Cognitive disorders in HIV-infected patients

Bonnet, Fabrice; Amieva, Hélène; Marquant, Fabienne; Bernard, Charlotte; Bruyand, Mathias; Dauchy, Frédéric‐Antoine; Mercié, P.; Greib, C.; Richert, Laura; Néau, Didier; Catheline, Gwénaëlle; Dehail, Patrick; Dabis, François; Morlat, Philippe; Dartigues, Jean‐François; Chêne, Geneviève

doi:10.1097/qad.0b013e32835b1019

Cited by 126 publications

(113 citation statements)

References 32 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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“…[5,27] The challenge of studying HAND is having an adequate well-matched control group in which all these confounding factors may be accounted for. [28] Nevertheless some HIV-associated (CD4 cell count at nadir below 200/mm 3 , plasmatic or CSF HIV replication, cell-associated HIV DNA) and some other risk factors (age above 50 years, HCV infection, metabolic and glucose abnormalities, cardiovascular risk) have been identified and they may help selecting patients for accurate neurocognitive screening and follow up.…”

Section: Methodsmentioning

confidence: 99%

“…[2,3] With the introduction of highly active antiretroviral treatment (HAART) the incidence of dementia significantly declined; nevertheless cognitive impairment (asymptomatic and moderate according to the impact on everyday life and globally defined as HIV-associated neurocognitive disorders, HAND) remains highly prevalent. [4] Although several authors highlight the impact of traditional risk factors (age, drug and alcohol abuse, previous head injuries, cardiovascular risk abnormalities, opportunistic infections) [5] on neurocognitive impairment in HIV-positive subjects the role of neuro-effective HAART is crucial: it is significantly associated with CSF viral control but inconsistently with the prevention and treatment of HAND.…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics and Pharmacodynamics of Antiretrovirals in the Central Nervous System

2014

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“…Prevalence estimates of NCI in the era of wide use of ART vary from 20% to more than 50%. [1][2][3][4] Etiology of NCI is likely to be multifactorial but is still not well understood. 5 Associations with both HIV-related determinants, ART characteristics and other factors not directly HIV-related, such as smoking, hypertension, and metabolic syndrome (MetS), have been described with inconsistent evidence across studies.…”

mentioning

confidence: 99%

“…18 There has been a consecutive enrollment invitation of Aquitaine cohort's participants in the longitudinal substudy CO-GLOC, which focused on cognitive and motor functions. 1,19 Substudy took place in 5 clinical centers of Bordeaux University Hospital from June 2007 to November 2009, so that the expected 400 participants were recruited. 1,19 A follow-up wave was performed on average 2 years after enrollment (n 5 283).…”

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confidence: 99%

Diabetes and cognitive decline in a French cohort of patients infected with HIV-1

et al. 2015

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Objective: We investigated the relationship of diabetes and prediabetes with cognitive performances, assessed through raw test and z scores and according to neurocognitive impairment (NCI) classification in a cohort of individuals infected with HIV. Methods:The ANRS CO3 Aquitaine cohort is a prospective hospital-based cohort of HIV-1-infected patients under routine clinical management in 6 public hospitals in southwestern France. Between 2007 and 2009, an ancillary study consisted of a neuropsychological battery of 10 tests at baseline and 2-year follow-up. The severity of NCI (normal, asymptomatic, mild, HIV dementia) was assessed according to international guidelines.Results: At baseline (400 patients, 33 with prediabetes, 39 with diabetes), in cross-sectional multivariable analyses, patients with diabetes performed significantly worse on 9 neuropsychological tests that assessed memory, executive functions, attention, psychomotor speed, language, and manual dexterity. Participants with prediabetes had worse performances compared with those who had normal glycemia in 5 tests. The longitudinal analysis of the association between glycemia status at baseline and change in cognitive performances over 2-year follow-up (n 5 283) suggested that patients with diabetes also showed a slightly higher decline on 5 of the 10 tests, those involving executive functions and memory functioning. Glycemia status at baseline was not significantly associated with NCI severity in cross-sectional (p 5 0.44) and longitudinal (p 5 0.64) analyses. Conclusions:In this hospital-based cohort of people living with HIV, diabetes, but not the other cardiovascular risk factors, is associated with worse cognitive performances in several cognitive domains and with larger decline in fewer domains over the short term.

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Cognitive disorders in HIV-infected patients

Abstract: In this large unselected cohort, a high prevalence of symptomatic neurocognitive disorders was mainly related to its traditional determinants and associated with gray matter atrophy at early stages of the disease.

Cited by 126 publications

References 32 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

Pharmacokinetics and Pharmacodynamics of Antiretrovirals in the Central Nervous System

Diabetes and cognitive decline in a French cohort of patients infected with HIV-1

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