Genes and HIV Progression

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-American Society of Internal Medicine.

The summary below is from the full report titled "Effects of CCR5-32, CCR2-64I, and SDF-1 3'A Alleles on HIV-1 Disease Progression: An International Meta-Analysis of Individual-Patient Data." It is in the 6 November 2001 issue of Annals of Internal Medicine (volume 135, pages 782-795). The authors are JPA Ioannidis, PS Rosenberg, JJ Goedert, LJ Ashton, TL Benfield, SP Buchbinder, RA Coutinho, J Eugen-Olsen, T Gallart, TL Katzenstein, LG Kostrikis, H Kuipers, LG Louie, SA Mallal, JB Margolick, OP Martinez, L Meyer, NL Michael, E Operskalski, G Pantaleo, GP Rizzardi, H Schuitemaker, HW Sheppard, GJ Stewart, ID Theodorou, H Ullum, E Vicenzi, D Vlahov, D Wilkinson, C Workman, J-F Zagury, and TR O'Brien, for the International Meta-Analysis of HIV Host Genetics.

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

There are more than 30,000 genes in a human body cell. Each gene in a pair is located in the same place on a pair of similar chromosomes. Genes have alternate forms that are known as alleles. A gene may have a few or several hundred different alleles. Different alleles account for inherited differences between individuals, such as varying eye color. Alleles may also play a part in the cause and progression of diseases. For example, individuals differ in the likelihood of developing AIDS after becoming infected with HIV-1. Differences in alleles probably cause these differences between individuals. However, whether specific alleles promote progression to AIDS has not been clear.

Why did the researchers do this particular study?

To see whether certain genetic alleles are associated with progression of HIV-1 disease.

Who was studied?

4504 people with HIV-1 infection who were of African or European descent.

How was the study done?

The researchers analyzed information from previous studies that had tested for associations between genetic alleles and the course of HIV-1 infection. The studies had been conducted by 19 groups of researchers in the United States, Europe, and Australia. In each study, the authors periodically checked a group of people with HIV-1 infection to see who developed AIDS or died. All study participants had had special genetic testing to determine whether or not they carried particular alleles (CCR5- 32, CCR2-64I, SDF-1 3'A) that have been suspected to affect progression of HIV infection. The authors combined the results from all of the studies in a special way (individual-patient–based meta-analysis) to see which alleles were associated with AIDS or death.

What did the researchers find?

The CCR5- 32 and CCR2-64I alleles were associated with a decreased risk for progression to AIDS and a decreased risk for death. These alleles did not protect against death once AIDS had developed. In contrast to some prior reports, having the SDF-1 3'A allele was not associated with progression to AIDS or death.

What were the limitations of the study?

Some patients had had HIV-1 infection for varying periods of time when they entered the studies. Patients who had rapidly progressed from HIV-1 infection to AIDS or death may not have been included in the study. This might mean that alleles responsible for rapid progression or death were not identified. Moreover, only patients of African or European descent were included in the meta-analysis.

What are the implications of the study?

Particular alleles (CCR5- 32 and CCR2-64I) protect against disease progression in patients with HIV-1 infection. Drugs that imitate the effect of these alleles might delay progression of HIV infection. Whether and how such alleles influence response to antiviral therapies are currently being studied.