HIV Treatment Adherence, Drug Resistance, Virologic Failure: Evolving Concepts

Departments of International Health and Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, MD 21205, USA.
Infectious disorders drug targets 03/2011; 11(2):167-74. DOI: 10.2174/187152611795589663
Source: PubMed


Poor adherence to combined antiretroviral therapy (cART) has been shown to be a major determinant of virologic failure, emergence of drug resistant virus, disease progression, hospitalizations, mortality, and health care costs. While high adherence levels can be achieved in both resource-rich and resource-limited settings following initiation of cART, long-term adherence remains a challenge regardless of available resources. Barriers to optimal adherence may originate from individual (biological, socio-cultural, behavioral), pharmacological, and societal factors. Although patients and providers should continuously strive for maximum adherence to cART, there is accumulating evidence that each class of antiretroviral therapy has specific adherence-drug resistance relationship characteristics allowing certain regimens more flexibility than others. There is not a universally accepted measure for cART adherence, since each method has distinct advantages and disadvantages including cost, complexity, accuracy, precision, intrusiveness and bias. Development of a real-time cART adherence monitoring tool will enable the development of novel, pre-emptive adherence-improving strategies. The application of these strategies may ultimately prove to be the most cost-effective method to reduce morbidity and mortality for the individual and decrease the likelihood of HIV transmission and emergence of resistance in the community.

Download full-text


Available from: Vincent C Marconi, Jan 07, 2015
  • Source
    • "Long-term adherence to antiretroviral treatment (ART) is a challenge in children, and children have lower virological suppression rates on ART compared to adults (Davies et al., 2011; Kamya et al., 2007). Adherence decreases over time, and may be linked to caregiver " treatment fatigue " and depression (Byakika-Tusiime et al., 2009; Nachega et al., 2011). Paediatric ART formulations may have complex dosage schedules which increase the difficulty with adherence. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Adherence to antiretroviral treatment (ART) is a challenge in childhood, and children on ART have reduced virological suppression compared to adults. This study evaluated the effect of community-based adherence support (CBAS) on virological outcomes amongst children receiving ART in four South African provinces. Patient Advocates are lay CBAS workers who provide adherence and psychosocial support for patients, undertaking home visits to address household challenges affecting adherence. Patient Advocates provide counselling for children's carers regarding adherence and psychosocial problems. A multicentre cohort study using routinely collected data was conducted at 57 public ART sites including ART-naive children (
    AIDS Care 11/2013; 26(4). DOI:10.1080/09540121.2013.855699 · 1.60 Impact Factor
  • Source
    • "Moreover, HIV transmission risks are reduced substantially in patients with lower viral loads, which is beneficial from a public health perspective [3-5]. Although full viral suppression can be achieved by (some) patients with lower adherence levels (70-90%) [6-8], it is generally recommended that patients take at least 90-95% of their medication for long-term suppression of viral replication, to minimise the risk of developing viral resistance [9-11]. Meta-analyses have shown that the quality of adherence support delivered by health care professionals during usual care is key to achieving adequate adherence levels and viral suppression [12,13]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Non-adherence to HIV-treatment can have a negative impact on patients treatment success rates, quality of life, infectiousness, and life expectancy. Few adherence interventions have shown positive effects on adherence and/or virologic outcomes. The theory- and evidence-based Adherence Improving self-Management Strategy (AIMS) is an intervention that has been demonstrated to improve adherence and viral suppression rates in a randomised controlled trial. However, evidence of its cost-effectiveness is lacking. Following a recent review suggesting that cost-effectiveness evaluations of adherence interventions for chronic diseases are rare, and that the methodology of such evaluations is poorly described in the literature, this manuscript presents the study protocol for a multi-centre trial evaluating the effectiveness and cost-effectiveness of AIMS among a heterogeneous sample of patients. The study uses a multi-centre randomised controlled trial design to compare the AIMS intervention to usual care from a societal perspective. Embedded in this RCT is a trial-based and model-based economic evaluation. A planned number of 230 HIV-infected patients are randomised to receive either AIMS or usual care. The relevant outcomes include changes in adherence, plasma viral load, quality of life, and societal costs. The time horizon for the trial-based economic evaluation is 12-15 months. Costs and effects are extrapolated to a lifetime horizon for the model-based economic evaluation. The present multicentre RCT is designed to provide sound methodological evidence regarding the effectiveness and cost-effectiveness of a nurse-based counselling intervention (AIMS) to support treatment adherence among a large and heterogeneous sample of HIV-infected patients in the Netherlands. The objective of the current paper is to describe the trial protocol in sufficient detail to allow full evaluation of the quality of the study design. It is anticipated that, if proven cost-effective, AIMS can contribute to improved evidence-based counselling guidelines for HIV-nurses and other health care professionals. The study has been registered on (Identifier: NCT01429142).
    BMC Health Services Research 07/2013; 13(1):274. DOI:10.1186/1472-6963-13-274 · 1.71 Impact Factor
  • Source
    • "However, limitations and concerns regarding cost, complexity of treatment, and long-term side effects have led to lower adherence to treatment regimens by some patients. Also, the development of drug-resistant mutants, either through a lack of protocol adherence or supervised/structured treatment interruptions (STIs), has increasingly become problematic [2,3]. Due to the persistence and continuous alteration of HIV-1 viral infections, a better understanding of all underlying molecular mechanisms involved in the viral life cycle is critical to battling this pathogen. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Gene silencing via non-coding RNA, such as siRNA and miRNA, can occur at the transcriptional, post-transcriptional, and translational stages of expression. Transcriptional gene silencing (TGS) involving the RNAi machinery generally occurs through DNA methylation, as well as histone post-translational modifications, and corresponding remodeling of chromatin around the target gene into a heterochromatic state. The mechanism by which mammalian TGS occurs includes the recruitment of RNA-induced initiation of transcriptional gene silencing (RITS) complexes, DNA methyltransferases (DNMTs), and other chromatin remodelers. Additionally, virally infected cells encoding miRNAs have also been shown to manipulate the host cell RNAi machinery to induce TGS at the viral genome, thereby establishing latency. Furthermore, the introduction of exogenous siRNA and shRNA into infected cells that target integrated viral promoters can greatly suppress viral transcription via TGS. Here we examine the latest findings regarding mammalian TGS, specifically focusing on HIV-1 infected cells, and discuss future avenues of exploration in this field.
    Biology 12/2012; 1(2):339-69. DOI:10.3390/biology1020339
Show more