Botswana-Baylor ANtiretroviral Assessment: A study comparing the management of human immunodeficiency virus (HIV) in children using continuous or structured interrupted antiretroviral treatment

• Register: ISRCTN
• Last refreshed on: 13 January 2015
• Main ID: ISRCTN14354426
• Date of registration: 18/09/2013
• Prospective Registration: No
• Primary sponsor: Botswana-Baylor Children's Clinical Centre of Excellence (Botswana)
• Public title: Botswana-Baylor ANtiretroviral Assessment: A study comparing the management of human immunodeficiency virus (HIV) in children using continuous or structured interrupted antiretroviral treatment
• Scientific title: A randomized, CD4+ cell guided, Kaletra-based, structured interrupted antiretroviral treatment in HIV infected infants and children in Botswana
• Date of first enrolment: 11/02/2004
• Target sample size: 600
• Recruitment status: Completed
• URL: http://isrctn.com/ISRCTN14354426
• Study type: Interventional
• Study design: Randomized un-blinded clinical trial (Treatment)

Countries of recruitment

Botswana

Contacts

• Name: Gabriel Anabwani

Key inclusion & exclusion criteria

Inclusion criteria: 1. Children between 6 months up to the 13th birthday who weigh >7kg at the time of enrolment are invited to participate if they have documented laboratory evidence of HIV-1 infection, have received <6 weeks of antiretroviral therapy and are Center for Disease Control and Prevention (CDC) immunologic category 2 or 3.
2. Children aged <18 months of age are considered infected if they have two positive PCR tests - qualitative DNA or quantitative RNA, or combination of both. For those aged >18 months, a positive HIV antibody test [(enzyme-linked immunosorbent assay (ELISA) or enzyme immunoassay (EIA)] can substitute for one of the PCR-based tests. Children who were enrolled in the BANA1 study are eligible after a one-week washout period.
BANA1 was the first trial that started in 2001 to show that antiretrovirals (ARVs) would work in African as well as in western children, as the prevailing view at that time was not so. The study was stopped after one year when the standard of care in Botswana changed. BANA2, this study, is the sequential successor of BANA1.
3. Written informed consent is obtained from all participant's legal guardians. Assent is obtained from children aged 6 years or more.
Exclusion criteria: 1. Liver function test values >5x above the upper limit of normal and documented or suspected acute hepatitis within 30 days prior to study entry, irrespective of [aspartate transaminase (serum glutamic oxaloacetic transaminase) (AST(SGOT)] and alanine transaminase (serum glutamic pyruvate transaminase) ALT(SGPT) values
2. Any grade 3 or greater toxicity
3. Known intolerance to study drug and current use of medications likely to interact with study drug (including rifampicin)

Age minimum:
Age maximum:
Gender: Both

Health Condition(s) or Problem(s) studied

HIV in children
Infections and Infestations
Unspecified human immunodeficiency virus [HIV] disease

Intervention(s)

Those randomized to the continuous arm are treated continuously while those randomized to the treatment interruption arm (STI) are treated initially for a minimum of six months and until the CDC immunologic category improves to category 1 for at least three months. At that time, treatment is interrupted until the CDC immunologic category deteriorated to 2 or 3. This cycle of interruption and resumption of therapy is repeated if the child recovers to CDC immunologic category 1 for 3 months or deteriorated to category 2 or 3. Participants are treated with stavudine(d4T)/lamivudine(3TC)/Kaletra(ritonavir-boosted lopinavir) or received zidovudine(ZDV)/3TC/Kaletra. Dosing is as follows: d4T at 1 mg/kg twice a day (bid) (up a maximum of 80 mg per day) until (yr) when the maximum dosing of d4T was reduced to 60mg/day in accordance with the Botswana HIV treatment guidelines; 3TC at 4 mg/kg bid (up to a maximum of 300 mg per day); ZDV at 180 mg/m2 bid (up to a maximum of 600 mg per day); and Kaletra in accordance with the package insert dosing table up to a maximum of 800 mg lopinavir daily. Interim analyses of study data are conducted at such intervals as was determined by the Data Safety and Monitoring Board.

Primary Outcome(s)

1. Drug associated toxicity or intolerance
2. Disease progression [growth failure, neuropsychological / neurological deterioration, opportunistic infections or conditions) or death]
3. Development of major genotypic resistance mutations

The study was not designed to have a fixed end point in time. Rather it was designed to generate a working database with oversight by a Data and Safety Monitoring Board. The primary outcomes (death, growth failure; change in neurodevelopment status and major reverse transcriptase or protease resistance mutations) are measured by events (rates/1000 person yrs). Patients have been followed up for >2000 person years.

Secondary Outcome(s)

Cost of treatment

Secondary ID(s)

RES227-01

Source(s) of Monetary Support

The Botswana-Baylor Children's Clinical Centre of Excellence (Botswana), The Ministry of Health, Government of Botswana (Botswana), Bristol-Myers Squibb - provides study products and other support free of charge but was not involved in the initiation or conduct of the study