Cognitive dysfunction in HIV patients despite long-standing suppression of viremia

Simioni, Samanta; Cavassini, Matthias; Annoni, Jean Marie; Abraham, Aline Rimbault; Bourquin, I.; Schiffer, V.; Calmy, Alexandra; Chave, Jean Philippe; Giacobini, Ezio; Hirschel, Bernard; Pasquier, Renaud Du

doi:10.1097/qad.0b013e3283354a7b

Cited by 634 publications

(614 citation statements)

References 30 publications

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“…The results indicated that the prevalence of NCI in HIV-positive MSM in the UK was 21%, 31% or 40% depending on the standardised scoring criteria used. All these levels are much lower than those reported by previous studies, [43][44][45] and there was no difference between the deficit scores in the HIV-positive group and comparable control data from the general population or HIV-negative MSM. In addition, it was noted that large numbers of the general population would be classified as having some form of NCI based on the standard scoring criteria.…”

Section: The Antiretrovirals Sexual Transmission Risk and Attitudes contrasting

confidence: 64%

Implications for a policy of initiating antiretroviral therapy in people diagnosed with human immunodeficiency virus: the CAPRA research programme

Miltz

Phillips

Speakman

et al. 2017

Programme Grants Appl Res

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BackgroundMore than 100,000 people in the UK are living with a human immunodeficiency virus (HIV) infection. There are currently estimated to be around 4000 people newly infected in the UK per year, mostly men who have sex with men (MSM). It has become increasingly clear that antiretroviral therapy (ART) used to treat people infected with HIV also has a profound effect on infectivity. At the initiation of the programme, it was the policy in the UK to initiate ART in people when their cluster of differentiation 4 (CD4) count was approaching 350/µl.ObjectivesTo assess what would be the effectiveness and cost-effectiveness of a policy of immediate initiation of ART at diagnosis among MSM, taking into account the potential reductions in new infections.DesignWe calibrated an individual-based model of HIV transmission, progression and the effect of ART in MSM, informed by a series of studies on sexual behaviour in relation to ART use and the transmission risk in people with viral suppression on ART, and by surveillance data collected by Public Health England.Setting, participants and interventionsThe series of studies used to inform the model included (1) the Antiretrovirals, Sexual Transmission Risk and Attitudes (ASTRA) study, a cross-sectional self-administered questionnaire study of people diagnosed with HIV attending eight HIV outpatient clinics in the UK (2011–12); (2) the Cognitive Impairment in People with HIV in the European Region (CIPHER) study, a study of levels of neurocognitive impairment in HIV-positive ASTRA participants and people from HIV clinics in Rome, Copenhagen and Minsk; (3) the Attitudes to, and Understanding of, Risk of Acquisition of HIV (AURAH) study, a cross-sectional self-administered questionnaire study of individuals who have not been diagnosed as HIV-positive attending 20 genitourinary medicine clinics across the UK (2013–14); (4) a substudy of sexual behaviour among individuals enrolled in an open-label multicentre international randomised trial (from 2013) of immediate versus deferred ART (to CD4 cell counts of 350/µl) in people with CD4 cell counts of > 500/µl [the Strategic Timing of Antiretroviral Therapy (START) trial]; and (5) Partners of People on ART: a new Evaluation of the Risks (PARTNER), an observational multicentre longitudinal study of HIV serodifferent heterosexual and MSM couples, in which the HIV-positive partner is on ART (2010–14).Main outcome measuresThe main outcome measures were the clinical effectiveness and cost-effectiveness of a policy of immediate initiation of ART at diagnosis.ResultsBased on data from studies (i)–(v), we estimated from our modelling work that increases in condomless sex (CLS) among MSM as a whole may explain the increase in HIV infection incidence in MSM epidemics over a time when ART coverage and viral suppression increased, demonstrating the limiting effects of non-condom use on the HIV epidemic among MSM. Accordingly, an increase in the overall proportion of MSM living with HIV who are virally suppressed on ART from the current level of < 60% to 90% without increases in CLS was required to achieve a reduction in the incidence of HIV among MSM to < 1 per 1000 person-years. The incremental cost-effectiveness ratio associated with the fourfold increase in levels of HIV testing and ART at diagnosis required to provide this increase from < 60% to 90% was £20,000 if we assumed continuation of current ART prices. However, this value falls to £3500 if we assume that ART prices will fall to 20% of their current cost as a result of the introduction of generic drugs. Therefore, our evaluation suggests that ART initiation at diagnosis is likely to be highly cost-effective in MSM at a population level, particularly accounting for future lower ART costs as generic drugs are used. The impact will be much greater if levels of HIV testing can be enhanced.LimitationsIt was necessary to make some assumptions beyond the available data in order to extrapolate cost-effectiveness through modelling.ConclusionsOur findings suggest that ART initiation at diagnosis is likely to be cost-effective in MSM. Of note, after this programme of work was completed, results from the main START trial demonstrated benefit in ART initiation even in people with CD4 cell counts of > 500/µl, supporting ART initiation in people diagnosed with a HIV infection.Future workThere is a need for future research into the means of increasing the frequency with which MSM test for HIV.FundingThe National Institute for Health Research Programme Grants for Applied Research programme.

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Section: The Antiretrovirals Sexual Transmission Risk and Attitudes contrasting

confidence: 64%

Implications for a policy of initiating antiretroviral therapy in people diagnosed with human immunodeficiency virus: the CAPRA research programme

Miltz

Phillips

Speakman

et al. 2017

Programme Grants Appl Res

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“…Neuropsychological studies have confirmed that cognitive impairment occurs in 15-50% of patients, being one of the most feared complications of HIV-1-infection. Neurocognitive impairment can also affect adherence to treatment and, ultimately, result in increased morbidity [33,34]. HIV-related neuropathology consists of microglial infiltration throughout white and grey matter, reactive astrogliosis in the cortex and in the central grey structures, and loss of neurons in the hippocampus and in the basal ganglia [35].…”

Section: Mtor and Hiv-associated Neurocognitive Disordersmentioning

confidence: 99%

“…HIV enters the CNS through infected macrophages and resides in the microglia. The number of infected glial cells in HIV patients is highly variable but generally too low to explain the underlying process of encephalitis [33,34]. Thus, it is believed that immunoinflammatory and/or degenerative responses of the microglial cells to infection rather than virus-mediated cell death can explain AIDS-related neuropathogenesis [33,34].…”

Section: Mtor and Hiv-associated Neurocognitive Disordersmentioning

confidence: 99%

mTOR as a multifunctional therapeutic target in HIV infection

Nicoletti

Fagone

Meroni

et al. 2011

Drug Discovery Today

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“…3 Although incidence rates for HIVassociated dementia have declined, the prevalence of mild to moderate forms of cognitive dysfunction remains high, 4 with neuropsychological deficits reported in 15-50% of patients despite long-term cART and suppression of viraemia. 5 Rapid, sensitive and reliable screening tool for the presence of HIV-associated cognitive disorders are needed. Specific bedside tools such as the HIV dementia scale and the International HIV Dementia Scale have been shown to lack diagnostic effectiveness owing to inconsistencies in language comprehension and confounding clinical parameters.…”

mentioning

confidence: 99%

A comparison of two post-processing analysis methods to quantify cerebral metabolites measuredviaproton magnetic resonance spectroscopy in HIV disease

Scott¹,

Underwood²,

Garvey³

et al. 2016

BJR

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Objective: Non-invasive biomarkers to monitor cerebral function in treated human immunodeficiency virus (HIV) disease are required. Cerebral metabolite ratios (CMRs) measured by proton-MR spectroscopy ( 1 H-MRS) are a potential biomarker. Here, we compare two postprocessing software packages to quantify CMRs. Methods: Cerebral 1 H-MRS data from 11 HIV-positive subjects before and after antiretroviral therapy intensification with maraviroc were quantified using a java-based version of the MR user interface package (jMRUI) and the totally automatic robust quantitation in nuclear MR (TARQUIN). 1 H-MRS data included N-acetylaspartate (NAA), creatine (Cr), choline (Cho) and myo-inositol (mI) from three cerebral locations. Differences in quantification and clinical associations of CMRs measured by the two packages were evaluated. Results: Mean CMRs were generally lower when measured by TARQUIN than by jMRUI (NAA/Cr, Cho/Cr, mI/ Cr ratios of 1.78, 0.83, 0.81 for jMRUI, and 1.27, 0.25, 0.81 for TARQUIN). Longitudinal changes were observed in CMRs in the basal ganglia voxel although these changes were not statistically significant [17.1% (p 5 0.18), 10.0% (p 5 0.91) and 26.6% (p 5 0.61) and 114.8% (p 5 0.18), 1 17.9% (p 5 0.07) and 134.8% (p 5 0.17) for NAA/Cr, Cho/Cr and mI/Cr ratios measured by TARQUIN and jMRUI, respectively]. Plasma maraviroc concentration was associated with a decrease in mI/Cr ratio measured via TARQUIN (p 5 0.049). Conclusion: Although CMRs differed when quantified by jMRUI vs TARQUIN, these differences were consistently observed across three cerebral locations, and clinical associations were evident by both methods. Advances in knowledge: TARQUIN and jMRUI are viable options to use in the post-processing of cerebral MRS data acquired in HIV disease.

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Cognitive dysfunction in HIV patients despite long-standing suppression of viremia

Cited by 634 publications

References 30 publications

Implications for a policy of initiating antiretroviral therapy in people diagnosed with human immunodeficiency virus: the CAPRA research programme

Implications for a policy of initiating antiretroviral therapy in people diagnosed with human immunodeficiency virus: the CAPRA research programme

mTOR as a multifunctional therapeutic target in HIV infection

A comparison of two post-processing analysis methods to quantify cerebral metabolites measuredviaproton magnetic resonance spectroscopy in HIV disease

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