Patients with HIV-associated cancers have evidence of increased T cell dysfunction and exhaustion prior to cancer diagnosis.

BACKGROUND: People living with HIV (PLWH) have increased risk of developing cancers after controlling traditional risk factors and viral suppression. This study explores whether T cells can serve as a marker of risk for cancer among HIV-infected virally suppressed patients. METHODS: A nested case control study design was pursued with 17 cancer cases and 73 controls (PLWH without cancer)ouidentified among the US Military HIV Natural History Study cohort, and were matched for CD4 + count, duration of HIV infection, and viral suppression. Cells were obtained from PLWH on an average of 12 months prior to clinical cancer diagnosis. Expression of inhibitory receptors (PD-1, CD160, CD244, Lag-3, and TIGIT), and transcription factors (T-bet, Eomesodermin, TCF-1, and (TOX) was measured on CD8 +T cells from that early time point. RESULTS: We found that cases have increased expression of PD-1 +CD160+CD244+ ('triple positive') on total and effector CD8 + compared with controls (p=0.02). Furthermore, CD8 +T cells that were both PD-1 +CD160+CD244+ and T-betdimEomeshi were significantly elevated in cases at time point before cancer detection, compared with controls without cancer (p=0.008). This was driven by the finding that transcriptional factor profile of cells was altered in cancers compared with controls. Triple-positive cells were noted to retain the ability for cytotoxicity and cytokine secretion mediated by expression of CD160 and PD-1, respectively. However, triple-positive cells demonstrated high expression of TOX-1, a transcription factor associated with T cell exhaustion. CONCLUSION: In conclusion, we have found a subset of dysfunctional CD8 +T cells, PD-1 +CD160+CD244+T-betdimEomeshi, that is elevated 12 months before cancer diagnosis, suggesting that peripheral T cell alterations may serve as a biomarker of increased cancer risk among PLWH.

The Intersection of HIV, Diabetes, and Race: Exploring Disparities in Diabetes Care among People Living with HIV.

In a setting of universal health care access, we compared diabetes control between Caucasians and African Americans (AA) living with HIV. This was a cross-sectional analysis of data from a cohort study among military members living with HIV and diabetes. Using adjusted logistic regression models, we compared proportions of Caucasians and AA meeting the following diabetes treatment goals: hemoglobin A1c <7.0%, blood pressure (BP) <140/90 mm Hg, low density lipoprotein cholesterol <100 mg/dL, and not smoking. We included 107 Caucasian (mean age 37 years) and 126 AA (mean age 33 years) participants. A similar proportion of Caucasians and AA were prescribed diabetes (∼60%) and BP (∼80%) medications. Yet, more Caucasians met the BP treatment goal (77% [54%, 90%]) than AA (61% [36%, 82%]). Thus, more Caucasians met the combined A1c, BP, and cholesterol goals for diabetes control (25% [10%, 49%]) than AA (13% [5%, 31%]). Despite having equal access to health care, AA in this study have poorer diabetes control than Caucasians.

The US Military HIV Natural History Study: Informing Military HIV Care and Policy for Over 30 Years.

INTRODUCTION: In October 1985, 4 years after the initial descriptions of the acquired immunodeficiency syndrome (AIDS), the U.S. Department of Defense (DoD) began routine screening for human immunodeficiency virus (HIV) infection to prevent infected recruits from exposure to live virus vaccines, implemented routine active-duty force screening to ensure timely care and help protect the walking blood bank, and initiated the U.S. Military HIV Natural History Study (NHS) to develop epidemiologic, clinical, and basic science evidence to inform military HIV policy and establish a repository of data and specimens for future research. Here, we have reviewed accomplishments of the NHS over the past 30 years and sought to describe relevant trends among NHS subjects over this time, with emphasis on combination antiretroviral therapy (cART) use and non-AIDS comorbidities. METHODS: Subjects who were prospectively enrolled in the NHS from 1986 through 2015 were included in this analysis. Time periods were classified by decade of study conduct, 1986-1995, 1996-2005, and 2006-2015, which also correlate approximately with pre-, early-, and late-combination ART (cART) eras. Analyses included descriptive statistics and comparisons among decades. We also evaluated mean community log10 HIV viral load (CVL) and CD4 counts for each year. RESULTS: A total of 5,758 subjects were enrolled between 1986 and 2015, of whom 92% were male with a median age of 28 years, and 45% were African-American, 42% Caucasian, and 13% Hispanic/other. The proportion of African-Americans remained stable over the decades (45%, 47%, and 42%, respectively), while the proportion of Hispanic/other increased (10%, 13%, and 24%, respectively). The CD4 count at HIV diagnosis has remained high (median 496 cells/uL), while the occurrence of AIDS-defining conditions (excluding low CD4 count) has decreased by decade (36.7%, 5.4%, and 2.9%, respectively). Following the introduction of effective cART in 1996, CVL declined through 2000 as use increased and then plateaued until guidelines changed. After 2004, cART use again increased and CVL declined further until 2012-15 when the vast majority of subjects achieved viral suppression. Non-AIDS comorbidities have remained common, with approximately half of subjects experiencing one or more new diagnoses overall and nearly half of subjects diagnosed between 2006 and 2015, in spite of their relatively young age, shorter median follow-up, and wide use of cART. CONCLUSIONS: The US Military HIV NHS has been critical to understanding the impact of HIV infection among active-duty service members and military beneficiaries, as well as producing insights that are broadly relevant. In addition, the rich repository of NHS data and specimens serves as a resource to investigators in the DoD, NIH, and academic community, markedly increasing scientific yield and identifying novel associations. Looking forward, the NHS remains relevant to understanding host factor correlates of virologic and immunologic control, biologic pathways of HIV pathogenesis, causes and consequences of residual inflammation in spite of effective cART, identifying predictors of and potential approaches to mitigation of excess non-AIDS comorbidities, and helping to understand the latent reservoir.

Refractive surgery in the HIV-positive U.S. Military Natural History Study Cohort: complications and risk factors.

PURPOSE: This study sought to assess the frequency of refractive surgery complications in HIV+ individuals and related risk factors. SETTINGS: Multiple centers in the United States. DESIGN: Prospective observational cohort study. METHODS: The U.S. Military HIV Natural History Study is a prospective observational cohort study of HIV+ service members and beneficiaries. Participants were selected who had Current Procedural Terminology codes for laser in situ keratomileusis (LASIK), photorefractive keratectomy (PRK), and other refractive surgeries. The frequency of complications was determined using International Classification of Diseases-9 codes. Covariates included age, sex, antiretroviral therapy, time since HIV diagnosis, history of AIDS, and CD4 (T lymphocytes) count and viral load. Statistical analysis was completed using univariate (χ2 and Wilcoxon-Mann-Whitney tests) and multivariate analyses. RESULTS: Seventy-nine of 2073 participants had refractive surgery. Fifty-three patients underwent PRK, 23 LASIK, 2 radial keratotomy (RK), and 1 astigmatic correction. Complications occurred in 6 (7.6%) of 79 participants, including 5 patients who underwent PRK and 1 after RK, occurring between 8 and 217 days after surgery. Five ulcers and 1 unspecified keratitis were noted. In the univariate analysis, type of surgery (P = .02) and history of AIDS (P = .02) were risk factors for complications. In logistic regression analysis, no variables were found to be risk factors for complications. CONCLUSION: Complications were infrequent among HIV+ participants after refractive surgery. Point estimates suggest that PRK might have more complications than LASIK and that advanced HIV, reflected by previous AIDS, might be associated with an increased risk for complications. Further study will be required to confirm these findings.