CD4 cell count below 250 associated with shorter treatment break

A lowest ever CD4 cell count between 200 – 250 cells/mm³ is associated with faster reinitiation of therapy in patients who took a break from antiretroviral therapy, according to a Canadian study published in the November 15^th edition of the Journal of Infectious Diseases (now available online). The investigators also found that the presence of specific HIV genotypes, which studies before the availability of effective anti-HIV therapy had shown to be a predictor of rapid loss of CD4 cells, were associated with a shorter duration of treatment interruption.

“The results of our study suggest that treatment interruption is a viable option for HIV-positive adults without an AIDS-defining illness and with nadir CD4 cell counts above 250 cells/mm³”, write the investigators.

Treatment interruptions are being explored as ways of reducing HIV-positive patients’ exposure to antiretrovirals. The aims are to reduce side-effects, make adherence easier, and reduce the costs of therapy.

Investigators in British Columbia wished to determine the factors associated with the reinitiation of antiretroviral in patients taking a break from anti-HIV therapy between 1999 and 2003. In particular, the Canadian researchers wanted to see if a patient’s lowest ever – nadir – CD4 cell count was associated with the duration of a treatment break.

They also hypothesised that the presence of “11/25” HIV genotypes would be associated with a shorter duration of treatment interruption. These HIV genotypes are associated with syncytium-inducing HIV phenotype, which in the era before effective anti-HIV drugs became available, was associated with a rapid loss of CD4 cells and a shorter survival time.

The investigators conducted a retrospective chart review to identify patients who had a nadir CD4 cell count above 200 cells/mm³ who took a treatment break. Genotyping was performed on stored plasma samples. Information was also gathered on the date when the treatment break was initiated, the date when antiretroviral therapy was restarted, CD4 cell count and viral load before the treatment break, during the treatment interruption, and after the treatment interruption. Individuals were monitored monthly and were advised to restart anti-HIV treatment if their CD4 cell count fell below 200 cells/mm³ (indicating a risk of potentially life-threatening opportunistic infections), or if they developed symptoms of HIV disease.

A total of 197 patients were included in the investigators’ analysis. Most (91%) were male and the median pre-antiretroviral CD4 cell count was 385 cells/mm³. At the time when the treatment break was started, the median CD4 cell count was 620 cells/mm³ and median viral load was under 50 copies/ml.

By the end of February 2003, 30% of patients had restarted antiretroviral therapy. The median duration of the break from anti-HIV treatment in these patients was 15 months. Factors significantly associated with restarting treatment in the investigators’ initial analysis included a pretreatment baseline CD4 cell count below 250 cells/mm³ (p 3 (p 3 when the treatment break was taken (p = 0.007), the presence of the 11/25 genotype (p = 0.069) and a detectable viral load at the time the interruption of therapy was initiated (p = 0.05).

In further analysis which adjusted for a patient’s age and viral load at the time the treatment break was started, the investigators found that only a lowest ever CD4 cell count below 250 cells/mm³ (p

Of the patients who restarted treatment, 81% had a viral load below 50 copies/ml after 15 months of therapy. Six deaths occurred in patients taking a break from antiretrovirals, but none were related to the treatment interruption.

“This information should be valuable when considering a treatment interruption”, conclude the investigators.