By Liz Highleyman

The advent of effective combination antiretroviral therapy has dramatically improved the prognosis for people with HIV, but at the same time, the virus may be evolving to be more aggressive, according to an analysis presented this week at the 48th International Conference on Antimicrobial Agents and Chemotherapy (ICAAC) in Washington, DC.

One indicator of HIV virulence is how rapidly it kills CD4 T-cells. Nancy Crum-Cianflone and colleagues from the Infectious Disease Clinical Research Program at Uniformed Services University of the Health Sciences sought to determine whether initial post-seroconversion CD4 counts have changed over the course of the epidemic.

The investigators evaluated 1944 racially diverse HIV seroconverters who received care at 7 military HIV clinics across the U.S. from 1985 through 2004. Participants were treatment-naive, had documented HIV negative and positive dates (an average of 18 months apart), and had a CD4 count measurement within 6 months of their HIV diagnosis. Most (96%) were men, about half were white, about 40% were black, and the mean age was about 29 years (increasing over the study period).

Linear regression was used to assess trends in initial CD4 cell count across calendar periods, adjusted for patient age, sex, race/ethnicity, enrollment site, length of seroconverting window, time from HIV positive test to CD4 cell measurement, and HIV viral load when available (n = 990).

Results

• The average post-seroconversion CD4 count decreased by 133 cells/mm3 over the course of the HIV epidemic:

• 632 cells/mm3 for 1985-1990;
• 555 cells/mm3 for 1991-1995;
• 495 cells/mm3 for 1996-2001;
• 499 cells/mm3 for 2002-2004.

• CD4 count was < 350 cells/mm3 -- the current threshold for starting antiretroviral therapy -- in 12% of patients who seroconverted in 1985-1990 compared to 25% who did so in 2002-2004 (P < 0.0001).

• After adjusting for all covariates, seroconverters during 2002-2004 had post-seroconversion CD4 counts 113 cells/mm3 lower than seroconverters during 1985-1990 (P < 0.001).

• Patients who seroconverted during 1991-1995 and 1996-2001 also had CD4 cell counts significantly lower than those who did so during 1985-1990 (P < 0.0001).

• There was no significant difference, however, between CD4 counts of people who seroconverted during 1996-2001 compared with 2002-2004.

• Higher CD4 count correlated with younger age, white race/ethnicity, lower initial HIV viral load, and shorter seroconverting window.

• Similar decreasing trends in CD4 percentage and total lymphocyte count were also observed, but not in CD8 T-cell count or white blood cell count.

Based on these findings, the researchers concluded, "A significant decline in initial CD4 counts among seroconverters occurred during the first decade of the epidemic, with stabilization since the mid-1990s."

"These data provide an important clinical correlate to studies suggesting that HIV may have adapted to the host, by HLA adaptation or [cytotoxic T-lymphocyte] escape, resulting in a more virulent infection," they continued.

"The AIDS virus may have learned how to evade early detection from the body's own defenses," Dr. Crum-Cianflone explained in an ICAAC media release. "This means that when a person contracts the AIDS virus, the virus may begin to spread and severely weaken the body (by destroying vital immune "CD4" cells) before the body even has a chance to try to respond."

TriService AIDS Clinical Consortium/Infectious Disease Clinical Res. Program, Bethesda, MD.

10/31/08

Reference
NF Crum-Cianflone, l Eberly, Y Zhang, and others. Is HIV Becoming More Virulent? Initial CD4 Cell Counts among HIV Seroconverters Across the HIV Epidemic: 1985-2007. 48th International Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2008). Washington, DC. October 25-28, 2008. Abstract H-4051.