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Some studies have suggested that as the HIV epidemic progresses, infected patients are presenting at progressively lower CD4-cell counts, perhaps reflecting an increase in the virulence of the virus. However, the results have been inconsistent and often confounded by a lack of information about known dates of seroconversion.
The U.S. military provides a unique opportunity to study this issue because active-duty personnel are screened for infection at regular intervals and thus have reliable seroconversion windows. In the Tri-Service AIDS Clinical Consortium, investigators evaluated initial CD4-cell counts (assessed within 6 months of HIV diagnosis) among 2174 treatment-naive individuals with documented HIV seroconversions between 1985 and 2007.
Initial CD4 counts declined during the study period, from a mean of 632 cells/mm3 in 1985–1990 to 553 cells/mm3 in 1991–1995, 493 cells/mm3 in 1996–2001, and 514 cells/mm3 in 2002–2007. The absolute decline across time blocks was statistically significant, and the decreases were similar between blacks and whites. In addition, the proportion of patients with initial CD4 counts <350 cells/mm3 increased over time, from 12% to 21%, 26%, and 25%, respectively.
Crum-Cianflone N et al. Is HIV becoming more virulent? Initial CD4 cell counts among HIV seroconverters during the course of the HIV epidemic: 1985–2007. Clin Infect Dis 2009 May 1; 48:1285.
Comment
Whether the observed decrease in initial CD4-cell counts after seroconversion is attributable to changes in the host, virus, or environment is unclear. The authors speculate that most of the change is due to the virus, with HIV adapting to host defenses, specifically by evolving in ways that engender poorer initial cytotoxic T-lymphocyte responses. Of note, the biggest decline in CD4-cell counts was observed early in the HIV epidemic, which suggests that the introduction of potent antiretroviral therapy might have inhibited the pace of viral evolution, perhaps by increasing the transmission of drug-resistant viruses that have impaired virulence or by limiting viral diversity over time. These intriguing observations illuminate the fascinating interplay between virus and host and suggest that the interaction continues to evolve in ways that could influence treatment decisions and patient outcomes in the future.