Acute HIV infection: impact on the spread of HIV and transmission of drug resistance

Yerly, Sabine; Vora, Samir; Rizzardi, P; Chave, Jean-Philippe; Vernazza, Pietro; Flepp, Markus; Telenti, Amalio; Battegay, Manuel; Veuthey, Anne‐Lise; Bru, J P; Rickenbach, Martin; Hirschel, Bernard; Perrin, Luc

doi:10.1097/00002030-200111230-00010

Cited by 220 publications

(167 citation statements)

References 27 publications

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“…We have assumed that unlike human immunodeficiency virus (HIV) (Yerly et al, 2001), where viral loads are highest, acute HCV infection is not more infectious than chronic stage disease.…”

Section: Discussionmentioning

confidence: 99%

Optimal targeting of Hepatitis C virus treatment among injecting drug users to those not enrolled in methadone maintenance programs

Zeiler

Langlands

Murray

et al. 2010

Drug and Alcohol Dependence

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Background: This work used mathematical modelling to explore effective policy for hepatitis C virus (HCV) treatment in Australia in the context of methadone maintenance treatment (MMT).Method: We consider two models to depict HCV in the population of injecting drug users (IDU) within Australia. The first model considers the IDU population as a whole. The second model includes separate components for those that are or are not enrolled in MMT. The impact of different levels of HCV treatment and its allocation dependent on MMT status were then determined in terms of the steady state levels of each of these models.Results: Although increasing levels of HCV treatment decrease chronic infection prevalence, initially numbers of acutely infected can rise. This is caused by the high rate of reinfection. We find that no matter the extent of HCV treatment, HCV prevalence cannot be eliminated without limiting risk behaviour. Assuming equal adherence to HCV therapy between MMT and non-MMT, over 84% of HCV treatment should be allocated to those not in MMT. Only if adherence to HCV therapy in non MMT patients falls below 44% of that in MMT then treatment should be preferentially directed to those in MMT.Conclusions: Contrary to generally held beliefs regarding HCV treatment the majority of therapy should be allocated to those that are still actively injecting. This is due to rates of reinfection and to the high turnover of individuals in MMT. Higher adherence to HCV therapy in MMT would need to be achieved before this changed.

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“…We have assumed that unlike human immunodeficiency virus (HIV) (Yerly et al, 2001), where viral loads are highest, acute HCV infection is not more infectious than chronic stage disease.…”

Section: Discussionmentioning

confidence: 99%

Optimal targeting of Hepatitis C virus treatment among injecting drug users to those not enrolled in methadone maintenance programs

Zeiler

Langlands

Murray

et al. 2010

Drug and Alcohol Dependence

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“…Clusters of related virus are often interpreted as epidemiologically linked. For example, clusters of acute HIV infections may represent short transmission chains between high-risk individuals (Yerly et al 2001;Hue et al 2005;Pao et al 2005;Goodreau 2006;Brenner et al 2007;Drumright and Frost 2008;Lewis et al 2008). Because our model reproduces the moments of the cluster size distribution, it can be used to predict the level of clustering as a function of epidemiological conditions.…”

mentioning

confidence: 99%

Phylodynamics of Infectious Disease Epidemics

et al. 2009

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We present a formalism for unifying the inference of population size from genetic sequences and mathematical models of infectious disease in populations. Virus phylogenies have been used in many recent studies to infer properties of epidemics. These approaches rely on coalescent models that may not be appropriate for infectious diseases. We account for phylogenetic patterns of viruses in susceptibleinfected (SI), susceptible-infected-susceptible (SIS), and susceptible-infected-recovered (SIR) models of infectious disease, and our approach may be a viable alternative to demographic models used to reconstruct epidemic dynamics. The method allows epidemiological parameters, such as the reproductive number, to be estimated directly from viral sequence data. We also describe patterns of phylogenetic clustering that are often construed as arising from a short chain of transmissions. Our model reproduces the moments of the distribution of phylogenetic cluster sizes and may therefore serve as a null hypothesis for cluster sizes under simple epidemiological models. We examine a small cross-sectional sample of human immunodeficiency (HIV)-1 sequences collected in the United States and compare our results to standard estimates of effective population size. Estimated prevalence is consistent with estimates of effective population size and the known history of the HIV epidemic. While our model accurately estimates prevalence during exponential growth, we find that periods of decline are harder to identify.

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“…Surveillance studies have demonstrated that approximately 10 to 20% of recently infected patients carry drug-resistant strains of HIV-1 (74,101,157,183). In addition, approximately 8 to 10% of drug-resistant isolates are identified in treatment-naive, chronically infected patients (178).…”

Section: Transmission Efficiencymentioning

confidence: 99%

Clinical Significance of Human Immunodeficiency Virus Type 1 Replication Fitness

Dykes

Demeter

2007

Clin Microbiol Rev

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SUMMARY The relative fitness of a variant, according to population genetics theory, is that variant's relative contribution to successive generations. Most drug-resistant human immunodeficiency virus type 1 (HIV-1) variants have reduced replication fitness, but at least some of these deficits can be compensated for by the accumulation of second-site mutations. HIV-1 replication fitness also appears to influence the likelihood of a drug-resistant mutant emerging during treatment failure and is postulated to influence clinical outcomes. A variety of assays are available to measure HIV-1 replication fitness in cell culture; however, there is no agreement regarding which assays best correlate with clinical outcomes. A major limitation is that there is no high-throughput assay that incorporates an internal reference strain as a control and utilizes intact virus isolates. Some retrospective studies have demonstrated statistically significant correlations between HIV-1 replication fitness and clinical outcomes in some patient populations. However, different studies disagree as to which clinical outcomes are most closely associated with fitness. This may be in part due to assay design, sample size limitations, and differences in patient populations. In addition, the strength of the correlations between fitness and clinical outcomes is modest, suggesting that, at present, it would be difficult to utilize these assays for clinical management.

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Acute HIV infection: impact on the spread of HIV and transmission of drug resistance

Cited by 220 publications

References 27 publications

Optimal targeting of Hepatitis C virus treatment among injecting drug users to those not enrolled in methadone maintenance programs

Optimal targeting of Hepatitis C virus treatment among injecting drug users to those not enrolled in methadone maintenance programs

Phylodynamics of Infectious Disease Epidemics

Clinical Significance of Human Immunodeficiency Virus Type 1 Replication Fitness

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