Development of AntiRetroviral Therapy in Africa - a randomised trial of monitoring practice and structured treatment interruptions in the management of antiretroviral therapy in adults with HIV infection in Africa

Not Applicable

Completed

Conditions: Infections and Infestations
Human Immunodeficiency Virus (HIV), Acquired Immunodeficiency Syndrome (AIDS)
Human immunodeficiency virus (HIV)

Registration Number: ISRCTN13968779

Lead Sponsor: Medical Research Council (MRC) (UK)

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: All

Target Recruitment: 3300

Inclusion Criteria

1. Documentation of HIV-1 infection: antibody positive serology by enzyme-linked immunosorbent
assay (ELISA) test (confirmed by licensed second ELISA or Western Blot)
2. Age =18 years
3. Symptomatic WHO stage 2, 3 or 4 HIV disease and CD4 <200 cells/mm3
4. ART naïve (except for ART use during pregnancy for the prevention of mother-to-child HIV transmission)
5. Agreement and documented informed consent to be randomised to CMO or LCM and to STI or continuous ART, if eligible
6. Life expectancy of at least 3 months

Exclusion Criteria

1. Cannot or unlikely to attend regularly (e.g. usual residence too far from Study Centre)
2. Likelihood of poor compliance
3. Presence of acute infection (e.g. malaria, acute hepatitis, pneumococcal pneumonia, non-typhoid salmonella septicaemia, cryptococcal meningitis). Patients may be admitted after recovery of an acute infection. Patients with tuberculosis (TB) will not be enrolled while on the intensive phase of anti-tuberculosis therapy, but should be re-evaluated after the intensive phase and a decision made then about starting ART. Patients starting ART whilst on anti-tuberculosis therapy after the intensive phase will not receive NVP, nor will they be randomised into the NORA substudy.
4. On chemotherapy for malignancy
5. Laboratory abnormalities which are a contraindication for the patient to start ART (e.g. haemoglobin <8 g/dl, total white blood cell count [WBC] <0.75 x 10^9/l, aspartate aminotransferase [AST] or alanine aminotransferase [ALT] >5 x the upper limit of normal [ULN], grade 3 renal dysfunction - creatinine >360 µmol/l and/or urea >5 x ULN)
6. Pregnancy or breastfeeding

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
1. Efficacy: Progression to a new WHO stage 4 HIV event or death<br>2. Safety: Any serious adverse event, which is not HIV related

Secondary Outcome Measures

Name	Time	Method
1. Progression to a new or recurrent WHO stage 4 HIV event or death<br>2. Progression to a new WHO stage 4 HIV event or death from 6 weeks after randomisation<br>3. Progression to a new or recurrent WHO stage 4 HIV event or death from 6 weeks after randomisation<br>4. Any grade 3 or 4 adverse events<br>5. Number and class of anti-HIV drugs received by 3 years<br>6. Time to cessation of first-line regimen for failure<br>7. Adherence as measured by questionnaire and pill counts<br>8. CD4 count at 3 years (provided that it is at least 2 months after restarting ART for those in the STI group)<br>9. HIV RNA viral load (performed retrospectively) at 3 years (providing that it is at least 2 months after restarting ART for those in the STI group)<br>10. HIV resistance profiles at 3 years in those with detectable viral load (providing that it is at least 2 months after restarting ART for those in the STI group)