HIV Becoming More Virulent? |
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.
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.
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).
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).
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
Higher CD4 count correlated with younger
age, white race/ethnicity, lower initial HIV viral load, and shorter seroconverting
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.
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."
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.
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.
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.