An open randomised trial to evaluate different therapeutic strategies of combination therapy for HIV-1 infection.

This trial is designed to compare different strategies in using combinations of HIV drugs from the time of starting HIV treatment. It includes both the first and subsequent combinations of HIV drugs (each combination of drugs is called a regimen) as a change in treatment may be necessary over time if there is evidence of treatment failure or for side-effects. HIV treatment consists of various drug combinations chosen from up to three classes of drugs:

• nucleoside reverse transcriptase inhibitors, known as NRTIs
• non-nucleoside reverse transcriptase inhibitors, known as NNRTIs
• protease inhibitors, known as PIs

For further information about types of HIV drugs see Background Information

A randomised trial means that each individual who agrees to join the trial will be assigned to o­ne of the three strategies for treating HIV infection at random, that is, by a chance process like tossing a coin. Neither the individual nor their doctor can influence the assignment.

An open trial means that the exact trial treatment will be known to the participant and his or her doctor and nurse.

To be eligible to participate in INITIO, individuals will have HIV infection but never have taken HIV treatment before. Their doctors will have recommended that their state of health now requires HIV treatment. Participants will be expected to commit themselves to the study for at least three years, with check-ups and blood tests every month for the first three months, and then o­nce every three months after that. This is similar to the clinic visits which patients would make if starting HIV treatment for the first time outside a trial.

Approximately 1,000 patients from 17 countries will enter this study and start o­ne of the following HIV treatments:

- didanosine (ddI), stavudine (d4T) and nelfinavir. Nelfinavir is a protease inhibitor. If this later becomes ineffective, treatment with zidovudine (AZT), lamivudine (3TC), abacavir plus efavirenz may be started. Efavirenz is a non-nucleoside reverse transcriptase inhibitor. ddI, d4T, AZT, 3TC and abacavir are all nucleoside reverse transcriptase inhibitors.

- didanosine, stavudine and efavirenz. If this later becomes ineffective, treatment with zidovudine,
lamivudine, abacavir plus nelfinavir may be started.

- didanosine, stavudine, nelfinavir and efavirenz. This group receives both a protease inhibitor and a non-nucleoside reverse transcriptase inhibitor. If this later becomes ineffective, treatment with zidovudine, lamivudine, abacavir, ritonavir plus saquinavir may be started. Ritonavir and saquinavir are both protease inhibitors.

Diagram of the trial design:




Key to drug

Standard trial visits are at weeks 4, 8 and 12, then every 12 weeks. A patient-completed questionnaire o­n his or her adherance in taking the treatment will be offered at each visit.

Participants will have regular blood tests. These will be used to decide whether a particular regimen is working well or not. If necessary a change to the next regimen will be made. Doctors at each hospital will use the same criteria to make a decision to change to a new regimen as for their other patients. It is anticipated that many participants will not have to change their first regimen during the trial.

If a patient develops an intolerable side-effect to a particular drug another drug from the same class (for example, another NNRTI) may be used in its place if possible, without changing the other drugs in the regimen.

The researchers involved in INITIO are using two main measures to assess the HIV treatments. They are the amount of change in the CD4+ cell count at three years and the number of patients whose HIV viral load is below 50 copies (often called 'undetectable') at three years of treatment.

Participants will be recruited over o­ne year. The first regimen should be taken for at least six months (except in cases of intolerance). Trial treatment should be taken for at least three years and can continue until the trial is closed overall.

Updated: 04 Oct 2010