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CD4 below 400 and platelets at 50000
Jun 18, 2009

Hello! My 28-year-old bf has been hiv positive for 20 months.His first tests (January 2008) : VL 10000 and CD4 840.He has blood taken for tests every 4 months since. His latest tests (May 2009) :CD4 below 400 said the doctor, although his VL has fortunately not gone up. The thing is that his platelet count has been dropping this 1,5 half year to the point of 50000 ,while giant platelets are identified under the microscope. Is thrombocytopenia itself causing a drop in CD4 number? The doctors say he should start therapy (Reyataz/Norvir/Truvada) by the end of June. Would you recommend the starting of therapy too? Will waiting a little more put him at risk both as HIV and thrombocytopenia are concerned? Thank you so much in advance!

Response from Dr. Frascino

Hi,

Thrombocytopenia is not a cause of decreasing CD4 counts. However, HIV itself can cause both a drop in platelets and CD4 cells. There are a number of causes for thrombocytopenia other than HIV that your HIV specialist (or a hematologist) should screen for.

Starting combination antiretroviral therapy is a personal decision and often a difficult one. Personally I favor very early intervention if the HIVer is motivated and ready to start. You can read much more about this in the archives of this forum. I'll repost below a small sample of what you can find there.

Good luck to both you and your boyfriend. Make sure your boyfriend knows about this site, as there is a wealth of information here that he may find beneficial.

Dr. Bob

should I start med with 8ooo vdl (WHEN TO START TREATMENT, 2009) May 31, 2009

I have been recently diagnose hiv My wife tested neg I would like to know should I begin med now with vidal 856 or waituntil they go down

Response from Dr. Frascino

Hi,

I've addressed this topic numerous times. See below.

Dr. Bob

Tired (WHEN TO START TREATMENT, 2009) May 31, 2009

Hi Dr Bob. 2 weeks ago i had a routine blood test whch gave low neutrophile counts 1.200 X mm3 an d low Hb 11 and Hematocrit of 34 I got concerned and had an HIV test, this came back positive. My viral load is 6.000 and my CD4 257, the Dr says I must start treatment, is this correct? Besides feeling a bit tired sometimes, I feel fine. Thank you Paco

Response from Dr. Frascino

Hello Paco,

I'm sorry to hear about your recent diagnosis. If indeed your CD4 count is in the middle-250 range, I would strongly suggest you begin combination antiretroviral therapy without delay. Since this was your first test, if possible I would recommend repeating your CD4 count and HIV plasma viral load and also obtaining a resistance test (genotype). This will allow for confirmation that there was no laboratory or clerical error. Plus, the resistance test will help in selecting the best medications to include in your first regimen. I'll reprint some information from the archives that discusses beginning treatment. I would also suggest you read the information in the chapter "Just Diagnosed" that can be easily accessed on The Body's homepage. From there you can proceed to review the wealth of other information on this site.

Good luck. I'm here if you need me, OK?

Dr. Bob

Should meds be NOW considered? (WHEN TO BEGIN TREATMENT) Dec 26, 2008

Hello Dr. Bob.. Happy Holidays.. and may your coming year be as bright as a shining star.. I recently did my labs on received my results..CD4..453 and viral load 44,000. I have some minor discomfort such as swollen lymph nodes in the groin area and infrequent joint pains in elbow and knees. Do u recommend and consider the start of ARV treatment? Please give me your feedback because I am getting worried whether my immune system is rapidly degenerating.

Response from Dr. Frascino

Hello,

The optimal time to begin antiretroviral therapy remains a hotly debated topic as we learn more about HIV pathogenesis and natural history and develop new, more potent, less toxic medications. I'll try to give you an update on where things stand at the moment, but I would strongly suggest you discuss your situation with your HIV physician specialist, as there are many variables that must be taken into consideration for each individual situation. There is no one right answer for everyone. When it comes to beginning antiretroviral therapy it's a case of "one size fits one!"

A new study presented at the recent AIDS meetings in Washington, D.C. suggested HIV-positive folks should begin antiretroviral therapy sooner than the guidelines currently recommend (CD4 count of 350). The large study found that delaying the start of treatment until the CD4 count falls to 350 nearly doubles the risk of death during the next few years when compared to the risk of death in patients who began treatment earlier (CD4 count under 500). The survival benefit, however, must be weighed against the chances of drug toxicities and side effects. There is also the risk that poor regimen adherence could breed a drug-resistant strain of virus. There are, however, now three recent studies all showing that HIV-positive folks who begin antiretrovirals while CD4 counts are above 350 have a better chance of their counts returning to the normal range (600-1,200) than those who delay treatment until the CD4 count falls below 350.

Personally, as an immunologist, I strongly recommend early intervention with antiretrovirals if the person is ready, willing and motivated to begin taking the medications.

I should also mention there are situations in which we currently start antiretroviral therapy immediately despite CD4 cell counts. These conditions include patients with concurrent hepatitis and certain types of kidney disease and those who are pregnant.

Ultimately, I'm confident there will come a day when any HIV positive patient diagnosed will be advised to begin antiretroviral therapy as soon as they are diagnosed. This year we've seen treatment guidelines for beginning antiretrovirals increase from a CD4 count of 200 to 350. I think it's likely that this trend will continue with a formal recommendation to consider treatment at a CD4 count of 500 in the near future. Stay tuned to The Body. We'll keep you posted as the guidelines are revised. My personal recommendation is to begin antiretroviral therapy as early as possible in most situations, being fully cognizant that there are risks involved and that our scientific knowledge is still incomplete.

Hope that helps.

Dr. Bob

Shingles Starting Treatment & Queen Issues (SHINGLES AND HIV, 2009) (WHEN TO START ANTIRETROVIRAL TREATMENT, 2009) Feb 18, 2009

Hi Dr Bob, Three weeks ago I came down with Shingles. A small patch on the back of my neck and a little across my chest all on the left side. I went to my local GP and he gave me Valtrex ( the 7 day shingle pack)Since then the pain has gone and the Shingles have crusted over ...yet are still present albeit not as visible. Ive been POZ since 20th july 2007 and am NOT ON HAART....do you think having Shingles is a sign that my CD4T cells have fallen below 500??? I have a meeting with my HIV Dr in 1 months time for my usual LABS (cd4 & viral load) Do you think if my CD4 T cells have fallen below 500( even though experts say below 350) i should start treatment?

Also im seeing dark circles appear under my eyes...Im 33 yrs old ..is this simply age related or Low CD4 T cells and high viral load?? I drink plenty of water and have no family background of "dark circles /bags " under eyes...maybe its AGE ..aaarrrggghh And Mardi Gras is only a few weeks away...HELP!?!?!

Thanks, Drew (Sydney, Australia)

Response from Dr. Frascino

G'day Aussie Drew,

Relax mate! Approximately 95% of healthy adults are seropositive for varicella zoster virus (VZV), the virus that causes shingles. Of this 95%, about 5% of healthy adults develop zoster (shingles). The risk for those of us with HIV is between 15 and 25 times greater. However, getting shingles (unlike many opportunistic infections) does not correlate with CD4 counts.

As for what your next CD4 count and/or HIV plasma viral load will be, I really have no way of predicting. (I don't know what your previous counts have been.) It's a good idea to wait a month or so after an intercurrent infection (like shingles) before checking your counts, because viral loads may well rise transiently and CD4 counts fall transiently as a consequence of any infection.

As for the optimal time to begin antiretrovirals, having just returned from the HIV/AIDS meetings in Montreal, I can advise you this topic continues to stimulate lively debate among HIV specialists. Recent studies, such as the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD), which included more than 8,000 patients from 22 North American prospective clinical cohorts, are designed to answer the question of when to start therapy. The investigators in this study found a 70% greater mortality in patients who deferred beginning treatment until their counts dropped to 350 compared to those who started treatment with counts between 350 and 500. This study was an "observational" cohort study and therefore there is the possibility of selection bias, etc. However, the results are certainly intriguing. It's also worth noting there are now several other studies that have also found lower mortality, morbidity, drug toxicity and/or improved CD4 counts with initiation of antiretroviral therapy at CD4 counts above 350. Current guidelines, as you mention, recommend treatment for all patients with CD4 counts below 350. However, with results of large studies suggesting earlier treatment is better coupled with the recent approval of new and novel antiretroviral therapies which appear to be better tolerated, less toxic, more convenient and less risky if adherence is not perfect, the treatment pendulum certainly seems to be swinging back in the direction of early intervention. Personally, I encourage earlier intervention if the HIVer is willing and motivated to begin. Ultimately, I think we'll be discussing "when not to start" rather than "when to start" treatment.

Would I recommend treatment if your counts are 500 or less at your next blood draw? I certainly would discuss the option of starting with you to ascertain if indeed you were ready, willing and motivated to do so. If so, yes, I'd recommend you start.

As for the dark circles, no, that's not HIV related. You've just probably had too many Fosters at the pub plus too many late nights at the Midnight Shift.

Enjoy Mardi Gras, Drew. I've got plenty of fond memories of the many Sydney Mardi Gras that I attended! I've even toyed with the idea of heading to Oz for this year's party as well. (Save me a dance, OK?)

Dr. Bob

Early Initiation of Antiretroviral Therapy Improves HIV Survival Rates, Study Says

April 30, 2009

The New York Times on Thursday examined a study that found asymptomatic HIV-positive people who delayed antiretroviral treatment until their disease reached an advanced stage faced higher mortality rates than those who initiated treatment earlier. According to the Times, current national guidelines recommend starting HIV-positive people on antiretroviral treatment when CD4+ T cell counts fall below 350; however, the recent study suggests that initiating treatment earlier could reduce the risk of death. The study, as well as a related editorial, appeared online in the New England Journal of Medicine earlier this month and both will appear in the April 30 edition of the journal. In addition, a separate study published online earlier this month in the journal Lancet developed similar conclusions about the benefits of earlier antiretroviral therapy initiation, the Times reports.

For the NEJM study, researchers led by Mari Kitahata, director of clinical epidemiology at the Center for AIDS and Sexually Transmitted Infections at the University of Washington, tracked survival rates for 17,517 asymptomatic HIV-positive people in the U.S. and Canada who received care from 1996 to 2005 and who had never previously taken antiretroviral therapy. For their first analysis, the researchers examined a group of 8,362 patients, 2,084 of whom started therapy when CD4+ counts were between 351 and 500. They also examined 6,278 participants with similar CD4+ counts who delayed therapy until their counts declined below 350. According to the study, the patients who delayed treatment had a 69% higher risk of death compared with those who initiated treatment earlier. For the researchers' second analysis, they examined 9,155 HIV-positive people with CD4+ counts of more than 500. Of those, 2,220 started therapy within six months, while 6,935 delayed therapy. Among those who postponed treatment, 3,881 experienced a decline in CD4+ levels and 539 started antiretroviral treatment within six months of having a CD4+ count of 500 or less. In addition, the researchers found that those who deferred therapy had a 94% greater mortality risk than those who initiated treatment earlier.

According to Kitahata, the study examined "one of the most important questions in the last decade: what the optimal timing is for starting therapy." She added that the recent research "provides evidence that patients would live longer if antiretroviral treatment was begun when their CD4+ count was above 500." According to the Times, the study is "not the final word on the matter" (Rabin, New York Times, 4/30).

The study is available online.

Related Editorials Two related editorials also appeared in the April 30 edition of NEJM. Summaries appear below.

"When To Start Antiretroviral Therapy: Ready When You Are?:" Although the results of Kitahata's study are "striking," they "cannot be considered definitive evidence that everyone with HIV should start receiving antiretroviral therapy," Paul Sax and Lindsey Baden of the Division of Infectious Diseases at Brigham and Women's Hospital write. They continue that despite the researchers' "relatively large" sample size and use of "advanced statistical methods," their study 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." Sax and Baden add that "a conclusion would require data from a randomized, prospective clinical trial, and at least three such studies are either ongoing or planned." They conclude that despite the study's "limitations," evidence supporting the benefits of earlier antiretroviral therapy "continues to increase, making strategies to identify patients with HIV infection before the onset of substantial immunodeficiency all the more compelling" (Sax/Baden, New England Journal of Medicine, 4/30).

"Rationing Antiretroviral Therapy in Africa: Treating Too Few, Too Late:" Although the international health community has achieved "striking advances" in increasing access to antiretroviral treatment in Africa, "too few people are receiving treatment" and health workers "are waiting until people are symptomatic" before administering antiretroviral therapy, Nathan Ford -- head of the medical unit of Medicines Sans Frontieres in Cape Town, South Africa, and research associate at the School of Public Health and Family Medicine at the University of Cape Town -- and colleagues write. They continue that although "delaying therapy may mean saving money on drugs," the "long-term cost of such delays is increased substantially by the need for more intensive clinical care, decreased income and likely regimen switches." In addition, later antiretroviral initiation "encourages the spread of tuberculosis" and could increase the risk of HIV transmission "by allowing patients to remain viremic longer," the authors write. They conclude, "The battle to start providing antiretroviral therapy in the developing world has been won. The battle to provide the best care we can is just beginning" (Ford et al., New England Journal of Medicine, 4/30).

Study Supports Earlier Antiretroviral Treatment, Researchers Call for Amended Recommendations

April 9, 2009

In in the journal Lancet on Thursday, researchers published findings that they say support calls for starting antiretroviral treatment earlier than some current recommendations, AFP/Yahoo! News reports. According to AFP/Yahoo! News, there are no universal guidelines for when HIV-positive people should begin highly active antiretroviral therapy, but a common recommendation is to begin the treatment when CD4+ T cell counts decline below 200 to 250. Some researchers argue that this recommendation is too low and that more lives could be saved if the treatment was started sooner, according to AFP/Yahoo! News.

For the study, Jonathan Sterne of the University of Bristol and colleagues compared previous studies that followed more than 45,000 HIV-positive people in Europe and North America (AFP/Yahoo! News, 4/8). The data for the study included 21,247 HIV-positive people followed from 1989 to 1995 -- before antiretroviral treatments were developed -- and 24,444 HIV-positive people since 1998, according to Reuters. All of the participants had not progressed to AIDS and had CD4 cell counts of less than 550. In addition, none of the participants reported a history of injection drug use (Reuters, 4/8). According to the study, people who began antiretroviral treatment when their CD4 counts were less than 350 were 28% more likely to develop AIDS or die prematurely than those who began treatment with CD4 counts of 351 to 450. The study also said that the findings support earlier HIV treatment initiation, particularly as new antiretrovirals have fewer side effects than earlier treatments. The study said, "In view of diminished concerns about toxic effects and resistance, our results suggest that 350 cells per microliter should be the minimum threshold at which antiretroviral therapy is started" (AFP/Yahoo! News, 4/8). According to the researchers, the beneficial effects of earlier treatment initiation were especially significant during the first two years of treatment.

The researchers also conducted a repeat analysis among 4,605 HIV-positive injection drug users, which showed similar results. The authors said the results "should be applicable to many patients starting or considering starting combination therapy in developed countries." In a related commentary also published in Lancet, Robin Wood and Stephen Lawn -- both of the University of Cape Town in South Africa -- said that the "question of when to start [antiretroviral treatment] might have more than one right answer." Wood and Lawn noted that the risk-to-benefit ratio of early antiretroviral treatment initiation remains uncertain in developed countries, adding that in low-income settings, the prevalence of AIDS and AIDS-related deaths are typically higher both before and after starting treatment. In the commentary, the authors suggested randomized trials that take into consideration such issues in both types of settings (Reuters, 4/8).

Study Supporting Earlier Antiretroviral Treatment "Not Definitive," NEJM Editorial Says

April 10, 2009

Although the results of a study comparing early and deferred antiretroviral treatment scheduled to be published in the April 30 issue of the New England Journal of Medicine are "striking," they "cannot be considered definitive evidence that everyone with HIV should start receiving antiretroviral therapy," Paul Sax and Lindsey Baden of the Division of Infectious Diseases at Brigham and Women's Hospital write in an NEJM editorial.

According to the authors, 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." Current antiretroviral treatment guidelines state that the "optimal time to start therapy for an asymptomatic patient ... is unknown." The study found that patients who did not begin antiretroviral therapy until their CD4+ T cell counts were 350 or less had a 69% increased risk of death, while those who did not begin antiretroviral therapy until their T cell counts were 500 or less had an "increased risk of death of 94%." The authors add that although the study had a "relatively large" sample size, used "advanced statistical methods" and used "survival (rather than AIDS progression or death) as the end point," it 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."

The editorial adds that the study could not measure the "sort of 'health-seeking' behavior" of "patients who were offered and began potent combination antiretroviral therapy with a high T cell count in the late 1990s." The authors write that these patients were "ideal" because they were "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." In addition, about 45% of patients in "each study-specified stratum of T cell counts either did not initiate antiretroviral therapy or did not have a decline in the T cell count," yet because they are not a part of the comparative analysis, "we have no way of knowing whether antiretroviral therapy would have been beneficial in this group," the authors write. They add that it "will be important" to follow up with these patients to "better understand the deleterious effects of poorly controlled HIV infection on end-organ dysfunction" and determine whether "some of the deaths might have been related to underlying differences (including lifestyle choices) between the two nonrandomized study groups."

AdvertisementSax and Baden add that although the study has some "limitations," it "adds to a growing body of data supporting earlier treatment for HIV infection." The editorial concludes that "a conclusion would require data from a randomized, prospective clinical trial, and at least three such studies are either ongoing or planned" but that evidence supporting the benefits of earlier antiretroviral therapy "continues to increase, making strategies to identify patients with HIV infection before the onset of substantial immunodeficiency all the more compelling" (Sax/Baden, New England Journal of Medicine, 4/30).



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