Disadvantage from prior nucleoside therapy persists for years during HAART

Even a short period of nucleoside therapy prior to highly active antiretroviral therapy (HAART) confers an increased risk of viral rebound, researchers report in the 15 October issue of The Journal of Infectious Diseases. What’s more, they found, the greater risk of rebound persists for several years.

Dr Andrew N Phillips, of Royal Free and University College Medical School in London, and colleagues there and at Goethe University in Frankfurt reviewed data that are routinely collected on HIV-infected patients at their centres. They selected 1433 patients who achieved viral suppression, defined as viral load <400 HIV RNA copies/mL, within 24 weeks after first starting HAART. Of these, 409 were nucleoside experienced and 1024 were naive to antiretrovirals.

Confirming previous research, the risk of viral rebound was greater among the patients with pre-HAART nucleoside experience (relative hazard [RH], 2.86; p < 0.0001) than among drug-naive patients, the researchers determined. This was true even for the group of 94 nucleoside-experienced patients who started two new nucleoside drugs as part of starting HAART.

“This perhaps suggests that there is more cross-resistance between nucleoside analogue drugs than has been appreciated,” Dr Phillips and his associates comment.

They found that the risk of viral rebound was elevated even for patients who used nucleoside therapy for <2 months before beginning HAART (RH, 1.95; p = 0.009). “A period of suboptimal adherence to a HAART regimen, for example by taking only two of the three drugs, could have similar long-term consequences,” Dr Phillips told Reuters Health.

He and his colleagues note that the finding “may have consequences for the use of short-term monotherapy regimens in pregnant women”.

Among both nucleoside-experienced and drug-naive patients, the risk of viral rebound decreased as the duration of viral suppression increased (p < 0.0001). But the greater risk for nucleoside-experienced patients compared with drug-naive patients persisted into the third year of viral suppression (p = 0.0007).

“We need to extend follow-up to see if the rate of rebound continues to decline, and if it becomes similar in people with similar duration of viral suppression, regardless of pre-HAART nucleoside experience,” said Dr Phillips. “We also need to see if particular changes in nucleosides when starting HAART are associated with more durable suppression.”

Findings such as those reported here, he said, “illustrate the value of the observational clinic-based cohorts which follow patients for very long periods of time, documenting all treatment changes prospectively.”

Phillips AN, Staszewski S, Lampe F et al. Human Immunodeficiency Virus Rebound after Suppression to <400 Copies/mL during Initial Highly Active Antiretroviral Therapy Regimens, according to Prior Nucleoside Experience and Duration of Suppression. J Infect Dis 2002 Oct 15;186(8):1086-91