Immediate versus Delayed Treatment for HIV Infection

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The summary below is from the full report titled "Survival Benefit of Initiating Antiretroviral Therapy in HIV-Infected Persons in Different CD4⁺Cell Strata." It is in the 15 April 2003 issue of Annals of Internal Medicine (volume 138, pages 620-626). The authors are F.J. Palella Jr., M. Deloria-Knoll, J.S. Chmiel, A.C. Moorman, K.C. Wood, A.E. Greenberg, S.D. Holmberg, and the HIV Outpatient Study (HOPS) Investigators.

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

HIV is the cause of AIDS. AIDS is a potentially deadly illness that interferes with the body's ability to fight infection and certain types of cancer. Treatments containing several drugs (called antiretroviral therapy) have greatly improved outcomes for HIV-infected patients. A powerful category of drugs called protease inhibitors can be particularly effective. Patients often have difficulty adhering to these treatments, however, because they need to take many pills several times a day and side effects are common. The best time to start antiretroviral therapy for HIV infection is controversial. Starting too early exposes patients to side effects, and the benefits of such early therapy are unclear. Starting too late deprives patients of the benefits. Doctors use blood tests called CD4 cell counts and HIV viral loads to determine when they should start treatment for HIV. CD4 cell counts decrease as the disease advances, so higher counts are desirable. Viral load increases as the disease advances, so starting therapy at lower viral loads is more desirable.

Why did the researchers do this particular study?

To find out whether patients with HIV infection do better if they start therapy earlier in the course of HIV infection rather than waiting until their CD4 count decreases.

Who was studied?

1464 patients with HIV infection who were participating in larger study called the HIV Outpatient Study (HOPS). Patients could be included in this study if they had no previous HIV treatment and had undergone multiple CD4 and viral load tests.

How was the study done?

The researchers divided the patients into three groups according to the CD4 count when they entered the study: 0.201 to 0.350 x 10⁹ cells/L, 0.351 to 0.500 x 10⁹ cells/L, or 0.501 to 0.750 x 10⁹ cells/L. They then compared the death rates in people who started treatment immediately with the death rates in people who started treatment after their CD4 count decreased.

What did the researchers find?

For people with a CD4 count of 0.201 to 0.350 x 10⁹ cells/L, those who started treatment did better (that is, death rates were lowered) than those who delayed treatment. For people with higher CD4 counts (0.351 to 0.500 x 10⁹ cells/L or 0.501 to 0.750 x 10⁹ cells/L), death rates were again lower for those who started treatment than for those who delayed treatment; however, we cannot be sure that this finding is real because it was based on too few cases. For those with the highest CD4 counts (0.501 to 0.750 x 109 cells/L), death rates were similar regardless of whether people started or delayed treatment. People who started rather than delayed therapy when their initial CD4 count was 0.201 to 0.350 x 10⁹ cells/L or 0.351 to 0.500 x 10⁹ cells/L were more likely to have an undetectable viral load, which suggests that the drugs effectively fight HIV.

What were the limitations of the study?

Because of its design, this study could not identify the best time to start HIV treatment with certainty.

What are the implications of the study?

This study suggests that it may be reasonable to start HIV treatment immediately in patients with CD4 counts of 0.350 x 10⁹ cells/L or less rather than waiting for the CD4 count to drop further. However, for patients with CD4 counts greater than 0.350 x 10⁹ cells/L, it is less clear whether therapy should begin immediately or after CD4 counts decrease further.