French investigators have found no evidence that HIV is becoming more virulent. In a study published in the online edition of AIDS, they report that three important prognostic markers, CD4 cell count, viral load and HIV DNA levels, remained unchanged in patients recently infected with HIV between 1996 and 2007. “We observed no temporal trends in the values of three major predictors of HIV-1 disease progression…as measured during primary HIV-1 infection”, comment the investigators.
The virulence of infectious agents often changes over the course of an epidemic. There are a large number of HIV subtypes and the virus is constantly mutating. This suggests that it is theoretically possible that it could evolve to become more virulent.
Earlier research investigating the virulence of HIV over time has yielded conflicting results. Although some research has found no such evidence, a recently published US study found that the CD4 cell counts of individuals recently infected with HIV fell significantly in the early stages of the epidemic.
Much of the previous research into the virulence of HIV has been limited because it did not control for potentially confounding factors such as smoking, symptoms of primary HIV infection or ethnicity.
Investigators from the French ANRS PRIMO cohort of HIV seroconvertors therefore conducted an analysis of the CD4 cell counts, viral load and HIV DNA levels of individuals recently infected with HIV between 1996 and 2007. Their study involved 903 patients, and their analyses were controlled to take account of patient characteristics.
The patients were diagnosed with HIV a median of 47 days after infection. Mean age was 35 years and 94% were infected via sex. Most (84%) were gay men and the predominant strain of HIV was subtype B. However, over the course of the study the proportion of patients diagnosed with non-B subtypes increased, and there was also a small increase in the proportion of African patients.
Median CD4 cell count was 519 cells/mm3, with median viral load being 125,000 copies/ml and median HIV DNA 3.33 log10 copies/106.
The investigators’ first set of statistical analysis showed that neither CD4 cell count nor viral load at diagnosis changed significantly over the period of analysis. However, there was a significant increase in HIV DNA level (p = 0.01). This disappeared once the investigators introduced calendar year into their model, with all three prognostic markers remaining stable throughout the period 1996 to 2007.
Further analysis showed that certain patient characteristics could affect all three prognostic markers. For example, women had higher CD4 cell counts and lower viral loads and HIV DNA levels than men. CD4 cell counts were approximately 100 cells/mm3 higher in smokers than non-smokers. Patients born in Africa had lower CD4 cell counts than individuals born in other regions (p
“We found that initial CD4 cell counts and HIV RNA [viral load] and DNA levels were stable across 12 consecutive years…suggesting that HIV-1 virulence has remained stable”, comment the investigators.
They add, “to our knowledge this is the first study of calendar trends in three major prognostic markers of HIV-1 disease progression measured at the time of primary infection. Moreover, contrary to most previous studies, the analyses were adjusted for most known confounding factors”.
Troude P et al. No evidence of a change in HIV-1 virulence since 1996 in France: a study based on the CD4 cell count and HIV RNA/DNA levels at the time of primary infection. AIDS 23 (online edition), 2009.