Clinical issues arising from a single treatment interruption
Simon Collins, HIV i-Base
Further caution on the effects of a single treatment interruption (TI) was suggested from results of a German study presented by Dr C. Hoffman. Although the study was non-randomised (probably the only ethical arrangement for such a study) it was prospective, and importantly compared the results of a drug holiday to a matched control group who continued HAART without a break.
All patients were monitored for HIV-related history, and at 3-month intervals for CD4 cells, VL, triglycerides (TG), cholesterol, ALT, G-GT, AP, lipase, bilirubin, ART and HIV/AIDS events. In TI patients laboratory parameters are also assessed during TI. Follow-up was available of 110 TI patients and 140 controls. Mean baseline CD4 was 439 and 427 respectively with around 20% of each group with viral load <20 copies/mm3 and 20% detectable. 31% in each group had experienced a previous AIDS defining illness.. The median period of drug interruption was 5.6 weeks.
As would be expected, viral load levels increased following a break in treatment, and as with similar studies, even among those patient who had undetectable viral load at baseline, only 67% regained this level at 12 months after the break. After 4 weeks of treatment interruption, CD4 counts dropped by an average of – 56 cells/mm3. Although this returned to baseline 6-12 months after restarting treatment. Patients in the control arm had a continued increase of approximately 60 cells/mm3 over the same period.
Two people in the TI group, and one in the continued treatment arm developed new AIDS defining illnesses. However, the interruption produced a significant reduction in blood lipid levels but only minor changes in ALT and G-GT.
Apart from people who originally started treatment earlier than recommended by current guidelines, the patient group likely to benefit from a treatment interruption strategy, looks increasingly likely to be dependent on whether their baseline CD4 count can withold such a drop.
Other studies has have also shown that there is little overlap between the brevity of the risk period for CD4 decline and longer period required to reverse either toxicity or resistance.
C. Hoffmann, E. Wolf, J. Schardt, et al – Drug holidays (DH) in HIV+ patients: clinical issues. In: Program and Abstracts of the Fifth International Congress on Drug Therapy in HIV Infection, October, 2000, Glasgow, Scotland. Poster 68.