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Objective: Neurocognitive impairment (NCI) is a well-known complication of human immunodeficiency virus (HIV) infection and may be influenced by a number of psychological factors. We examined the relationship between NCI and mental health disorders, including posttraumatic stress disorder (PTSD), in a cohort of 189 active-duty and retired U.S. military men living with HIV. Methods: Participants completed selected modules of the Composite International Diagnostic Interview (CIDI) to ascertain the presence of PTSD, major depressive disorder, and other mental health diagnoses. We also obtained demographic data, including history of head trauma, via personal interview. NCI was assessed with a comprehensive battery of standardized neuropsychological tests. Results: The median age of study subjects was 36 years (interquartile range [IQR] 28 to 43) and median total years of education was 14 (IQR 12 to 16). NCI was diagnosed in 19% of subjects. Individuals with and without a history of PTSD were similar with respect to most HIV-related characteristics; however, the former were significantly more likely to have a prior acquired immunodeficiency syndrome (AIDS) diagnosis. In multivariate analysis, lifetime history of PTSD was independently associated with NCI (odds ration [OR] = 6.12; 95% confidence interval [CI] = 1.85, 20.27), while a history of head of trauma was negatively associated (OR = 0.37 95% CI = 0.15,0.92). Conclusions: Our findings demonstrate that PTSD is an important predictor of NCI in this U.S. military cohort. HIV-infected individuals with cognitive difficulties should be screened for mental health disorders, including PTSD, and prospective studies of the longitudinal relationship between PTSD and NCI, as well as the impact of PTSD treatment on future NCI, are warranted.

ImportanceIn individuals with human immunodeficiency virus 1 (HIV-1) infection who are receiving antiretroviral therapy (ART), factors that promote full immune recovery are not well characterized.ObjectiveTo investigate the influence of the timing of ART relative to HIV-1 infection on normalization of CD4+ T-cell counts, AIDS risk, and immune function.Design, setting, and participantsParticipants in the observational US Military HIV Natural History Study with documented estimated dates of seroconversion (EDS) who achieved virologic suppression with ART were evaluated. Markers indicative of immune activation, dysfunction, and responsiveness were determined. Responses to hepatitis B virus (HBV) vaccine, an indicator of in vivo immune function, were also assessed. The timing of ART was indexed to the EDS and/or entry into the cohort. The CD4+ counts in HIV-1-uninfected populations were surveyed.Main outcomes and measuresNormalization of CD4+ counts to 900 cells/μL or higher, AIDS development, HBV vaccine response, as well as T-cell activation, dysfunction, and responsiveness.ResultsThe median CD4+ count in HIV-1-uninfected populations was approximately 900 cells/μL. Among 1119 HIV-1-infected participants, CD4+ normalization was achieved in 38.4% vs 28.3% of those initiating ART within 12 months vs after 12 months from the EDS (P = .001). Incrementally higher CD4+ recovery (

Variation in the 3' untranslated region (3'UTR) of the HLA-C locus determines binding of the microRNA Hsa-miR-148a, resulting in lower cell surface expression of alleles that bind miR-148a relative to those alleles that escape its binding. The HLA-C 3'UTR variant was shown to associate with HIV control, but like the vast majority of disease associations in a region dense with causal candidates, a direct effect of HLA-C expression level on HIV control was not proven. We demonstrate that a MIR148A insertion/deletion polymorphism associates with its own expression levels, affecting the extent to which HLA-C is down-regulated, the level of HIV control, and the risk of Crohn disease only among those carrying an intact miR-148a binding site in the HLA-C 3'UTR. These data illustrate a direct effect of HLA-C expression level on HIV control that cannot be attributed to other HLA loci in linkage disequilibrium with HLA-C and highlight the rich complexity of genetic interactions in human disease.

ObjectiveTo describe the prevalence of neurocognitive impairment (NCI) among early diagnosed and managed HIV-infected persons (HIV+) compared to HIV-negative controls.MethodsWe performed a cross-sectional study among 200 HIV+ and 50 matched HIV-uninfected (HIV-) military beneficiaries. HIV+ patients were categorized as earlier (200 cells/mm(3)) or later stage patients (n = 100 in each group); both groups were diagnosed early and had access to care. NCI was diagnosed using a comprehensive battery of standardized neuropsychological tests.ResultsHIV+ patients had a median age of 36 years, 91% were seroconverters (median window of 1.2 years), had a median duration of HIV of 5 years, had a CD4 nadir of 319, had current CD4 of 546 cells/mm(3), and 64% were on highly active antiretroviral therapy (initiated 1.3 years after diagnosis at a median CD4 of 333 cells/mm(3)). NCI was diagnosed among 38 (19%, 95% confidence interval 14%-25%) HIV+ patients, with a similar prevalence of NCI among earlier and later stage patients (18% vs 20%, p = 0.72). The prevalence of NCI among HIV+ patients was similar to HIV- patients.ConclusionsHIV+ patients diagnosed and managed early during the course of HIV infection had a low prevalence of NCI, comparable to matched HIV-uninfected persons. Early recognition and management of HIV infection may be important in limiting neurocognitive impairment.

BackgroundSleep disturbances are reportedly common among persons infected with human immunodeficiency virus (HIV), but recent data, including comparisons with HIV-uninfected persons, are limited.MethodsWe performed a cross-sectional study among early-treated HIV-infected military beneficiaries (n = 193) to determine the prevalence and factors associated with insomnia (Pittsburgh Sleep Quality Index [PSQI]) and daytime sleepiness (Epworth Sleepiness Scale [ESS]). Data were compared with HIV-uninfected persons (n = 50) matched by age, sex, race or ethnicity, and military rank.ResultsForty-six percent of HIV-infected persons had insomnia (PSQI >5), and 30% reported daytime drowsiness (ESS ≥10). The prevalence of insomnia and daytime sleepiness was not significantly higher compared with the HIV-uninfected group (38% [P = .30] and 20% [P = .18], respectively). In the multivariate model, factors associated with insomnia among HIV infected patients included depression (odds ratio [OR], 16.8; 95% confidence interval [CI], 2.0-142.1; P = .01), increased waist size (OR, 2.7; 95% CI, 1.4-5.1; P = .002), and fewer years of education (OR, 0.8; 95% CI, .7-.95; P = .006). Neurocognitive impairment (diagnosed in 19% of HIV-infected participants) was not associated with insomnia; however, HIV-infected persons with insomnia were 3.1-fold more likely to have a decline in activities of daily living than those without insomnia (23% vs 9%; P = .01). Only 18% of HIV-infected persons reported using a sleep medication at least weekly.ConclusionsHIV-infected persons have a high prevalence of insomnia, but among an early-treated cohort this rate was not significantly higher compared with HIV-uninfected persons. Factors associated with insomnia among HIV-infected patients include depression and increased waist size. Prompt diagnosis and treatment of sleep disturbances are advocated and may improve quality of life.

Background: Numerous studies have found higher rates of sexually transmitted infections (STIs) among military personnel than the general population, but the cumulative risk of acquiring STIs throughout an individual’s military career has not been described. Methods: Using ICD-9 diagnosis codes, we analyzed the medical records of 100,005 individuals from all service branches, divided in equal cohorts (n = 6,667) between 1997 and 2011. As women receive frequent STI screening compared to men, these groups were analyzed separately. Incidence rates were calculated for pathogen-specific STIs along with syndromic diagnoses. Descriptive statistics were used to characterize the individuals within each accession year cohort; repeat infections were censored. Results: The total sample included 29,010 females and 70,995 males. The STI incidence rates (per 100 person-years) for women and men, respectively, were as follows: chlamydia (3.5 and 0.7), gonorrhea (1.1 and 0.4), HIV (0.04 and 0.07) and syphilis (0.14 and 0.15). During the study period, 22% of women and 3.3% of men received a pathogen-specific STI diagnosis; inclusion of syndromic diagnoses increased STI prevalence to 41% and 5.5%, respectively. In multivariate analyses, factors associated with etiologic and syndromic STIs among women included African American race, younger age and fewer years of education. In the overall sample, increasing number of years of service was associated with an increased likelihood of an STI diagnosis (p<0.001 for trend). Conclusion: In this survey of military personnel, we found very high rates of STI acquisition throughout military service, especially among women, demonstrating that STI-related risk is significant and ongoing throughout military service. Lower STI incidence rates among men may represent under-diagnosis and demonstrate a need for enhancing male-directed screening and diagnostic interventions. [ABSTRACT FROM AUTHOR]

The mechanism underlying the excess risk of non-AIDS diseases among HIV infected people is unclear. HIV associated inflammation/hypercoagulability likely plays a role. While antiretroviral therapy (ART) may return this process to pre-HIV levels, this has not been directly demonstrated. We analyzed data/specimens on 249 HIV+ participants from the US Military HIV Natural History Study, a prospective, multicenter observational cohort of >5600 active duty military personnel and beneficiaries living with HIV. We used stored blood specimens to measure D-dimer and Interleukin-6 (IL-6) at three time points: pre-HIV seroconversion, ≥6 months post-HIV seroconversion but prior to ART initiation, and ≥6 months post-ART with documented HIV viral suppression on two successive evaluations. We evaluated the changes in biomarker levels between time points, and the association between these biomarker changes and future non-AIDS events. During a median follow-up of 3.7 years, there were 28 incident non-AIDS diseases. At ART initiation, the median CD4 count was 361cells/mm3; median duration of documented HIV infection 392 days; median time on ART was 354 days. Adjusted mean percent increase in D-dimer levels from pre-seroconversion to post-ART was 75.1% (95% confidence interval 24.6–148.0, p = 0.002). This increase in D-dimer was associated with a significant 22% increase risk of future non-AIDS events (p = 0.03). Changes in IL-6 levels across time points were small and not associated with future non-AIDS events. In conclusion, ART initiation and HIV viral suppression does not eliminate HIV associated elevation in D-dimer levels. This residual pathology is associated with an increased risk of future non-AIDS diseases. [ABSTRACT FROM AUTHOR]

Background: Hepatitis B virus (HBV) vaccine responsiveness is associated with reduced risk of AIDS or death in HIV-infected individuals. Although HIV controllers (HIC) typically have favorable immunologic and clinical characteristics compared to non-controllers, vaccine responsiveness has not been studied. Methods and Findings: In the U.S. Military HIV Natural History Study, HBV vaccine response was defined as antibody to hepatitis B surface antigen (anti-HBs) ≥10 IU/L after last vaccination. For determination of vaccine responsiveness, HIC (n = 44) and treatment-naïve non-controllers (n = 476) were not on highly active antiretroviral therapy (HAART) when vaccinated while treated non-controllers (n = 284) received all HBV vaccine doses during viral load (VL)-suppressive HAART. Progression to AIDS or death was also compared for all HIC (n = 143) and non-controllers (n = 1566) with documented anti-HBs regardless of the timing of HBV vaccination. Positive vaccine responses were more common in HIC (65.9%) compared to HAART-naïve non-controllers (36.6%; P<0.001), but similar to non-controllers on HAART (59.9%; P = 0.549). Factors associated with vaccine response for HIC compared to HAART-naïve non-controllers include HIC status (OR 2.65, 95% CI 1.23–5.89; P = 0.014), CD4 count at last vaccination (OR 1.28, 1.15–1.45 for every 100 cells/uL; P<0.001), and number of vaccine doses administered (OR 0.56, 0.35–0.88; P = 0.011). When HIC were compared to non-controllers on HAART, only CD4 count at last vaccination was significant (OR 1.23, 1.1–1.38 for every 100 cells/uL; P<0.001). The rate of AIDS or death per 100 person/years for HIC compared to non-controllers was 0.14 (95% CI 0–0.76) versus 0.98 (95% CI 0.74–1.28) for vaccine responders and 0 (95% CI 0–2.22) versus 4.11 (95% CI 3.38–4.96) for non-responders, respectively. Conclusions: HIC have improved HBV vaccine responsiveness compared to treatment-naïve non-controllers, but similar to those on VL-suppressive HAART. Progression to AIDS or death can be predicted by HBV vaccine responder status for non-controllers, however these events are rarely observed in HIC. [ABSTRACT FROM AUTHOR]