Structured Treatment Interruptions for the Management of HIV Infection

Abstract

Antiretroviral drugs constitute a milestone in the treatment of human immunodeficiency virus (HIV) infection; however, emerging problems limit their long-term use, and an increasing number of patients interrupt the prescribed continuous drug therapy for short or long periods. Some patients appear to benefit from structured treatment interruptions (STI), involving monitored repetition of on-and-off cycles of drugs; however, it is unclear whether patients and/or physicians should consider STI as a treatment option. This review is intended to provide a comprehensive update on the use of STI in clinical settings, and to carefully evaluate the advantages and potential risks for patients infected with HIV. We used a MEDLINE search to find all English-language articles published January 1999 to August 2001 regarding patients treated with highly active antiretroviral therapy for whom treatment interruption was investigated. Priority was assigned to peer-reviewed sources, when available. Otherwise, abstracts from authoritative international conferences were selected through the AIDSLINE database. Results from various studies with respect to type of drug treatment, baseline patient status, number of treatment interruptions, duration of treatment and interruption, changes in viral load, and immune system parameters were analyzed. Patients could be categorized into 3 distinct clinical scenarios: acute infection, chronic drug-suppressed infection and virological drug failure. The STI approach may offer more benefit during acute infection when the patient's immune system remains nearly intact. It is yet to be determined whether STI will facilitate the long-term management of chronic infection by decreasing drug-associated toxicity and improving quality of life without jeopardizing the efficacy of the treatment. Results from randomized controlled trials and more definitive means of gauging the status of the patient's immune system must be available before this treatment method is extended beyond the research setting. Ultimately, a safer approach using therapeutic immunization or vaccination would be preferable for stimulating vigorous T-cell-mediated immune responses and control of HIV during treatment interruption.

Generation of HIV Latency in Humanized BLT Mice

“…1C). We also noted that, similar to what occurs in patients taking ART (6,15,21), during structured treatment interruption, there is a rapid rebound of plasma viremia to levels comparable to those detected prior to therapy (Fig. 1D).…”

ART influences HIV persistence in the female reproductive tract and cervicovaginal secretions

“…This triple-drug combination has been shown to strongly suppress viral load in both humans and BLT mice with continuous dosing (51)(52)(53). However, ART discontinuation in patients results in a rapid rebound of plasma viremia as well as a loss of PB CD4 + T cells (54,55). These phenomena are also fully recapitulated in BLT mice (53,56).…”

An Optimal Control Approach to Structured Treatment Interruptions for HIV Patients: A Personalized Medicine Perspective

“…We develop treatments known as structured treatment interruptions (STI), wherein the effective treatment is terminated at specified times and then restarted in an attempt to increase an in-host immune response and provide a drug holiday for the patient. These treatment methods have been studied in detail, though a lack of double-blind, randomized clinical trials has lead to a lack of consensus on the effectiveness of these types of treatments [22] [23] [24] [25]. We implement the optimal STI using the receding horizon control (RHC) methodology [12].…”