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Did HIV Become More Virulent in First Decade of US Epidemic?
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48th ICAAC, October 25-28, 2008, Washington, DC
Mark Mascolini
HIV-1 appeared to become nastier in the first 10 years of the US epidemic, according to results of a study tracking first CD4 count and other immune cell levels after diagnosis [1]. But since about 1996, virulence of the retrovirus appeared to be stable in this largely male US population.
Tri-Service AIDS Clinical Consortium investigators analyzed first CD4 counts after HIV diagnosis in 1944 people diagnosed in four periods: 1985-1990, 1991-1995, 1996-2001, and 2002-2004. This prospective cohort study includes US Department of Defense beneficiaries seen at 7 centers.
All 1944 people in this analysis had a documented HIV-negative test followed by an HIV-positive test an average of 18 months apart. The negative-to-positive window stretched up to 4 years. No one took antiretrovirals before their first CD4 count, and everyone had their count measured within 6 months of HIV diagnosis. The study cohort was 47.2% white, 39.7% black, and 13.1% of other racial or ethnic groups. Only 4.4% were women.
Average first CD4 count fell by 133 cells from 1985 through 2004:
⋅ 632 (standard deviation [SD] 276) in 1985-1990
⋅ 555 (SD 249) in 1991-1995 (P < 0.0001 versus 1985-1990)
⋅ 495 (SD 213) in 1996-2001 (P < 0.0001 versus 1985-1990)
⋅ 499 (SD 216) in 2002-2004 (P < 0.0001 versus 1985-1990)
The first-CD4 difference between 1996-2001 and 2002-2004 was not statistically significant. In the 1985-1990 group, 12% had a first count below 350, compared with 26% in 1996-2001 and 25% in 2002-2004.
A statistical model that adjusted for length of seroconverting window, time from positive HIV test to first CD4 count, age, gender, race, enrollment site, body mass index (when available), and viral load (when available) determined that the 1991-1995 cohort had an average initial CD4 count 62 cells lower than the 1985-1990 group (P < 0.0001); the 1996-2001 cohort had an average first CD4 count 105 cells lower than the 1985-1990 group (P < 0.0001); and the 2002-2004 cluster had an average first CD4 count 113 cells lower than the 1985-1990 group (P < 0.0001). Four variables independently predicted a higher initial CD4 count--shorter seroconverting window, lower initial viral load, younger age, and white, non-Hispanic race. Gender and body mass index did not predict initial CD4 count.
First total lymphocyte count and first white blood cell count followed the CD4 trends, but first CD8 count did not change substantially over the study periods. Changing patterns of these other immune cells did not account for the falling initial CD4 counts in these analyses.
The researchers suggested their findings "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." Whether results in a military population with free medical care apply to the whole US population is uncertain.
An 800-person Swiss study using different measures of HIV virulence found no evidence of increasing or decreasing virulence in European residents of Switzerland diagnosed with HIV from 1984 through 2003 [2]. The Swiss team reckoned virulence in three ways--declining CD4 count slope, declining CD4-CD8 ratio slope, and first stable viral load after infection (viral set point), all measured before antiretroviral therapy began. The first two of these yardsticks account for changing T-cell quotients over time, while all the yardsticks in the US study involved measures at a single point.
"Both highly virulent and attenuated strains have apparently been unable to spread at the population level," the Swiss researchers concluded. "This result suggests that either the evolution of virulence may be slow or inhibited due to evolutionary constraints, or HIV-1 may have already evolved to optimal virulence in the human host."
References
1. Crum-Cianflone NF, Eberly L, Zhang Y, et al. Is HIV becoming more virulent? Initial CD4 cell counts among HIV seroconverters across the HIV epidemic: 1985-2007. 48th Annual International Conference on Antimicrobial Agents and Chemotherapy (ICAAC). October 25-28, 2008. Washington, DC. Abstract H-4051.
2. Muller V, Ledergerber B, Perrin L, et al. Stable virulence levels in the HIV epidemic of Switzerland over two decades. AIDS. 2006;20:889-894.
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