HIV This Week

Müller V, von Wyl V, Yerly S, Böni J, Klimkait T, Bürgisser P, Ledergerber B, Günthard HF, Bonhoeffer S; the Swiss HIV Cohort Study. African descent is associated with slower CD4 cell count decline in treatment-naive patients of the Swiss HIV Cohort Study. AIDS. 2009 May 20. [Epub ahead of print]

Miller and colleagues investigated the effect of descent (African versus European) on the progression of untreated HIV infections in a prospective cohort study of HIV-1-infected individuals. They estimated the linear rate of decline of the CD4 cell count and the setpoint viral load in patients with sufficient data points. The effect of descent was assessed by multivariate regression models including descent, sex, viral subtype, the earliest date of confirmed infection, age, and the baseline CD4 cell count; the rate of CD4 cell count decline was also analyzed with mixed-effect models and with matched comparisons between patients of African and European descent based on the baseline CD4 cell count. The authors found that the decline slope of the CD4 cell count was significantly less steep (+26.6 cells/mul per year; 95% confidence interval, 12.3-41.0; P < 0.001) in patients of African descent (n = 123) compared with patients of European descent (n = 463), and this effect was independent of differences in the infecting viral subtypes. Matched comparisons confirmed the effect of African descent (P < 0.001). Remarkably, the rate of CD4 cell count decline depended strongly on the viral setpoint in patients of European descent (-46.3 cells/microl per year/log10 RNA copies/ml; 95% confidence interval, -55.8 to -36.7; P < 0.001) but not in patients of African descent. Slower disease progression in patients of African descent might be related to host factors allowing better tolerance of high virus levels in patients of African descent compared with patients of European descent.

Editors’ note: Faster rates of HIV disease progression have been associated with immune activation. Even HIV-negative Africans have evidence of increased immune activation, likely due to prevalent co-infections. Comparing HIV–infected individuals of African and European descent who are exposed to the same low-antigen environment of Switzerland can narrow down differences in disease progression to viral and host factors. This study found no effect of viral sub-type suggesting that host factors must be key in the slower CD4 count decline observed in people of African origin living with HIV in Switzerland. Perhaps it is the lack of Duffy antigen receptors for chemokines (DARC-negative status) on the red blood cells in patients of African descent (see Weijing et al in HIV This Week issue 56).

Crum-Cianflone N, Eberly L, Zhang Y, Ganesan A, Weintrob A, Marconi V, Barthel RV, Fraser S, Agan BK, Wegner S. 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;48(9):1285-92.

Whether human immunodeficiency virus (HIV) seroconverters have been presenting with progressively lower CD4 cell counts over the course of the HIV epidemic is controversial. Additional data on whether HIV might have become more virulent on a population level (measured by post-seroconversion CD4 cell counts) may provide important insights regarding HIV pathogenesis. To determine whether post-seroconversion CD4 cell counts have changed over time, Crum-Cianflone and colleagues evaluated 2174 HIV seroconverters as part of a large cohort study during the period 1985-2007. Participants were documented antiretroviral-naive HIV seroconverters who had a CD4 cell count measured within 6 months after receiving a diagnosis of HIV infection. Multiple linear regression models were used to assess trends in initial CD4 cell counts. The mean initial CD4 cell count decreased during the study period from 632 cells/mm(3) in 1985-1990 to 553 cells/mm(3) in 1991-1995, 493 cells/mm(3) in 1996-2001, and 514 cells/mm(3) in 2002-2007. During those periods, the percentages of seroconverters with an initial CD4 cell count <350 cells/mm(3) were 12%, 21%, 26%, and 25%, respectively. In the multiple linear model, the mean decrease in CD4 cell count from 1985-1990 was 65 cells/mm(3) in 1991-1995 (P < .001), 107 cells/mm(3) in 1996-2001 (P < .001), and 102 cells/mm(3) in 2002-2007 (P < .001). Similar trends occurred with regard to CD4 cell percentage and total lymphocyte count. Similar decreases in initial CD4 cell counts were observed among African American and white persons during the epidemic. A significant decrease in initial CD4 cell counts among HIV seroconverters in the United States has occurred during the HIV epidemic. These data provide an important clinical correlate to suggestions that HIV may have adapted to the host, resulting in a more virulent infection.

Editors’ note: The findings for this large incident cohort (i.e. with a known date of seroconversion), in which 93% had a CD4 cell count measured within 3 months of seroconversion, suggest that initial CD4 counts among seroconverting military men (96% of the cohort were men) declined early in the HIV epidemic in the USA. Possible explanations include changes in the host, virus, or environment over time. Because the decline stabilized after introduction of potent antiretroviral therapy in 1996, it is plausible that treatment has stimulated a loss of viral fitness and diversity. The findings in the literature are conflicting and there are insufficient data to warrant a change in the assumptions about disease progression used in epidemiological modelling. Therefore further studies of the complexities of HIV virulence and host susceptibility are clearly warranted.