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

HIV Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01088516
• Other study ID #: Aluvia Breastfeeding Study
• Secondary ID: A10-324
• Status: Completed
• Phase: Phase 4
• First received: January 25, 2010
• Last updated: June 22, 2015
• Start date: December 2008
• Est. completion date: May 2012

Study information

• Verified date: June 2015
• Source: University of Zambia
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Ethics Review CommitteeZambia: Ministry of HealthZambia: Pharmaceutical Regulatory AuthorityZambia: Research Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 280
• Est. completion date: May 2012
• Est. primary completion date: November 2011
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 15 Years and older

Eligibility

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 Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• HIV

Intervention

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

Locations

Country	Name	City	State
Zambia	Chelstone Clinic	Lusaka

Sponsors (3)

Lead Sponsor	Collaborator
University of Zambia	Abbott, University of Toronto

Country where clinical trial is conducted

Zambia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	HIV Negative Survival of Infants		to be assessed at: infant age 6 months, 3 months post-weaning from breastfeeding, infant/child age 24 months	Yes
Secondary	Maternal survival, viral suppression and CD4 response		End-of-Study (Infant actual/predicted age 18-24 months)	Yes
Secondary	Emergence of viral drug resistance in mothers or infants		End-of-Study (infant actual/predicted age 18-24 months)	No
Secondary	Incidence of diarrhea, malnutrition/growth failure and pneumonia in infants		Infant actual/predicted age 1 year and 18-24 months	No
Secondary	Cost-effectiveness analysis		End-of-Study (infant actual/predicted age 24 months)	No
Secondary	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	No