Viral response to antiretroviral therapy slower during acute HIV-1 infection

The decline in plasma HIV-1 RNA following the initiation of highly suppressive antiretroviral therapy is slower in acutely infected patients than in those with chronic HIV-1 infection, according to a report in the December 22nd issue of AIDS. Dr. Frank de Wolf, of the University of Amsterdam, the Netherlands, and colleagues compared the rates of decline in plasma HIV-1 RNA following the start of highly suppressive antiretroviral therapy in five patients with acute HIV-1 infection. The patients began treatment within 2 to 5 weeks of their first symptoms. The researchers also looked at 12 patients with chronic infection.

Consistent with prior reports, the rate of decline in plasma HIV-1 RNA increased significantly after the start of therapy in the acutely infected patients. “This suggests that large amounts of drug-sensitive virus have escaped the immune system early in infection, assuming the immune response plays a role at this early stage,” Dr. de Wolf’s group writes. However, the rate of decline in plasma HIV-1 RNA was significantly slower in acutely infected patients than in chronically infected patients at 2 weeks. The less rapid decline in viral load persisted in the acutely infected patients at 2 months, but it was not statistically significant. While the slopes of the HIV-1 RNA curves were inversely correlated with baseline HIV-1 RNA levels, this association did not entirely account for the difference in response rates between the two groups of patients, the researchers report. Proportions of activated CD4+ and CD8+ T cells did not differ between the two groups.

After discounting the possibility of a difference in antiretroviral sensitivity or pharmacokinetics between the acutely and chronically infected patients, the authors found that the difference in RNA slope with therapy was “the result of lower clearance of productively infected cells and higher burst size per cell per unit time.”

“This may be the result of a still growing immune response,” Dr. de Wolf’s group suggests, “allowing infected cells to live longer and produce more virus per unit time and giving HIV-1 the opportunity to establish the infection, despite antiretroviral therapy.”