Transmission of HIV-1 drug resistance

Tang, Julian W.; Pillay, Deenan

doi:10.1016/j.jcv.2003.12.002

Cited by 79 publications

(51 citation statements)

References 127 publications

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“…Transmission of drug resistances following poor treatment adherence can lead to suboptimal response to first-line therapy in newly diagnosed PLHIV [68]. However, the prevalence of transmitted drug resistances is increasing, but at lower rates than some had feared based on the significant expansion of ART coverage [69].…”

Section: Consequences Of Inadequate Retention In Care and Adherence Tmentioning

confidence: 99%

Retention in Care and Adherence to ART are Critical Elements of HIV Care Interventions

et al. 2013

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Retention in care and adherence to antiretroviral treatment (ART) are critical elements of HIV care interventions and are closely associated with optimal individual and public health outcomes and cost effectiveness. This literature review was conducted to analyse how the roles of clients in HIV care and treatment are discussed, from terminology used to measurement methods to consequences of a wide range of patient-related factors impacting client adherence to ART and retention in care. Unfortunately, data suggests that clients find it hard to follow recommended behaviour. For HIV, the greatest loss to follow-up occurs before starting treatment, though each step of the continuum of care is affected. Measurement approaches can be divided into 'direct' and 'indirect' methods; in practice, a combination is often considered the best strategy. Inadequate retention and adherence lead to decreased health outcomes (morbidity, mortality, drug resistances, risk of transmission) and cost effectiveness (increased costs and lower productivity).

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Section: Consequences Of Inadequate Retention In Care and Adherence Tmentioning

confidence: 99%

Retention in Care and Adherence to ART are Critical Elements of HIV Care Interventions

et al. 2013

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“…HAART is used (taken from Table 1 of Tang and Pillay, 2004). In some surveys, annual variations in primary HIV drug-resistance prevalence were recorded, but in others the data are "lumped" and the latter are indicated by horizontal lines.…”

Section: Starting Parameters Identicalmentioning

confidence: 99%

“…However, resistant strains of HIV-1 arise due to drug failure or poor drug adherence, leading to the potential for drug-resistant HIV strains to be transmitted to susceptible individuals. Transmitted resistance has been documented for each of the three classes of widely-used anti-retroviral drugs: nucleoside reversetranscriptase inhibitors (NRTIs), non-nucleoside reverse-transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) (for recent reviews see Tang and Pillay, 2004;Geretti, 2007).…”

Section: Introductionmentioning

confidence: 99%

The effect of intrinsic stochasticity on transmitted HIV drug resistance patterns

Marks

Pillay

McLean

2010

Journal of Theoretical Biology

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“…Compensatory evolution through the acquisition of additional mutations generally results in partial restorations of viral fitness (19). Despite the accumulation of compensatory mutations, drug-resistant viruses tend to replicate less efficiently than wild-type viruses.The transmission of drug-resistant mutants with diminished fitness and the evolution of these viruses in the absence of drug are typically associated with the reversion and loss of resistance mutations (3,9,22). Different rates of persistence and reversion of mutations have been documented in vivo and have usually been explained by the impact of mutations on viral fitness.…”

mentioning

confidence: 99%

The Fitness Cost of Mutations Associated with Human Immunodeficiency Virus Type 1 Drug Resistance Is Modulated by Mutational Interactions

Cong

Heneine

Garcı́a-Lerma

2007

J Virol

112

100

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It is generally accepted that the fitness cost of resistance mutations plays a role in the persistence of transmitted drug-resistant human immunodeficiency virus type 1 and that mutations that confer a high fitness cost are less able to persist in the absence of drug pressure. Here, we show that the fitness cost of reverse transcriptase (RT) mutations can vary within a 72-fold range. We also demonstrate that the fitness cost of M184V and K70R can be decreased or enhanced by other resistance mutations such as D67N and K219Q. We conclude that the persistence of transmitted RT mutants might range widely on the basis of fitness and that the modulation of fitness cost by mutational interactions will be a critical determinant of persistence.Antiretroviral drug resistance is an important cause of treatment failure in human immunodeficiency virus type 1-infected persons treated with reverse transcriptase (RT) and protease inhibitors. Emergence of resistance during treatment usually involves the initial selection of deleterious mutations that reduce drug susceptibility and decrease replicative capacity. Compensatory evolution through the acquisition of additional mutations generally results in partial restorations of viral fitness (19). Despite the accumulation of compensatory mutations, drug-resistant viruses tend to replicate less efficiently than wild-type viruses.The transmission of drug-resistant mutants with diminished fitness and the evolution of these viruses in the absence of drug are typically associated with the reversion and loss of resistance mutations (3,9,22). Different rates of persistence and reversion of mutations have been documented in vivo and have usually been explained by the impact of mutations on viral fitness. For instance, less-fit zidovudine-resistant mutants carrying T215Y/F are generally replaced by more-fit 215D/C/S revertants within less than a year, while more-fit M41L or D67N mutants tend to revert more slowly (1-3, 5, 6, 8, 13, 17, 20, 25). However, in vivo observations do not always show the expected relationship between fitness cost and persistence, and a range of persistence for the same mutation has been noted among patients infected with multidrug-resistant viruses. For instance, M184V mutants have been found to persist between 4 and 16 months after primary infection, while persistence of K103N can range between 1 and 3 years (2,3,5,17). We hypothesize that mutational interactions in multidrug-resistant viruses might modulate the fitness cost of resistance mutations and might influence the rate of reversion and persistence of mutations.

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Transmission of HIV-1 drug resistance

Cited by 79 publications

References 127 publications

Retention in Care and Adherence to ART are Critical Elements of HIV Care Interventions

Retention in Care and Adherence to ART are Critical Elements of HIV Care Interventions

The effect of intrinsic stochasticity on transmitted HIV drug resistance patterns

The Fitness Cost of Mutations Associated with Human Immunodeficiency Virus Type 1 Drug Resistance Is Modulated by Mutational Interactions

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