Treatment interruptions are safe in patients with CD4+ count between 300 to 500 cells/mm3 and viral loads lower than 70,000 copies/mL

Treatment interruptions are of great interest to patients and clinicians, especially those patients who have been on antiretroviral medications for some time or who started highly active antiretroviral therapy (HAART) when their CD4+ count was still relatively high.

The primary reasons for considering treatment interruptions (TI) are to decrease the toxicity of HAART and improve the immune response to HIV, although the likelihood of the latter appears dubious in chronically-infected patients, but TI carries some risk, including significant declines in CD4+ counts and the risk of opportunistic infections and other adverse events that can occur.

Several studies presented at the 42nd ICAAC examined the safety of treatment interruptions.

In an observational study by Molina and colleagues, HAART was discontinued in a cohort of 49 patients who started antiretroviral therapy with CD4+ counts between 300 to 500 cells/mm3 and viral loads between 10,000 and 70,000 copies/mL. Nineteen of the patients were on dual antiretroviral therapy and 30 were on HAART at the time of discontinuation.

At the time ART was discontinued, the patients’ mean CD4+ count was 769 cells/mm3 and viral load was 704 copies/mL. Four months after stopping therapy, the mean CD4+ count was slightly less than 600 cells/mm3 and the viral load was approximately 35,000 copies/mL.

At the end of follow up (about 16 months), the mean CD4+ count in patients continuing off therapy was approximately 500 cells/mm3 and the viral load was approximately 45,000 copies/mL. Of 10 patients who restarted therapy the only difference between these patients and those who remained off therapy was their time of maintaining a viral load <200 copies/mL, 27.7 and 15 months, respectively (p=0.006).

The patients who restarted the same therapy that they had discontinued did well, with overall a significant recovery in CD4+ count and decrease in viral load, with seven of 10 reaching <20 copies/mL and the other three being ≤500 copies/mL.

The authors conclude: “Discontinuation of HAART in asymptomatic HIV-infected patients with baseline values of CD4+ greater than 350 cells/mm3 and viral loads lower than 70,000 copies/mL is a safe practice that may improve quality of life, avoid drug side-effects and save money. It did not seem to compromise the activity of ART in the future.

Multiple studies have shown that patients who were not treated too early in the HAART euphoria in the late 90s will loose CD4-cells and will have a viral rebound.

The concept of structured treatment interruptions (off and on) is currently flawed by the fact that resistance can occur and that the concept is often not so attractive to patients. Currently the concept of drug holidays limited by CD4 and/or viral load end points (e.g. <300 CD4, >100.000 copies/ml) appear to be gaining favour. These may lead to clinically relevant periods without drug toxicity.

The prerequisite of this approach is that you have enough CD4’s to sacrifice and that you have no AIDS related disease which may worsen (CMV-retinitis, systemic KS etc.).

M Molina et al. Discontinuation of Highly Active Antiretroviral Therapy (HAART) in Asymptomatic HIV-Infected patients with CD4+ Counts Greater Than 350 and Viral Load Lower Than 70.000 Copies. Abstract 1082. 42nd ICAAC, September 27 – 30, 2002, San Diego, CA.

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