Mycobacterium avium complex and Mycobacterium tuberculosis in patients infected with the human immunodeficiency virus

Primary care physicians play an important role in identifying and treating bacterial infections in adults infected with the human immunodeficiency virus (HIV). Mycobacterium avium complex and Mycobacterium tuberculosis are pathogens that can cause systemic or local infection in these patients. We review the epidemiology, pathogenesis, clinical presentation, and principles of treatment for these two mycobacterial pathogens. Because M tuberculosis disease is preventable and curable and yet communicable, physicians should maintain a high degree of suspicion for tuberculosis in HIV-infected adults. In comparison, the goal of treating M avium complex in patients with advanced HIV disease is to reduce constitutional symptoms and improve survival.     

Evolving trends revealed by autopsies of patients with the acquired immunodeficiency syndrome. 565 autopsies in adults with the acquired immunodeficiency syndrome, Los Angeles, Calif, 1982-1993 [corrected

OBJECTIVE: To determine changes in causes of death, survival, and organ system distribution of major opportunistic infections and neoplasms in adults dying with the acquired immunodeficiency syndrome (AIDS) following the widespread use of antiretroviral therapy and prophylaxis for opportunistic infections since 1988. DESIGN: A retrospective review of autopsy records with gross and microscopic pathologic findings, laboratory data, and clinical histories in cases of AIDS, comparing findings from 1982 through 1988 with those from 1989 through May 1993. SETTING: All autopsies were performed on persons dying in the metropolitan Los Angeles, Calif, area from January 1982 through May 1993. RESULTS: In 565 adult cases of AIDS at autopsy, Pneumocystis carinii pneumonia (PCP) remained the most common cause of death, but both the frequency of and number of deaths of PCP declined over time. Deaths from bacterial sepsis, cytomegalovirus infection, Mycobacterium avium complex infection, and toxoplasmosis also declined during this period, but mortality from fungal infections, tuberculosis, encephalopathy, and causes unrelated to AIDS increased. The death rate from malignant lymphoma remained high. Kaposi's sarcoma (KS) continued to occur more frequently in patients whose risk factor for human immunodeficiency virus infection (HIV) was homosexuality or bisexuality, but the death rate from KS was greatest for patients with a risk factor of blood exposure to HIV. Survival was shorter and deaths from tuberculosis more common in patients with a history of intravenous drug use. Overall survival of patients in other AIDS risk groups increased over time, particularly in those treated with antiretroviral therapy. The organ system distribution of major opportunistic infections and neoplasms was similar throughout the years of the study. The lung was the most frequent organ involved by AIDS-associated diseases leading to death, followed by the gastrointestinal tract and the central nervous system. CONCLUSIONS: The causes of death in AIDS have evolved since 1988 following the widespread use of prophylactic and antiretroviral therapies in patients with HIV infection. This has occurred primarily from changes in overall frequency and death rates from infections. Organ system involvement by AIDS-associated diseases has not changed significantly over time.     

Management of HIV infection. A 1995-96 overview for the clinician

Although the challenges of HIV/AIDS care may seem overwhelming, we are better able than ever to positively affect the course of HIV for each individual patient. Treatment goals involve three areas: 1) Antiretroviral drugs aimed at retarding the rate of HIV replication, thus reducing the rate of damage to the immune system; 2) drugs used to treat or prevent opportunistic infections seen in the context of HIV-related immune deficiency; and 3) drugs used to treat symptoms or syndromes commonly seen in these patients (including dementia and wasting syndrome). The multitude of clinical problems seen in advanced HIV disease leads to significant polypharmacy and costs resulting in a very complex and confusing situation. I recommend that physicians with little HIV experience link up with an HIV specialist when caring for HIV-infected patients to optimize access to the best therapies or research studies currently available. With no cure in sight, physicians need to focus on educating the public and patients about how to avoid HIV infection and to identify persons who are infected to minimize spread.     

Etiology of lymphadenopathy in patients with AIDS in Taiwan

From 1986 to 1995, we retrospectively reviewed the records of 40 of 125 patients (32.0%) with acquired immunodeficiency syndrome (AIDS) who presented with extrainguinal lymphadenopathy. Most of the patients had an advanced stage of HIV infection with a mean CD4 lymphocyte count of 44/mm3. AIDS-defining opportunistic infections and malignancies were present in most patients and the neck region was the most common site of involvement. The etiology of lymphadenopathy was established in 26 patients. Tuberculous lymphadenitis was the most common cause, followed by lymphadenopathic Kaposi's sarcoma, benign reactive hyperplasia, cryptococcal lymphadenitis and disseminated Mycobacterium avium complex infection. Characteristic histopathologic findings were detected in 19 patients and 7 had presumptive tuberculous infections. The remaining 14 patients had no definitive etiology for their lymphadenopathy. As the causes are variable and the number of HIV/AIDS cases is increasing in Taiwan, more patients with lymphadenopathy, especially in the early stages of HIV infection will be encountered. Therefore, it is essential that diagnostic histopathologic and microbiologic studies be performed for appropriate and timely treatment.     

Human immunodeficiency virus infection, Part I

Initially recognized in 1982, acquired immunodeficiency syndrome (AIDS) has been the leading cause of death among young adults in the United States for much of this decade, and it has had a devastating impact on people in the developing world. It is estimated that 42 million people worldwide have been infected with human immunodeficiency virus (HIV), the virus that causes AIDS, and that almost 12 million people have died from AIDS-related diseases through 1997. Among these 12 million are 3 million children. Two thirds of the more than 30 million people with HIV or AIDS reside in sub-Saharan Africa. In the United States, 641,086 patients have been diagnosed with AIDS through 1997, and at least 385,000 have died. However, for the first time, new highly active antiretroviral therapies that include multiple drugs that attack the virus at several sites have slowed the progression from HIV to AIDS and from AIDS to death for those infected with HIV. The cumulative effect of these changes has been a reduction in both AIDS incident cases and AIDS deaths. Recent epidemiologic trends indicate that the proportion of AIDS incident cases and new HIV infections are increasing among women, African-Americans, and Hispanics, and the infections are more likely to be acquired through heterosexual transmission. The clinical management of HIV infection and AIDS has become increasingly complex in recent years. In addition to complete medical and social histories and physical examinations, hematologic, biochemical, serologic, and immunologic laboratory tests are required to predict the likelihood that patients will develop opportunistic infections and other complications related to HIV infection. Among the most important laboratory tests are measurements of HIV in plasma (viral load) in conjunction with peripheral blood CD4+ helper T lymphocyte counts. These tests are potent predictors of disease progression and their results have become markers for clinical response to therapy. The development of highly active antiretroviral therapy has had a profound impact on the epidemiology of AIDS and on the lives of individual patients. Through combinations of antiretroviral drugs, especially protease inhibitors, viral suppression can be achieved. However, adherence to these complex medical regimens and drug interactions have been problems for many patients. In addition, numerous questions remain unanswered, most importantly those regarding the timing of the initiation of treatment, the durability of viral suppression and clinical response, and the optimal "salvage" regimens for patients failing therapy either clinically or virologically.     

Treatment of infections in the patient with acquired immunodeficiency syndrome

Modern technology has led to a contemporary medical practice that must be able to manage a variety of opportunistic infections in the immunocompromised host. The most common causes of immune suppression are immunosuppressive therapy after organ transplantation, granulocytopenia secondary to cancer chemotherapy, and the human immunodeficiency virus (HIV). All of these forms of immunosuppression predispose patients to a wide variety of opportunistic infections caused by reduction in T- and B-cell lymphocyte function as well as depression of neutrophils. However, the acquired immunodeficiency syndrome (AIDS) has presented the clinician with the greatest challenge in this area. Therefore, it is imperative that physicians and other health care professionals have a comprehensive understanding of the recommended therapy as well as the epidemiology, pathogenesis, and diagnosis of the various infections in these patients.     

Current issues in the midwifery management of women living with HIV/AIDS

Changes in the clinical management of women living with human immunodeficiency virus (HIV) have occurred as a result of significant gains in the scientific knowledge of this retrovirus. As the incidence of HIV/AIDS continues to escalate among female adults and adolescents in the United States, all primary health care providers must anticipate the likelihood of encountering clients with HIV infection. Midwives must be adequately prepared to meet the challenges of managing women with HIV in the early stages of the disease. This article presents a comprehensive review of current demographic trends related to the HIV/AIDS epidemic among U.S. women and a brief overview of the essential immunopathogenesis of HIV. Contemporary issues related to universal counseling, updated testing procedures, and reproductive decision-making are covered. Initial primary care concerns and the management of newly infected seropositive women are included, with a focus on gynecologic issues. Guidance in the current management of HIV-positive pregnant women is offered. Updated antiretroviral prophylaxis recommendations are presented, to prevent perinatal transmission and to delay maternal immunosuppression with subsequent opportunistic infections. The article concludes with implications for health care professionals who provide care for this unique cohort of women.     

A changed pattern of opportunistic infections and malignancies in HIV-seropositive patients after the introduction of intensive anti-HIV-combination therapy

The application of potent combinations of antiretroviral drugs ('highly active antiretroviral therapy' (HAART)) makes effective therapy of HIV infection feasible. Consequently, the pattern of opportunistic infections and other secondary complications has changed. The incidence of infections and mortality due to aids has declined significantly. Further, the occurrence of other infections and syndromes, till now unknown in patients with aids, has been observed. It is thought that these are caused by HAART-induced inflammation, a phenomenon due to immune enhancement following HAART. An important issue is whether primary and secondary prophylaxis against opportunistic infections can be discontinued after improvement of the immune system: indeed, there are reports that discontinuation is safe in patients with persistent CD4+ cell counts above the critical level for that particular infection while CD4+ cell counts are monitored carefully.     

Congenital toxoplasmosis and seroconversion at the end of pregnancy: clinical observations

OBJECTIVE: To determine the knowledge of HIV-disease management and the adherence to contemporary guidelines among British Columbia physicians whose practices focused on HIV/AIDS. DESIGN: Self-administered mail survey. PARTICIPANTS: All 659 physicians registered in a province-wide HIV/AIDS drug treatment program. OUTCOME MEASURES: Data on demographic and personal characteristics of respondents, level of HIV-related experience, use of preventive vaccinations and tests, and preferred approaches to the prophylaxis and treatment of common opportunistic infections. Knowledge scores in 4 areas of patient care, as well as an overall score, were computed by comparing respondents' answers with the therapeutic strategies recommended at the time of the survey. Associations between physician characteristics and knowledge scores were identified by linear regression analysis. RESULTS: Of the 659 physicians surveyed, 65% returned responses: only 38% returned completed surveys while a further 27% returned a follow-up survey that asked nonrespondents about their demographic characteristics and HIV-related experience. Scores for specific areas of patient management ranged from 29% for the treatment of opportunistic infections to 62% for preventive measures, with a mean overall score of 47%. Physician knowledge in all areas of patient care was associated with the number of HIV-positive patients in the practice (p = 0.003 to p < 0.001). Physicians who were younger were more knowledgeable regarding preventive measures (p = 0.001); those whose practice location was in Vancouver had a greater knowledge of prophylaxis (p = 0.047); and those who had medical specialty training were more knowledgeable about the treatment of opportunistic infections (p = 0.009). CONCLUSIONS: There is substantial disparity in how physicians approach the management of HIV and related conditions. Deviations from therapeutic guidelines are common and may be associated with physician characteristics, particularly lack of experience in managing HIV.     

Protection from Mycobacterium avium complex disease in human immunodeficiency virus-infected persons with a history of tuberculosis

Risk of Mycobacterium avium complex disease was examined in human immunodeficiency virus (HIV)-infected patients with and without a history of tuberculosis. Information was obtained by retrospective review of charts of patients in HIV clinics in 10 US cities. Among 1363 patients with <200 CD4 cells/mm3 seen at Grady Memorial Hospital (GMH), 11 (17%) of 66 with a history of a positive purified protein derivative (PPD) skin test acquired M. avium infection, while 29 (16%) of 185 who were PPD-negative (but not anergic) did not (P = .85). Only 4 (8%) of 49 GMH patients with a history of tuberculosis acquired M. avium infection compared with 252 (19%) of 1314 GMH patients without a history of tuberculosis (P = .05). Proportional hazards analysis of risk factors for M. avium infection among 441 persons with and 8702 persons without a history of tuberculosis in 9 other cities confirmed protection from M. avium infection in persons with a history of tuberculosis (relative risk, 0.52; 95% confidence interval, 0.36-0.76; P < .001). Prior tuberculosis provides protection against M. avium infection in HIV-infected persons, possibly by stimulation of antimycobacterial immunity.     

Tuberculosis among urban health care workers: a study using restriction fragment length polymorphism typing

Cases of tuberculosis identified during 1992-1994 through an active tuberculosis surveillance network among six hospitals that serve New York City (the TBNetwork) were analyzed according to the occupational status of the patients. Clinical data were obtained by review of medical records, and restriction fragment length polymorphism (RFLP) typing of Mycobacterium tuberculosis isolates was performed. No known nosocomial outbreaks of tuberculosis occurred at these hospitals in the study period. Occupational status was known for 142 of 201 patients whose isolates were available for strain typing. Patients infected by organisms with a clustered strain typing pattern, as determined by RFLP analysis, were presumed to have recently acquired disease. RFLP typing revealed that isolates from 13 (65%) of 20 health care workers and 50 (41%) of 122 non-health care workers had a clustered RFLP pattern. The strains infecting eight (89%) of nine health care workers seropositive for human immunodeficiency virus (HIV) had a clustered RFLP pattern. Multivariate analysis of 75 patients with known HIV and occupational status revealed that HIV status (P = .03) and health care worker status (P = .02; RR = 2.77) were independent risk factors for a clustered RFLP strain. These findings suggest that many of the apparently sporadic cases of tuberculosis among health care workers may be due to unrecognized occupational transmission.     

Anal neoplasia. Pathogenesis, diagnosis, and management

Prolonged, severe immunodeficiency provides the necessary milieu for the emergence of anogenital neoplasia caused by human papillomaviruses. Anal neoplasia is likely to become a more common manifestation of HIV disease as patients with profound immunodeficiency, who would have succumbed to opportunistic infections earlier in the epidemic, are now surviving for extended periods of time because of increasingly effective antiretroviral, prophylactic, and antimicrobial therapies. The screening and treatment strategies described for use in HIV-infected patients with anal neoplasia are currently being investigated and refined.     

T-lymphocytopaenia, opportunistic infections and pathological findings in Ghanaian AIDS patients and their sexual partners

Ninety-nine patients at Center for Disease Control (CDC) clinical stage IV were studied. Twelve (12.12%) of these patients turned out to be HIV seronegative. Ten out of the 12 HIV negative patients were immunocompetent whereas the other two had proportional decreases in both CD4+ and CD8+ T-lymphocytes. HIV-1, HIV-2, and dual infection, were detected in 51.5%, 2%, and 22.2% respectively of clinical AIDS patients. The other 12.12% of clinical AIDS patients were indeterminate for HIV antibodies. All HIV positive patients with the exception of two, were immunocompromised with respect to CD4+ and CD8+ T-lymphocyte counts. Two healthy spouses and three children of patients who died from the disease were seronegative for HIV antibodies. Herpes simplex virus type 2 (HSV-2) and cytomegalovirus (CMV) antibody titres were higher in HIV infected than uninfected blood. Patients with chronic diarrhoea, lymphadenopathy, pneumonia, and tuberculosis, either alone or in combination of two or more of such symptoms, were found to be more likely to be confirmed by serology and immunology as definitive AIDS patients in Ghana. In postmortem studies on 20 patients, pneumonia due to tuberculosis constituted the major cause of death. Toxoplasmosis, cytomegaloviral eosophagitis and enteritis, and cryptococcosis were the major opportunistic infections detected. Programmed cell death (apoptosis) was found by the DNA gel electrophoresis method to be an unlikely major mechanism of accelerated culture induced death of PBMCs from CDC stage IV AIDS patients.     

Effect of prophylaxis on the clinical manifestations of AIDS-related opportunistic infections

Administration of targeted prophylaxis for AIDS-related opportunistic infections has contributed significantly to the recent decrease in mortality among patients with AIDS in the United States. Most reported prophylaxis trials have focused on determining (a) the percentage of cases prevented and (b) the effect of widespread antibiotic use on drug susceptibility. A third phenomenon that is seldom reported on is the attenuating effect of failed prophylaxis on the clinical presentation of opportunistic infections (OIs). With the increasingly widespread use of prophylaxis for OIs, more atypical "breakthrough" cases of opportunistic infections will be seen. Reports of clinical changes are reviewed below. Investigators should routinely report the clinical manifestations of breakthrough cases in all articles pertaining to prophylaxis for opportunistic infections in patients with AIDS.     

Cavitary pulmonary lesions in patients infected with human immunodeficiency virus

The differential diagnosis of cavitary pulmonary lesions in individuals infected with human immunodeficiency virus (HIV) is broad, especially in patients with advanced disease. In patients with Pneumocystis carinii pneumonia, cavitation is an uncommon manifestation of a common disease. It is unusual in patients with pulmonary cryptococcosis, coccidioidomycosis, and histoplasmosis but occurs frequently in patients with invasive pulmonary aspergillosis. In patients with pulmonary tuberculosis, cavities are more common during earlier stages of HIV disease, when cellular immunity is relatively preserved. Mycobacterium avium complex is an uncommon cause of lung disease and infrequently produces cavities. However, Mycobacterium kansasii, is often associated with cavitation. Cavities can complicate any bacterial pneumonia and are especially common with pneumonia due to Pseudomonas aeruginosa, Nocardia asteroides, and Rhodococcus equi. Noninfectious causes of cavitary lesions are rare, but cavitary lesions caused by pulmonary Kaposi's sarcoma and non-Hodgkin's lymphoma have been reported. Because of the broad differential diagnosis and because most cavities are caused by treatable opportunistic infections, a definitive diagnosis is essential.     

Opportunistic infections occurring during highly active antiretroviral treatment

OBJECTIVE: To analyse the characteristics of opportunistic infections in patients receiving highly active antiretroviral treatment (HAART). DESIGN AND METHODS: A retrospective study performed in seven hospitals, included all patients starting treatment by ritonavir or indinavir between 26 March and 31 December 1996. Patients were evaluated for the development of AIDS-defining events. Clinical evaluation, plasma HIV-1 RNA quantification, CD4 cell count were recorded at baseline and at the onset of the event. RESULTS: Four hundred and eighty-six patients were included: 44.2% had a CD4 cell count below 50 x 10(6) cells/l. Fifty clinical events were recorded in 46 patients with a mean follow-up of 6.1 months, of which 34 events (68%) were observed during the first 2 months of HAART. Eighteen of these occurred despite a reduction of viral load by at least 1.5 log10) and a 100% increase of the CD4 cell count compared with that at the onset of the event, corresponding to 11 cytomegalovirus infections, five mycobacterial infections, one case of cryptococcosis, and one case of Varicella-Zoster virus-related acute retinal necrosis. Among the 16 events observed after the second month, six occurred despite a marked biological improvement, corresponding to a recurrence in five of six patients who had stopped their maintenance therapy. Events were one cytomegalovirus infection, two mycobacterial infections, one episode of oesophageal candidiasis and one cryptococcal meningitis. CONCLUSION: In patients at high risk of developing an opportunistic infection prior to the institution of a HAART regimen, prophylaxis should not be discontinued during the first 2 months of treatment, and maintenance therapy should be carried on despite a significant increase in the CD4 cell count.     

Radiolabelled monoclonal antibodies (McAb): an alternate approach to the conventional methods for the assessment of cardiomyocyte damage in an experimental brain-death pig model

BACKGROUND: According to the Ministry of Health and Welfare AIDS Surveillance Committee's report on vertically transmitted human immunodeficiency virus (HIV) infection, there have been eight children with acquired immune deficiency syndrome (AIDS) and 18 children with HIV infection in Japan, totalling 26 in all as of February 1997. A search of the literature fails to reveal any report that deals with many cases of vertically transmitted HIV infection in Japan. METHODS: A primary questionnaire survey was taken of the main medical institutions across the country, followed by a secondary questionnaire survey of physicians and pediatricians who treated the disease. A clinical review was made of 19 children with vertically transmitted HIV infection (including eight AIDS children) according to the 1994 Revised Classification System for HIV Infection in Children. RESULTS: The mean age at diagnosis was 14.5 months and the diagnosis was made at less than 18 months of life in approximately 70% of infected children. In the mean observation period of 16 months, six of eight AIDS children (75%), and one child of group B died. The mean period of observation for the seven dead children was 7 months, and six of seven children died by 36 months of life. The survival period after the diagnosis of AIDS was 15 months. The diagnosis of HIV infection was made based on the clinical symptoms of all children with AIDS. Of 11 children, six (45%) presented with symptoms of HIV infection by 6 months of life, and 10 of 11 children (91%) presented with symptoms by 26 months of life. The noteworthy clinical findings included hepatomegaly, splenomegaly, recurrent respiratory tract infection, lymph node swelling, oral candidiasis, hepatitis, wasting syndrome, HIV encephalopathy and severe pneumonia. The favored age for the start of complications and the magnitude of decrease in the HIV helper cell count varied with each case of complications of HIV infection (wasting syndrome, HIV encephalopathy) or opportunistic infections (cytomegalovirus infection, Mycobacterium avium complex infection). Anti-HIV drugs (mainly zidovudine) had been used in five of eight children with AIDS and were effective in two long survivors alone. CONCLUSIONS: Children who are diagnosed with HIV infection, based on their clinical symptoms, carry a poor prognosis. In this respect, early diagnosis and progress in anti-HIV therapy are necessary.     

Human immunodeficiency virus replication in AIDS patients with Mycobacterium avium complex bacteremia: a case control study. California Collaborative Treatment Group

The development of opportunistic infections and the administration of vaccines have been associated with transient increases of human immunodeficiency virus (HIV) RNA plasma levels in HIV-infected patients. To determine the relationship between Mycobacterium avium complex (MAC) bacteremia and HIV RNA levels, HIV RNA levels in patients who developed MAC bacteremia (cases) were compared with levels in patients who remained free of MAC disease (controls). Cases and controls were matched for CD4 cell count, prophylaxis against MAC disease, antiretroviral therapy, and duration of follow-up. Mean baseline HIV RNA levels were 4.8 log10 copies/mL in cases and 4.6 log10 copies/mL in controls (P = 0.22). HIV RNA levels increased by a median of 0.4 log in cases but not controls at the time of MAC bacteremia (P = 0.01). In AIDS patients, the onset of MAC bacteremia is associated with a modest but significant increase in serum HIV RNA levels. Increased HIV replication may contribute to the higher mortality associated with MAC bacteremia.     

New beginnings: the National Blood Data Resource Center

A case of pulmonary Mycobacterium avium (M. avium) disease associated with idiopathic CD4+ T lymphocytopenia is reported. A rapidly growing pulmonary nodule was detected on a chest roentgenogram in a young man. Bronchoscopic examination revealed M. avium infection. Hematological studies showed a low CD4+ cell count in the absence of any identifiable immunodeficiency, including human immunodeficiency virus (HIV) infection. With the combination of chemotherapy and surgery, he had a good clinical outcome. Idiopathic CD4+ T lymphocytopenia should be considered in patients with unexplained opportunistic infection.     

Seasonal variation of disseminated Penicillium marneffei infections in northern Thailand: a clue to the reservoir?

Disseminated Penicillium marneffei infections are common AIDS-defining opportunistic infections among persons with human immunodeficiency virus (HIV) infection in northern Thailand. Penicilliosis due to P. marneffei is the third most frequent AIDS-defining infection in this population, after tuberculosis and cryptococcosis. Very little is known about the epidemiology and natural reservoir of P. marneffei. The seasonal distribution of two common AIDS-defining fungal infections was compared among patients diagnosed between 1991 and 1994 at Chiang Mai University Hospital. There were 550 cases (492 male, 58 female patients) of P. marneffei and 793 cases (685 male, 108 female patients) of Cryptococcus neoformans infection diagnosed. In each year, P. marneffei but not C. neoformans infections were more frequent in the rainy than the dry season. Seasonal variation of P. marneffei infections in AIDS patients in northern Thailand may provide valuable information in determining the important reservoirs and exposures to this organism that lead to disseminated disease in these patients.