HIV 'Viral load' not indicative of AIDS progress - study

[Guest guest]

[Moderators note: Abstract of the original article and the summary

of this week's Journal of the American Medical Association. (JAMA)

follows the news item]

HIV 'Viral load' not indicative of AIDS progress - study

Wed Sep 27, 2006 1:45 AM IST

CHICAGO (Reuters) - Measuring the amount of AIDS virus circulating

in the blood of HIV-positive patients is not a good indicator of the

health of their immune systems, researchers said on Tuesday.

Physicians often assess the amount of HIV particles in the blood --

known as the viral load -- along with the decline in CD4 cells that

help the body fight infections to measure the disease's progress and

decide when to prescribe drug therapy.

But a study of 2,800 untreated HIV-positive individuals found only

about 5 percent of the variations in viral load corresponded to

variations in immune system damage.

Depletion of CD4 cells is therefore not a simple consequence of the

amount of virus circulating, said the study published in this week's

Journal of the American Medical Association.

" The results of this nationwide study may have profound implications

in our understanding of how HIV causes disease and in our approach

to the management of HIV-infected patients, " said lead investigator

Dr. Benigno of Case Western Reserve University in

Cleveland.

Estimating damage to the immune system is critical in deciding when

it is best to start antiretroviral therapy, the AIDS-fighting drugs

credited with allowing millions of infected people to live with the

disease.

Because of issues of drug resistance and the potent side effects of

the drugs, doctors and patients often defer starting medications

until medically necessary.

The study challenges the current belief that the degree to which the

virus replicates itself is the trigger for the loss of CD4 cells,

white blood cells that are a key component of the body's immune

system.

An accompanying editorial in the journal said the findings were

exciting because they suggested that researchers should look for and

target non-viral factors that set off the eventual decline in the

immune system.

http://in.today.reuters.com/news/newsArticle.aspx?

type=worldNews & storyID=2006-09-27T013224Z_01_NOOTR_RTRJONC_0_India-

269451-1.xml & archived=False

___________________________

Editorial

Explaining, Predicting, and Treating HIV-Associated CD4 Cell Loss:

After 25 Years Still a Puzzle

W. Henry, MD; Pablo Tebas, MD; H. Clifford Lane, MD

JAMA. 2006;296:1523-1525.

(This article does not have an abstract, the first 150 words of the

full text is provided)

The clinical syndrome of AIDS is due to infection with the human

immunodeficiency virus (HIV), which causes a progressive

immunodeficiency characterized by the loss of CD4 T lymphocytes

coupled with an immunosuppression related to global activation of

the immune system. Since the seminal article by Mellors et al in

1996,1 it has been known that as a group, individuals with a higher

HIV RNA viral load tend to progress to AIDS and death at a more

rapid rate than those with lower viral loads, and that different

prognostic information can be derived from the CD4 cell count and

the viral load. The conventional wisdom is that the CD4 cell count

represents the current state of immune deficiency, whereas the viral

load reflects the rate at which the immune system will further

deteriorate.2

________________________

Predictive Value of Plasma HIV RNA Level on Rate of CD4 T-Cell

Decline in Untreated HIV Infection

Benigno Rodríguez, Ajay K. Sethi, Vinay K. Cheruvu, Wilma Mackay,

J. Bosch, Mari Kitahata, L. Boswell, W.

Mathews, R. Bangsberg, , C. Whalen,

Sieg, Suhrida Yadavalli, G. Deeks, and M.

Lederman

JAMA. 2006;296:1498-1506.

Context: Plasma human immunodeficiency virus (HIV) RNA level

predicts HIV disease progression, but the extent to which it

explains the variability in rate of CD4 cell depletion is poorly

characterized.

Objective: To estimate the proportion of variability in rate of CD4

cell loss predicted by presenting plasma HIV RNA levels in untreated

HIV-infected persons.

Design: Repeated-measures analyses of 2 multicenter cohorts,

comprising observations beginning on May 12, 1984, and ending on

August 26, 2004. Analyses were conducted between August 2004 and

March 2006.

Setting Two cohorts of HIV-infected persons: patients followed up

at 4 US teaching medical institutions or participating in either the

Research in Access to Care for the Homeless Cohort (REACH) or the

San Francisco Men's Health Study (SFMHS) cohorts and participants in

the Multicenter AIDS Cohort Study (MACS) cohort.

Participants: Antiretroviral treatment–naive, chronically HIV-

infected persons (n = 1289 and n = 1512 for each of the 2 cohorts)

untreated during the observation period ( 6 months) and with at

least 1 HIV RNA level and 2 CD4 cell counts available. Approximately

35% were nonwhite, and 35% had risk factors other than male-to-male

sexual contact.

Main Outcome Measures: The extent to which presenting plasma HIV

RNA level could explain the rate of model-derived yearly CD4 cell

loss, as estimated by the coefficient of determination (R2).

Results In both cohorts, higher presenting HIV RNA levels were

associated with greater subsequent CD4 cell decline. In the study

cohort, median model–estimated CD4 cell decrease among participants

with HIV RNA levels of 500 or less, 501 to 2000, 2001 to 10 000, 10

001 to 40 000, and more than 40 000 copies/mL were 20, 39, 48, 56,

and 78 cells/µL, respectively. Despite this trend across broad

categories of HIV RNA levels, only a small proportion of CD4 cell

loss variability (4%-6%) could be explained by presenting plasma HIV

RNA level. Analyses using multiple HIV RNA measurements or

restricting to participants with high HIV RNA levels improved this

correlation minimally (R2, 0.09), and measurement error was

estimated to attenuate these associations only marginally

(deattenuated R2 in the 2 cohorts, 0.05 and 0.08, respectively).

Conclusions Presenting HIV RNA level predicts the rate of CD4 cell

decline only minimally in untreated persons. Other factors, as yet

undefined, likely drive CD4 cell losses in HIV infection. These

findings have implications for treatment decisions in HIV infection

and for understanding the pathogenesis of progressive immune

deficiency.

Author Affiliations: Center for AIDS Research (Drs Rodríguez, Sieg,

and Lederman, and Mrs Yadavalli), Center for Modern Epidemiology of

Infectious Diseases (Drs Sethi and Whalen and Mr Cheruvu and Ms

Mackay), Case Western Reserve University, Cleveland, Ohio;

Department of Biostatistics, Harvard School of Public Health,

Harvard University, Boston, Mass (Dr Bosch); Department of Medicine,

University of Washington, Seattle (Dr Kitahata); Department of

Medicine, Harvard University School of Medicine, Boston, Mass (Dr

Boswell); Department of Medicine, University of California, San

Diego (Dr Mathews); Department of Medicine and Epidemiology (Drs

Bangsberg and ) and Department of Medicine (Dr Deeks),

University of California, San Francisco.