
7. Measure the proportion of mothers presenting clinical events [ Time Frame: Week 72 ]
   • Proportion of mothers presenting clinical events
8. Describe the immunological outcomes in mothers [ Time Frame: Week 72 ]
   • Value of CD4 (absolute number)
9. Describe the virological outcomes in mothers [ Time Frame: Week 72 ]
   • Value of HIV RNA (copies/mL)
10. Describe the clinical outcomes in HIV-infected children [ Time Frame: Week 48 ]
    • Description of clinical events occurring in HIV-infected children
11. Measure the proportion of HIV-infected children presenting clinical events [ Time Frame: Week 48 ]
    • Proportion of HIV-infected children presenting clinical events
12. Describe the immunological outcomes in HIV infected children [ Time Frame: Week 48 ]
    • Value of CD4 (absolute number)
13. Describe the virological outcomes in HIV infected children [ Time Frame: Week 48 ]
    • Value of HIV RNA (copies/mL)
14. Describe the clinical outcomes in HIV-non-infected children [ Time Frame: Week 72 ]
    Nature of clinical events occurring in HIV-non-infected children
15. Measure the proportion of HIV-non-infected children presenting clinical events [ Time Frame: Week 72 ]
    • Proportion of HIV-non-infected children presenting clinical events
16. Describe the rate of mother to child transmission of HIV [ Time Frame: Week 72 ]
    • Proportion of HIV infected children (based on PCR ADN or ARN)
17. Describe the risk factors of mother to child transmission of HIV [ Time Frame: week 72 ]
    Description of risk factors for HIV transmission

Eligibility Criteria

• Ages Eligible for Study: Child, Adult, Older Adult
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Mother-child pairs whose mother is HIV-infected and received less than 4 weeks of antiretroviral therapy before delivery or whose HIV infection has been diagnosed at delivery
• Mother who signed the informed consent form to participate in the study.

Exclusion Criteria:

• Mother treated with antiretrovirals during the month preceding delivery
• No inclusion for precautionary reason : clinical symptoms suggesting an opportunistic infection of the central nervous system.
• No inclusion for monitoring difficulties
• History or presence of allergy to the study drugs or their components
• Symptoms, physical signs or laboratory values suggestive of systemic disorders, (including renal, hepatic, cardiovascular, pulmonary, skin, or psychiatric and other conditions, which could interfere with the interpretation of the trial results

Contacts and Locations

Locations

Guinea

Hôpital National Ignace Deen

Conakry, Guinea

Sponsors and Collaborators

ANRS, Emerging Infectious Diseases

Investigators

• Principal Investigator: Guillaume Breton, MD; Solthis
• Principal Investigator: Mohamed Cisse, MD; CHU Donka

More Information

• Responsible Party: ANRS, Emerging Infectious Diseases
• ClinicalTrials.gov Identifier: NCT03642704
• Other Study ID Numbers: ANRS12344-DIAVINA
• First Posted: August 22, 2018
• Last Update Posted: October 22, 2019
• Last Verified: October 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by ANRS, Emerging Infectious Diseases:

PMTCT; HIV early diagnosis; HIV preventive therapy; prevention of mother to child HIV transmission