A Smart + Strong Site
Subscribe to:
Newsletters
POZ magazine
JOIN AIDSMEDS YouTube

Back to home » Treatment News » Top Stories

Most Popular Stories
Undetectable Viral Load Essentially Eliminates Transmission Risk in Straight Couples
FDA Approves New Single-Tablet HIV Regimen, Triumeq
Life Expectancy for Young People With HIV Is Nearly Normal
A 15-Year Jump in Life Expectancy for People With HIV
Scientists Devise Method of Snipping HIV From Immune Cells
Monkey HIV Vaccine Success Opens Door for Human Trials
HIV Combo Pill Less Toxic Thanks to New Form of Tenofovir
What's That Mean?
(just double-click it!)

If you don't understand one of the words in this article, just double-click it. A window will open with a definition from mondofacto's On-line Medical Dictionary. If the double-click feature doesn't work in your browser, you can enter the word below:

Most Popular Lessons
Aging & HIV
The HIV Life Cycle
Shingles
Herpes Simplex Virus
Syphilis & Neurosyphilis
Treatments for Opportunistic Infections (OIs)
What is AIDS & HIV?
More News

Have medical or treatment news about HIV? Send press releases, news tips and other announcements to news@aidsmeds.com.

Click here for more news


emailprint

October 11, 2011

Cohort Study: No AIDS-Free Survival Benefit to Starting HIV Treatment at CD4s of 500 or More

Starting antiretroviral (ARV) therapy with a CD4 count above 500 doesn’t decrease the risk of AIDS or death from any cause—at least over an average follow-up period that approached five years—according to a new report from a large cohort study published in the September 26 issue of Archives of Internal Medicine.

For people living with HIV with CD4s below 350, the Concerted Action on SeroConversion to AIDS and Death in Europe (CASCADE) study confirmed the clinical benefits of starting and remaining on ARV treatment. As for those with CD4s between 350 and 500, CASCADE indicated slower rates of disease progression associated with starting treatment, though there were too few new AIDS cases or deaths in this particular group during the study to yield firm conclusions. 

The question of when ARV therapy should be started has not yet been answered. Though there are data from at least one major study indicating that HIV treatment, initiated as early as possible, profoundly reduces the risk of ongoing transmission of the virus--an important public health benefit of ARV therapy--many advocates contend that it will be necessary to prove that early treatment also protects the health and lives of those actually taking the medications, without an increased risk of side effects or drug resistance.

Three large cohort studies indicate that people should not wait until their CD4s fall below 350 to start ARV therapy to protect their own health. As for waiting until the CD4 count falls below 500, one cohort—the NA-ACCORD study—suggested this is detrimental, whereas another did not; the third cohort only included patients with fewer than 500 CD4s, thus a detailed analysis was not possible. NA-ACCORD also pointed to disease-free survival advantages when therapy is started when the CD4 count is between 500 and 800.

Acting on the initial cohort findings, the U.S. Department of Health and Human Services changed its ARV treatment recommendations in 2009. Whereas the guidelines previously recommended treatment for all people living with HIV with CD4s below 350, the threshold was increased to below 500 in light of the important—but inconclusive—findings.

Some experts argue that the only way to know the absolute benefits and risks of starting therapy early—indeed, even immediately after HIV is diagnosed—is to examine the results of a randomized prospective study. The international Strategic Timing of Antiretroviral Treatment (START) trial is exploring this question, but data are unlikely to be available until 2015. Taking place at roughly 90 sites in nearly 30 countries, START is randomizing more than 4,000 antiretroviral-naive HIV-positive individuals with CD4s above 500 cells to either begin treatment immediately or defer treatment until their CD4s are less than 350 cells.

In the meantime, additional data are available from the CASCADE study, a large cohort consisting of 23 small cohort studies being conducted throughout Europe, Australia and Canada. The report published in Archives of Internal Medicine by Michele Jonsoon-Funk, PhD, of the University of North Carolina at Chapel Hill and her colleages is similar to a preliminary review of the data orally presented in July 2010 at the XVIII International AIDS Conference in Vienna, which involved a little more than three years of follow up data.

Unlike other cohorts, which began following people from the time they started therapy, the new CASCADE analysis involved 9,455 people who were infected within the previous two years and followed them until they started ARV therapy. In other words, CASCADE researchers were in the unique position to document what happened to patients before they began treatment.

Between January 1996 and May 2009, the CASCADE researchers enrolled new patients every month, thereby created 161 small groups of patients for comparisons purposes. Patients were followed, on average, for 4.7 years in the study. When ARV treatment was started, the investigators noted the patients’ CD4 counts. Where there were AIDS-defining conditions or deaths, the investigators noted how long they occurred after each patient joined the cohort.

The greatest benefits were seen among those who started therapy with immune systems that were clearly compromised. For example, those who started treatment as soon as their CD4 count fell below 50 were nearly 70 percent less likely to develop an AIDS-defining illness or die, compared with those who waited. Among those with CD4s between 50 and 200, starting therapy as quickly as possible reduced the risk of AIDS or death by 70 percent, compared with those who delayed treatment.

Of interest, the researchers reported a number-needed-to-treat (NNT) analysis for patients starting HIV treatment in each CD4 group. An NNT analysis is a relatively simple measure of effectiveness of a particular medical intervention, and it aims to determine the average number of people living with a disease who need to be treated to prevent one additional outcome. For example, the NNT analysis employed in CASCADE set out to determine the number of people living with HIV and a CD4 count within a particular range who need to be treated with ARV therapy to prevent one new AIDS case or death.

Not surprisingly, the NNT among patients starting with very low CD4s was also low—a total of three people living with HIV with CD4s below 50 needed to be treated with ARV therapy to prevent one AIDS case or death. Among those with CD4s between 50 and 100, the NNT was 7. The NNT for those with CD4s between 200 and 350 was 21.

There was also an appreciable benefit for those who started therapy as soon as their CD4s landed between 350 and 500, compared with those who delayed therapy—a 25 percent reduction in the risk of AIDS or death. However, Funk and her colleagues note, when treatment was started with CD4s in this range, “the benefits of treatment initiation become evident only beyond two years, suggesting that patients need to consider the long-term course of treatment, including the risk of adverse effects of [ARV therapy] during an extended period.”

Here the NNT was significantly higher—34 HIV-positive individuals with CD4s between 350 and 500 needed to be treated with ARV therapy to prevent a new AIDS case or death.

As for those with CD4s above 500, there was no advantage in terms of AIDS-free survival. Here, no NNT could be calculated in terms of preventing AIDS or death, though the researchers did suggest that 239 people living with HIV and high CD4 counts would need to be treated with ARV therapy to prevent a single death, from any cause.

A limitation of the CASCADE study is that it didn’t monitor participants for some of the non-AIDS-related health complications that are believed to be more common among people living with HIV. “Patient well-being is adversely affected by many serious non-AIDS-defining conditions,” Funk’s team writes. “For example, immunodeficiency and uncontrolled viremia have been implicated in the development of cardiovascular disease and non-AIDS-defining malignancies. Although CASCADE does not pool data on non-AIDS morbidity, this analysis reflects the most serious outcome (death) due to non-AIDS conditions.”
 
Another limitation is that the average length of follow-up for the individuals participating in CASCADE is under five years, at least thus far. In turn, it is not yet possible to determine if there are any long-term AIDS-free survival benefits—or, conversely, untoward effects—associated with starting therapy when the CD4 count is above 500.  

While awaiting the results of SMART, treatment decisions for those with CD4s above 350 “will need to be made based on the available evidence from observation cohorts,” Funk’s team concludes. “We used a novel approach applied to a unique cohort of seroconverters to reduce the potential for lead time bias. We found that treatment initiation and CD4 cell counts of 350 to 499 was associated with slower disease progression. We did not observe any benefit to treatment initiated at 500 to 799.”

Search: CASCADE, NA-ACCORD, treatment, start, antiretroviral, ARV, Funk, Archives of Internal Medicine, IAS


Scroll down to comment on this story.



Name:

(will display; 2-50 characters)

Email:

(will NOT display)

City:

(will display; optional)

Comment (500 characters left):

(Note: The AIDSmeds team reviews all comments before they are posted. Please do not include ":" "@" "<" ">" in your comment. The opinions expressed by people providing comments are theirs alone. They do not necessarily reflect the opinions of Smart + Strong, which is not responsible for the accuracy of any of the information supplied by people providing comments.)

Comments require captcha.
Please enter this number for verification:

| Posting Rules



Show comments (7 total)


[Go to top]

Quick Links
About HIV and AIDS
The Cure
Lab Tests
Clinical Trials
HIV Meds
Starting Treatment
Switching Treatment
Drug Resistance
Side Effects
Disclosure
Lipodystrophy
Hepatitis & HIV
Women & Children
Fact Sheets
Treatment News
Community Forums
Blogs
Conference Coverage
Health Services Directory
POZ Magazine


    dave41
    Bethany
    Oklahoma


    zeze42
    Bay Area - Peninsula
    California


    Sexynyrican
    Brooklyn
    New York


    josebos
    Boston strong
    Massachusetts
Click here to join POZ Personals!
Conference Coverage

XX International AIDS Conference
(AIDS 2014)
Melbourne, Australia
July 20 - 25, 2014


21st Conference on Retroviruses and Opportunistic Infections
(CROI 2014)
Boston, MA
March 3 - 7, 2014


7th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention
(IAS 2013)
Kuala Lumpur, Malaysia
June 30 - July 3, 2013


more conference coverage

[ about AIDSmeds | AIDSmeds advisory board | our staff | advertising policy | advertise/contact us]
© 2014 Smart + Strong. All Rights Reserved. Terms of use and Your privacy.
Smart + Strong® is a registered trademark of CDM Publishing, LLC.