A Prognostic Model for HIV Seroconversion Among Injection Drug Users as a Tool for Stratification in Clinical Trials

Boileau, Cathérine; Bruneau, Julie; Al-Nachawati, H.; Lamothe, F; Vincelette, Jean

doi:10.1097/01.qai.0000153424.56379.61

Cited by 21 publications

(17 citation statements)

References 37 publications

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“…In agreement with previous reports [22, 32], we estimate the HIV-1 and HCV sero-prevalence among high-risk needle-sharing HESN-IDU subjects in risk pockets within Philadelphia to be approximately 20% and 70%, respectively. We utilized the “Prognostic Model for Sero-conversion Among Injection Drug Users” [33] to identify high-risk HESN-IDU subjects for our study based upon their frequency of injection and needle sharing behavior. Briefly, subjects from known risk pockets were identified as HESN-IDU if they remained HIV-1 IgG sero-negative despite a history of greater than 2 years of daily injection and frequent (weekly or greater) needle sharing with partners of unknown HIV status.…”

Section: Methodsmentioning

confidence: 99%

Innate Activation of MDC and NK Cells in High-Risk HIV-1–Exposed Seronegative IV-Drug Users Who Share Needles When Compared With Low-Risk Nonsharing IV-Drug User Controls

Tomescu

Seaton

Smith

et al. 2015

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Background Previous studies have described increased innate immune activation in HIV-1 exposed, sero-negative intra-venous drug users (HESN-IDU), but have not addressed the independent role of injected drugs and/or repeated injections in driving immune activation. Methods Here, we investigated innate (NK cells and dendritic cells) and adaptive (HIV-specific antibody and CD8+ T cell) immune parameters among a high-risk cohort of needle-sharing HESN-IDU subjects and compared them to low-risk non-sharing IDU subjects (NS-IDU) and non drug-user controls. Results We observed that HIV-specific antibody and CD8+ T cell responses were not detected in HESN-IDU subjects, yet innate immune cell activation was found to be significantly increased on NK cells (CD69 and CD107a upregulation) and MDCs (CD40 and CD83 upregulation) when compared to NS-IDU subjects or non drug-user controls (p<0.01, and p<0.05, respectively). HESN-IDU subjects maintained strong NK cell CD107a degranulation and cytokine (IFN-gamma, TNF-alpha and MIP-1 beta) production following target cell-incubation suggesting that constitutive innate activation does not induce functional exhaustion of innate cells in HESN-IDU subjects. NK activation in HESN-IDU subjects was independent of drug use patterns but was durable over time and correlated with plasma levels of IP-10 by Luminex analysis (rho=0.5073, p=0.0059, n=28). Conclusions Our results indicate that heightened innate immune cell activation in HESN-IDU subjects is not the result of the IV-drugs and repeated injection practice itself, but to repeated exposure to factors intrinsic to sharing needles (i.e., exposure to pathogens or heterologous cells among donor blood).

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Section: Methodsmentioning

confidence: 99%

Innate Activation of MDC and NK Cells in High-Risk HIV-1–Exposed Seronegative IV-Drug Users Who Share Needles When Compared With Low-Risk Nonsharing IV-Drug User Controls

Tomescu

Seaton

Smith

et al. 2015

JAIDS Journal of Acquired Immune Deficiency Syndromes

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“…These were recruited from amongst the participants of the St. Luc injection drug user (IDU) cohort or were the seronegative partner in a serodiscordant couple (13,32,33). Twenty-nine met the criteria for inclusion in an HIV EU population because they had at least five documented parenteral or mucosal exposures to HIV.…”

Section: Study Populationmentioning

confidence: 99%

HIV Protective KIR3DL1 and HLA-B Genotypes Influence NK Cell Function Following Stimulation with HLA-Devoid Cells

Boulet

Song

Kamya

et al. 2010

The Journal of Immunology

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“…Nevertheless, studies of commercial sex workers and i.v. drug users have inferred exposure to HIV-1 based upon mathematical models of the frequency of high-risk activity and the prevalence of HIV-1 in the community being studied [1,18,22].…”

Section: Introductionmentioning

confidence: 99%

Evidence for the innate immune response as a correlate of protection in human immunodeficiency virus (HIV)-1 highly exposed seronegative subjects (HESN)

Tomescu

Abdulhaqq

Montaner

2011

Clinical and Experimental Immunology

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SummaryThe description of highly exposed individuals who remain seronegative (HESN) despite repeated exposure to human immunodeficiency virus (HIV)-1 has heightened interest in identifying potential mechanisms of HIV-1 resistance. HIV-specific humoral and T cell-mediated responses have been identified routinely in HESN subjects, although it remains unknown if these responses are a definitive cause of protection or merely a marker for exposure. Approximately half of HESN lack any detectible HIV-specific adaptive immune responses, suggesting that other mechanisms of protection from HIV-1 infection also probably exist. In support of the innate immune response as a mechanism of resistance, increased natural killer (NK) cell activity has been correlated with protection from infection in several highrisk cohorts of HESN subjects, including intravenous drug users, HIV-1 discordant couples and perinatally exposed infants. Inheritance of protective NK KIR3DL1 high and KIR3DS1 receptor alleles have also been observed to be over-represented in a high-risk cohort of HESN intravenous drug users and HESN partners of HIV-1-infected subjects. Other intrinsic mechanisms of innate immune protection correlated with resistance in HESN subjects include heightened dendritic cell responses and increased secretion of antiviral factors such as b-chemokines, small anti-viral factors and defensins. This review will highlight the most current evidence in HESN subjects supporting the role of epithelial microenvironment and the innate immune system in sustaining resistance against HIV-1 infection. We will argue that as a front-line defence the innate immune response determines the threshold of infectivity that HIV-1 must overcome to establish a productive infection.

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A Prognostic Model for HIV Seroconversion Among Injection Drug Users as a Tool for Stratification in Clinical Trials

Abstract: If validated in other settings, this risk score may improve the prediction of outcome and allow more accurate stratification in clinical trials.

Cited by 21 publications

References 37 publications

Innate Activation of MDC and NK Cells in High-Risk HIV-1–Exposed Seronegative IV-Drug Users Who Share Needles When Compared With Low-Risk Nonsharing IV-Drug User Controls

Innate Activation of MDC and NK Cells in High-Risk HIV-1–Exposed Seronegative IV-Drug Users Who Share Needles When Compared With Low-Risk Nonsharing IV-Drug User Controls

HIV Protective KIR3DL1 and HLA-B Genotypes Influence NK Cell Function Following Stimulation with HLA-Devoid Cells

Evidence for the innate immune response as a correlate of protection in human immunodeficiency virus (HIV)-1 highly exposed seronegative subjects (HESN)

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