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CD4 counts linked with nonopportunistic diseases.

LOS ANGELES -- The risk of nonopportunistic diseases in HIV-infected patients increases as CD4 counts fall, and the impact of such diseases overshadows that of opportunistic diseases at CD4 counts above 200 cells/mcL, said Dr. Jason Baker of the University of Minnesota in Minneapolis.

The impact of nonopportunistic diseases on people with HIV is increasingly under scrutiny in an era when antiretroviral therapy (ART) has led to a decline in morbidity and mortality from "classic" opportunistic diseases, Dr. Baker said at the 14th Conference on Retroviruses and Opportunistic Infections.

The discovery that rates of nonopportunistic diseases vary according to CD4 counts "starts to build a case that people aren't just ... living longer and ... dying of other causes," Dr. Baker said at a press conference following his presentation.

Rates of liver, renal, and cardiovascular diseases, as well as of non-HIV-related cancers, were all associated with CD4 counts in a group of 1,397 patients who were followed for at least 5 years after enrollment in a study sponsored by the National Institutes of Health.

Dr. Baker and his associates randomly assigned ART-naive patients to one of three drug regimens and carefully monitored all fatal and nonfatal opportunistic and nonopportunistic events, while tracking patients' CD4 counts. Over the 5-year follow-up, there were 266 opportunistic disease events with 89 related deaths and 166 nonopportunistic disease events with 25 deaths.

Nonopportunistic diseases seen in the cohort included cirrhosis and grade 4 transaminitis; myocardial infarctions, strokes, and coronary artery disease requiring intervention; renal insufficiency and end-stage renal disease; and 32 malignancies other than non-Hodgkin's lymphoma or Kaposi's sarcoma, including five cases each of anal, lung, and skin cancers.

Liver disease disproportionately included grade 4 elevated liver enzymes, which may be related to medications. Whether or not this diagnosis was included in the analysis, however, CD4 counts were related to disease events.

Both opportunistic and nonopportunistic events were less likely in patients with higher CD4 counts.

"The decline was steeper for opportunistic disease events, but nonopportunistic disease became at least as significant if not more so at higher CD4 levels," Dr. Baker said.

In patients with CD4 counts above 200 cells/mcL, mortality and morbidity were higher for nonopportunistic than for opportunistic disease, Dr. Baker reported.

The univariate hazard ratios for the difference in risk for an incremental increase of 100 cells/mcL in the CD4 count was 0.49 for opportunistic disease and 0.78 for nonopportunistic disease, and remained powerful (0.57 and 0.84, respectively) even after adjustment for age, sex, race, prior AIDS, hepatitis B and C, baseline CD4 and RNA viral load, and latest RNA viral load.

The findings suggest that strategies aimed at preserving high CD4 counts may reduce mortality and morbidity in the HIV-positive population, as higher counts are associated with lower overall rates of both opportunistic and nonopportunistic diseases, Dr. Baker said.

Participating institutions in the study, besides the University of Minnesota, included the Terry Beirn Community Programs for Clinical Research on AIDS; the Hennepin County Medical Center in Minneapolis; the University of California, San Francisco; Kaiser Permanente of Oakland, Calif.; and Wayne State University in Detroit.


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Author:Bates, Betsy
Publication:Internal Medicine News
Geographic Code:1USA
Date:Mar 15, 2007
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