Individuals who started highly active antiretroviral therapy (HAART) when their CD4 cell count was still reasonably strong and their viral load was below 70,000 copies/ml may be able to safely interrupt HIV therapy for a protracted period of time, according to a study published in the August 1st edition of Clinicial Infectious Diseases. Although two thirds of patients restarted anti-HIV therapy within three years of commencing a treatment break, there were no AIDS-defining events, and all patients achieved good immunological results after restarting HAART.
Guidelines concerning the best time to initiate anti-HIV therapy have evolved since HAART first became available. Most current guidelines, including those of the British HIV Association (BHIVA), recommend that HAART should be initiated in asymptomatic individuals when their CD4 cell count falls to 200 cells/mm3 and considered on an individual basis when the CD4 cell count is between 200 and 350 cells/mm3.
Many patients who had no symptoms of HIV infection commenced therapy under more conservative guidelines at higher CD4 cell counts. However, there are limited data concerning the safety of interrupting anti-HIV treatment in patients whose CD4 cell count was between 300 – 500 cells/mm3 when HAART was started.
Spanish investigators therefore wished to "evaluate the long-term effect of discontinuation of therapy and to assess how asymptomatic HIV-infected patients could safely remain free of therapy." The endpoints of the study were the slope of CD4 cell decline in the absence of HIV therapy, and the investigators also assessed the factors associated with longer duration of treatment interruption.
A total of 46 individuals were enrolled to the study starting in December 1999. All the patients started HAART with a CD4 cell count between 300 – 500 cells/mm3 and a viral load below 70,000 copies/ml. Individuals were also required to have been taking HAART for a minimum of six months and to have had a viral load below 50 copies/ml for at least four months.
The patients had a median age of 41 years, three quarters were male, 66% had sex between men as their HIV risk activity and just under 25% were coinfected with hepatitis C virus.
Median CD4 cell count nadir before HAART initiation was 488 cells/mm3 with median pre-HAART viral load being a little under 35,000 copies/ml. At the time of treatment interruption the median CD4 cell count was 793 cells/mm3 and the median period for which patients had had an undetectable viral load was 19 months.
"A rapid rebound of viral load to baseline levels occurred after four months without therapy, followed by a relatively stable plateau during the rest of the follow-up period", observed the investigators.
Decrease in CD4 cell count occurred in two phases. In the first four months a steep decline in CD4 cell count, by a median of 173 cells/mm3 occurred. Between months five and 20 of follow-up CD4 cell count continued to decline, but less steeply, falling by a median of 234 cells/mm3.
In multivariate analysis, the increase in CD4 cell count during HIV therapy (p = 0.001) and CD4 cell count at the time of the discontinuation of HAART (p = 0.002) respectively were associated with the slope of CD4 cell decline in the first four months of treatment interruption and CD4 cell decline between months five to 36 of discontinuation.
After twelve months of treatment interruption, 71% of patients remained off therapy; this figure falling to 48% after 24 months and 35% after 36 months. No new AIDS-defining events were recorded.
In multivariate analysis, longer duration of an undetectable viral load whilst taking HAART was significantly associated with a higher probability of reinitiating therapy (p = 0.003).
Genotypic analysis was performed on 30 patients who restarted HAART and none had resistance to antiretroviral drugs. Patients restarted their earlier HAART regimen and after four months the median increase in CD4 cell count was 161 cells/mm3 and 90% had a viral load below 50 copies/ml.
It was estimated that the treatment break saved the hospital pharmacy department over 600,000 euros in drug costs.
"This study suggests that asymptomatic HIV-infected patients with a low risk of progression to AIDS who started antiretroviral therapy with a CD4 cell count of 300 – 500 cells/mm3 and a HIV viral load below 70,000 copies can safely discontinue therapy for prolonged periods", conclude the investigators. However they caution, "because of the risk of immunological deterioration during the period without therapy, patients who discontinued treatment should be closely monitored."
Fernandez Guerrero ML et al. Long-term follow-up of asymptomatic HIV-infected patients who discontinued antiretroviral therapy. Clin Infect Dis 41: 390 – 393, 2005.