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Author Topic: Starting Medication Early  (Read 2172 times)

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Offline veritas

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Starting Medication Early
« on: April 02, 2009, 05:00:23 AM »


Early Use of AIDS Drugs Cuts Patients’ Risk of Death (Update1)
By Rob Waters

April 1 (Bloomberg) -- Patients who start antiviral drugs before their immune systems are damaged by the AIDS virus substantially cut their risk of death, according to a study published today in the New England Journal of Medicine.

Researchers reviewed the medical records of more than 17,000 patients infected with HIV, the virus that causes AIDS. Patients who started treatment before their infection-fighting cells had fallen below a certain level cut their risk of dying by as much as 94 percent compared with those who waited longer.

The study lends support to revising current treatment guidelines, by adding weight to a growing body of research that suggests treating HIV at earlier stages can help save lives. Doctors and patients have been wrestling for years with the question of when best to start AIDS medications, which can cause substantial side effects including stomach upset, nausea, altered mental processes and disturbances in blood fat levels.

“The pendulum has shifted,” said Richard Moore, an author of the study and professor of medicine at the Johns Hopkins Bloomberg School of Public Health in Baltimore. “The drugs are now safer and the evidence mounting from our data and other data suggests it makes sense to start therapy earlier.”

While the findings were already known to many doctors who treat patients with HIV, the publication is likely to spur greater use of antiviral drugs, said Jason Kantor, an analyst with RBC Capital Markets in San Francisco. This will benefit Gilead Sciences Inc., the Foster City, California-based company that is the leading seller of AIDS drugs, Kantor said in a telephone interview today.

AIDS Drugs

In the fourth quarter of 2208, sales of Gilead’s top- selling AIDS drug Truvada, a two-drug combination pill, rose 25 percent to $562.1 million from a year earlier. Its three-drug AIDS pill Atripla had sales of $465.5 million, a 79 percent increase from a year earlier.

More people are being tested and diagnosed early for HIV infection, Kantor said. “So now you have earlier diagnosis and earlier treatment and that leads to market expansion,” he said.

Today’s study, known as NA-ACCORD, was sponsored by two U.S. agencies including the National Institutes of Health.

The project analyzed two large groups of patients by looking at the number of white blood cells known as CD4+ in their blood stream. Patients with higher CD4+ counts have greater infection-fighting ability because their immune systems haven’t yet been depressed by the virus.

Starting Treatment

Current federal guidelines call for patients whose CD4+ counts fall below 350 to be started on medications and leave it to doctors to decide whether to treat patients with higher levels.

One group started taking drugs when their CD4+ counts were from 351 to 500 per cubic millimeter of blood. They cut their risk of death by 69 percent compared with those who waited longer to start therapy.

The second analysis looked at people who started taking medications even earlier, when their CD4+ counts were 500 or higher. That group lowered their risk of death by 94 percent compared with those who started medication later.

“I think this article really does provide a scientific foundation for a practice that a lot of patients and doctors have already been doing, namely starting medications earlier,” said Brad Hare, medical director of the University of California, San Francisco’s Positive Health Program at San Francisco General Hospital, in a telephone interview today.

Not Conclusive

The results of the study can’t be considered conclusive because the study looked at patient records rather than randomly assigning new patients to take drugs at different stages, said two Harvard Medical School researchers who weren’t involved in the study. Still, the study shows the importance of investigating benefits of earlier treatment, they said.

“The supportive evidence for the benefits of earlier therapy continues to increase,” said Paul Sax and Lindsey Baden, writing in an editorial that accompanied the study. Still, the Harvard researchers wrote, data from the study “do not provide definitive proof that we should start antiretroviral therapy in all patients with HIV infection.”

The study will help guide a debate over whether to change the current federal guidelines and whether the U.S. government should now fund a randomized clinical trial, Hare said.

To contact the reporter on this story: Rob Waters in San Francisco at rwaters5@bloomberg.net.

Last Updated: April 1, 2009 20:50 EDT

Offline jampdx

  • Member
  • Posts: 89
Re: Starting Medication Early
« Reply #1 on: April 02, 2009, 09:12:00 AM »
Could be an April Fools joke. ;) 

Ok, seriously, I've been going back and forth in my head, because so many people support starting right away, and so many don't and say there is no evidence starting before 350 does anything.

My Dr is with the 350 idea.  I'll start reading more and if you find anything else, I'd love to see it.  Thank you for sharing this.
*-*-*-*-*-*-*-*-*-*-*-*-*-*-*-*-*-*-*-*-*-*-Infected 1/6/2009
Positive 2/9/2009
3/8/2009:  CD4 603  VL f\'d up by lab and having to redraw
4/7/2009 CD4 650 VL 348
6/24/2009 cd4 964 VL 850
9/26/2009 CD4 546 VL 822
7/22/13 CD4 1080 VL 2,220

Offline veritas

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Re: Starting Medication Early
« Reply #2 on: April 03, 2009, 05:20:38 AM »


When to Start Antiretroviral Therapy - Ready When You Are?
EDITORIAL (NA-ACCORD)
 
 
 
  NEJM April 1 2009
 
Paul E. Sax, M.D., and Lindsey R. Baden, M.D.
 
The optimal time to start antiretroviral therapy in asymptomatic patients has been one of the central controversies in the care of patients with the human immunodeficiency virus (HIV) since the introduction of the first antiretroviral agent, zidovudine, more than two decades ago.1 Since then, periods of enthusiasm for aggressive early intervention2 have been followed by a more cautious approach.3 This slowly swinging pendulum has been pushed back and forth by the extraordinary benefits of antiretroviral therapy on one side4 and emerging data on its adverse effects on the other.5
 
The absence of a controlled, prospective study comparing early and deferred therapy has forced treatment guidelines to rely largely on data from observational cohort studies.6,7 Currently, these guidelines state that the optimal time to start therapy for an asymptomatic patient with a CD4+ count of more than 350 cells per cubic millimeter is unknown.
 
In this issue of the Journal, Kitahata and colleagues present data from the one of the largest of these observational cohorts, the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD).8 The combined effort of 22 North American prospective research groups, NA-ACCORD evaluated patients with HIV infection who had not undergone previous therapy and who were stratified according to their CD4+ count at baseline: 351 to 500 cells per cubic millimeter or more than 500 cells per cubic millimeter. The investigators compared survival between patients who started antiretroviral therapy within the given CD4+ stratum with those who waited until after the CD4+ count fell below the stratum.
 
The results are striking. Among the 8362 patients with a CD4+ count of 351 to 500 cells per cubic millimeter, deferral of therapy until the CD4+ count had fallen to 350 cells or less was associated with an increase of 69% in the risk of death, as compared with patients who initiated therapy when their CD4+ count was within the designated range. Similarly, among the 9155 patients with a CD4+ count of more than 500 cells per cubic millimeter, deferral of therapy until the CD4+ count fell below 500 cells was associated with a significantly increased risk of death of 94%.
 
The strengths of this study included its relatively large size, the use of advanced statistical methods that attempted to analyze the data in a fashion similar to that of a randomized trial, and the use of survival (rather than AIDS progression or death) as the end point. The use of death from any cause is important in evaluating patients who have higher CD4+ counts, since HIV-related opportunistic infections and cancers develop relatively infrequently in such patients.9 Indeed, in the NA-ACCORD study, the majority of deaths for which cause was available were from "non-AIDS-defining" causes. An additional strength of the study was its ability to minimize lead-time bias by having access to data for patients before antiretroviral therapy was started. In many other cohort studies, such events are either not accounted for10 or must be estimated with the use of historical data.11
 
The strengths of the study notwithstanding, the results of the NA-ACCORD study cannot be considered definitive evidence that everyone with HIV should start receiving antiretroviral therapy. This was not a randomized trial, and the patients who chose to begin therapy early might have differed in other important ways from those who chose to defer therapy - ways that improved survival but were not measured. Although NA-ACCORD investigators tried to account for this potential bias by controlling for known associations with an increased risk of death in patients with HIV infection (e.g., increased rates of coinfection with hepatitis C virus and of injection-drug use), some unmeasured factors inevitably remain. For example, in many ways, patients who were offered and began potent combination antiretroviral therapy with a high CD4+ count in the late 1990s were the ideal patients: highly adherent, committed to doing whatever they could to prevent AIDS, and willing to push through the sometimes punishing side effects and drug-regimen burdens of the early therapies. This sort of "health-seeking" behavior cannot be measured in the NA-ACCORD study yet could still substantially influence outcomes; its effects can be accounted for only in a randomized, prospective study. In addition to differences in baseline factors, such as HCV infection and injection-drug use, the rates of virologic suppression after 12 months of therapy differed between the two groups among patients with a CD4+ count of more than 500 cells per cubic millimeter (81% in the early-therapy group vs. 71% in the deferred-therapy group), which suggests different levels of adherence to therapy.
 
Some additional limitations should be considered. A relatively high proportion (approximately 45%) of patients in each study-specified stratum of CD4+ counts either did not initiate antiretroviral therapy or did not have a decline in the CD4+ count. These patients are not included in the comparative analysis, and we have no way of knowing whether antiretroviral therapy would have been beneficial in this group. Broader use of antiretroviral agents may increase the incidence of viral resistance. However, since data regarding resistance are unavailable at this time, we do not know how an earlier starting strategy would influence future treatment options. Data on certain toxic effects of antiretroviral therapy (most notably, metabolic and morphologic side effects) are not provided, and potential long-term toxicity cannot be addressed. The causes of death are available for only 16% of the patients who died; it will be important to obtain more complete follow-up on these patients to better understand the deleterious effects of poorly controlled HIV infection on end-organ dysfunction. It also must be determined whether some of the deaths might have been related to underlying differences (including lifestyle choices) between the two nonrandomized study groups.
 
Finally, the specific therapies that patients underwent reflected an earlier era in HIV therapy (the median year for starting treatment in these patients was 2000), so a high proportion of patients began regimens containing an unboosted protease inhibitor, a strategy that is no longer recommended, in part because of reduced efficacy in patients with more advanced HIV infection. Conversely, one could argue that the results of the NA-ACCORD study are all the more remarkable, given the numerous improvements in treatment since that time.
 
Even with the above limitations, the NA-ACCORD study adds to a growing body of data supporting earlier treatment for HIV infection. The Strategies for Management of Antiretroviral Therapy (SMART) trial (ClinicalTrials.gov number, NCT00027352 [ClinicalTrials.gov] ) showed that continuous antiretroviral therapy was safer than intermittent antiretroviral therapy; this was true even among patients who had a CD4+ count of more than 350 cells per cubic millimeter but who were not receiving antiretroviral therapy at baseline. Therefore, in some ways, the SMART trial mimicked a study of early versus deferred therapy.12 Another critical observation of the SMART trial was that non-AIDS complications occurred more commonly in patients in the intermittent-therapy group, which suggests that whatever the side effects of antiretroviral therapy, they were not as deleterious as untreated HIV infection.13
 
Potential additional benefits of earlier therapy for HIV may include a lower rate of drug-specific toxic effects, a greater likelihood of achieving a normal CD4+ count, a reduction in immune activation and inflammation, and a decreased risk of HIV transmission. Analyses of cost-effectiveness have shown that antiretroviral therapy also compares favorably with other widely adopted medical interventions.4 Increasing the CD4+ threshold to start therapy at a range of 350 to 500 cells per cubic millimeter would add only a few years of additional therapy onto projected decades of treatment and hence generate a relatively small added lifetime cost. The impending availability of a greater number of generic antiretroviral drugs, including lamivudine in 2010, could further reduce the cost of treatment.
 
As we learned regarding the use of estrogen in postmenopausal women,14 we must be cautious in interpreting observational data despite efforts to control for confounding. The NA-ACCORD data do not provide definitive proof that we should be starting antiretroviral therapy in all patients with HIV infection. Such a conclusion would require data from a randomized, prospective clinical trial, and at least three such studies are either ongoing or planned. However, the supportive evidence for the benefits of earlier therapy continues to increase, making strategies to identify patients with HIV infection before the onset of substantial immunodeficiency all the more compelling.15
 
Five years ago, if an asymptomatic patient with HIV infection and a CD4+ count of more than 500 cells per cubic millimeter wished to start antiretroviral therapy, most experienced clinicians could have made an excellent case why treatment should be deferred. Today, if a similar patient were eager to start, we should be ready and willing to prescribe therapy - with ongoing careful monitoring of toxic effects that could arise during decades of treatment.
 
Dr. Sax reports receiving research support from GlaxoSmithKline, Merck, and Tibotec and consulting fees from Abbott, Bristol-Myers Squibb, Gilead, GlaxoSmithKline, Merck, Pfizer, and Tibotec. No other potential conflict of interest relevant to this article was reported.
 
Source Information
 
From the Division of Infectious Diseases and the Department of Medicine, Brigham and Women's Hospital and Harvard Medical School - both in Boston..
 
This article (10.1056/NEJMe0902713) was published at NEJM.org on April 1, 2009. It will appear in the April 30 issue of the Journal.
 
References
 
1. Friedland GH. Early treatment for HIV: the time has come. N Engl J Med 1990;322:1000-1002.
 

Offline veritas

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Re: Starting Medication Early
« Reply #3 on: April 03, 2009, 05:25:24 AM »

Offline veritas

  • Member
  • Posts: 1,408
Re: Starting Medication Early
« Reply #4 on: April 03, 2009, 05:28:54 AM »

Finally:

'When to Start HAART' Experts Disagree-NEJM Study
 
 
 
  At CROI 2009 the NA-ACCORD group and Dr, Mari Kitahata presented a new analysis: Summary of Antiretroviral Treatment Naïve Studies from CROI: Still Looking for a Consensus on When to Start - written by Susan J. Little, M.D. Associate Professor of Medicine University of California San Diego, USA - (02/27/09)
 
"Participants were randomized to immediate or deferred HAART, beginning at the first CD4 cell count >500 cells/mm3 and using an intention to treat analysis. Patients in the immediate treatment group were required to initiate HAART within 1.5 years of study entry or they were censored and considered protocol "failures". Those in the deferred arm were required to initiate ART within 1.5 years of the time that their CD4 cell count fell below 500 cells/mm3"...."The absolute, all cause mortality for patients who deferred ART was 60% higher and relatively stable for the entire 10 year study period compared to those who initiated immediate ART"....."The median CD4 cell count just prior to initiation of ART was 674 for the immediate HAART group and 390 for the deferred HAART group, with a nearly identical viral load response following 12 months of HAART in the immediate and deferred groups (% with VL <500, 79 vs. 73, respectively)." and Doug Richman came to the microphone and said: "I'm really compelled by Mari's data.....the argument that a randomized trial makes any sense bothers me for several reasons, it would take many many years, hundreds of millions of dollars, and wouldn't it make more sense, since most of the patients who present even in the developed world have low CD4 counts, to identify people who need access to care, use all that money and energy to treat people of higher risk"
 
3 Known Researchers Disagree: Starting HIV Therapy Earlier Saves Lives
 
03.31.09, 08:00 PM EDT
Study casts doubt on notion that antiretrovirals can be postponed till later in infection
 
".....Kitahata said. "We think antiretroviral treatment should be started when the CD4 count is above 500. I feel these data are strong enough that I would start a patient who is ready and willing to begin therapy at a CD4 count above 500.....Five years ago, if a patient with HIV had no symptoms and a CD4 cell count greater than 500, most experienced HIV clinicians would in general counsel not to initiate therapy, due to concerns about drug toxicity, Sax said. Studies such as this suggest that probably all patients with HIV would benefit from treatment. "We'll need to continue monitoring for drug side effects," he said.....Five years ago, if an asymptomatic patient with HIV infection and a CD4+ count of more than 500 cells per cubic millimeter wished to start antiretroviral therapy, most experienced clinicians could have made an excellent case why treatment should be deferred. Today, if a similar patient were eager to start, we should be ready and willing to prescribe therapy - with ongoing careful monitoring of toxic effects that could arise during decades of treatment. Sax & Baden said in their NEJM Editorial........"It must still be recognized that the long-term side effects of the anti-HIV drugs we now use are unknown, and could alter this recommendation after longer patient follow-up," said Dr. Jeffrey Laurence, a professor of medicine at Weill Cornell Medical College in New York City......And A. David Paltiel, an associate professor of public health at Yale University School of Medicine, said the findings highlight one more important point: HIV testing......"We've got to be doing more testing..."
 
"Although the results do not come from a randomized trial, they seem likely to add impetus to a growing movement to start HIV treatment early, according to Paul Sax, M.D., and Lindsey Baden, M.D., both of Harvard Medical School.....The so-called NA-CCORD study "adds to a growing body of data supporting earlier treatment for HIV infection,"....only a full-scale randomized trial -- and several are in the works -- can actually account for all possible confounding factors. For that reason, they argued, the results "cannot be considered definitive evidence that everyone with HIV should start receiving antiretroviral therapy.".....Nonetheless, they said, "the supportive evidence for the benefits of earlier therapy continues to increase."....On the other hand, Dr. Kitahata said earlier this year, the study may not have an immediate real-world impact. "One of the difficult things for us in our population of patients is that we see patients presenting very late in disease and even below 350 (CD4 cells per cubic millimeter),"......"Such delays -- combined with the evidence of the benefit of early treatment -- make "strategies to identify patients with HIV infection before the onset of substantial immunodeficiency all the more compelling," Drs. Sax and Baden said."
 
WEDNESDAY, April 1 (HealthDay News) -- Initiating HIV treatment before the patient's immune system is too badly compromised can dramatically improve survival, a new study finds.
 
The finding may help settle a debate among AIDS experts as to whether powerful antiretroviral drug therapy can be deferred until later in the infection process.
 
On the one hand, experts worry that starting patients early on the potent drug cocktail could increase the medicines' toxic effects. But if treatment begins too late, the drugs might not be as effective.
 
Because patients must continue to take these drugs for the rest of their lives, weighing toxicity against efficacy has been a difficult balance.
 
"The optimal time to initiate therapy for asymptomatic HIV-infected individuals has been unclear," explained lead researcher Dr. Mari M. Kitahata, of the University of Washington, Harborview Medical Center, in Seattle.
 
But in the new study, the Seattle group found that, compared with patients who started treatment early, patients who delayed therapy boosted their odds of dying by either 69 percent or 94 percent, depending on how low the patient's CD4 blood cell count was.
 
The study was released ahead of schedule April 1 by the New England Journal of Medicine. It will appear in the journal's April 30 print issue.
 
For the study, Kitahata's team collected data on 17,517 American and Canadian HIV patients who were receiving treatment from 1996 through 2005. Patients were classified by their CD4+ immune T-cell count, a measure of the strength of the immune system. As HIV disease progresses, the CD4 count drops.
 
Participants were divided into two groups: one group had CD4 counts between 351 and 500 cells per millimeter, while the other group was comprised of patients with CD4 counts above 500.
 
In a first analysis, involving 8,362 of the patients, 25 percent started therapy when their CD4 counts were between 351 to 500, while the other 75 percent deferred treatment until their CD4 counts fell below that threshold.
 
Patients who deferred treatment experienced a 69 percent increase in their risk of dying compared with those who began treatment, the researchers found.
 
In a second analysis, this time including 9,155 patients, 24 percent started treatment at CD4 counts of more than 500 cells per millimeter, while the other 76 percent delayed therapy till after their counts fell below that threshold. In this group, patients who deferred therapy experienced a 94 percent rise in death risk compared to those who began their therapy earlier.
 
"Our study adds to the growing evidence that support earlier initiation of therapy to improve survival," Kitahata said. "We think antiretroviral treatment should be started when the CD4 count is above 500. I feel these data are strong enough that I would start a patient who is ready and willing to begin therapy at a CD4 count above 500 and certainly between 350 and 500," she said.
 
Dr. Paul E. Sax, from the division of infectious diseases and the department of medicine at Brigham and Women's Hospital in Boston, said the study does seem to tilt the argument in favor of earlier treatment.
 
"This study provides us with some of the strongest data that earlier treatment for HIV infection prolongs survival," said Sax, who authored an accompanying journal editorial. "While this study alone doesn't prove the point, it adds to an accumulating body of data that earlier HIV therapy is preferred to waiting."
 
Five years ago, if a patient with HIV had no symptoms and a CD4 cell count greater than 500, most experienced HIV clinicians would in general counsel not to initiate therapy, due to concerns about drug toxicity, Sax said. Studies such as this suggest that probably all patients with HIV would benefit from treatment. "We'll need to continue monitoring for drug side effects," he said.
 
Another expert agreed.
 
"It must still be recognized that the long-term side effects of the anti-HIV drugs we now use are unknown, and could alter this recommendation after longer patient follow-up," said Dr. Jeffrey Laurence, a professor of medicine at Weill Cornell Medical College in New York City.
 
And A. David Paltiel, an associate professor of public health at Yale University School of Medicine, said the findings highlight one more important point: HIV testing.
 
"We've got to be doing more testing," Paltiel said. "There are some 250,000 to 300,000 Americans who don't know that they are HIV infected and therefore cannot enjoy the benefits of earlier intervention."   
 
 
 
 
 
 
 
    view older Articles   Back to Top   www.natap.org   
 
 
 
 
 
 

Offline boi2kwik4u

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  • Posts: 14
Re: Starting Medication Early
« Reply #5 on: April 03, 2009, 03:41:27 PM »
This is frustrating.  My doctors usually follow the CD4 350 idea b4 starting meds...for some?  I have a bud who was at 450 and they started meds on him right away, his VL wasn't that high.

I've been poz 7 years now, no meds, average CD-4 570, VL 20k.   Last check up though my CD-4 was at its lowest 460, VL 13k(previous 101k, a first)  Also I read somewhere to go by ur CD-8 ratio?  .5 down from .7 in 2007.    ???

Offline veritas

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Re: Starting Medication Early
« Reply #6 on: May 05, 2009, 11:11:07 AM »

Another study in favor of starting meds early:
 

Incomplete Reconstitution of T Cell Subsets on Combination Antiretroviral Therapy in the AIDS Clinical Trials Group Protocol 384.
 Gregory K Robbins, John G Spritzler, Ellen S Chan, David M Asmuth, Rajesh T Gandhi, Benigno A Rodriguez, Gail Skowron, Paul R Skolnik, Robert W Shafer, Richard B Pollard
1Massachusetts General Hospital, Harvard Medical School, 2Harvard School of Public Health, and 3Boston University School of Medicine, Boston, Massachusetts; 4University of California-Davis Medical Center, Sacramento, and 5Stanford University Medical Center, Stanford, California; 6Case Western Reserve University School of Medicine, Cleveland, Ohio; and 7Roger Williams Medical Center, Providence, Rhode Island.
Background.@nbsp; Initiation of combination antiretroviral therapy (ART) results in higher total CD4 cell counts, a surrogate for immune reconstitution. Whether the baseline CD4 cell count affects reconstitution of immune cell subsets has not been well characterized. Methods.@nbsp; Using data from 978 patients (621 with comprehensive immunological assessments) from the AIDS [Acquired Immunodeficiency Syndrome] Clinical Trials Group protocol 384, a randomized trial of initial ART, we compared reconstitution of CD4(+), CD4(+) naive and memory, CD4(+) activation, CD8(+), CD8(+) activation, B, and natural killer cells among patients in different baseline CD4(+) strata. Reference ranges for T cell populations in control patients negative for human immunodeficiency virus (HIV) infection were calculated using data from AIDS Clinical Trials Group protocol A5113. Results.@nbsp; Patients in the lower baseline CD4(+) strata did not achieve total CD4(+) cell counts similar to those of patients in the higher strata during 144 weeks of ART, although CD4(+) cell count increases were similar. Ratios of CD4(+) naive-memory cell counts and CD4(+):CD8(+) cell counts remained significantly reduced in patients with lower baseline CD4(+) cell counts (</=350 cells/mm(3)). These immune imbalances were most notable for those initiating ART with a baseline CD4(+) cell count </=200 cells/mm(3), even after adjustment for baseline plasma HIV RNA levels. Conclusions.@nbsp; After nearly 3 years of ART, T cell subsets in patients with baseline CD4(+) cell counts >350 cells/mm(3) achieved or approached the reference range those of control individuals without HIV infection. In contrast, patients who began ART with </=350 CD4(+) cells/mm(3) generally did not regain normal CD4(+) naive-memory cell ratios. These results support current guidelines to start ART at a threshold of 350 cells/mm(3) and suggest that there may be immunological benefits associated with initiating therapy at even higher CD4(+) cell counts. © BioInfoBank Institute   


v


   

 

Offline elf

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Re: Starting Medication Early
« Reply #7 on: May 10, 2009, 07:46:01 PM »
Quote
Early treatment is somewhat controversial but has been shown to restore important virus-specific cellular immune responses that appear to be involved in host responses that control viremia. Early treatment also may limit the extent of viral dissemination, restrict damage to the immune system, protect antigen-presenting cells, and reduce the chance of disease progression. Administration of potent antiretroviral therapy can result in a rapid and sustained decline in the viral load to below the limit of detection within 3 months. Some patients will rebound sooner than others if treatment is not continued. Furthermore, studies of CD4 and CD8 lymphocyte dynamics show restoration of the normal ratio, reflecting recovery of the immune system. Early institution of antiretroviral therapy has the advantage of keeping the viral load low by reducing replication and the appearance of resistant HIV phenotypes. It also may prevent immune depletion because of increased immune stimulation resulting from the strong antigenicity of HIV during primary infection. If acute HIV infection is not treated, the signs and symptoms disappear, along with the viremia. The person enters a prolonged stage of hidden viral replication during which the virus may not be culturable from the blood, and HIV-1 RNA levels may be low or undetectable. During the next 5 to 10 years, lymph node architecture is destroyed, certain CD4 and CD8 cell lines are gradually depleted, and progression to symptomatic disease ultimately occurs.
Manual of Clinical Problems in Infectious Diseases, 5th Edition
Copyright ©2006 Lippincott Williams & Wilkins
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