Treatment interruptions in HIV-infected subjects

Abstract

Despite a high antiviral efficacy, the use of highly active antiretroviral therapy (HAART) in clinical practice is often impaired by the long-term toxicity of antiretroviral treatment, the increased rate of human immunodeficiency virus-1 (HIV-1) drug resistance in treated patients and the cost of therapies, so that possible interruption of HAART has to be considered as part of the current clinical practice. However, this strategy is usually followed by a rapid viral rebound with a substantial loss of CD4 T lymphocytes because the HIV suppression with HAART does not result in reconstitution of the HIV-specific immune response. Structured treatment interruption (STI) has already been investigated in HIV-infected subjects with well-controlled viral replication (initiating treatment during primary or chronic HIV infection) and in those with multiple treatment failures. A clear benefit of STI in patients with chronic infection remains controversial and these benefits are more often observed in patients starting treatment during primary HIV infection.

Are previous treatment interruptions associated with higher viral rebound rates in patients with viral suppression?

“…Although previous studies have considered the short to medium-term effects of interrupting therapy [1][2][3][4][5][6][7][8][9][10][11][12][13], this is the first study to look at the long-term effects of treatment interruptions among those who subsequently achieve an undetectable viral load. In our study, a substantial minority of patients with an undetectable viral load whilst on HAART had previously interrupted therapy.…”

“…Although it has been shown that patients who have interrupted HAART have a raised risk of drug resistance and increased immunosuppression [2][3][4][5][6][7][8][9][10], many patients are able to suppress their viral load upon restarting therapy [11][12][13]. Presently lacking in the literature, however, is information on the risk of subsequent viral rebound in these patients.…”

Post-Treatment HIV-1 Controllers with a Long-Term Virological Remission after the Interruption of Early Initiated Antiretroviral Therapy ANRS VISCONTI Study

“…Combined antiretroviral therapy (cART) suppresses viral replication and drastically reduces morbidity and mortality [1]. However, cART does not eradicate infected cells [2], and plasma viremia generally rebounds quickly after treatment is discontinued [3]. The existence of a few HIV-infected patients who spontaneously controlled HIV replication to undetectable levels for many years (HIV controllers [HICs]) suggests that a functional HIV cure or remission might be possible.…”

Acute HIV Infection in Youth: Protocol for the Adolescent Trials Network 147 (ATN147) Comprehensive Adolescent Research and Engagement Studies (CARES) Study (Preprint)

“…The inability of cART to eradicate infected cells [40] and the fact that plasma viremia rebounds quickly after treatment discontinuation [41] are reasons why remission as a functional cure is considered a more viable goal [28]. So far, studies have shown that HIV remission is possible in both perinatally infected infants and acutely infected adults [18,28].…”