Anogenital HIV RNA in Thai men who have sex with men in Bangkok during acute HIV infection and after randomization to standard vs. intensified antiretroviral regimens

Introduction

HIV transmission risk is highest during acute HIV infection (AHI). We evaluated HIV RNA in the anogenital compartment in men who have sex with men (MSM) during AHI and compared time to undetectable HIV RNA after three-drug versus five-drug antiretroviral therapy (ART) to understand risk for onward HIV transmission.

Methods

MSM with AHI (n=54) had blood, seminal plasma and anal lavage collected for HIV RNA at baseline, days 3 and 7, and weeks 2, 4, 12 and 24. Data were compared between AHI stages: 1 (fourth-generation antigen-antibody combo immunoassay [IA]–, third-generation IA–, n=15), 2 (fourth-generation IA+, third-generation IA–, n=9) and 3 (fourth-generation IA+, third-generation IA+, western blot–/indeterminate, n=30) by randomization to five-drug (tenofovir+emtricitabine+efavirenz+raltegravir+maraviroc, n=18) versus three-drug (tenofovir+emtricitabine+efavirenz, n=18) regimens.

Results

Mean age was 29 years and mean duration since HIV exposure was 15.4 days. Mean baseline HIV RNA was 5.5 in blood, 3.9 in seminal plasma and 2.6 log₁₀ copies/ml in anal lavage (p<0.001). Blood and seminal plasma HIV RNA were higher in AHI Stage 3 compared to Stage 1 (p<0.01). Median time from ART initiation to HIV RNA <50 copies/ml was 60 days in blood, 15 days in seminal plasma and three days in anal lavage. Compared with the three-drug ART, the five-drug ART had a shorter time to HIV RNA <1500 copies/ml in blood (15 vs. 29 days, p=0.005) and <50 copies/ml in seminal plasma (13 vs. 24 days, p=0.048).

Conclusions

Among MSM with AHI, HIV RNA was highest in blood, followed by seminal plasma and anal lavage. ART rapidly reduced HIV RNA in all compartments, with regimen intensified by raltegravir and maraviroc showing faster HIV RNA reductions in blood and seminal plasma.     

Analysis of human platelet glycoproteins IIb-IIIa and Glanzmann's thrombasthenia in whole blood by flow cytometry

Antibodies that bind to human platelet membrane glycoproteins IIb and IIIa were used to develop methods for analyzing platelet membrane components by flow cytometry. Platelets were tentatively identified by their low-intensity light scatter profiles in whole blood or platelet- rich plasma preparations. Identification of this cell population as platelets was verified by using platelet-specific antibodies and fluorescein-conjugated antiimmunoglobulin. Two-parameter analysis of light scatter versus fluorescence intensity identified greater than 98% of the cells in the "platelet" light scatter profile as platelets due to their acquired fluorescence. Both platelet-rich plasma and whole blood were used to study platelet membrane glycoproteins IIb and IIIa on a single cell basis in an unwashed system. Prostacycline was included in these preparations as a precautionary step to inhibit platelet aggregation during analysis. Flow cytometry is a successful technique for rapid detection of platelet membrane defects such as Glanzmann's thrombasthenia. Platelets from Glanzmann's thrombasthenic individuals were readily distinguished from platelets with normal levels of glycoprotein IIb and IIIa and from platelets with glycoprotein levels characteristic of heterozygote carriers of this disorder. This technique provides a sensitive tool for investigating platelet functional defects due to altered expression or deficiency of platelet surface proteins.     

Hypoglycemia and Clinical Outcomes in Patients With Diabetes Hospitalized in the General Ward

OBJECTIVE

Hypoglycemia is associated with adverse outcomes in mixed populations of patients in intensive care units. It is not known whether the same risks exist for diabetic patients who are less severely ill. In this study, we aimed to determine whether hypoglycemic episodes are associated with higher mortality in diabetic patients hospitalized in the general ward.

RESEARCH DESIGN AND METHODS

This retrospective cohort study analyzed 4,368 admissions of 2,582 patients with diabetes hospitalized in the general ward of a teaching hospital between January 2003 and August 2004. The associations between the number and severity of hypoglycemic (≤50 mg/dl) episodes and inpatient mortality, length of stay (LOS), and mortality within 1 year after discharge were evaluated.

RESULTS

Hypoglycemia was observed in 7.7% of admissions. In multivariable analysis, each additional day with hypoglycemia was associated with an increase of 85.3% in the odds of inpatient death (P = 0.009) and 65.8% (P = 0.0003) in the odds of death within 1 year from discharge. The odds of inpatient death also rose threefold for every 10 mg/dl decrease in the lowest blood glucose during hospitalization (P = 0.0058). LOS increased by 2.5 days for each day with hypoglycemia (P < 0.0001).

CONCLUSIONS

Hypoglycemia is common in diabetic patients hospitalized in the general ward. Patients with hypoglycemia have increased LOS and higher mortality both during and after admission. Measures should be undertaken to decrease the frequency of hypoglycemia in this high-risk patient population.In recent years, there has been an increasing focus on controlling hyperglycemia in hospitalized patients (1). Hyperglycemia is associated with adverse clinical outcomes, and randomized controlled trials in intensive care units (ICUs) have shown that aggressive treatment of elevated blood glucose improves outcomes. Tight glucose control, however, is not without risk. Studies have suggested that the benefits of tight glycemic control may be at least partially offset by the increased risk of hypoglycemia (2,3). In particular, hypoglycemia in ICUs has been linked to increased risk of mortality, seizures, and coma (4).It remains unknown whether the risks associated with hypoglycemia found in critically ill patients can be generalized to non-ICU settings. The etiology of hypoglycemia in ICU patients may be different from that in patients hospitalized in the general ward. A number of risk factors for hypoglycemia in critically ill patients, including continuous venovenous hemofiltration, inotropic support, or sepsis are absent or less common outside of the ICU (5).It also remains unknown whether reported risks of hypoglycemia in ICU studies, which included primarily nondiabetic patients, also apply to patients with known diabetes. Several studies have demonstrated that the relationship of elevated blood glucose with clinical outcomes may be quantitatively and qualitatively different between patients with and without a diagnosis of diabetes. Hyperglycemic patients with diabetes have been found to have lower mortality than nondiabetic hyperglycemic patients; they may also derive less or no benefit from intensive glycemic control (3,6–10). It is possible that a similar divergence exists for hypoglycemia as well.Because the majority of hospitalized patients with diabetes are treated in the general ward, it is important to understand the relationship of hypoglycemia in diabetic patients in the general ward with clinical outcomes. To this end, we examined whether hypoglycemia in patients with diabetes hospitalized in the general ward is associated with adverse outcomes. We assessed the relationship between the number and severity of hypoglycemic episodes with in-hospital mortality and the length of hospital stay. We also evaluated the association between hypoglycemia and outpatient mortality 1 year after discharge.