US researchers say that only 30% of those in the CD4 cell count band between 200 and 250 cells/mm3 can expect to defer treatment for more than a year once they fall into this category. The findings are published in the December 6 edition of AIDS.
The study was a reanalysis of the Multicenter AIDS Cohort, a group of almost 5000 gay men recruited between 1985 and 1988. An initial analysis of the cohort, published in 1997, has been widely used to support starting antiretroviral therapy before the CD4 cell count falls below 350 cells/mm3. The new analysis seeks to illuminate more clearly the risk of developing AIDS within three years in people with CD4 cell counts between 200 and 350 cells/mm3.
The study is likely to be helpful in clarifying who can safely defer treatment once their CD4 cell count falls below 350 cells/mm3. Current US guidelines recommend that people with CD4 cell counts below 350 should start antiretroviral treatment, but British HIV Association guidelines suggest that treatment can be deferred until the CD4 cell count approaches 200 cells/mm3 – unless viral load is high or the CD4 cell count is falling fast.
The authors say that immediate therapy should be recommended to any patient with viral load above 20,000 copies and a CD4 cell count between 200 and 350 cell/mm3. Current UK guidelines (published in 2001) are not explicit about the viral load level at which therapy should be recommended in this group of patients, noting only that an increased risk of disease progression has been observed at a viral load above 55,000 copies/ml.
The cut off point identified in the study published this week that predicted no progression to AIDS within one year was 20,000 copies/ml. All viral load measurements reported in this study represent the values that would be obtained from using the RT-PCR assay.
The findings show that only 30% of patients with CD4 cell counts between 200 and 350 are likely to be able to safely defer therapy for another year; amongst those in this group with viral load below 20,000 copies, none developed an AIDS-defining illness within one year.
However, within the first year that risk was concentrated very strongly in the group with baseline viral load above 60,000 copies/ml. Only 3% of those with viral load below 60,000 copies/ml developed AIDS within a year, compared to 14% of those with viral load between 60,000 and 100,000 copies/ml, and 31% of those with viral load above 100,000 copies/ml.
The risk of a CD4 cell decline below the 200 cell threshold was greater however; within one year, more than half of patients with viral load in the 20,000-60,000 copies band had experienced a CD4 cell decline to below 200 cells/mm3.
In other words, although the risk of AIDS was not great in those with viral load below 60,000 copies/ml, the risk of deferring treatment would be substantial. A number of cohort studies have now shown that the response to treatment, as measured by illness and death, is significantly poorer in people who start treatment with a CD4 cell count below 200 cells/mm3.
The median CD4 cell decline at different levels of viral load was inconsistent, probably due to small numbers. In those with viral load above 100,000 copies/ml counts in the 350-200 band, the median decline within six months of baseline was –41 cells/mm3. In contrast, a median rise of 42-120 cells was observed in those with viral load below 40,000 copies/ml.
The findings suggest that frequency of monitoring in patients with CD4 cell counts below 350 not on treatment needs to be emphasised in discussions with patients about when to start treatment.
Phair JP et al. Virologic and immunologic values allowing safe deferral of antiretroviral therapy. AIDS 16: 2455-2459, 2002.