Although discontinuation of suppressive antifungal therapy for acquired immunodeficiency syndrome (AIDS)-associated histoplasmosis is accepted for patients with immunologic recovery, there have been no published studies of this approach in clinical practice, and minimal characterization of individuals who relapse with this disease. We performed a multicenter retrospective cohort study to determine the outcome in AIDS patients following discontinuation of suppressive antifungal therapy for histoplasmosis.Ninety-seven patients were divided into a physician-discontinued suppressive therapy group (PD) (38 patients) and a physician-continued suppressive therapy group (PC) (59 patients). The 2 groups were not statistically different at baseline, but at discontinuation of therapy and at the most recent follow-up there were significant differences in adherence to therapy, human immunodeficiency virus (HIV) RNA, and urinary Histoplasma antigen concentration. There was no relapse or death attributed to histoplasmosis in the PD group compared with 36% relapse (p < 0.0001) and 5% death (p = 0.28) in the PC group. Relapse occurred in 53% of the nonadherent patients but not in the adherent patients (p < 0.0001). Sixty-seven percent of patients with initial central nervous system (CNS) histoplasmosis relapsed compared to 15% of patients without CNS involvement (p = 0.0004), which may be accounted for by nonadherence. In addition, patients with antigenuria above 2.0 ng/mL at 1-year follow-up were 12.82 times (95% confidence interval, 2.91–55.56) more likely to relapse compared to those with antigenuria below 2.0 ng/mL.Discontinuation of antifungal therapy was safe in adherent patients who completed at least 1 year of antifungal treatment, and had CD4 counts >150 cells/mL, HIV RNA <400 c/mL, Histoplasma antigenuria <2 ng/mL (equivalent to <4.0 units in second-generation method), and no CNS histoplasmosis.
Both medications increased the secretion of saliva at the end of four weeks. However, there was a slightly higher increment in saliva with pilocarpine. However, the difference was not statistically significant.
Two adult patients living with AIDS presented with severe bone pain associated with tenofovir (TDF) use. Both were unable to walk without assistance and were severely restricted in their movement due to the bone pain. Both had mild renal impairment, Fanconi syndrome, and bone mineral density (BMD) loss. Bone pain and inability to walk were reversible with the cessation of TDF and supplementation with Vitamin D 3 , calcium, and phosphate. These cases appear to be examples of the severity of BMD loss associated with TDF use and suggest not only attention to renal function with TDF use, but also monitoring of alkaline phosphatase (bone fraction) and plasma phosphorus as indicators of BMD loss.
BackgroundGlial dysfunction has been purported to be important to the pathophysiology of bipolar illness. However, manic behavior has not been previously demonstrated to result as a consequence of glial pathology. The aim of the current study was to assess the behaviors of the glial-specific sodium pump alpha2 subunit (ATP1A2) knockout (KO) heterozygote mice to determine if a glial-specific abnormality can produce manic-like behavior.MethodsActivity and behavior of hemideficient sodium pump alpha2 KO mice and wild-type (WT) littermates (C57BL6/Black Swiss background) were examined at baseline, following forced swimming stress and restraint stress and after 3 days of sleep deprivation.Results and discussionAt baseline, the 24-h total distance traveled and center time were significantly greater in KO mice, but there were no behavioral differences with sweet water preference or with inactivity time during forced swim or tail suspension tests. After restraint stress or forced swimming stress, there were no differences in activity. Three days of sleep deprivation utilizing the inverted flowerpot method induced a significant increase in the distance traveled by the KO versus WT mice in the 30-min observation period (p=0.016). Lithium pretreatment has no effect on WT animals versus their baseline but significantly reduces hyperactivity induced by sleep deprivation in KO. Knockout of the glial-specific alpha2 isoform is associated with some manic behaviors compared to WT littermates, suggesting that glial dysfunction could be associated with mania.
Although established in controlled studies that there is no advantage to 4-drug highly active antiretroviral therapy (HAART) or regimens with or without protease inhibitors (PIs), we questioned this finding in a clinical setting (ie, no inclusion criteria). Ours is a single clinic retrospective study including all participants >18 years of age during their first year of HAART. A total of 190 participants were reviewed, with 168 (88%) attaining a viral load <400 copies/mL at the end of a year of HAART; 144 of 164 (88%) succeeded with 3 drugs and 24 of 26 (92%) with 4 drugs (P = .51). In all, 59 of 71 (83%) succeeded using a PI versus 109 of 119 (92%) without a PI (P = .08). Male gender and exposure time to HAART were significant variables for a successful outcome. Failures were due to side effects (50%), nonadherence (45%), and drug allergy (5%). Our results support current guidelines recommending 3-drug HAART.
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