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The association of ?4?7 expression with HIV acquisition and disease progression in people who inject drugs and men who have sex with men: Case control studies.

ABSTRACT: BACKGROUND:?4?7 is a gut-homing integrin heterodimer that can act as a non-essential binding molecule for HIV. A previous study in heterosexual African women found that individuals with higher proportions of ?4?7 expressing CD4+ T cells were more likely to become infected with HIV, as well as present with faster disease progression. It is unknown if this phenomenon is also observed in men who have sex with men (MSM) or people who inject drugs (PWID). METHODS:MSM and transgender women who seroconverted as part of the HVTN 505 HIV vaccine trial and PWID who seroconverted during the ALIVE cohort study were selected as cases and matched to HIV-uninfected controls from the same studies (1:1 and 1:3, respectively). Pre-seroconversion PBMC samples from cases and controls in both studies were examined by flow cytometry to measure levels of ?4?7 expression on CD4+ T cells. Multivariable conditional logistic regression was used to compare ?4?7 expression levels between cases and controls. A Kaplan-Meier curve was used to examine the association of ?4?7 expression pre-seroconversion with HIV disease progression. FINDINGS:In MSM and transgender women (n = 103 cases, 103 controls), there was no statistically significant difference in the levels of ?4?7 expression on CD4+ T cells between cases and controls (adjusted odds ratio [adjOR] =1.10, 95% confidence interval [CI]=0.94,1.29; p?=?0.246). Interestingly, in PWID (n?=?49 cases, 143 controls), cases had significantly lower levels of ?4?7 expression compared to their matched controls (adjOR?=?0.80, 95% CI?=?0.68, 0.93; p?=?0.004). Among HIV-positive PWID (n?=?47), there was no significant association in HIV disease progression in individuals above or below the median level of ?4?7 expression (log-rank p?=?0.84). INTERPRETATION:In contrast to findings in heterosexual women, higher ?4?7 expression does not predict HIV acquisition or disease progression in PWID or MSM. FUNDING:This study was supported in part by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health. The study was also supported by extramural grants from NIAID T32AI102623 (E.U.P.), and UM1AI069470.

SUBMITTER: Martin AR

PROVIDER: S-EPMC7658649 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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The association of α4β7 expression with HIV acquisition and disease progression in people who inject drugs and men who have sex with men: Case control studies.

Martin Alyssa R AR Patel Eshan U EU Kirby Charles C Astemborski Jacquie J Kirk Gregory D GD Mehta Shruti H SH Marshall Kyle K Janes Holly H Clayton Ashley A Corey Lawrence L Hammer Scott M SM Sobieszczyk Magdalena E ME Arthos James J Cicala Claudia C Redd Andrew D AD Quinn Thomas C TC

EBioMedicine 20201107

<h4>Background</h4>α4β7 is a gut-homing integrin heterodimer that can act as a non-essential binding molecule for HIV. A previous study in heterosexual African women found that individuals with higher proportions of α4β7 expressing CD4<sup>+</sup> T cells were more likely to become infected with HIV, as well as present with faster disease progression. It is unknown if this phenomenon is also observed in men who have sex with men (MSM) or people who inject drugs (PWID).<h4>Methods</h4>MSM and tra ...[more]

PMID: 33166790

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Project description:BackgroundThe assessment of geographical heterogeneity of HIV among men who have sex with men (MSM) and people who inject drugs (PWID) can usefully inform targeted HIV prevention and care strategies.ObjectiveWe aimed to measure HIV seroprevalence and identify hotspots of HIV infection among MSM and PWID in Nigeria.MethodsWe included all MSM and PWID accessing HIV testing services across 7 prioritized states (Lagos, Nasarawa, Akwa Ibom, Cross Rivers, Rivers, Benue, and the Federal Capital Territory) in 3 geographic regions (North Central, South South, and South West) between October 1, 2016, and September 30, 2017. We extracted data from national testing registers, georeferenced all HIV test results aggregated at the local government area level, and calculated HIV seroprevalence. We calculated and compared HIV seroprevalence from our study to the 2014 integrated biological and behavioural surveillance survey and used global spatial autocorrelation and hotspot analysis to highlight patterns of HIV infection and identify areas of significant clustering of HIV cases.ResultsMSM and PWID had HIV seroprevalence rates of 12.14% (3209/26,423) and 11.88% (1126/9474), respectively. Global spatial autocorrelation Moran I statistics revealed a clustered distribution of HIV infection among MSM and PWID with a <5% and <1% likelihood that this clustered pattern could be due to chance, respectively. Significant clusters of HIV infection (Getis-Ord-Gi* statistics) confined to the North Central and South South regions were identified among MSM and PWID. Compared to the 2014 integrated biological and behavioural surveillance survey, our results suggest an increased HIV seroprevalence among PWID and a substantial decrease among MSM.ConclusionsThis study identified geographical areas to prioritize for control of HIV infection among MSM and PWID, thus demonstrating that geographical information system technology is a useful tool to inform public health planning for interventions targeting epidemic control of HIV infection.

Project description:Key populations (KPs) are particularly vulnerable to HIV infection and efforts to prevent HIV infections among KPs have been less successful, largely due to existing laws and legislation that classify the groups as illegal. Understanding the HIV infection pathway and the burden of HIV infection among Female Sex Workers (FSWs), Transgender people (TG), Men who have sex with Men (MSM), People who Inject Drugs (PWID), and Prison Inmates (PIs) is critical to combatting the HIV epidemic globally. This study aims to estimate HIV prevalence and model the risk factors of HIV positivity rate among the aforementioned KPs in Sierra Leone. This study used Time Location Sampling, Respondent Driven Sampling (RDS), and Conventional cluster Sampling designs to generate a representative sample of FSWs, MSM, TG, PI, and PWID. HIV prevalence and the corresponding 95% confidence intervals among each KP were estimated by adjusting for sampling weight using the logit-transformed confidence intervals. To determine correlates of HIV test positivity among KPs, a multivariable modified Poisson regression model that adjusts for RDS survey weights was used and sensitivity analysis was conducted using a multivariable logistic regression model with cluster robust standard errors. The prevalence of HIV among FSWs in the six regional headquarter towns was estimated to be 11.8% (95% CI: 7.9-17.1); MSM was 3.4% [95% CI: 1.9-5.8]; TGs was 4.2% (95% CI: 2.9-6.1); PWIDs was 4.2% (95% CI: 2.7-6.4) and PI was 3.7% (95% CI: 1.4-9.6). The correlates of HIV test positivity among KPs and PIs include HIV-related knowledge, marital status, district, income, age and sex of KP, level of education, alcohol intake, injecting drugs, and use of lubricants. HIV prevalence is relatively high among FSWs, MSMs, PWID, and TGs as compared to the previous estimate of the general population. There is a need to scale up and strengthen evidence-based HIV prevention interventions such Pre-Exposure Prophylaxis and needle and syringe exchange programmes targeting KPs, including prison inmates. Government must scale up both non-clinical and clinical routine HIV and STI testing and counseling services at the correctional center and drop-in centers for KPs screening/testing, and ensure that services are responsive to the needs of KP.

Dataset Information

The association of ?4?7 expression with HIV acquisition and disease progression in people who inject drugs and men who have sex with men: Case control studies.

Publications

The association of α4β7 expression with HIV acquisition and disease progression in people who inject drugs and men who have sex with men: Case control studies.

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