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PubMed1994

Disease due to the Mycobacterium avium complex in patients with AIDS: epidemiology and clinical syndrome.

Infection due to the Mycobacterium avium complex (MAC) is the most common opportunistic disease of bacterial origin among patients with AIDS in the United States. The incidence of disseminated disease due to MAC (DMAC) has risen dramatically in recent years. The risk of developing DMAC increases as the CD4+ lymphocyte count declines to < 100/mm3. Preliminary analyses of several studies suggest that gender, racial or ethnic group, and individual risk factors for human immunodeficiency virus infection do not influence the incidence of DMAC but that prior Pneumocystis carinii pneumonia, the development of severe anemia, or the interruption of antiretroviral therapy may increase risk. Both the respiratory and the gastrointestinal tracts probably serve as portals of entry for MAC. Colonization may potentiate the risk of DMAC but does not always precede dissemination. Patients with AIDS and DMAC have a shorter duration of survival than do those with AIDS but without DMAC. While treatment for DMAC may extend survival, no well-controlled, prospective, randomized clinical trial has documented this point. Most patients with AIDS and DMAC have disseminated multiorgan disease; the most frequently described symptoms include fever, night sweats, weight loss or wasting, diarrhea, and abdominal pain. The most commonly identified laboratory abnormalities are anemia and elevated serum levels of alkaline phosphatase. Localized disease syndromes related to MAC infection occur less often.

AIDS-Related Opportunistic Infections↗
PubMed1994

Serious Pseudomonas aeruginosa infections in patients infected with human immunodeficiency virus: a case-control study.

We conducted a case-control study to determine the incidence and clinical features of and risk factors for Pseudomonas aeruginosa infections in patients infected with human immunodeficiency virus (HIV). Twenty-five patients who had 37 episodes of P. aeruginosa infection from 1990 through 1992 were identified. Most of the patients (92%) were homosexual men with low CD4+ lymphocyte counts and a history of AIDS. The annual incidence rates of P. aeruginosa infection were 3.5% (1990), 6.3% (1991), and 8.7% (1992). Most infections were community-acquired (68%) and involved the respiratory tract (73%). Patients were more likely than HIV-infected controls to have AIDS and had more AIDS-defining opportunistic illnesses. The overall mortality was 36%. Recurrent episodes were common (39%). We conclude that P. aeruginosa infections may be an increasing problem in patients with extremely advanced HIV infection. Clinicians should consider including antibiotics with activity against P. aeruginosa in the empirical treatment for suspected bacterial infection in patients with advanced HIV infection.

AIDS-Related Opportunistic Infections↗
PubMed1994

Transient exacerbation of tuberculous lymphadenitis during chemotherapy in patients with AIDS.

We describe three men with disseminated, drug-sensitive tuberculosis and advanced human immunodeficiency virus disease (CD4+ lymphocyte count, < 50/mm3) who had flares of tuberculous lymphadenitis with suppuration during the initial weeks of successful chemotherapy. Bactericidal drugs may kindle these transient exacerbations, which involve neutrophils but apparently do not require normal helper T cell function. In patients with AIDS, as in immunocompetent individuals, treatment-related flares of lymphadenitis are usually not an adverse sign, provided that drug resistance and nonadherence have been excluded.

AIDS-Related Opportunistic Infections↗
PubMed1995

Infection due to parvovirus B19 in patients infected with human immunodeficiency virus.

Parvovirus B19 has been described as a cause of chronic anemia in immunosuppressed patients, including those infected with human immunodeficiency virus (HIV). In this study serological assays and the polymerase chain reaction (PCR) were used to establish the prevalence of both prior and active infection due to parvovirus B19 among a general population of 105 HIV-infected individuals (cohort I) and among 22 HIV-infected patients with anemia (cohort II). Eight individuals in cohort I (7.6%) had IgG antibodies to parvovirus B19, while none had B19-specific IgM antibodies. In cohort II, four patients (18.2%) had B19-specific IgG antibodies and none had IgM antibodies. Only one person in cohort I (0.95%) and one person in cohort II (4.5%) had evidence on PCR of persistent infection with parvovirus B19; both of these patients lacked IgG and IgM antibodies to parvovirus. Both individuals with B19 viremia were anemic and had CD4 lymphocyte counts suggesting advanced immunosuppression (< 50/mm3). The observed low prevalences of B19 seropositivity and active B19 infection differ from the rates documented in previous studies and indicate that infection with parvovirus B19 is uncommon in some groups of HIV-infected patients.

AIDS-Related Opportunistic Infections↗
PubMed1995

Disseminated microsporidiosis due to Septata intestinalis in nine patients infected with the human immunodeficiency virus: response to therapy with albendazole.

Disseminated microsporidiosis due to the newly described species Septata intestinalis in nine patients infected with human immunodeficiency virus is described. All patients were male homosexuals; the mean age was 41 years (range, 35-58 years). They were all severely immunocompromised, with a mean CD4 lymphocyte count of 15/mm3 (range, 0-32/mm3). Infection by S. intestinalis was seen in duodenal biopsy specimens from all patients, and dissemination was demonstrated by the presence of microsporidial spores in urine (9 of 9 patients), sinonasal secretions and/or nasal mucosal biopsy specimens (6 of 6), and sputum (6 of 6). Seven patients were treated with albendazole (400 mg twice daily), resulting in significant dissipation or complete resolution of diarrhea for six patients and abatement of symptoms for the six patients with chronic rhinosinusitis. There was a parallel parasitological response, with clearance of S. intestinalis infection from almost all sites.

AIDS-Related Opportunistic Infections↗
PubMed1995

Predictors and outcome of multidrug-resistant tuberculosis.

We identify early predictors of multidrug-resistant tuberculosis and describe improved clinical outcomes, including survival, for patients with human immunodeficiency virus (HIV)-related multidrug-resistant tuberculosis (MDR-TB) when they are prospectively identified and receive treatment under direct observation. Analysis by means of a Cox proportional hazards model revealed that failure to defervesce while receiving a standard four-drug antituberculous regimen was independently associated with multidrug resistance (P = .004). When patients with HIV-related MDR-TB were prospectively identified and treated with at least two agents that were active in vitro, 100% bacteriologic conversion and improved survival (> or = 4 months for 88% of patients and > or = 1 year for 59% of patients) were observed. For patients with HIV-related tuberculosis, poorer survival was associated with a CD4+ lymphocyte count of < 25 mm3 (P = .03); multidrug resistance was not a predictor of poor outcome (P = .82). These data suggest that patients with prolonged fever who are receiving antituberculous therapy may be an appropriate subgroup to target for broader empirical therapy. The findings also demonstrate that improved outcomes can be achieved with HIV-related MDR-TB when patients are prospectively identified and treated with agents that are active in vitro.

AIDS-Related Opportunistic Infections↗
PubMed1995

Disseminated histoplasmosis in persons infected with human immunodeficiency virus.

Disseminated histoplasmosis is an AIDS-defining illness that occurs in about 5% of AIDS patients residing in histoplasmosis-endemic areas of the United States (the Mississippi and Ohio river valleys). This disease develops as a result of acute infection and perhaps also as the result of reactivation of latent infection: cases reported from areas such as New York City, where histoplasmosis is not endemic, are most likely due to reactivation of an infection acquired earlier in a histoplasmosis-endemic area, while cases in histoplasmosis-endemic areas are most likely due to acute infection, especially in outbreak settings. Disseminated histoplasmosis in HIV-infected patients is usually associated with advanced immunosuppression, with CD4+ lymphocyte counts of < 75/mm3. Currently, histoplasmin skin testing of HIV-infected patients does not seem to be useful in detecting previous exposure and therefore is not helpful in identifying groups of patients who are at risk for dissemination and who should be targeted for preventive efforts. The current public health recommendation for HIV-infected patients is to avoid exposure to sites likely to harbor high levels of Histoplasma capsulatum, such as chicken coops and bird roosts. The role of chemoprophylaxis is not clear, but an ongoing study by the Mycoses Study Group is evaluating the role of prophylactic itraconazole. If strategies for the prevention of disseminated histoplasmosis in HIV-infected patients are to be improved, studies must better define the risk factors for this opportunistic infection, describe its natural history, and develop more reliable tests to predict its development.

AIDS-Related Opportunistic Infections↗
PubMed1995

Opportunistic coccidioidomycosis in patients infected with human immunodeficiency virus: prevention issues and priorities.

Coccidioidomycosis is an uncommon AIDS-defining illness that is endemic in the southwestern United States. In profoundly immunodeficient patients infected with human immunodeficiency virus (HIV), the disease is usually manifest as severe pulmonary infection and is associated with high mortality. Although diagnosis is often made by routine serological tests, these appear to be less sensitive than when used for patients who are not HIV-infected. New ways to diagnose the infection in HIV-infected patients earlier and with more certainty are urgently needed. The optimal antifungal regimen for active disease in HIV-infected patients is currently undefined, but following acute disease in severely immunocompromised HIV-infected patients (CD4 lymphocyte count, < 200/microL), lifelong systemic antifungal therapy is recommended. The role of chemoprophylaxis for HIV-infected patients in the area of endemic disease is also unclear. Improvement of preventive strategies must await the results of well-designed future studies to determine risk factors, particularly environmental factors, for development of coccidioidomycosis and to determine the proportion of disease due to new vs. reactivated infection. These studies are also needed to elucidate the role and efficacy of different types of antifungal drug therapies and the specific dosages useful for prevention, treatment, and long-term control of these infections.

AIDS-Related Opportunistic Infections↗
PubMed1996

Cryptococcus neoformans infection in France: epidemiologic features of and early prognostic parameters for 76 patients who were infected with human immunodeficiency virus.

We retrospectively carried out a descriptive and prognostic study of 76 human immunodeficiency virus-infected patients with cryptococcosis diagnosed by a positive culture of cerebrospinal fluid (CSF), blood, urine, or other body fluid or tissue. We focused on the 65 patients with cryptococcal meningitis. At diagnosis, the mean CD4 lymphocyte count was 46/mm3; 86% of patients had fever; 67%, headache; 37%, stiff neck; 29%, altered mentation or confusion; 20% cranial nerve deficiency; and 48%, other focal deficiencies. Analysis of CSF specimens revealed the following results: normal (25% of the specimens), leukocyte count of < 20/mm3 (62%), positive India ink smear (87%), and positive cryptococcal antigen (92%). Twenty patients died within the first 3 months (3-month survival rate, 70%). A Cox regression model selected the following as prognostic parameters: age older than 30 years (relative risk [RR] = 2.1), CSF glucose level of < 2 mmol/L (RR = 3.7), previous admission to an intensive care unit (RR = 4.7), and mechanical ventilation (RR = 4.6). The outcome of cryptococcal meningitis in patients with AIDS remains difficult to predict at admission, and every case should be considered as potentially severe.

AIDS-Related Opportunistic Infections↗
PubMed1996

Pulmonary toxoplasmosis in patients infected with human immunodeficiency virus: a French National Survey.

We reviewed all cases of pulmonary toxoplasmosis (PT) that were documented by detection of Toxoplasma gondii in bronchoalveolar lavage fluid specimens during a French nationwide review of extracerebral toxoplasmosis in patients infected with human immunodeficiency virus (HIV). Only 64 cases of proven PT were recorded during the 33-month survey. The patients were similar to other patients with AIDS in terms of age, sex, and risk factors for HIV infection. PT occurred mainly in patients with advanced immunodeficiency (mean [+/- SD] CD4+ lymphocyte count, 40 +/- 75/mm3). Clinical features of PT usually include fever, cough and dyspnea; the associated radiological findings were mainly diffuse interstitial infiltrates. Serological data were uninformative. The treatment for PT was the same as that for cerebral toxoplasmosis. A clinical response was observed for 47% of patients, 23% of whom relapsed. Twenty-four patients (37%) died of toxoplasmosis, and 17 (27%) died of other causes. The median survival time was 150 days. We conclude that PT is an infrequent but severe infection in HIV-patients in France.

AIDS-Related Opportunistic Infections↗
PubMed1997

Survival of AIDS patients according to type of AIDS-defining event. The AIDS in Europe Study Group.

BACKGROUND: There are known to be wide differences in the prognosis of patients with a diagnosis of AIDS. In this study of 6578 patients with AIDS form 17 European centres, we develop a ranking of AIDS-defining illnesses, and determine how well this ranking holds after adjustment for potential confounding variables. METHODS: Survival from each AIDS-defining event was calculated and ranked using Kaplan-Meier estimation of median survival. Cox proportional hazards models with each disease modelled as a time dependant covariate were used to determine the risk of death after each diagnosis, before and after adjustment for potential confounders. RESULTS: Median survival after an initial AIDS-defining diagnosis of progressive multifocal leukoencephalopathy and malignant lymphoma was particularly poor (2 and 5 months respectively), while the longest median survival occurred after initial AIDS-defining illnesses of Kaposi's sarcoma and extrapulmonary tuberculosis (17 and 22 months respectively) Patients diagnosed with a primary brain lymphoma had shorter median survival times than patients with a peripheral lymphoma (median survival of 1 month and 4 months respectively P < 0.0001). In general, median survival in patients with cutaneous Kaposi's sarcoma (skin, oral) was between two and four times longer than patients with systemic involvement The ranking of diseases was found to be generally similar after adjustment for all potential confounders. CONCLUSIONS: AIDS-defining events can be grouped into three categories with median survival after diagnosis of < 6 months. 6-12 months and > 12 months. The assigned ranking of disease would not be altered by prognostic factors such as age or CD4 lymphocyte count. These results have important implications in the design of clinical trials and patient management.

AIDS-Related Opportunistic Infections↗
PubMed1993

Detection of human immunodeficiency virus type 1 in semen: effects of disease stage and nucleoside therapy.

The effects of clinical stage of infection and antiviral therapy on the detection of human immunodeficiency virus type 1 (HIV-1) nucleic acids in semen were investigated by the polymerase chain reaction. HIV-1 was detected in 45 (87%) of 52 semen specimens from 29 (81%) of 36 men. Seventeen (77%) of 22 stage II or III subjects and 12 (86%) of 14 stage IV subjects had positive specimens. The CD4+ lymphocyte count was not significantly different comparing subjects with positive and negative semen. Moreover, 6 (67%) of 9 untreated men had positive specimens compared with 23 (85%) of 27 men treated with zidovudine, 2',3'-dideoxyinosine, or both for a mean of 20 months. Thus, the detection of HIV-1 in semen was independent of both stage of infection and long-term treatment. In a semiquantitative analysis of 6 men followed for 8 weeks after the start of nucleoside therapy, a decrease in HIV-1 RNA in seminal plasma was demonstrated in 2.

Anti-Bacterial Agents↗
PubMed1993

Depressed neutrophil superoxide production in human immunodeficiency virus infection.

Neutrophil (PMNL) superoxide (O2-) production was evaluated in 71 patients with human immunodeficiency virus (HIV) infection at different stages of disease. In vitro O2- production was significantly depressed for PMNL isolated from HIV-positive patients compared with control PMNL at rest and after stimulation. The degree of impairment of O2- production was more pronounced for patients with lower absolute CD4+ lymphocyte counts. Antiretroviral therapy with zidovudine was also associated with impaired O2- production, but this may reflect a longer duration of disease for treated patients. Zidovudine had no direct inhibitory effect on O2- production by control PMNL in vitro, and serial measurements of O2- production by PMNL from patients before and after initiation of zidovudine did not demonstrate an in vivo inhibitory effect. Impaired PMNL oxidative metabolism in HIV infection may contribute to the increased risk of serious bacterial infections, certain opportunistic infections, and perhaps the pathogenesis of HIV infection itself.

Adult↗
PubMed1993

Defective antifungal activity of monocyte-derived macrophages from human immunodeficiency virus-infected children against Aspergillus fumigatus.

Invasive aspergillosis recently has been encountered in adults and children with human immunodeficiency virus (HIV) infection even without known risk factors, such as neutropenia or corticosteroid therapy. Macrophages play a significant role in the host defenses against Aspergillus organisms by ingesting conidia and preventing their germination to hyphae. The antifungal activity of peripheral blood monocyte-derived macrophages (MDM) from 19 HIV-infected children was compared with that of 16 normal controls. The phagocytic activity of patients' MDM, measured as percentage of phagocytosis, was significantly decreased compared with normal donors (P = .014). In addition, the inhibitory activity of MDM on germination of intracellular A. fumigatus conidia was significantly impaired in patients compared with normal controls (P = .016). There was no significant difference in the defects between patients with lower or higher CD4 lymphocyte counts. Impairment of antifungal activity of macrophages may contribute to the susceptibility of HIV-infected patients to aspergillosis.

Adolescent↗
PubMed1993

Detection of Toxoplasma gondii by competitive DNA amplification of bronchoalveolar lavage samples.

The prevalence of pulmonary toxoplasmosis was assessed by a prospective analysis of 144 bronchoalveolar lavage (BAL) samples using competitive polymerase chain reaction (PCR) to avoid false-negative results due to PCR techniques. Six samples were excluded because they contained amplification reaction inhibitors. None of the samples from the 37 immunocompetent patients and only 1 sample (1.7%) from the 59 immunocompromised patients without human immunodeficiency virus infection were PCR-positive. In contrast, Toxoplasma gondii DNA was found in 6 (14%) of 42 samples from patients with AIDS. All 6 patients had < or = 40 CD4 cells/microL and anti-Toxoplasma antibodies, and 5 had other sites of Toxoplasma infection. Six other AIDS patients who had received treatment for cerebral toxoplasmosis were PCR-negative. Thus, pulmonary toxoplasmosis is frequent in AIDS patients who have other sites of Toxoplasma infection and low CD4 lymphocyte counts and who are not receiving prophylaxis.

Adolescent↗
PubMed1994

Primary prophylaxis with pyrimethamine for toxoplasmic encephalitis in patients with advanced human immunodeficiency virus disease: results of a randomized trial. Terry Beirn Community Programs for Clinical Research on AIDS.

Pyrimethamine, 25 mg thrice weekly, was evaluated as primary prophylaxis for toxoplasmic encephalitis (TE) in a double-blind, randomized clinical trial in patients with human immunodeficiency virus (HIV) disease, absolute CD4 lymphocyte count of < 200/microL (or prior AIDS-defining opportunistic infection), and the presence of serum IgG to Toxoplasma gondii. Leucovorin was coadministered only for hematologic toxicity. There was a significantly higher death rate among patients receiving pyrimethamine (relative risk [RR], 2.5; 95% confidence interval [CI], 1.3-4.8; P = .006), even after adjusting for factors predictive of survival. The TE event rate was low in both treatment groups (not significant). Only 1 of 218 patients taking trimethoprim-sulfamethoxazole but 7 of 117 taking aerosolized pentamidine for prophylaxis against Pneumocystis carinii pneumonia developed TE (adjusted RR for the trimethoprim-sulfamethoxazole group, 0.16; 95% CI, 0.01-1.79; P = .14). Thus, for HIV-infected patients receiving trimethoprim-sulfamethoxazole, additional prophylaxis for TE appears unnecessary.

AIDS-Related Opportunistic Infections↗
PubMed1994

Secretory IgA antibodies to Cryptosporidium parvum in AIDS patients with chronic cryptosporidiosis.

Immune mechanisms that may control Cryptosporidium parvum infection remain unknown. The role of T cell-mediated immunity is suggested by the chronic disease observed in AIDS patients and in athymic or CD4+ T cell-depleted mice. The role of specific antibodies is also unclear. This study sought to determine serum and secretory antibodies to C. parvum in patients infected with human immunodeficiency virus type 1 (HIV-1) with or without chronic cryptosporidiosis. C. parvum-specific antibodies and specific secretory antibodies were determined by ELISA in saliva and sera from 50 HIV-1-infected patients, 27 healthy adults, and 21 healthy children. Despite lower CD4+ lymphocyte counts, patients with chronic cryptosporidiosis had increased levels of C. parvum-specific antibodies in saliva and serum and higher specific secretory antibody levels in saliva than did controls. Persistence of protracted diarrhea despite high levels of both serum and secretory antibodies suggests that specific secretory antibodies are not sufficient to control this protozoan parasite infection of intestinal mucosa.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Risk factors for Chlamydia trachomatis pelvic inflammatory disease among sex workers in Nairobi, Kenya.

Among 302 female sex workers in Nairobi, Kenya, who were followed for 17.6 +/- 11.1 months, 146 had one or more infections with Chlamydia trachomatis; 102 had uncomplicated cervical infection only, 23 had C. trachomatis pelvic inflammatory disease (PID), and 21 had combined C. trachomatis and Neisseria gonorrhoeae PID. As determined by multivariate logistic regression analysis, risk factors for C. trachomatis PID included repeated C. trachomatis infection (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.3-2.4; P = .0004), antibody to C. trachomatis heat-shock protein 60 (OR, 3.9; CI, 1.04-14.5; P = .04), oral contraceptive use (OR, 0.28; 95% CI, 0.08-0.99; P = .048), and number of episodes of nongonococcal nonchlamydial PID (OR, 1.7; 95% CI, 1.1-2.7; P = .02). Among human immunodeficiency virus (HIV)-seropositive women, a CD4 lymphocyte count of <400/mm3 was an additional independent risk factor for C. trachomatis PID (OR, 21.7; 95% CI, 1.2-383; P = .036); among HLA-typed women, HLA-A31 was independently associated with C. trachomatis PID (OR, 5.6; 95% CI, 1.1-29.4; P = .043). The results suggest an immune-mediated pathogenesis for C. trachomatis PID.

Adult↗