Incidence and risk factors for incomplete HBV DNA suppression in HIV/HBV-co-infected patients initiating tenofovir-based therapy.

Suppression of hepatitis B virus (HBV)-DNA to undetectable levels is an important goal for HIV/HBV-co-infected patients receiving anti-HBV-active antiretroviral therapy (ART), and current guidelines recommend that this outcome should be reached by 1 year of treatment. However, the proportion of patients that fail to achieve an undetectable HBV DNA at this time point and its determinants remain unknown in clinical practice. The objective of this study was to determine the incidence and risk factors for incomplete HBV suppression following 1 year of tenofovir-based ART. We performed a cohort study among tenofovir-treated HIV/HBV-co-infected patients. Patients had HBV viraemia, initiated tenofovir-based ART and had HBV DNA measured at 1 year of therapy. The primary outcome was incomplete HBV suppression (HBV DNA ≥2.6 log IU/mL) at 1 year. Logistic regression determined odds ratio (ORs) of incomplete HBV suppression for risk factors of interest. Among 133 patients, 54% (95% CI, 46-63%) had incomplete HBV suppression at 1 year. Incomplete suppression was associated with higher baseline HBV DNA (OR, 1.46 per log IU/mL increase; 95% CI, 1.1-1.94) and detectable HIV viraemia at 1 year (OR, 2.52; 95% CI, 1.19-5.32). Among 66 patients with suppressed HIV RNA at 1 year, 28 (42%) failed to achieve an undetectable HBV DNA. Failure to suppress HBV DNA by 1 year occurred in a sizeable proportion of tenofovir-treated HIV/HBV-co-infected patients. Higher HBV DNA and detectable HIV viraemia were risk factors for incomplete HBV suppression.

Oral fluconazole therapy for patients with acquired immunodeficiency syndrome and cryptococcosis: experience with 22 patients.

PURPOSE: Cryptococcus neoformans causes infections in up to 10 percent of patients with the acquired immunodeficiency syndrome (AIDS). Nearly 50 percent of AIDS patients with previously treated cryptococcal meningitis will experience a relapse within six months. To reduce the likelihood of relapse, a maintenance regimen of amphotericin B is often administered weekly. However, the drug's intravenous route of administration and considerable toxicity have led to a search for alternative antifungal agents. In this report, we document our experience with fluconazole, a new oral triazole antifungal agent. PATIENTS AND METHODS: Twenty-two patients with AIDS and various forms of cryptococcosis were treated in an open-label study with 50 to 400 mg/day of fluconazole. The following laboratory studies were done on a monthly basis: complete blood cell count, liver function tests, serum creatinine level, serum cryptococcal antigen level, and serum fluconazole level. Lumbar puncture was performed in patients with meningitis every four to eight weeks to evaluate cerebrospinal fluid cryptococcal antigen, India ink preparation findings, fungal culture, fluconazole level, and protein, glucose, and cell count. RESULTS: Of seven patients with active culture-positive infections, four showed clinical and microbiologic responses (three of four with meningitis, one of three with extraneural cryptococcosis). Fifteen patients who had already undergone successful amphotericin B therapy for either meningitis (n = 14) or pneumonia (n = 1) received fluconazole as prophylaxis against relapse. Fourteen patients remained free of infection during 11 to 64 weeks of suppressive therapy; one patient with meningitis experienced relapse after 26 weeks of treatment. Reverse reactions were limited to increases in hepatic enzyme levels in four patients. CONCLUSION: These results appear sufficiently encouraging to warrant further trials of this oral agent in the suppression of chronic cryptococcosis and perhaps in the treatment of acute infection.

Incidence of antiphospholipid antibodies in patients with monoclonal gammopathy of undetermined significance.

The incidence of antiphospholipid antibodies in patients with monoclonal gammopathy of undetermined significance (MGUS) was studied. Antiphospholipid antibodies were measured in the sera of 93 patients (49 women, 44 men; mean age 70 [+/- 21] years) with MGUS by using an enzyme-linked immunosorbent assay (ELISA). The phospholipids tested were cardiolipin (CL), phosphatidylserine (PS), phosphatidylinositol (PI), phosphatidylglycerol (PG), phosphatidic acid (PA), phosphatidylcholine (PC), and phosphatidylethanolamine (PE). Positive results were defined as a value higher than the number of multiples of the mean per phospholipid, which included 76 of 80 (95%; 20 age-matched) control individuals. The immunoglobulin-G (IgG) or IgM antiphospholipid antibodies isotype varied among the patients, as did the phospholipid specificity. For IgG, PI was found elevated in 32% of the MGUS samples, whereas the other phospholipid antigens ranged from 9% to 15%. The percentage of patients with IgM antiphospholipid antibodies was higher. The authors observed PS, PI, PA, and PC as positive in 45%, 35%, 25%, and 25% of patients, respectively. Of the 12 sera studied for IgA isotype, three (25%) were positive for PS, six (50%) for CL, and none for PE. Patients with MGUS manifested a significantly higher (P < .01) incidence of antiphospholipid antibodies in their blood than did the control persons. No difference in the incidence of antiphospholipid antibodies was seen between younger and older (age-matched) control patients. No correlation was found between serum levels of immunoglobulins and optical density reading of the blank plates used as ELISA controls.

Murine amebiasis: the role of the macrophage in host defense.

The congenitally athymic nude (nu/nu) mouse was studied as a model for amebic liver disease, using Entamoeba histolytica. Despite intrahepatic inoculation of massive numbers of amebae, we could not produce sustained infections in nu/nu mice. We also failed to induce hepatic amebiasis in thymus-intact nu/+ and +/+ littermates, or in nu/+ mice pretreated with rabbit antimouse thymocyte globulin. Humoral response was measured in both the nu/nu and nu/+ mice. Nu/+ but not nu/nu animals developed a specific IgG response after challenge with E. histolytica. There were no significant IgM responses. Pretreatment with silica increased susceptibility of both nu/nu and nu/+ mice to development of liver abscesses. These studies suggest that host resistance in murine amebiasis is critically dependent upon the macrophage, but not upon T cell-mediated defenses.

Ultrasonographic findings of pregnancy losses after treatment for recurrent pregnancy loss: intravenous immunoglobulin versus placebo.

OBJECTIVE: To describe the ultrasonographic findings of pregnancies that terminated in repeat abortion in women participating in an ongoing randomized placebo-controlled clinical trial evaluating the efficacy of intravenous (IV) immunoglobulin (Ig) in the treatment of recurrent spontaneous abortion (SA). DESIGN: A prospective descriptive study of ultrasonographic findings of pregnancies from 27 women experiencing repeated recurrent SAs after entry into a clinical trial. SETTING: Clinical practice at the Genetics & IVF Institute in Fairfax, Virginia. PATIENTS: Women experiencing two or more consecutive recurrent SAs received either 500 mg/kg per mo IV Ig or placebo (albumin). To date 90 women have been enrolled in the clinical trial and 52 have achieved pregnancy. The outcome of the 52 pregnancies include 16 deliveries, 9 ongoing pregnancies, and 27 losses. INTERVENTIONS: Ultrasonographic examinations performed in 27 women experiencing pregnancy loss are the subject of this study. MAIN OUTCOME MEASURES: The frequency of ultrasonographic findings of empty gestation sac (blighted ovum) and intrauterine fetal demise (IUFD) is compared between patients receiving IV Ig and placebo. RESULTS: Ultrasonographic findings of the 27 pregnancies losses included 11 blighted ova and 16 IUFDs. Of 11 blighted ova, 8 (73%) were in women receiving IV Ig and 3 (27%) were receiving placebo. Sixteen IUFDs were observed: 3 (19%) in women receiving IV Ig and 13 (81%) in women receiving placebo. Of 11 pregnancy losses occurring in women receiving IV Ig, 8 (73%) were blighted ova, 3 (27%) were IUFDs. Sixteen pregnancy losses occurred in women receiving placebo: 3 (19%) were blighted ova and 13 (81%) were IUFDs. The differences in frequency of blighted ova between IV Ig- and placebo-treated women was significant. CONCLUSION: IV Ig is not effective in preventing blighted ova and may be effective in preventing IUFDs.

Serum progesterone and estradiol concentrations in the early diagnosis of ectopic pregnancy after in vitro fertilization-embryo transfer.

To determine if discriminatory P or E2 concentrations can be established for early diagnosis of EP after IVF, 282 pregnancies were studied 11, 13, 15, and 17 days after ET. Receiver-operator characteristic analysis of P and E2 indicated no clinically useful threshold value for EP. No significant differences in P or E2 was seen when intrauterine and extrauterine pregnancies or viable and nonviable pregnancies were compared. All EPs had P < 50 ng/mL and E2 < 500 pg/mL at 11 days after ET. Serum P and E2 cannot differentiate EPs from intrauterine pregnancies nor viable from nonviable pregnancies resulting from IVF.

Frequency of abnormal karyotypes among abortuses from women with and without a history of recurrent spontaneous abortion.

OBJECTIVE: To compare the frequency of chromosomal abnormalities in products of conception from women with and without a history of recurrent spontaneous abortion. DESIGN: Retrospective analysis of prospectively collected material. SETTING: Private practice at the Genetics and IVF Institute, Fairfax, Virginia and Grupo de Reproducción AGY Asociados, México City, México. PATIENTS: Women with (n = 94) and without (n = 130) a history of recurrent spontaneous abortion who had a spontaneous abortion between January 1, 1992 and November 1, 1994. INTERVENTION: Chromosomal analysis performed on products of conception using standard G-banding technique. MAIN OUTCOME MEASURE: The percentage of chromosomal abnormalities among products of conception from women with and without recurrent spontaneous abortion was compared. RESULTS: Among products of conception from women with recurrent spontaneous abortion, 57% (54/94) had abnormal and 43% (40/94) had normal chromosome analyses. Products of conception from women without recurrent spontaneous abortion had abnormal chromosome analyses in 57% (74/130) and normal results in 43% (56/130). CONCLUSIONS: No differences in frequency of abnormal karyotype were observed in products of conception from women with recurrent spontaneous abortion compared with women without recurrent spontaneous abortion.

A near-fatal hypersensitivity reaction to abacavir: case report and literature review.

A near-fatal hypersensitivity reaction to abacavir developed in a 62-year-old HIV-seropositive man who had been sensitized 17 months before presentation. Six days after he was rechallenged, acute respiratory distress developed, requiring mechanical ventilation for 2 weeks. Four days after extubation, he was again rechallenged. Hours later, the patient experienced anaphylactic shock, requiring mechanical ventilation for 3 weeks, aggressive volume resuscitation, and vasopressor support. Recovery was complicated by acute tubular necrosis, digital necrosis, and a GI bleed. This report reviews the mechanisms of action, efficacy, and adverse reactions of abacavir and illustrates the danger of serially rechallenging patients with this agent.