Human Immunodeficiency Virus (HIV)-Negative Men Who Have Sex With Men Have Higher CD8+ T-Cell Counts and Lower CD4+/CD8+ T-Cell Ratios Compared With HIV-Negative Heterosexual Men.
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ABSTRACT: Background
We previously reported T-cell senescence to be similar in people with human immunodeficiency virus (PWH) with suppressed viremia (predominantly men who have sex with men [MSM]) and human immunodeficiency virus (HIV)-negative otherwise comparable controls but greater than in healthy blood donors. This led us to compare CD4+ and CD8+ T-cell counts and CD4+/CD8+ ratios between HIV-negative MSM and men who only have sex with women (MSW) and relate observed differences in behavioral factors and infectious exposures, including cytomegalovirus (CMV) infection.Methods
In 368 HIV-negative MSM and 72 HIV-negative MSW, T lymphocyte phenotyping was performed 3 times biennially. Baseline CMV serology and sexually transmitted infection (STI) incidence and/or STI seroprevalence, sexual, and substance-use behavior data were collected during study visits.Results
Men who have sex with men, compared with MSW, had higher CD8+ counts (551 vs 437 cells/mm3, P < .001), similar CD4+ counts (864 vs 880 cells/mm3, P = .5), and lower CD4+/CD8+ ratios (1.84 vs 2.47, P < .001). Differences were most pronounced for MSM with >10 recent sex partners and partly explained by higher CMV seroprevalence in MSM.Conclusions
These findings suggest that factors other than HIV may, in both PWH and certain HIV-negative MSM, contribute to a low CD4+/CD8+ ratio. Whether this, like in PWH, contributes to comorbidity risk in HIV-negative MSM requires further study.
SUBMITTER: Verboeket SO
PROVIDER: S-EPMC8514179 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundThis study investigated the prevalence of HPVs in heterosexual South African men and the impact of HIV co-infection.MethodsHPV was detected in penile swabs from 195 HIV-infected and 140 HIV-uninfected men using PCR with FAP59/64 primers and Roche Linear Array HPV genotyping (LA). Genotyping of FAP positive specimens was achieved by high-throughput sequencing of amplicons.ResultsHPV was detected by FAP PCR and LA in 79% (266/335) of the men. Men with HIV co-infection and men with HIV infected sexual partners had a significantly (p<0.0001) higher HPV infection risk (adjusted odds ratio 4.0 (2.1-8.2) and 3.7 (2.1-6.7), respectively). LA genotyping and 454 sequencing of 218 FAP positive specimens detected 45 known ?-HPV types, 45 ?-HPV types (34 known, 10 putative and 1 novel putative), and 91 ?-HPV types (26 known, 51 putative and 14 novel putative). Alpha, beta and gamma types were detected in 89.8%, 51.4% and 62.4% of the 218 men with HPV-62, HPV-5 and HPV-121 most common in each genus, respectively.ConclusionA great diversity of known and novel alpha, beta and gamma HPV types were detected with higher prevalence in HIV co-infected men and unknown associations, if any, with genital lesions and cancers.
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Project description:BackgroundWe tested the hypothesis that patient-centered, streamlined human immunodeficiency virus (HIV) care would achieve lower mortality than the standard treatment model for persons with HIV and CD4 ≤ 350/uL in the setting of population-wide HIV testing.MethodsIn the SEARCH (Sustainable East Africa Research in Community Health) Study (NCT01864603), 32 communities in rural Uganda and Kenya were randomized to country-guided antiretroviral therapy (ART) versus streamlined ART care that included rapid ART start, visit spacing, flexible clinic hours, and welcoming environment. We assessed persons with HIV and CD4 ≤ 350/uL, ART eligible in both arms, and estimated the effect of streamlined care on ART initiation and mortality at 3 years. Comparisons between study arms used a cluster-level analysis with survival estimates from Kaplan-Meier; estimates of ART start among ART-naive persons treated death as a competing risk.ResultsAmong 13 266 adults with HIV, 2973 (22.4%) had CD4 ≤ 350/uL. Of these, 33% were new diagnoses, and 10% were diagnosed but ART-naive. Men with HIV were almost twice as likely as women with HIV to have CD4 ≤ 350/uL and be untreated (15% vs 8%, respectively). Streamlined care reduced mortality by 28% versus control (risk ratio [RR] = 0.72; 95% confidence interval [CI]: .56, .93; P = .02). Despite eligibility in both arms, persons with CD4 ≤ 350/uL started ART faster under streamlined care versus control (76% vs 43% by 12 months, respectively; P < .001). Mortality was reduced substantially more among men (RR = 0.61; 95% CI: .43, .86; P = .01) than among women (RR = 0.90; 95% CI: .62, 1.32; P = .58).ConclusionsAfter population-based HIV testing, streamlined care reduced population-level mortality among persons with HIV and CD4 ≤ 350/uL, particularly among men. Streamlined HIV care models may play a key role in global efforts to reduce AIDS deaths.
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Project description:Background:We recently reported that the levels of activation, exhaustion, and terminal differentiation within the peripheral T-cell compartment were increased in men who have sex with men (MSM) compared with blood bank donors. During activation and differentiation, T cells undergo metabolic changes to maintain their energy demand. Methods:The effect of cytomeglovirus (CMV) infection and risk behavior on the immune phenotype of peripheral T cells and the immune bioenergy metabolism profile in human immunodeficiency virus-negative MSM (with high or low sexual risk behavior) and blood bank donors was evaluated. Results:Men who have sex with men exhibited increased levels of T-cell activation and terminal differentiation and an impairment of the bioenergy metabolism (mitochondrial respiration and glycolysis) compared with blood bank donors. Cytomeglovirus infection was associated with increased terminal differentiation of CD4+ (B?=?3.41; 95% confidence interval [CI], 1.98-4.85; P?<?.0001) and CD8+ T cells (CD57+: B?=?1.21, 95% CI?=?0.41-2.02, P?=?.004; CD27-CD28-: B?=?2.20, 95% CI?=?1.21-3.18, P?<?.0001; and CD57+ of CD28-: B?=?1.02, 95% CI?=?0.38-1.66, P?=?.002) and increased glycolysis (B?=?0.97; 95% CI, 0.27-1.67; P?=?.007). Risk behavior was associated with increase activation of CD4+ T cells (B?=?0.22; 95% CI, 0.07-0.37; P?=?.005), increased terminal differentiation of CD4+ (B?=?0.82; 95% CI, 0.44-1.20; P?<?.0001) and CD8+ T cells (B?=?1.55; 95% CI, 0.58-2.51; P?=?.002), and decreased glycolysis (glycolysis: B?=?-0.40, 95% CI?=?-0.68 to 0.12, P?=?.006; and glycolytic capacity: B?=?-0.54, 95% CI?=?-0.91 to 0.16, P?=?.005). Conclusions:Men who have sex with men show an increased prevalence of bloodborne and sexually transmitted infection, indicating that immunological changes in the T-cell population and the bioenergy metabolism observed in MSM can most likely be attributed to chronic antigen exposure.
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Project description:Purpose: Tumor-infiltrating lymphocytes (TIL) in pretreatment biopsies are associated with improved survival in triple-negative breast cancer (TNBC). We investigated whether higher peripheral lymphocyte counts are associated with lower breast cancer-specific mortality (BCM) and overall mortality (OM) in TNBC.Experimental Design: Data on treatments and diagnostic tests from electronic medical records of two health care systems were linked with demographic, clinical, pathologic, and mortality data from the California Cancer Registry. Multivariable regression models adjusted for age, race/ethnicity, socioeconomic status, cancer stage, grade, neoadjuvant/adjuvant chemotherapy use, radiotherapy use, and germline BRCA1/2 mutations were used to evaluate associations between absolute lymphocyte count (ALC), BCM, and OM. For a subgroup with TIL data available, we explored the relationship between TILs and peripheral lymphocyte counts.Results: A total of 1,463 stage I-III TNBC patients were diagnosed from 2000 to 2014; 1,113 (76%) received neoadjuvant/adjuvant chemotherapy within 1 year of diagnosis. Of 759 patients with available ALC data, 481 (63.4%) were ever lymphopenic (minimum ALC <1.0 K/μL). On multivariable analysis, higher minimum ALC, but not absolute neutrophil count, predicted lower OM [HR = 0.23; 95% confidence interval (CI), 0.16-0.35] and BCM (HR = 0.19; CI, 0.11-0.34). Five-year probability of BCM was 15% for patients who were ever lymphopenic versus 4% for those who were not. An exploratory analysis (n = 70) showed a significant association between TILs and higher peripheral lymphocyte counts during neoadjuvant chemotherapy.Conclusions: Higher peripheral lymphocyte counts predicted lower mortality from early-stage, potentially curable TNBC, suggesting that immune function may enhance the effectiveness of early TNBC treatment. Clin Cancer Res; 24(12); 2851-8. ©2018 AACR.
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Project description:Objectives. To identify the impact of a strengths-focused HIV prevention program among high-risk heterosexual Black men. Methods. Barbershops in Brooklyn, New York, neighborhoods with high rates of heterosexually transmitted HIV were randomized to the intervention or an attention control program. Men were recruited from barbershops between 2012 and 2016 and participated in a single small group, peer-led session focused on HIV risk reduction skills and motivation, community health empowerment, and identification of personal strengths and communication skills. The outcome was defined as 1 or more acts of condomless anal or vaginal sex in the preceding 90 days at a 6-month interview. Results. Fifty-three barbershops (24 intervention, 29 control) and 860 men (436 intervention, 424 control) were recruited; follow-up was completed by 657 participants (352 intervention, 305 control). Intervention exposure was associated with a greater likelihood of no condomless sex (64.4%) than control group participation (54.1%; adjusted odds ratio = 1.61; 95% confidence interval = 1.05, 2.47). Conclusions. Program exposure resulted in reduced sexual risk behaviors, and the program was acceptable for administration in partnership with barbershops. Public Health Implications. Dissemination of similar programs could improve public health in communities with high rates of HIV attributable to heterosexual transmission.
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