Clinical Study of an Aluvia-based HAART Regimen for Prevention of Mother-to-child HIV Transmission in Africa

NCT01088516 | Completed Phase 4 DMC

• 2 other identifiers: Aluvia Breastfeeding StudyA10-324
• Study Type: interventional
• Target: 280
• Locations: 1 country
• Sites: 1

Brief Summary

Therapeutic options to prevent vertical transmission of HIV remain limited. Combination antiretroviral therapy in the form of HAART (Highly Active Anti Retroviral Therapy) is generally recommended in the developed world, both for its ability to reduce maternal viral load, and thus the likelihood of transmission, as well as for its prevention of drug resistance mutations, which might otherwise reduce future options for therapy in the mother, infant, or both. Exclusive formula-feeding is also recommended in the developed world (where clean water sources \& adequate hygiene is reliably available) to prevent HIV transmission through breastmilk, however, this is not yet a feasible option in many developing world settings due to economic, infrastructure, social and infant-health reasons. The investigators propose use of a HAART regimen during pregnancy and breastfeeding that is based upon the recently released Aluvia tablets (tablet form of LOPINAVIR/RITONAVIR or LOP; established capsule form is known as Kaletra) to improve maternal virological control and thus mother-to-child-transmission (MTCT). Hypothesis: Maternal use of HAART containing Zidovudine, 3TC and Aluvia (Lopinavir/Ritonavir) can prevent antepartum, and intrapartum transmission of HIV, as well as allow exclusive and then subsequent complementary feeding to be carried out with minimum risk to the mother and infant.

• Study regimen: ZDV/3TC (combivir) + 2 Aluvia Tabs all PO BID to start at 14-30 weeks gestational age (GA) and continue through labor and as long as the mother breastfeeds
• Peripartum single dose Nevirapine (sdNVP) (Note: Mothers will also be receiving ZDV as part of the study regimen) to mother and sdNVP + 5 days postpartum ZDV to the infant will be given as per current Zambian practice
• Exclusive breastfeeding (EBF) x 6 months then complementary foods to be added, with aim for a gradual wean of breastfeeding by infant age of 12-13 months. In case of inability to wean by 13 months, however, drug will be continued until the mother has achieved a complete wean.
• Follow-up period: Mother \& child will be followed to an infant age of 24 months, as per schedule-of-visits (approx every 3 months) Major outcome measure: infant survival and negative dbs (dried blood spot) PCR 3 months post weaning.

Conditions

HIV

Keywords

Human Immunodeficiency Virus; Vertical Transmission; Pregnancy; Breastfeeding; Prevention of mother to child transmission; HAART; Aluvia; Lopinavir; Africa; Infectious Disease Transmission, Vertical

Outcome Measures

Primary Outcomes (1)

• HIV Negative Survival of Infants

  to be assessed at: infant age 6 months, 3 months post-weaning from breastfeeding, infant/child age 24 months

Secondary Outcomes (5)

• Maternal survival, viral suppression and CD4 response

  End-of-Study (Infant actual/predicted age 18-24 months)

• Emergence of viral drug resistance in mothers or infants

  End-of-Study (infant actual/predicted age 18-24 months)

• Incidence of diarrhea, malnutrition/growth failure and pneumonia in infants

  Infant actual/predicted age 1 year and 18-24 months

• Cost-effectiveness analysis

  End-of-Study (infant actual/predicted age 24 months)

• Efficacy of therapy in prevention of transmission with supplemental feeding among those infants who remain PCR negative at 6 months of age

  Infant age 6 months and 3-months post-wean

Study Arms (1)

Aluvia-based HAART

EXPERIMENTAL

Study regimen: ZDV/3TC (combivir) + 2 Aluvia Tabs all PO BID to start at 14-30 weeks gestational age (GA) and continue through labor and as long as the mother breastfeeds

Drug: Lopinavir/Ritonavir (200/50 mg) Tablets + Zidovudine + 3TC

Interventions

Lopinavir/Ritonavir (200/50 mg) Tablets + Zidovudine + 3TC DRUG

Zidovudine 300mg PO BID + 3TC 150 mg PO BID + Lopinavir/Ritonavir (200/50 mg) two tablets PO BID

Also known as: Combivir (Zidovudine or AZT + 3TC), Aluvia (Lopinavir/Ritonavir)

Aluvia-based HAART

Eligibility Criteria

• Age: 15 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Minimum age 15 years
• Pregnancy and ability to initiate therapy between 14-30 weeks gestation
• HIV seropositivity
• Intention to exclusively breastfeed for 6 months
• Ability to give informed consent
• Ability to attend follow-up visits

You may not qualify if:

• Previous HAART
• Pre-existing known major illnesses likely to influence pregnancy outcome or place participant at increased risk from adverse events from HAART therapy, including diabetes, severe renal, liver or heart disease, or active tuberculosis
• Severe anemia (Hemoglobin \<8 gm/dL)
• Current and continuing therapy with selected medications which are either absolutely or relatively contraindicated for co-administration with Aluvia

Sponsors & Collaborators

• University of Zambia: lead
• University of Toronto: collaborator
• Abbott: collaborator

Study Sites (1)

Chelstone Clinic

Lusaka, Zambia

Location

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome; Breast Feeding

Interventions

Lopinavir; Ritonavir; Zidovudine; lamivudine, zidovudine drug combination; lopinavir-ritonavir drug combination

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Thymidine; Pyrimidine Nucleosides; Dideoxynucleosides; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Michael Silverman, MD

  University of Toronto

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chair of Infectious Diseases, St.Joseph's Hospital, London, Ontario, Canada

Study Record Dates

• First Submitted: January 25, 2010
• First Posted: March 17, 2010
• Study Start: December 1, 2008
• Primary Completion: November 1, 2011
• Study Completion: May 1, 2012
• Last Updated: June 24, 2015

Record last verified: 2015-06

Locations

ZA (1)