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CD4 cell count changes in individuals with counts above 500 cells/mm3 and viral loads below 50 copies/ml on antiretroviral therapy

Phillips, Andrew N.a,b; Youle, Michaela; Lampe, Fionaa,b; Sabin, Caroline Aa,b; Hill, Andrewc; Ransom, Darrena; Gumley, Helena; Loveday, Clivea; Lipman, Marca; Johnson, Margareta

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We prospectively followed 166 individuals on antiretroviral therapy with viral loads less than 50 copies/ml and CD4 cell counts greater than 500 cells/mm3 to ascertain CD4 cell count changes while the viral load remained below 50 copies/ml. On average, CD4 cell counts remained stable and high. Only five patients experienced a decline to below 350 cells/mm3, and these were typically isolated low values with CD4 cell percentages remaining high. Our findings suggest that it may be possible to reduce the frequency of CD4 cell count monitoring in individuals with a value greater than 500 cells/mm3 so long as regular viral load monitoring indicates a value less than 50 copies/ml.

The CD4 cell count and viral load tend to be regularly monitored in individuals on antiretroviral therapy [1–5]. The current aim is to maintain viral load below 50 copies/ml, in order to minimize the risk of the development of resistance, whereas CD4 cell count monitoring is largely to assess the short-term risk of AIDS diseases [1,2,6]. However, increasing numbers of individuals on therapy have CD4 cell counts above 500 cells/mm3, for which the associated risk of AIDS diseases is very low [6,7]. Furthermore, CD4 cell counts tend to increase or remain stable in individuals with viral loads less than 50 copies/ml on antiretroviral therapy [4,5,8]. This suggests that in individuals on antiretroviral therapy with viral loads less than 50 copies/ml and CD4 cell counts greater than 500 cells/mm3, it may not be necessary to monitor CD4 cell counts frequently, so long as the viral load remains less than 50 copies/ml. In order to investigate this further we assessed CD4 cell count changes after two consecutive values greater than 500 cells/mm3 in individuals with viral loads continually less than 50 copies/ml on antiretroviral therapy.

We followed 166 patients from the Royal Free Clinic in London, from a time at which the viral load was less than 50 copies/ml and the CD4 cell count was greater than 500 cells/mm3. Baseline (time zero) was the date of the second consecutive CD4 count value greater than 500 cells/mm3. Follow-up was until the last viral load/last CD4 cell count or the time of the first viral load greater than 50 copies/ml (whichever occurred first). All patients were on at least three antiretroviral drugs. CD4 cell counts were measured with a frequency of one per 10 weeks [interquartile range (IQR) 8–12 weeks], whereas the while viral load was measured with a frequency of one per 12 weeks (IQR 9–15 weeks).

The median CD4 cell count at time zero was 657 cells/mm3 (IQR 582–790; range 501–1345), whereas the median previous CD4 cell count nadir was 253 (IQR 167–347; range 1–1294). At time zero patients had been on HAART for a median of 105 weeks. The median follow-up time was 47 weeks (IQR 24–73), over which time a median (IQR) of four (two to six) viral load measures (all < 50 copies/ml, by design of the analysis) and four (three to seven) CD4 cell counts were performed. The median change in the CD4 cell count per 4 weeks, from time zero until the final value during follow-up, was +2 cells/mm3 (IQR −9 to +12; range −286 to +127). The minimum value during follow-up ranged from 262 to 1222 cells/mm3 (median 580; IQR 486–676). A total of 46 patients (28%) had at least one value less than 500 cells/mm3. The median decline from time zero to this minimum value was 73 cells/mm3 (range 0–500). There was only one occurrence of an AIDS disease during the total 162 person-years of follow-up; a lymphoma that occurred at a CD4 cell count of 635 cells/mm3(CD4 cell count nadir 296 cells/mm3).

We investigated further the five individuals (3%) who experienced a CD4 cell count below 350 cells/mm3during follow-up. Details are given in Table 1. All five were aged under 50 years. The CD4 cell percentages at the time were available, and ranged from 22 to 32%. To put these values in perspective, we assessed the mean CD4 cell count according to the CD4 cell percentage, based on the first CD4 cell count in 2585 individuals in the entire Royal Free cohort. The median CD4 cell count among those with CD4 cell percentages of less than 5, 5–9, 10–14, 15–19, 20–24, 25–29, 30–34 and greater than 35% were 21, 129, 238, 344, 449, 548, 651 and 772 cells/mm3, respectively. Table 1 also includes the subsequent value for the patients who experienced a CD4 cell count below 350 cells/mm3. Each showed an increase.

Table 1:
Details of CD4 cell counts/percentagess experienced by five patients who experienced a CD4 cell count less than 350 cells/mm3 despite an initial CD4 cell count greater than 500 cells/mm3and a viral load continuously less than 50 copies/ml.

Taken together, these results suggest that the CD4 cell count decreases to levels below 350 cells/mm3 are rare in individuals with CD4 cell counts initially above 500 cells/mm3 and with continuing viral suppression. When this does occur it seems likely to be transient and to be associated with a CD4 cell percentage that is higher than that normally observed in individuals with such a CD4 cell count. Factors such as rest before blood sampling [9] and early morning sampling [10] are known to be associated with lower CD4 cell counts and these could have played a role. It is also important to consider the possibility of falsely negative viral load values, for example caused by non-B subtype virus.

The cost of diagnostic procedures such as CD4 cell counts are a small percentage of the total care costs [11], and newer technologies are resulting in considerably cheaper assays [12]. In addition, patients and clinicians use continuing high CD4 cell counts as positive feedback on the benefits of treatment. However, our results suggest that in those with a sustained viral load less than 50 copies/ml and two consecutive CD4 cell counts greater than 500 cells/mm3, CD4 cell counts tend to remain stable and high. Further follow-up on extended numbers of patients in a variety of settings is required, but our findings suggest that it may be possible to reduce the frequency of CD4 cell count monitoring in those with a value greater than 500 cells/mm3, so long as regular viral load monitoring indicates a value less than 50 copies/ml.

Andrew N. Phillipsa,b

Michael Youlea

Fiona Lampea,b

Caroline A Sabina,b

Andrew Hillc

Darren Ransoma

Helen Gumleya

Clive Lovedaya

Marc Lipmana

Margaret Johnsona


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© 2002 Lippincott Williams & Wilkins, Inc.