Treatment for Resistant HIV-1 Infection

Summaries for Patients are a service provided by Annals to help patients better understand the complicated and often mystifying language of modern medicine.

Summaries for Patients are presented for informational purposes only. These summaries are not a substitute for advice from your own medical provider. If you have questions about this material, or need medical advice about your own health or situation, please contact your physician. The summaries may be reproduced for not-for-profit educational purposes only. Any other uses must be approved by the American College of Physicians.

The summary below is from the full report titled "Tenofovir Disoproxil Fumarate in Nucleoside-Resistant HIV-1 Infection." It is in the 2 September 2003 issue of Annals of Internal Medicine (volume 139, pages 313-320). The authors are K. Squires, A.L. Pozniak, G. Pierone Jr., C.R. Steinhart, D. Berger, N.C. Bellos, S.L. Becker, M. Wulfsohn, M.D. Miller, J.J. Toole, D.F. Coakley, and A. Cheng, for the Study 907 Team.

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

HIV-1 infection is a serious chronic illness that is caused by a virus. The virus attacks the body's immune system and interferes with its ability to fight infection and certain types of cancer. Drugs (antiretroviral agents) have greatly improved outcomes for HIV-1–infected patients. These drugs can suppress viral levels below limits of detection and improve the immune function of cells. There are several types of antiretroviral drugs. Most people with HIV-1 infection are treated with combinations of different drugs.

Unfortunately, many people treated with antiretroviral drugs develop resistance to therapy. Their levels of virus (viral loads) increase despite continuing treatment. When this happens, doctors often switch or add different antiretroviral drugs. One new type of antiretroviral drug that is available is tenofovir disoproxil fumarate (tenofovir DF), a nucleotide analogue. The benefits of adding this drug to ongoing therapy with other antiretroviral drugs in people who already have some drug resistance aren't clear.

Why did the researchers do this particular study?

To find out whether adding a nucleotide analogue drug (tenofovir DF) to ongoing treatment with nucleoside antiretroviral drugs decreases viral loads in patients with HIV-1 infection and incomplete viral suppression.

Who was studied?

552 HIV-1–infected adults who had stable but detectable viral loads while taking antiretroviral drugs. Most had taken nucleoside antiretroviral drugs for about 5 years. Most had taken four or more antiretroviral drugs.

How was the study done?

The researchers recruited patients with stable, low levels of detectable virus (HIV-1 RNA levels between 400 and 10 000 copies/mL). The researchers randomly assigned these patients to receive placebo or tenofovir DF (300 mg once daily). Neither the researchers nor the patients knew who got which treatment. During the study, all patients continued their other antiretroviral drug therapy. The researchers monitored viral loads, measures of immune function (CD4 cell counts), and side effects for 6 months. Researchers also did special genotyping tests to help assess resistance to drugs in about half of the patients.

What did the researchers find?

The genotyping tests done at baseline showed that 94% of the patients had mutations associated with drug resistance to nucleoside antiretroviral drugs. Patients given tenofovir DF had greater reductions in viral loads than did those given placebo. They also had slight increases (improvements) in CD4 cell counts, while patients given placebo had slight decreases in CD4 cell counts. Adverse events were similar in patients taking tenofovir DF and those taking placebo: about 15% of patients in each group had severe diarrhea, pain, or depression, and about 25% to 40% had abnormal results on some laboratory tests.

What were the limitations of the study?

The trial was short and did not assess clinical outcomes, such as infections.

What are the implications of the study?

In HIV-1–infected patients with suboptimal viral suppression from nucleoside antiretroviral therapy, adding tenofovir DF to ongoing therapy reduces viral loads.