Alternating Drug Regimens To Treat HIV Infection

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The summary below is from the full report titled "Alternation of Antiretroviral Drug Regimens for HIV Infection. A Randomized, Controlled Trial." It is in the 15 July 2003 issue of Annals of Internal Medicine (volume 139, pages 81-89). The authors are J. Martinez-Picado, E. Negredo, L. Ruiz, A. Shintani, C.R. Fumaz, C. Zala, P. Domingo, J. Vilaró, J.M. Llibre, P. Viciana, K. Hertogs, C. Boucher, R.T. D'Aquila, B. Clotet, and the SWATCH Study Team.

What is the problem and what is known about it so far?

HIV is the cause of AIDS, a potentially deadly illness that interferes with the body's ability to fight off infections and certain types of cancer. Treatment regimens containing combinations of anti-HIV drugs have greatly improved outcomes for HIV-infected patients. Anti-HIV treatments can be difficult to follow. Patients need to take many pills several times a day, and side effects are common. It is also common for the virus to develop a resistance to the drugs after patients take the drugs for a while. Resistance means that the drug is no longer effective against the virus. Some people have wondered whether you can delay the development of resistance by switching HIV drug regimens every few months, before the virus can undergo the changes that lead to resistance. Doctors use blood tests called CD4 cell count and viral load to monitor patients with HIV infection. CD4 cell count drops as the disease advances, so higher is better. Viral load increases as the disease advances, so lower is better.

Why did the researchers do this particular study?

To find out whether patients with HIV infection do better if they alternate drug regimens rather than stay on the same regimen until it stops working.

Who was studied?

161 people with HIV infection who had not yet started anti-HIV drugs when they entered the study. The patients received care at one of 15 HIV clinics in Spain and Argentina.

How was the study done?

The researchers assigned patients at random to take either regimen A (stavudine, didanosine, and efavirenz) or regimen B (zidovudine, lamivudine, and nelfinavir) until the treatment failed or to alternate between regimen A and B every 3 months. They then compared how long patients in each group avoided treatment failure. The researchers defined treatment failure as viral load rising above 400 copies/mL after successfully being decreased below 400 copies/mL. They also looked at CD4 cell counts, side effects, drug resistance, how closely people followed the drug regimens, and quality of life.

What did the researchers find?

Patients taking regimen A or regimen B had similar rates of treatment failure. Patients who alternated between regimens A and B were slower to develop treatment failure than the other groups. CD4 cell counts, side effects, ability to take the drugs, and quality of life were similar in the alternating and other groups.

What were the limitations of the study?

Since the study began, drug regimens that may be more effective than those studied here have become available. In addition, the study did not follow patients long enough to see whether alternating regimens improves infection or death rates.

What are the implications of the study?

This study suggests that it may be reasonable to switch anti-HIV drug regimens every few months rather than continue the same regimen until it stops working. However, further research is needed to define the role of planned switching of drug regimens.