HAART can be safely interrupted for over a year by patients with lowest ever CD4 cell count above 250 and a sustained treatment CD4 cell count of 500 or more

Individuals who started HAART with a lowest ever CD4 cell count above 250 cells/mm³ and achieved a sustained increase in CD4 cell count above 500 cells/mm³ appear to be able to safely interrupt HIV therapy for over a year, according to an international study published in the February 18^th edition of AIDS. It is likely that the investigators’ findings will be viewed with considerable interest by researchers involved in the SMART study into the safety and efficacy of CD4 cell guided treatment interruptions.

The team of investigators from Italy and Sweden wished to determine the risks and benefits of CD4-guided treatment interruptions using data obtained from observational cohorts. In particular, they wished to see which patients with higher CD4 cell counts at the time of treatment interruption would be able to remain off treatment for longer. They therefore identified patients whose nadir CD4 cell count was between 250 – 350 cells/mm³ and who had a CD4 cell count of at least 500 cells/mm³ at the time of discontinuing HAART in seven patient cohorts in Italy and Sweden. Data were gathered on the duration of treatment interruption, new clinical events and the effect of interrupting treatment on fasting lipids. Study endpoints were a fall in CD4 cell count to below 350 cells/mm³ or patient request to recommence therapy.

A total of 139 patients were included in the investigators’ analysis. All were over 18 years of age, had been taking HAART for at least twelve months. At the time HAART was commenced, the patients had a median CD4 cell count of 417 cells/mm³, and at the time of treatment interruption this had increased to a median of 800 cells/mm³. In total 43 individuals (31%) had a nadir CD4 cell count between 250 – 350 cells/mm³.

When treatment was interrupted, HAART had been taken for a median of 3.5 years. Investigators included individuals who did not have full HIV suppression in their analysis, and at baseline only 63 patients (61%) had a viral load below 50 copies/ml.

In total, 63 patients resumed treatment or experienced a fall in their CD4 cell count to below 350 cells/mm³ over a median of 75 weeks of therapy interruption. Of these 63 patients, 33 (52%) experienced a fall in their CD4 cell count to below 350 cells/mm³, the remaining individuals recommencing treatment before their CD4 cell count fell to this level.

The investigators calculated that the rate of therapy resumption or CD4 cell count decline below 350 cells/mm³ was significantly lower in patients with a higher nadir CD4 cell count (p = 0.03), with HIV suppression below 50 copies/ml for twelve months or longer (p = 0.008), and for patients with higher viral loads at the time of interruption (p = 0.008). The investigators believe that patients with detectable HIV at baseline may have been non-adherent patients and that non-adherent patients may have been less likely to wish to resume therapy after interruption.

According to further calculations, the investigators estimated patients with a nadir CD4 cell count between 2510 – 350 cells/mm³with a CD4 cell count above 500 cells/mm³ at the time of treatment interruption would be able to interrupt therapy for a median of 61 weeks.

Clinical events

One patients developed disseminated herpes simplex and PCP pneumonia when his CD4 cell count was 205 cells/mm³ at week 87 of the study. In total 212 person years of follow-up were provided by patients in the study, giving an incidence rate of new AIDS events of 1 per 212 person years of follow-up. There were no deaths. Six patients developed minor symptoms of HIV infection, but non restarted HAART.

Lipids

At baseline 39 patients had elevated triglycerides and during the interruption of treatment they returned to normal at least once in 26 individuals (66%). Using the last available measurement, 30% of individuals had normal triglycerides.

In total 13 patients had abnormally high cholesterol before interruption HAART. During their break from treatment cholesterol levels returned to normal in ten patients ((77%), and were still normal in 61% when the investigators looked at the last available measures.

“Our analysis has shown that the duration of CD4 cell-guided interruptions was longer in patients who had a higher nadir CD4 cell count”, write the investigators, adding “most importantly, our data demonstrate that people starting therapy with a CD4 cell count between 250 – 350 cells/mm³, the level recommended by the current international treatment guidelines, can safely interrupt therapy - maintaining CD4 cell counts above 350 cells/mm³ - for a reasonably long time if they had previously attained a CD4 cell count above 500 cells/mm³ on therapy.”