Statin usage and cardiovascular risk among people living with HIV in the U.S. Military HIV Natural History Study.

OBJECTIVES: Using the American College of Cardiology/American Heart Association 2013 atherosclerotic cardiovascular disease (ASCVD) management guidelines, we conducted a retrospective cross-sectional analysis of people living with HIV in the US Military HIV Natural History Study to determine whether individuals were receiving statins when indicated. METHODS: Prescription data was taken from Military Health System data. Statin eligibility was defined by ASCVD guidelines. We used the 10-year ASCVD pooled cohorts' equation to evaluate risk for each participant. RESULTS: Across all categories, 31.9% (n = 390) of individuals met criteria for statin use, and when adding these subjects to the number of those already receiving statins (n = 96), 62.1% of all eligible subjects (n = 302/486) were actually receiving statin therapy. In multivariable analysis, individuals of African American race [odds ratio (OR) = 0.48, 95% confidence interval (CI): 0.31-0.73] or Hispanic ethnicity (OR = 0.42, 95% CI: 0.19-0.94) were less likely to receive statin prescriptions than white individuals. Individuals with a higher CD4 count (OR = 1.12, 95% CI: 1.05-1.20 per 100 cells/µL]) were significantly more likely to receive a statin prescription. CONCLUSIONS: These data highlight discrepancies between ASCVD guidelines and primary care management of people living with HIV (PLWH) in the military health system, along with important racial differences. Targeted interventions are critical to identify and treat appropriate candidates for statin therapy among PLWH in the military and other settings.

Characterizing the Association Between Alcohol and HIV Virologic Failure in a Military Cohort on Antiretroviral Therapy.

BACKGROUND: The effects of at-risk drinking on HIV infection remain controversial. We investigated the impact of self-reported alcohol consumption on surrogate markers of HIV progression among individuals initiated on highly active antiretroviral therapy (HAART). METHODS: We analyzed individuals who were surveyed on alcohol use within a year of HAART initiation between 2006 and 2014. At-risk drinking was defined as consumption of at least 3 or 4 drinks/d, or 7 and 14 drinks/wk among women and men, respectively. We performed time-updated generalized estimating equation logistic regression to determine the effect of at-risk drinking on virologic failure (VF) and mixed-effects linear regression on CD4 count reconstitution, controlling for potential confounders. RESULTS: Of 801 individuals initiated on HAART, 752 individuals with alcohol survey data were included in the analysis. Of these, 45% (n = 336) met criteria for at-risk drinking at HAART initiation on at least 1 survey. The rates of VF were 4.30 per 100 person-years (95% CI [2.86, 6.21]) for at-risk drinkers and 2.45 per 100 person-years (95% CI [1.57, 3.65]) for individuals without at-risk drinking. At-risk drinking was not significantly associated with VF (OR 1.73, 95% CI [0.92, 3.25]) (p = 0.087) or CD4 reconstitution (CD4 increase 11.4; 95% CI [-19.8, 42.7]) in univariate analyses; however, in our multivariate model, a statistically significant relationship between VF and at-risk drinking was observed (OR 2.28, 95% CI [ 1.01, 5.15]). CONCLUSIONS: We found a high proportion of at-risk drinking in our military cohort, which was predictive of VF in multivariate analysis. Given alcohol's effect on myriad HIV and non-HIV outcomes, interventions to decrease the prevalence of at-risk drinking among HIV-infected individuals are warranted.

Factors associated with 10 years of continuous viral load suppression on HAART.

BACKGROUND: The principal goal of HAART is sustained viral load (VL) suppression resulting in immune reconstitution and improved HIV outcomes. We studied the factors associated with 10 years of continuous VL suppression on HAART in the US Military HIV Natural History Study. METHODS: Participants with continuous VL suppression (CS, n = 149) were compared to those who did not have continuous viral load suppression (NCS, n = 127) for ≥10 years on HAART. Factors associated with >10 years of VL suppression were evaluated by multivariate logistic regression. Additionally, association between CS and CD4 reconstitution was analyzed with a mixed effects model. RESULTS: Compared to NCS participants, a lower proportion of CS participants started HAART in the early HAART era (66 vs 90 %, for years 1996-1999; p < 0.001) and had less antiretroviral use prior to HAART (37 vs 83 %; p < 0.001). At initial HAART, the median CD4 cell count was higher and VL was lower for CS compared to NCS participants (375 cells/uL [256, 499] vs 261 cells/uL [146, 400]; p < 0.001 and 4.4 log10 copies/mL [3.5, 4.9] vs 4.5 log10 copies/mL [3.8, 5.0]; p = 0.048, respectively). New AIDS events were lower during HAART (5 vs 13 %; p = 0.032) and post-HAART CD4 trajectories were greater for the CS compared to NCS group. Factors negatively associated with ≥10 years of VL suppression included log10 VL at first HAART (OR 0.61, 95 % CI 0.4, 0.92; p = 0.020) and antiretroviral use prior to HAART (OR 0.16, 95 % CI 0.06, 0.38; p < .001). CONCLUSIONS: Sustained VL suppression is a key to long-term health in HIV-infected patients, as demonstrated by the lower proportion of AIDS events observed 10 years after HAART initiation. The current use of more potent and well-tolerated regimens may mitigate the negative factors of pre-HAART VL and prior ARV use encountered by treatment initiated in the early HAART era.

Factors associated with HIV viral load "blips" and the relationship between self-reported adherence and efavirenz blood levels on blip occurrence: a case-control study.

BACKGROUND: The uncertain etiology of HIV viral load (VL) blips may lead to increased use of clinical resources. We evaluated the association of self-reported adherence (SRA) and antiretroviral (ART) drug levels on blip occurrence in US Military HIV Natural History Study (NHS) participants who initiated the single-tablet regimen efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF). METHODS: ART-naïve NHS participants started on EFV/FTC/TDF between 2006 and 2013 who achieved VL suppression (<50 copies/mL) within 12 months and had available SRA and stored plasma samples were included. Participants with viral blips were compared with those who maintained VL suppression without blips. Untimed EFV plasma levels were evaluated on consecutive blip and non-blip dates by high performance liquid chromatography, with a level ≥1 mcg/mL considered therapeutic. SRA was categorized as ≥85 or <85 %. Descriptive statistics were performed for baseline characteristics and univariate and multivariate Cox proportional hazard models were used to assess the relationship between covariates and blip occurrence. RESULTS: A total of 772 individuals met inclusion criteria, including 99 (13 %) blip and 673 (87 %) control participants. African-American was the predominant ethnicity and the mean age was 29 years for both groups. SRA ≥ 85 % was associated with therapeutic EFV levels at both blip and non-blip time points (P = 0.0026); however no association was observed between blips and SRA or EFV levels among cases. On univariate analysis of cases versus controls, blips were associated with higher mean pre-treatment VL (HR 1.45, 95 % CI 1.11-1.89) and pre-treatment CD4 count <350 cells/µL (68.1 vs 49.7 %). Multivariate analysis also showed that blips were associated with a higher mean VL (HR 1.42, 95 % CI 1.08-1.88; P = 0.0123) and lower CD4 count at ART initiation, with CD4 ≥500 cells/µL having a protective effect (HR 0.45, 95 % CI 0.22-0.95; P = 0.0365). No association was observed for demographic characteristics or SRA. CONCLUSION: Blips are commonly encountered in the clinical management of HIV-infected patients. Although blip occurrence was not associated with SRA or EFV blood levels in our study, blips were associated with HIV-related factors of pre-ART high VL and low CD4 count. Additional studies are needed to determine the etiology of blips in HIV-infected patients.

A single dose of benzathine penicillin G is as effective as multiple doses of benzathine penicillin G for the treatment of HIV-infected persons with early syphilis.

BACKGROUND: Treatment guidelines recommend the use of a single dose of benzathine penicillin G (BPG) for treating early syphilis in human immunodeficiency virus (HIV)-infected persons. However, data supporting this recommendation are limited. We examined the efficacy of single-dose BPG in the US Military HIV Natural History Study. METHODS: Subjects were included if they met serologic criteria for syphilis (ie, a positive nontreponemal test [NTr] confirmed by treponemal testing). Response to treatment was assessed at 13 months and was defined by a ≥4-fold decline in NTr titer. Multivariate Cox proportional hazard regression models were utilized to examine factors associated with treatment response. RESULTS: Three hundred fifty subjects (99% male) contributed 478 cases. Three hundred ninety-three cases were treated exclusively with BPG (141 with 1 dose of BPG). Treatment response was the same among those receiving 1 or >1 dose of BPG (92%). In a multivariate analysis, older age (hazard ratio [HR], 0.82 per 10-year increase; 95% confidence interval [CI], .73-.93) was associated with delayed response to treatment. Higher pretreatment titers (reference NTr titer <1:64; HR, 1.94 [95% CI, 1.58-2.39]) and CD4 counts (HR, 1.07 for every 100-cell increase [95% CI, 1.01-1.12]) were associated with a faster response to treatment. Response was not affected by the number of BPG doses received (reference, 1 dose of BPG; HR, 1.11 [95% CI, .89-1.4]). CONCLUSIONS: In this cohort, additional BPG doses did not affect treatment response. Our data support the current recommendations for the use of a single dose of BPG to treat HIV-infected persons with early syphilis.

Association between hepatitis B vaccine antibody response and CD4 reconstitution after initiation of combination antiretroviral therapy in HIV-infected persons.

BACKGROUND: Hepatitis B virus (HBV) vaccine antibody response has been associated with reduced risk of AIDS or death. However, it is unknown whether HBV vaccine responsiveness is associated with improved immune reconstitution during treatment with combination antiretroviral therapy (cART). We evaluated the relationship between HBV vaccine response status and CD4 reconstitution on cART in the U.S Military HIV Natural History Study. METHODS: Participants with viral load <400 copies/mL within 1 year on initial cART and documented HBV vaccination and surface antibody (anti-HBs) prior to cART were included. Participants were characterized as HBV vaccine responders (anti-HBs ≥10 IU/L) or non-responders (<10 IU/L) and further divided into 2 groups based on vaccine administration before or after HIV diagnosis. Linear mixed regression was used to model CD4 reconstitution during the first year of cART. RESULTS: Of the 307 and 169 participants vaccinated before or after HIV diagnosis, HBV vaccine response occurred in 288 (94%) and 74 (44%), respectively. For those vaccinated before HIV diagnosis, CD4 counts increased by a median 190 [IQR 99-310] cells/mm(3) for responders and 186 [IQR 116-366] cells/mm(3) for non-responders during the first year (P = 0.684). Participants vaccinated after HIV diagnosis had median increases of 185 [IQR 76-270] and 143 [IQR 47-238] cells/mm(3) for responders and non-responders, respectively (P = 0.134). In contrast to those with CD4 > 350 cells/mm(3) at cART initiation, participants with CD4 < 200 and 200-350 cells/mm(3) had significantly reduced CD4 gains in both groups by longitudinal mixed models, but there was no difference in CD4 recovery according to HBV vaccine seroresponse. CONCLUSIONS: Although HBV vaccine responsiveness is associated with a reduction in HIV disease progression, HBV vaccine responders do not achieve greater CD4 gains during the first year of cART. Additional clinical markers are needed to predict the magnitude of post-cART immune recovery.

Gender differences in the relationship of anti-parvovirus B19 IgG with antinuclear antibody and C-reactive protein in clinical adult serum samples.

Human parvovirus B19 (B19) infection is often suspected as an etiologic agent in a variety of rheumatologic diseases. It has been hypothesized that this virus potentially induces immune dysregulation by abnormal cytokine expression in susceptible hosts. The objective of this study is to examine the relationship between anti-parvovirus B19 IgG antibody (B19 IgG) and two common markers of immune dysregulation-antinuclear antibody (ANA) and C-reactive protein (CRP) in clinical sera. Qualitative B19 IgG antibody and levels of high-sensitivity CRP were determined in adult serum samples submitted to a university hospital clinical laboratory for ANA testing. Prevalence of B19 IgG was compared among groups by ANA status and CRP tertile. B19 IgG was detected in 72.3% of 318 samples. Among women above the first quartile of age (>38 years), presence of B19 IgG was associated with CRP tertile rank (P = 0.008) and CRP levels > or =1 mg/L (P = 0.001) independent of age and ANA status. B19 IgG was less frequent in ANA-positive than ANA-negative women < or =38 years of age (P = 0.009). Viral antibody was not associated with either biomarker in men. These data suggest parvovirus B19 infection may be associated with chronic inflammation in some women after the third decade of life.

Navigating the Gluten-Free Boom: The Dark Side of Gluten Free Diet.

In gluten dependent conditions the gluten free diet is the cornerstone of therapy, decreasing disease activity, improving health and quality of life and treating or preventing the associated complications. Gluten withdrawal implies strict and lifelong elimination not only of wheat, barley, rye, and wheat-contaminated oats, but also of numerous non-nutritional products where components of wheat are often added. Due to multiple reasons the diet is difficult to follow and the long-term adherence is decreased with time. The present review summarizes the dark side of gluten restriction where nutritional deficiencies, toxicity, morbidity, mortality, and mental health problems are reported. The aim being to increase awareness, avoid, detect and treat the side effects and to promote a healthier nutrition, for the patient's benefits.

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.

Toxoplasma gondii seroprevalence: 30-year trend in an HIV-infected US military cohort.

To determine if Toxoplasma gondii IgG antibody prevalence is declining in HIV-infected persons, we analyzed data (1984-2013) from the US Military HIV Natural History Study. We found that T. gondii seroprevalence at enrollment was associated with age and decreased significantly after 1995 (P=0.004), similar to the general US population.

D-Dimer Levels before HIV Seroconversion Remain Elevated Even after Viral Suppression and Are Associated with an Increased Risk of Non-AIDS Events.

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.

Trimethoprim-sulfamethoxazole revisited.

During the past 3 decades, the combination of trimethoprim and sulfamethoxazole has occupied a central role in the treatment of various commonly encountered infections and has also been particularly useful for several specific clinical conditions. However, changing resistance patterns and the introduction of newer broad-spectrum antibiotics have led to the need to carefully redefine the appropriate use of this agent in clinical practice. While trimethoprim-sulfamethoxazole's traditional role as empirical therapy for several infections has been modified by increasing resistance, it remains a highly useful alternative to the new generation of expanded-spectrum agents if resistance patterns and other clinical variables are carefully considered. It also seems to have an increasing role as a cost-effective pathogen-directed therapy with the potential to decrease or delay development of resistance to newer antibiotics used for empirical treatment. In addition, trimethoprim-sulfamethoxazole continues to be the drug of choice for several clinical indications.

Impact of the highly active antiretroviral therapy era on the epidemiology of primary HIV-associated thrombocytopenia.

BACKGROUND: Primary HIV-associated thrombocytopenia (PHAT) typically improves with highly active antiretroviral therapy (HAART); however, cases continue to occur. Data comparing the epidemiology of PHAT between the pre-HAART and HAART eras are limited. We retrospectively examined the incidence of PHAT over 28 years in the US Military HIV Natural History Study (NHS) from 1986 to 2013. RESULTS: Subjects had a nadir platelet count <100 × 10(9)/l with no other identifiable cause. Time periods were categorized as pre-HAART (1986-1995), early HAART (1996-2001), and later HAART (2002-2013). Incidence, demographic data, and CD4 count were compared across the three eras. A generalized estimating equations model was used to assess any association of platelet count and HIV viral load in cases diagnosed during the HAART eras. 218 participants met the case definition. 86.2 % of cases occurred prior to 2002. The incidence of PHAT per 1000 person-years of follow-up was 16.3, 4.6, and 1.9 during pre-HAART, early HAART and later HAART eras respectively. CD4 cell counts were significantly higher in the HAART eras at the time of thrombocytopenia (p < 0.001). Of patients diagnosed after 1996, 96.4 % were viremic within six months preceding the platelet nadir and over half were antiretroviral naïve. Viral load (per log10 copies/ml) inversely correlated with platelet count throughout the HAART eras (p < 0.0001). CONCLUSIONS: The incidence of PHAT has markedly decreased in the HAART era. However, viremic individuals, including those with healthy CD4 cell counts, may be at risk. Achieving viral suppression as early as possible may decrease the incidence further.

Self-administration of intranasal influenza vaccine: Immunogenicity and volunteer acceptance.

BACKGROUND: In outbreak settings, mass vaccination strategies could maximize health protection of military personnel. Self-administration of live attenuated influenza vaccine (LAIV) may be a means to vaccinate large numbers of people and achieve deployment readiness while sparing the use of human resources. METHODS: A phase IV, open-label, randomized controlled trial evaluating the immunogenicity and acceptance of self-administered (SA) LAIV was conducted from 2012 to 2014. SA subjects were randomized to either individual self-administration or self-administration in a group setting. Control randomized subjects received healthcare worker-administered (HCWA) LAIV. Anti-hemagglutinin (HAI) antibody concentrations were measured pre- and post-vaccination. The primary endpoint was immunogenicity non-inferiority between SA and HCWA groups. Subjects were surveyed on preferred administration method. RESULTS: A total of 1077 subjects consented and were randomized (529 SA, 548 HCWA). Subject characteristics were very similar between groups, though SA subjects were younger, more likely to be white and on active duty. The per-protocol analysis included 1024 subjects (501 SA, 523 HCWA). Post-vaccination geometric mean titers by vaccine strain and by study group (HCWA vs. SA) were: A/H1N1 (45.8 vs. 48.7, respectively; p=0.43), A/H3N2 (45.5 vs. 46.4; p=0.80), B/Yamagata (17.2 vs. 17.8; p=0.55). Seroresponses to A components were high (∼67%), while seroresponses to B components were lower (∼25%). Seroresponse did not differ by administration method. Baseline preference for administration method was similar between groups, with the majority in each group expressing no preference. At follow-up, the majority (64%) of SA subjects preferred SA vaccine. CONCLUSIONS: LAIV immunogenicity was similar for HCWA and SA vaccines. SA was well-tolerated and preferred to HCWA among those who performed SA.

Scedosporium apiospermum (Pseudallescheria boydii) endocarditis.

Scedosporium apiospermum, the asexual state of Pseudallescheria boydii, is increasingly recognized as an opportunistic pathogen. We report a case of native valve endocarditis due to this organism that developed in an elderly patient following a prolonged hospitalization. Literature on endocarditis caused by S. apiospermum and P. boydii is reviewed.

Human leukocyte antigens in Gulf War veterans with chronic unexplained multiple symptoms.

Several articles have suggested that immune dysregulation related to Gulf War deployment may be involved in chronic illnesses with an unclear etiology among Gulf War veterans. To determine whether genetic susceptibility related to the human leukocyte antigen (HLA) system might play a role in development of the veterans' illnesses, we examined the frequency distribution of HLA A, B, DR, and DQ antigens from symptomatic veterans residing in south-central Pennsylvania compared with a local healthy population database. Only HLA-A28 demonstrated statistical significance. A28 was present in 7 (21.9%) of 32 of the veterans and 15 (6.9%) of 217 of the healthy population (p = 0.01, Fisher's exact test). This accounts for a minority of the ill veterans tested and is not statistically significant when corrected for the number of antigens determined. We conclude that specific HLA antigens are not strongly associated with the illnesses of Gulf War veterans.

Hepatitis B vaccine responsiveness and clinical outcomes in HIV controllers.

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.

Pseudallescheriasis in the 21st century.

Since its discovery as an agent of mycetoma nearly a century ago, Pseudallescheria boydii with its asexual (synanamorphic) form, Scedosporium apiospermum, is now recognized as an important emerging opportunistic pathogen causing invasive mycosis in immunocompromised patients. The clinical spectrum of pseudallescheriasis is wide. Invasive disease of the lung, CNS and dissemination are serious manifestations in immunocompromised patients. This organism responds poorly to amphotericin B, and its histopathologic resemblance to aspergillosis often results in a delay in diagnosis. In vitro data, animal models and accumulating clinical experience support the use of voriconazole as a primary treatment for pseudallescheriasis. This paper reviews the microbiology, ecology, epidemiologic trends, clinical manifestations and current treatment options of pseudallescheriasis.

Course of renal injury in the Mpv17-deficient transgenic mouse.

The mutant Mpv17 mouse is a transgenic strain that fails to express a protein that is normally expressed in the kidney and that is associated with peroxisomes. The present studies provide a quantitative examination of renal function and structure in this strain compared to its control CFW strain. By 52 wk of age, the mutant strain developed proteinuria (urinary protein to creatinine ratio: 25 +/- 14 versus 3 +/- 1, mutant versus control), albuminuria (urinary albumin to creatinine ratio: 23 +/- 15 versus 0.1 +/- 0.1, mutant versus control), and hypoalbuminemia (2.1 +/- 0.4 versus 2.5 +/- 0.2 G/dl, mutant versus control), but without arterial hypertension or major reduction in filtration (serum creatinine 0.14 +/- 0.04 versus 0.18 +/- 0.12 mg/dl, mutant versus control). The Mpv17 glomeruli were enlarged (0.98 +/- 0.12 versus 0.52 +/- 0.02 micrometer(3) x 10(6), mutant versus control). Glomerular sclerosis became widespread (95 +/- 3 versus 23 +/- 32%, mutant versus control) and was preceded by mesangiolysis and microaneurysms. Tubulointerstitial disease was conspicuous by its absence. The intrarenal vasculature was normal in the mutant mice. Electron microscopy demonstrated focal foot process fusion and mesangiolysis. Thus, this mutant strain of mouse develops proteinuria and a distinct glomerulopathy including mesangiolysis but little interstitial injury all due to the loss of expression of a single gene.