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

Use of an Aluvia Based Highly Active Antiretroviral Therapy (HAART) Regimen in the Prevention of Mother to Child HIV Transmission (PMTCT) Antepartum, Intrapartum and Postpartum in Africa

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.

Study Overview

• Status: Completed
• Conditions: HIV
• Intervention / Treatment: Drug: Lopinavir/Ritonavir (200/50 mg) Tablets + Zidovudine + 3TC

Detailed Description

Study completed. Results are being published and the manuscript is in press as of June 2015

Ngoma MS, Misir A, Mutale W, Rampakakis E, Sampalis JS, Elong A, Chisele S, Mwale A, Mwansa JK, Mumba S, Chandwe M, Pilon R, Sandstrom P, Wu S, Yee K and Silverman MS. Efficacy of WHO recommendation for continued breastfeeding and maternal cART for prevention of perinatal and postnatal HIV transmission in Zambia. Journal of the International AIDS Society; 2015

• Study Type: Interventional
• Enrollment (Actual): 280
• Phase: Phase 4

Contacts and Locations

Study Locations

• Zambia
  • Lusaka, Zambia
    • Chelstone Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Aluvia-based HAART; 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; Zidovudine 300mg PO BID + 3TC 150 mg PO BID + Lopinavir/Ritonavir (200/50 mg) two tablets PO BID; Other Names: Combivir (Zidovudine or AZT + 3TC); Aluvia (Lopinavir/Ritonavir)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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 Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: University of Zambia
• Collaborators: University of Toronto; Abbott
• Investigators: Principal Investigator: Michael Silverman, MD, University of Toronto

Study record dates

Study Major Dates

• Study Start: December 1, 2008
• Primary Completion (Actual): November 1, 2011
• Study Completion (Actual): May 1, 2012

Study Registration Dates

• First Submitted: January 25, 2010
• First Submitted That Met QC Criteria: March 16, 2010
• First Posted (Estimate): March 17, 2010

Study Record Updates

• Last Update Posted (Estimate): June 24, 2015
• Last Update Submitted That Met QC Criteria: June 22, 2015
• Last Verified: June 1, 2015

More Information

Terms related to this study

• Keywords: Pregnancy; Africa; Human Immunodeficiency Virus; Breastfeeding; Vertical Transmission; HAART; Lopinavir; Infectious Disease Transmission, Vertical; Prevention of mother to child transmission; Aluvia
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Antimetabolites; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Ritonavir; Lopinavir; Zidovudine
• Other Study ID Numbers: Aluvia Breastfeeding Study; A10-324 (Other Grant/Funding Number: Abbott)