Inizio terapia sopra i 350 CD4:
raccomandazioni dei medici del Johns Hopkins
Iniziare la terapia quando anti hiv quando i CD4 sono 350:
la voce del British Medical Journal
Inizio terapia sopra i 350 CD4: raccomandazioni dei medici del Johns Hopkins
I ricercatori di uno dei centri leader nelle terapie anti-HIV americano suggeriscono di iniziare la terapia prima di quanto viene consigliato dalle linee guida per favorire il ritorno dei CD4 a livelli normali.
Lo studio è pubbicato nel numero di febbraio del Clinical Infectious Diseases e lo riportiamo a seguito, in lingua originale tratto dal sito di Aidsmap
Articolo di Michael Carter, Tuesday, January 09, 2007
Investigators from one of the US?s leading HIV treatment centres suggest that anti-HIV therapy may need to be started earlier than is currently recommended to enable CD4 cell counts to return to normal levels. In a study published in the February 15th edition of Clinical Infectious Diseases, researchers from Johns Hopkins University in Baltimore established that after six years of HIV suppression with antiretroviral therapy, individuals who started HIV therapy with a CD4 cell count above 350 cells/mm3 were much more likely to experience a sustained increase in their CD4 cell count to normal, or near normal levels. The investigators also established that in all patients, regardless of their immune status at baseline, CD4 cell increases leveled off after four years of anti-HIV treatment.
“These data suggest that commencement of [HIV therapy] at a lower CD4 cell count will result in a CD4 cell count that does not return to normal levels; this may be a reason to consider starting [treatment for HIV] before the CD4 cell count decreases to <350 cells/mm3”, write the investigators.
The aim of potent anti-HIV therapy is to achieve sustained suppression of HIV replication, which allows the recovery of the immune system. It is not yet clear if long-term use of HIV therapy will allow CD4 cell counts to return to normal levels. However, studies so far suggest that gains in CD4 cell counts may plateau within two years of treatment being commended, and only one study (which found increases up to seven years after treatment initiation) has looked at changes in CD4 cell count after five years of HIV therapy.
HIV treatment guidelines currently recommend that the initiation of HIV therapy should be delayed until CD4 cell counts have declined to 350 – 200 cells/mm3. Investigators at Johns Hopkins University wondered what the immunological outcome of six years of virologically effective HIV therapy would be, if it was commenced according to these guidelines: would CD4 cell counts would increase to normal levels, or would plateau at less-than-normal.
Their analysis included 655 patients who had sustained HIV suppression (a viral load below 400 copies/ml) after commencing HIV therapy. The patients were stratified according to their baseline CD4 cell counts (below 200 cells/mm3; 201 – 349 cells/mm3; and, above 350 cells/mm3) and annual changes in CD4 cell count were plotted for each group of patients. Analyses were also conducted to see if factors such as gender, race, age, HIV risk group, and hepatitis C coinfection status affected immune restoration during long-term HIV therapy.
The median age of the patients was 39 years, 69% were male, 70% were black, and injecting drug use was the commonest cause of HIV transmission (38%, followed by 31% sex between men, 22% heterosexual transmission).
After six years of HIV therapy, median CD4 cell count increased by a median of 274 cells/mm3, to a median of 544 cells/mm3.
Amongst patients whose baseline CD4 cell count was below 200 cells/mm3 median CD4 cell count increased to 493 cells/mm3. Patients who started HIV treatment with a baseline CD4 cell count between 201 – 349 cells/mm3 had a median CD4 cell count of 508 cells/mm3 after six years of potent HIV therapy, and individuals who initiated antiretroviral therapy with a CD4 cell count above 350 cells/mm3 had a median CD4 cell count of 829 cells/mm3 at the end of follow-up.
For all three groups of patients, there was a significant increase in CD4 cell count for the first four years of antiretroviral therapy (p < 0.05) before they reached a plateau for the final two years of analysis.
The investigators then looked to see what proportion of patients from each baseline strata achieved CD4 cell counts above 500 and 750 cells/mm3. They found that 42% of patients with a baseline count below 200 cells/mm3 had a CD4 cell count above 500 cells/mm3 after six years of HIV treatment, as did two-thirds of patients whose baseline CD4 cell count was between 201 ? 349 cells/mm3 and 85% if individuals who had a baseline CD4 cell count above 350 cells/mm3.
When the investigators looked to see what percentage of patients achieved CD4 cell counts of above 750 cells/mm3 after six years of viral suppression with HIV therapy, it was revealed that 12% of patients with an initial CD4 cell count of below 200 cells/mm3, 21% of those with baseline counts between 201 ? 349 cells/mm3, and 46% of individuals with a baseline CD4 cell count above 350 cells/mm3 achieved this outcome.
In multivariate anaylsis, a baseline CD4 cell count above 350 cells/mm3 was a significant predictor (p = 0.01) of greater CD4 cell gains with six years of suppressive HIV therapy. Older patients (above 45 years) experienced significantly lower gains in CD4 cell count (p = 0.03), as did individuals who had injecting drug use as their HIV risk activity (p = 0.001).
Choice of anti-HIV drug (protease inhibitor versus a non-nucleoside reverse transcriptase inhibitor) did not affect significantly affect CD4 cell gains, nor did coinfection with hepatitis C virus, gender or race.
“Among patients receiving [HIV therapy] who achieve durable suppression of HIV load to <400 copies/ml, an increase in CD4 cell count is achieved and maintained in all CD4 cell strata to 6 years”, write the investigators. However, they add, “only patients with a baseline CD4 cell count above 350 cells/mm3 had CD4 cell counts that returned to nearly normal levels.”
The investigators conclude, “we recommend that consideration be given to initiation of [HIV therapy] at a CD4 cell count above 350 cells/mm3 to achieve better immune recovery.”
Moore RD et al. CD4+ cell count 6 years after commencement of highly active antiretroviral therapy in persons with sustained virologic suppression. Clin Infect Dis 44 (on-line edition), 2007.
Iniziare la terapia quando i CD4 sono 350:la voce del British Medical Journal
Rivedere le linee guida per raccomandare l’inizio della terapia a 350 CD4: anche il leader medico del BMJ conferma la tendenza di molti medici nel voler anticipare l’inizio della terapia anti-HIV ed inoltre il governo USA ha deciso di finanziare un grande studio internazionale per indagare sui benefici ottenuti da un inizio accelerato.
A favore di questa raccomandazione c’è anche una migliore conoscenza dei reali effetti collaterali delle terapie (evitando quando possibile di inserire farmaci come il d4T e l’AZT che sono i responsabili delle maggiori modifiche lipidiche), del modo in cui evitarli o ridurli al minimo e della reale potenza, durata, tollerabilità e convenienza dei farmaci.
Riportiamo di seguito l’articolo in lingua originale tratto sempre dal sito di Aids Map
Start HIV treatment when CD4 cell count is 350, says leading HIV doctors in BMJ
Articolo di Michael Carter, Friday, January 12, 2007
HIV treatment guidelines should be revised to recommend the initiation of antiretroviral therapy when an individual?s CD4 cell count falls to 350 cells/mm3, according to leading HIV physicians writing in the January 13th edition of the British Medical Journal.
There is an increasing trend for doctors to consider the earlier initiation of HIV therapy. A study from United States reported recently on aidsmap found that patients who started HIV therapy with a CD4 cell count above 350 cells/mm3 were significantly more likely than those who delayed until their CD4 cell count was in the currently recommended 250 ? 200 cells/mm3 range to experience an increase in their CD4 cell count to normal levels after long-term antiretroviral therapy.
Furthermore, the US government is backing a large international trial to investigate the benefits of commencing HIV therapy at higher CD4 cell counts.
Why the current guidelines and why are they being questioned?
Side-effects, questions about the viability of long-term adherence, and fears about the exhaustion of HIV treatment options led to the development of treatment guidelines that favoured the postponement of HIV therapy.
Current UK HIV treatment guidelines state that, although HIV therapy should be considered when an patient’s CD4 cell count has fallen to 350 cells/mm3, it should only be strongly recommended to individuals whose CD4 cell count has fallen to between 250 – 200 cells/mm3, or who are ill because of HIV.
However, an increasing body of recent research is favouring the earlier initiation of HIV treatment. The SMART treatment interruption study found, for example, that patients with CD4 cell counts between 200 ? 250 cells/mm3 had a significantly greater risk of experiencing HIV disease progression. Furthermore, the DAD study of HIV treatment side-effects found that individuals with CD4 cell counts in the region of 200 – 250 cells/mm3 had an increased risk of death from certain non-AIDS-defining illness, such as heart disease, liver disease and some non-HIV-related cancers.
An improved understanding of side-effects also supports the earlier initiation of treatment, say the authors. The disfiguring body fat changes associated with early potent anti-HIV regimens have been found to be, primarily, caused by thymidine analogues (d4T, and to a lesser extent, AZT), the use of which is now avoided where-ever possible. It is also increasingly being understood how to avoid the cardiovascular complications that antiretroviral treatment can cause.
HIV therapy, the authors further argue, now has sufficient potency and convenience, to support its earlier initiation.
“e therefore suggest that guidelines should now recommend starting treatment at around 350 cells/mm3, so long as the patient is ready”, write the authors.
For patients with higher CD4 cell counts the authors say there is “need for an international randomised trial in patients with a CD4 count above 500 cells/mm3 comparing immediate treatment with deferral of treatment until CD4 cell count reaches 350 cells/mm,sup>3.” Such a study is being planned by the National Institutes of Health in the US, and aims to enroll 9,000 HIV-positive adults and children in both resource-rich and resource-poor countries around the world.
HIV therapy is now sufficiently potent, durable, convenient and tolerable to make such a study possible, the authors believe.
However, in resource limited settings the authors write, “the priority for initiation should continue to be those with the greatest level of immunodeficiency, where the clinical benefits are greatest.”
Phillips AN et al. When should antiretroviral therapy for HIV be started BMJ 334: 76 , 78, 2007.