Explore the vast range of titles available.

Two hundred eighty-one patients with the acquired immunodeficiency syndrome (AIDS) or advanced AIDS-related complex were enrolled in a double-blind, placebo-controlled trial of the efficacy and safety of orally administered zidovudine (azidothymidine or AZT). Significant clinical benefits and adverse experiences have been reported from this trial. Because neuropsychiatrie dysfunction is often associated with human immunodeficiency virus (HIV) infection, a brief affective and neuropsychological examination was administered over 16 weeks of the trial to evaluate any changes in neuropsychological function that occurred with drug administration. Patients receiving zidovudine, particularly those with AIDS, showed improved cognition as compared with patients receiving placebo. There were no changes in affective symptoms. The zidovudine recipients also had a statistically significant reduction in the intensity of symptomatic distress during the trial that may account in part for the observed cognitive changes. Some improvement in various cognitive measures was also seen in patients with AIDS-related complex. The results of this study suggest HIV-associated cognitive abnormalities may be partially ameliorated after the administration of zidovudine. (N Engl J Med 1988; 319: 1573–8.) HUMAN immunodeficiency virus (HIV) infection is a progressive, lethal disease that is often accompanied by neurologic disorders, including cognitive changes, progressive dementia, peripheral neuropathy, and paraplegia. 1 Patients who have neurologic symptoms of HIV infection and the acquired immunodeficiency syndrome (AIDS) often have a fairly rapid progression of symptoms 2 and an extremely poor prognosis, with an average survival period of approximately four months. 3 Although some neurologic manifestations of AIDS can result from tumors or opportunistic infection, 4 direct infection of the central nervous system by HIV 5 , 6 may cause the neurologic dysfunction described as AIDS encephalopathy 7 or AIDS dementia complex. 3 Neurologic and neuropsychiatric . . .

IN Western Europe and the United States, pneumonia due to Pneumocystis carinii (PCP) is the most important opportunistic infection in the acquired immunodeficiency syndrome (AIDS). 1 , 2 Therefore, its prevention would be a major step in controlling the consequences of human immunodeficiency virus (HIV) infection. Co-trimoxazole and pentamidine are effective treatments for PCP. 3 However, without prevention, relapses occur in a majority of patients less than a year after a first episode. 4 Attempts at prevention have involved low doses of oral drugs, such as daily co-tri-moxazole, 5 , 6 dapsone, 7 or weekly pyrimethamine—sulfadoxine. 8 Oral administration has the disadvantage of systemic side effects, 9 which may interfere with . . .

In a phase I dosage-finding trial, 2',3'-dideoxyinosine (didanosine; ddI) was administered once daily to 36 patients with AIDS or AIDS-related complex for up to 65 weeks (mean, 32.1 weeks) at six dosage levels. Thirteen of 18 patients previously treated with zidovudine had developed hematologic intolerance. The maximal tolerated dosage of ddI was 12 mg/(kg·d); dose-limiting toxicities were pancreatitis and peripheral neuropathy. Other toxicities included elevation in hepatic transaminase levels, rash, cardiac conduction abnormality, and asymptomatic hyperuricemia. Eighty-six percent of patients who completed 6 weeks of treatment showed improvement in constitutional symptoms and significant weight gain. In patients treated with ddI, the mean number of CD4⁺ lymphocytes increased from 124/mm³ at baseline to 199/mm³ at 24 weeks (P = .0027) and the mean leukocyte count, total lymphocyte count, and hemoglobin level showed increases (all P < .01) after 12 weeks. Serum levels of viral p24 antigen decreased ≥50% in 14 of 19 assessable patients. No differences between the responses of patients previously treated with zidovudine and those of zidovudine-naive patients were observed. These results indicate that ddI has significant antiretroviral activity in vivo and a toxicity profile different from that of zidovudine.

Both infection with the human immunodeficiency virus type 1 (HIV) and zidovudine (formerly called azidothymidine [AZT]) cause myopathy. To identify criteria for distinguishing zidovudine-induced myopathy from that caused by primary HIV infection, we reviewed the histochemical, immunocytochemical, and electron-microscopical features of muscle-biopsy specimens from 20 HIV-positive patients with myopathy (15 of whom had been treated with zidovudine) and compared the findings with the patients' clinical course and response to various therapies. Among the zidovudine-treated patients, the myopathy responded to prednisone in four, to the discontinuation of zidovudine in eight, and to nonsteroidal anti-inflammatory drugs in two. Numerous \"ragged-red\" fibers, indicative of abnormal mitochondria with paracrystalline inclusions, were found in the biopsy specimens from the zidovudine-treated patients but not in those from the other patients. The number of these fibers appeared to correlate with the severity of the myopathy. All the patients, regardless of whether they had been treated with zidovudine, had inflammatory myopathy characterized by degenerating fibers, cytoplasmic bodies, and endomysial infiltrates consisting of CD8+ cells (mean ±SD, 60.7±6.4 percent) and macrophages (39.2 ±6.4 percent) associated with Class I major histocompatibility complex (MHC-I) antigens (HLA-A, -B, and -C antigens) in the muscle fibers. The numbers and percentages of CD8+ cells and macrophages were similar in both the zidovudine-treated and the untreated HIV-positive patients. Specimens obtained on repeat muscle biopsy from two patients in whom the myopathy responded to the discontinuation of zidovudine showed remarkable histologic improvement. We conclude that long-term therapy with zidovudine can cause a toxic mitochondrial myopathy, which coexists with a T-cell—mediated inflammatory myopathy that is restricted to MHC-I antigen, and is indistinguishable from the myopathy associated with primary HIV infection or polymyositis in HIV-seronegative patients. (N Engl J Med 1990; 322:1098–105.) THE myopathies associated with infection with the human immunodeficiency virus type 1 (HIV) are a histologically heterogeneous group of disorders that include inflammatory myopathy identical to polymyositis, 1 2 3 4 5 noninflammatory destructive myopathy with granular fiber degeneration, 4 5 6 7 nemaline (rod) myopathy, 1 , 5 , 8 , 9 and some combination of these myopathies. 4 Before 1986, when zidovudine (formerly called azidothymidine [AZT]) was introduced for the treatment of the acquired immunodeficiency syndrome (AIDS), 10 11 12 the number of patients with HIV-associated myopathy was small, and myopathy was considered a rare complication of HIV infection. 1 2 3 4 5 6 7 8 9 During the past two years, an increasing number of patients receiving long-term zidovudine therapy have had myopathic symptoms such . . .

Pneumocystis carinii pneumonia and toxoplasmic encephalitis are frequent life-threatening opportunistic infections in patients with human immunodeficiency virus (HIV) infection. Primary prophylaxis against P. carinii pneumonia is now common, but there are few data on regimens for primary prophylaxis against toxoplasmosis. We conducted a randomized trial that compared two prophylactic regimens: dapsone (50 mg per day) plus pyrimethamine (50 mg per week) was compared with aerosolized pentamidine (300 mg per month). The patients had symptomatic HIV infection, no history of P. carinii pneumonia or symptomatic toxoplasmosis, and CD4+ counts below 200 per cubic millimeter (0.2 x 10(9) per liter). In an intention-to-treat analysis, after a median follow-up of 539 days P. carinii pneumonia developed in 10 patients in each group, whereas toxoplasmosis developed in 32 of 176 patients in the pentamidine group and 19 of 173 patients in the dapsone-pyrimethamine group. Those assigned to pentamidine had a risk of P. carinii pneumonia that was similar to the risk in those assigned to dapsone-pyrimethamine (adjusted relative risk, 1.13; 95 percent confidence interval, 0.44 to 2.92; P = 0.79), but a higher risk of toxoplasmosis (adjusted relative risk, 1.81; 95 percent confidence interval, 1.12 to 2.94; P = 0.02). Among the 262 patients with serologic evidence of past exposure to Toxoplasma gondii, the relative risk of symptomatic toxoplasmosis was 2.37 times higher in those assigned to pentamidine (95 percent confidence interval, 1.3 to 4.4; P = 0.006). More patients discontinued dapsone-pyrimethamine than pentamidine because of toxicity (42 vs. 3; P < 0.001). Survival was similar in the two groups. For primary prevention of P. carinii pneumonia, dapsone-pyrimethamine is as effective, though not as well tolerated, as aerosolized pentamidine. Dapsone-pyrimethamine also prevents first episodes of toxoplasmosis.

Fifty four patients with peripheral nerve syndromes were seen during a 15 month period in a population of about 1500 HIV infected patients at all stages of the disease. Distal symmetrical peripheral neuropathies were seen in 38 of the 54 patients, (11.5% of AIDS patients) and could be distinguished into two forms. The most common (n = 25) was a painful peripheral neuropathy during AIDS, which is distinct clinically and pathologically, having axonal atrophy, and is associated with cytomegalovirus infection at other sites. The 13 non-painful neuropathies seen were more heterogeneous. Lumbosacral polyradiculopathy associated with cytomegalovirus and lymphomatous mononeuritis multiplex occurred in fewer than 1% of AIDS patients. Mononeuropathies were seen in 3% of AIDS patients. No patients with acute or chronic inflammatory demyelinating polyradiculoneuropathies were seen. The annual incidence of neuropathies during the AIDS related complex stage was less than 1%; none were seen in asymptomatic HIV seropositive patients.

An HIV positive black African woman presented with widespread lymphadenopathy and pancytopenia that had been ascribed to tuberculosis. Lymph node biopsy showed both Kaposi’s sarcoma and multicentric Castleman’s disease. Despite antiretroviral therapy and chemotherapy the patient deteriorated, developing confusion and dysphasia. A cranial magnetic resonance scan showed central pontine myelinolysis. Despite supportive therapy the patient died.

A quantitative histological study was performed on small intestinal biopsies from eight ambulatory patients with HIV infection (AIDS/AIDS-related complex, ARC) and compared with those from 16 normal subjects. Enteropathy was assessed by measurement of villus area, crypt length and mitotic count, as well as duodenal counts of intraepithelial lymphocytes, mucosal mast cells and goblet cells. Enteropathy in subjects with AIDS/ARC was shown by reduced mean villus area of 0.363 (SD 0.081) compared with 0.500 (SD 0.064) mm2 in control subjects (p less than 0.0001), while intestinal crypts were of similar length with 239 (SD 36) compared with 225 (SD 28 microns, but mitotic count was increased to 3.8 (SD 1.2) compared with 2.4 (SD 0.8) (p = 0.01) in the same control subjects. These results indicate villous atrophy with impaired crypt hyperplasia. Duodenal cell counts showed similar numbers of mucosal mast cells, intraepithelial lymphocytes and goblet cells in AIDS/ARC patients and fifteen control subjects.

Retinitis reminiscent of the acute retinal necrosis syndrome was recognized in a patient with AIDS-related complex after he had experienced several episodes of a sacral, dermatomic zosteri-form eruption. Varicella-zoster virus (VZV) was subsequently recovered from cell culture of retinal tissue. The literature on VZV retinitis, including that on acute retinal necrosis, is reviewed. Dissemination of VZV infection in AIDS is also reviewed. Features that differentiate the findings and course of VZV retinitis in patients with AIDS from those in otherwise healthy adults are noted and related to potentially different pathogenic mechanisms. This unusual and recently recognized complication of herpesvirus infection may be promoted by AIDS-related immunosuppression. Acute retinal necrosis and other more-recently described forms of VZV retinitis, which have primarily been subjects of the ophthalmologic literature, merit the attention of clinicians and investigators of infectious diseases.

Antibody responses to 23-valent pneumococcal vaccine were studied in 38 individuals infected with human immunodeficiency virus (HIV), including 6 with asymptomatic infection, 24 with AIDS or AIDS-related complex (ARC) receiving treatment with zidovudine, and 8 untreated AIDS/ARC patients. Antibody responses were significantly higher for asymptomatic persons (aggregate geometric mean, 972 ng of antibody nitrogen (AbN)/ml; P < .001) and AIDS/ARC patients receiving a median of 12 weeks (range, 4–54) of zidovudine therapy (mean, 369 ng of AbN/ml; P < .001) when compared with untreated AIDS/ARC patients. Antibody responses among zidovudine-treated AIDS/ARC patients were independent of the dose (mean, 629.2 mgt day; range, 100–1200 mg) or duration of zidovudine therapy, For zidovudine-treated AIDS/ ARC patients, persistence of an aggregate antibody response 8 months after vaccination was associated with survival at 14 months after vaccination, whereas waning of response was not. Pneumococcal vaccine should be administered as early as possible in the course ofHIV infection. Immunization should be delayed for at least 4 weeks for AIDS/ARC patients initiating zidovudine therapy.