CD4 cell counts and CD4 percentages measured soon after infection with HIV declined significantly between 1985 and 2001 in a large group of patients who had recently seroconverted, according to a retrospective analysis of patient records by Dr Nina Crum-Cianflone and team at the AIDS Clinical Consortium, Bethesda. The downward trend in CD4 counts at seroconversion appears to have leveled off in more recent years.
This study set out to examine whether CD4 cell counts in people newly infected with HIV (seroconverters) are changing over time. Any such trends could reflect long-range changes in the virulence of the virus. Very few studies have looked at this question, with conflicting results; one large-scale analysis of multiple cohorts from Europe, Australia and Canada (published in 2007) did find that early CD4 cell counts declined between 1985 and 2002.
This investigating team evaluated retrospective data from 1944 patients who seroconverted between the years 1985 and 2004. The participants were racially diverse, from differing geographic areas, antiretroviral naïve, and had a CD4 cell count recorded within six months of their HIV diagnosis. The cohort was predominantly male. The mean age was 29 years. (Average age slowly increased over the time periods in the study, from 27 years to 30 years; this was controlled for in the results.)
Seroconversion was documented by consecutive HIV-negative and HIV-positive tests. For the majority of participants, the time at which they seroconverted could be determined within two years. The majority of participants (92%) had their first CD4 measurement within 90 days of their HIV diagnosis.
The unadjusted average CD4 cell count for the period from 1985-1990 was 632 cells/mm3, 555 cells/mm3 for the interval 1991-1995, 495 for 1996-2001, and 499 for 2002-2004. The raw analysis, not adjusting for any other variables, found that the average post-seroconversion CD4 cell count decreased by 133 cells/mm3 between 1985-1990 and 2002-2004.
In the full analysis, CD4 counts were adjusted for the period of uncertainty around the exact seroconversion date, the time from the HIV-positive test to the first CD4 cell count, age, gender, race, enrolment site, and viral load (in the 990 people for whom viral load data were available). This adjusted analysis found significant declines up until 2001 but not thereafter. Compared to the period 1985-1990, those who seroconverted in 1991-1995 had CD4 cell counts an average of 62 cells/mm3 lower, and, in 1996-2001, 105 cells/mm3 lower (p
However, the decline from the period 1996-2001 to 2002-2004 was not significant (p = 0.98).
Similar decreasing trends in CD4 percentage and total lymphocyte count were noted, but not in CD8 cell count. Higher post-seroconversion CD4 cell counts were also associated with lower initial viral load, younger age, and white/non-Hispanic race.
The investigators concluded that a "significant decline in initial CD4 counts among seroconverters occurred during the first decade of the epidemic, with stabilization since the mid-1990s. Patterns of change in other immune cells such as the white blood cell count do not account for [this] decline. These data provide an important clinical correlate to studies suggesting that HIV may have adapted to the host, by HLA adaptation or CTL escape, resulting in a more virulent infection."
Crum-Cianflone NF et al. Is HIV becoming more virulent? Initial CD4 cell counts among HIV seroconverters across the HIV epidemic: 1985-2007. 48th Interscience Conference on Antimicrobial Agents and Chemotherapy, poster abstract H-4051, Washington DC, 2008.