The acquired immune deficiency syndrome (AIDS) is thought to result from infection of T cells by a pathogenic human retrovirus, human T-lymphotropic virus type III (HTLV-III) or lymphadenopathy-associated virus (LAV). In this report, we describe the antiviral effects of a thymidine analogue,3'-azido-3'-deoxythymidine (BW A509U), which, as a triphosphate, inhibits the reverse transcriptase of HTLV-III/LAV. This agent blocks the expression of the p24 gag protein of HTLV-III/LAV in H9 cells following exposure to virus. The drug also inhibits the cytopathic effect of HTLV-IIIB (a virus derived from a pool of American patients) and HTLV-III/RF-II (an isolate obtained from a Haitian patient that differs by about 20% in the amino acid sequence of the envelope gene from several isolates of HTLV-III/LAV, including HTLV-IIIB, analyzed so far). 3'-Azido-3'-deoxythymidine also completely blocks viral replication as assessed by reverse transcriptase production in normal human peripheral blood mononuclear cells exposed to HTLV-IIIB. Finally, at concentrations of 3'-azido-3'-deoxythymidine that block the in vitro infectivity and cytopathic effect of HTLV-IIIB, the in vitro immune functions of normal T cells remain basically intact.

No abstract

Laryngopharyngeal reflux (LPR), an extraesophageal variant of gastroesophageal reflux disease, is associated with hoarseness, chronic cough, throat-clearing, sore throat, and dysphagia. But because these symptoms are nonspecific, laryngoscopy is often done and the diagnosis of LPR is considered if edema, erythema, ventricular obliteration, pseudosulcus, or postcricoid hyperplasia is noted. Most patients with suspected LPR are given a 2-month trial of a proton pump inhibitor. Yet there is still little or no solid evidence on which to base the diagnosis or the treatment of LPR. We review the current understanding of the pathophysiology and discuss current diagnostic tests and treatment regimens in patients with suspected LPR.

HE ADVENT OF HIGHLY ACTIVE antiretroviral therapy (HAART) dramatically changed the prognosis of human immunodeficiency virus (HIV) infection, but limitations of HAART regimens include short plasma and intracellular half-life, drug-drug interactions, high pill burden, and adverse effects. In a metaanalysis of 23 prospective clinical trials with varied first-generation HAART regimens, suppression of HIV-1 RNA levels to less than or equal to 50 copies/mL at week 48 occurred in only 47% of treatment-naive patients. 1 Oncedaily HAART provides a strategy that should increase adherence and thereby Author Affiliations, Financial Disclosures, and Members of the FTC-301A Study Team are listed at the end of this article.

Sequential isolates of herpes simplex virus type 1 (HSV-1) from a child with severe combined immunodeficiency were examined for sensitivity to acyclovir. Early intravenous courses of acyclovir resulted in dramatic clinical improvement and were associated with the isolation of sensitive strains of HSV-1 (ID50[dose inhibiting 50% of control plaques], 0.010-0.106 microgram/ml), whereas later recurrences following intravenous, oral, and ophthalmic therapy were characterized by low-grade chronic lesions (ID50, 1.04-9.43 microgram/ml) that were unresponsive to acyclovir despite serum levels of up to 10.45 microgram/ml. Diminished sensitivity was associated with reduced viral thymidine kinase activity, and linked resistance with idoxuridine was detected in the isolates from the patient's eye. Intracerebral and cutaneous snout inoculation of a resistant isolate into BALB/c, hairless, and athymic nude mice revealed a 100- to 1,000-fold decrease in virulence as compared with an early sensitive isolate. Acyclovir-resistant HSV-1 can emerge in certain clinical settings but may be associated with diminished virulence.