Antiretroviral Treatment Interruption Can Cause Long-term Problems

	SUMMARY: Taking breaks from antiretroviral therapy (ART) can lead to long-term adverse outcomes that do not reverse themselves even after treatment is restarted, according to a Swiss study described in the February 20, 2011, issue of AIDS. People who interrupted therapy had poorer CD4 T-cell recovery and were more likely to develop opportunistic illnesses or die than those who stayed on treatment.

By Liz Highleyman

The inconvenience, side effects, and cost of ART lead some people with HIV to interrupt therapy for brief or prolonged periods.

The large SMART study and other research has shown that treatment interruption -- especially when a patient's CD4 count is relatively low -- has detrimental effects in the short term, increasing the risk of both AIDS-related events and non-AIDS conditions such as cardiovascular disease.

Gilbert Kaufmann and fellow investigators with the Swiss HIV Cohort Study looked at the long-term effects of treatment interruption on CD4 cell recovery and clinical events.

The researchers evaluated immunological and clinical endpoints among 2491 participants in the Swiss cohort who started HIV treatment for the first time between 1996 -- the advent of effective combination ART -- and 2008, following them for an average of about 7 years.

Patients were classified according to treatment consistency:

	Group A: interrupted treatment at least once (n = 1271; 51%);
	Group B: continuous ART but intermittent viral suppression, defined as HIV RNA rising to at least 1000 copies/mL (n = 469; 19%);
	Group C: continuous ART with consistent viral suppression < 1000 copies/mL (n = 751; 30%).

Results

	At 8 years, CD4 T-cells levels rose in all groups, but more so in people with the most consistent treatment:
	427 cells/mm3 in the treatment interruption group; 525 cells/mm3 in the continuous therapy but intermittent viral suppression group; 645 cells/mm3 in the continuous therapy, consistent suppression group.
	Percentages of patients achieving a CD4 count > 350 cells/mm3 in the 3 groups were 63.0%, 76.3%, and 87.3%, respectively.
	Percentages reaching > 500 cells/mm3 were 37.2%, 55.8%, and 68.0%, respectively, a significant difference (P < 0.001).
	CD4 cell recovery was independently associated with cumulative duration of treatment interruptions; those with the longest interruptions experienced a CD4 cell decline.
	Participants in the treatment interruption group had more HIV-related symptoms (CDC class B events) and more AIDS-defining conditions (CDC class C events) than those on continuous therapy.
	People who interrupted ART also had an increased risk of death (20 deaths per 1000 person-year for interrupters vs 8 per 1000 person-years for those with continuous ART and consistent viral suppression).
	Major risk factors for inability to reach a CD4 count above 500 cells/mm3 included lower baseline CD4 cell count, older age, and hepatitis C virus (HCV) coinfection.

"In persons receiving continuous ART larger CD4 T-cell recovery and a reduced risk for opportunistic complications and death was observed," the study authors concluded. "CD4 T-cell recovery was smaller in persons with treatment interruptions more than 6 months."

"The results strongly support the concept that patients should be discouraged to discontinue antiretroviral therapy," they advised. "If any interruption is required, it should be as short as possible to avoid poor clinical outcomes."

Investigator affiliations: Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Switzerland; Division of Infectious Diseases and Hospital Epidemiology, University Hospital and University of Zurich, Zurich, Switzerland; Clinic for Infectious Diseases, Bern University Hospital and University of Bern, Bern, Switzerland; Division of Infectious Diseases, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; Department of Internal Medicine, Cantonal Hospital St. Gallen, St Gallen, Switzerland; Department of Internal Medicine, Regional Hospital, Lugano, Switzerland; Division of Infectious Diseases and Laboratory of Virology, University Hospital Geneva, Geneva, Switzerland.

2/11/11

Reference
GR Kaufmann, L Elzi, R Weber (Swiss HIV Cohort Study). Interruptions of cART limits CD4 T-cell recovery and increases the risk for opportunistic complications and death. AIDS 25(4): 441-451 (abstract). February 20, 2011.