Acceleration of increasing plasma HIV RNA load signals incipient progression

Disease progression among HIV-1-infected patients who are late progressors is accompanied by significant increases in HIV RNA load approximately 1 year prior to the onset of decline in CD4+ cell counts, according to results of a longitudinal study of participants in the Multicenter AIDS Cohort Study (MACS). The rise in HIV RNA precedes AIDS onset by nearly 5 years.

Dr. Stephen J. Gange, of Johns Hopkins University Bloomberg School of Public Health in Baltimore, and associates studied 62 HIV-infected individuals who had stable CD4+ cell counts and no clinical progression between 1985 and 1991. By 1996, the researchers found that 20 subjects, deemed “late progressors, ” had progressed to AIDS or had died.

As reported in AIDS Research and Human Retroviruses for September 1, the mean HIV RNA level in 1985 and the slope of viral load between 1985 and 1991 were significantly higher among the late progressors than for the other 42 patients who did not progress.

“Prior to the inflection point, the distribution of HIV RNA slopes of the late progressors…and the nonprogressors…were indistinguishable from each other and from zero, ” Dr. Gange’s group writes. The rate of increase accelerated by a median of 1.7-fold per year after the inflection point among the late progressors, but remained steady among the nonprogressors.

Dr. Gange and his associates suggest that a specific event, or series of events, takes place that knocks HIV out of its steady state of replication.

“One of the things that may be happening is a change in the phenotypic co-receptor usage of the virus, ” Dr. Gange told Reuters Health. The result, he said, could be viral escape from immune control.

The authors note that an HIV RNA increase of 35% per year yielded the best discrimination between the two groups. This rate of increase was associated with a 4.9 relative hazard of progression to AIDS after adjustment for CD4+ count in 1991.

“This raises the possibility that therapy could be deferred until the acceleration in HIV RNA levels begin, ” Dr. Gange’s group suggests. This would require frequent sampling of viral load around suspected inflection points, although this approach has yet to be investigated, the investigators add.

“Methods used to identify the inflection point are best applied to retrospective data, ” Dr. Gange pointed out. However, he added, “We are currently working on implementing a system in which data could be evaluated in a prospective manner, which would be more useful for clinical monitoring.”