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.

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 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.

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.

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.

BackgroundPrimary 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.ResultsSubjects had a nadir platelet count <100 × 109/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).ConclusionsThe 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.

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 2006-14. At-risk drinking was defined as consumption of at least three or four drinks/day, or seven and 14 drinks/week among women and men, respectively. We performed time-updated generalized estimating equation (GEE) 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 907 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 one 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]) 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.

BackgroundThe 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).MethodsART-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.ResultsA 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.ConclusionBlips 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.