Disseminated Mycobacterium Avium Complex Research Articles

Antiretroviral Therapy for Children

ACCORDING TO THE UNITED NATIONS PROGRAMME on HIV/AIDS (UNAIDS) global report on human immunodeficiency virus (HIV), in 2005 more than 2.3 million children were living with HIV infection, and 380 000 children with HIV had died. Most of the children who die from HIV have severe manifestations of common childhood illnesses, such as diarrhea, malnutrition, acute respiratory tract infection, and tuberculosis. These children often die before the diagnosis of HIV infection can be made, and mortality is often attributed to a background high rate of early childhood mortality. The United States is home for a diminishing proportion of HIV-infected children, with an estimated 11 000 cases in 2005. There are 2 reasons for this decreasing population of HIV-infected children in the developed world. First, pregnant women are increasingly being offered HIV testing, and HIV-infected women are receiving antiretroviral medications sufficient to reduce transmission to a rate of approximately 1% to 2%. Second, the population of HIV-infected children is diminishing because those children who had been infected are now growing up and becoming adults, following the introduction of potent new drugs in 1996. According to a longitudinal study by the Pediatric AIDS Clinical Trials Group (PACTG 219), the mortality rate for HIVinfected children and adolescents decreased from more than 5% in 1996 to less than 1% in 1998. Similar survival benefits have been observed among adults. The impact of highly active antiretroviral therapy (HAART) on survival and quality of life among patients affected by HIV is hardly disputable, but concise objective evidence of the benefit of treatment on infectious complications in children has been lacking in the medical literature. Before the availability of HAART, opportunistic infections such as Pneumocystis jiroveci pneumonia, bacteremia, bacterial pneumonia, and fungal sepsis were significant fatal diseases in patients infected with HIV and remain so among patients not receiving therapy. In this issue of JAMA, Gona and colleagues provide objective evidence to substantiate the benefit of HAART or, more correctly, the association of HAART and opportunistic infection prophylaxis with incidence of opportunistic infections before and after the advent of HAART. In a retrospective cohort study, Gona et al compared the incidence of 29 opportunistic infections in HIV-infected children who were treated in the HAART era with the incidence among those who were treated before the availability of HAART. They found that the incidence of P jiroveci pneumonia had decreased by 14-fold, disseminated Mycobacterium avium complex by 12-fold, bacteremia by 10-fold, and bacterial pneumonia by 5-fold. These reductions in opportunistic infections occurred despite a concomitant reduction in the use of specific prophylaxis medications, suggesting that immune reconstitution rather than improved prophylaxis was primarily responsible for better outcomes. The size and diversity of the population studied allows for generalizability of the results to the US population of children with HIV infection. There were approximately 3000 children in the cohort, which constitutes about 22% of children and adolescents living with HIV in the United States. Given the diminishing population of HIV-infected children, it is unlikely that additional data will become available in this country. There were limitations with the retrospective cohort study design, which evaluated available data from a database. Some events and clinical practices changed over time and could have affected case ascertainment and overall disease incidence. Although the incidence of bacterial pneumonia was reported, the diagnosis of this problem in children is difficult, because no consistent clinical or radiographic features reliably distinguish different etiologies of pneumonia. Radiographic pneumonia may or may not be associated with bacteremia. When such an association occurs, the relationship is not always a causal one. Specific etiologic diagnosis of bacterial pneumonia can be determined by diagnostic techniques, such as lung aspirates or bronchoalveolar lavage. These procedures are highly sensitive but are seldom used because they are considered too invasive.

Nontuberculous Mycobacterial Infections in Pediatric Hematopoietic Stem Cell Transplant Recipients

Nontuberculous mycobacterial (NTM) infections are rarely diagnosed in hematopoietic stem cell transplant (HSCT) recipients. We describe a case of disseminated Mycobacterium avium complex with gastrointestinal tract involvement in a HSCT recipient. We reviewed NTM infections among pediatric HSCT patients at our institution from 2000-2004 and identified 2 additional cases. Fourteen published case reports of NTM disease in children are reviewed.

Effective Combination Therapy Using Interferon- and Interleukin-2 for Disseminated Mycobacterium avium Complex Infection in a Pediatric Patient with AIDS

A 5-year-old girl presented with disseminated Mycobacterium avium complex infection during advanced human immunodeficiency virus infection. Interferon-gamma or interleukin-2 monotherapy showed only limited effects. Use of a combination of interferon-gamma and interferon-2 resulted in a remarkable improvement in the patient's condition, accompanied by an increase in circulating CD4+ T cells.

Pharmacokinetics of Clarithromycin Extended-Release (ER) Tablets in Patients with AIDS

Background: Clarithromycin is a key agent in effective antimycobacterial therapy and prophylaxis for AIDS-related disseminated Mycobacterium avium complex (dMAC) infection. Immediate-release (IR) clarithromycin tablets are dosed at 500 mg bid for these indications. A new extended-release (ER) tablet of clarithromycin has been developed and approved at a dosing interval of once every 24 hours for treatment of respiratory tract bacterial infections. However, the pharmacokinetics of clarithromycin ER in AIDS patients with or at risk for dMAC has not been previously investigated. Method: We conducted a randomized, crossover trial in which 14 AIDS patients received clarithromycin ER, 1000 mg once daily, and clarithromycin IR, 500 mg bid, each for 1 week, with pharmacokinetic sampling at the end of each week. Results: The mean of the individual AUC ratios for clarithromycin ER vs. IR was 1.09 (90% CI, 0.94-1.24). Adverse events were no more severe or frequent with clarithromycin ER than IR. Conclusion: Clarithromycin ER is a once-daily regimen that is as well tolerated as standard bid IR clarithromycin dosing and has average bioequivalence to the IR formulation in patients with AIDS.

Clinical, Microbiological, and Immunological Characteristics in HIV-Infected Subjects at Risk for DisseminatedMycobacterium aviumComplex Disease: An AACTG Study

The clinical, microbiologic, and immunologic parameters in HIV-infected subjects first presenting with disseminated Mycobacterium avium complex (DMAC) were determined. Four HIV-positive groups not yet on DMAC treatment were enrolled: 19 subjects with CD4 lymphocyte counts < or =50/microl thought to have DMAC on clinical grounds; 18 subjects newly found to have a positive blood culture for MAC; 25 asymptomatic controls (CD4 cell counts < or =50); and 25 asymptomatic controls (CD4 counts 100-250/microl). Outcome measures include comparisons between groups for clinical characteristics; results of cultures from blood, marrow, and gastrointestinal and respiratory tracts; immunological markers from staining of marrow and flow cytometry of circulating lymphocytes; and cytokine production of PBMCs. Only 21% of the 19 patients entered on suspicion of having DMAC grew MAC from blood or marrow. Neither clinical presentation nor laboratory tests differentiated those culture-positive from those culture-negative patients. However, prior PCP or multiple other opportunistic infections were more common in the DMAC group. MAC was isolated from 82% of marrow and 50% of blood specimens from the DMAC group. Respiratory or gastrointestinal colonization was present in 36% of DMAC subjects, but only 5% of non-DMAC subjects with CD4 counts <50 cells/microl. CD8+ cells were more frequent in bone marrow, and CD4 cells recognizing MAC antigen were more frequent in blood from DMAC subjects vs. controls. Results suggest an early stage of tissue dissemination preceding persistent bacteremia, and mucosal entry without persistence of colonization. MAC-specific T cell responses apparently develop and persist during DMAC, but are dysfunctional or too infrequent to prevent persistence.

Endoscopic appearance of GI mycobacteriosis caused by the Mycobacterium avium complex in a patient with AIDS: case report and review

Disseminated Mycobacterium avium complex (MAC) infection, an important AIDS-defining opportunistic infection in patients with advanced HIV infection (generally those with CD4 lymphocyte counts <50 cells/μL), is associated with significant morbidity and mortality, and with shortened survival.1,2 The incidence of disseminated MAC (DMAC) infection increased during the period 1982 to 1994, with the maturation of the AIDS epidemic,3 to an estimated cumulative incidence of 15% to 24% of patients with AIDS.

Disseminated mycobacterium avium complex infection in a patient with complete interferon gamma receptor deficiency

RATIONALE: Host defense against mycobacteria is dependent upon the functional integrity and interaction between mononuclear phagocytes, T cells and effective granuloma formation. Recent progress revealed the importance of IFN gamma (IFN-γ) and IL-12 axis for granuloma forming pathogens. An increased susceptibility to atypical mycobacterium is seen in patients with defects of IFN-γ and IL-12 axis. CASE REPORT: A Hispanic female born to consanguineous parents presented with persistent fever and cough at 12 months of age. A CT scan demonstrated left lower lobe consolidation and prominent mediastinal lymphadenopathy and she had a positive Mantaux test (12 X 12 mm). While she was started on a four drug regimen for tuberculosis, her blood cultures and gastric aspirates grew Mycobacterium avium that disseminated to bone marrow, spleen, liver and central nervous system, in spite of aggressive combination chemotherapy. RESULTS: Conventional immune workup results were unremarkable and given her clinical presentation, defects involving IFN-γ and IL-12 axis were suspected. Further studies revealed elevated IFN-γ production by her peripheral blood mononuclear cells with PHA and Con A, but normal production with IL-12. IL-12 production with these mitogens was low but her cells produced high normal levels of IL-12 with IL-12p70 and IL-18. ELISPOT revealed increase in IFN-γ production as well. With these findings, IFN-γ receptor (IFN-γR) defect was suspected and complete IFN-γR defect was confirmed by flow cytometry (Dr. Holland's laboratory at NIH). CONCLUSION: This case demonstrates an importance of IFN-γ for eradicating atypical mycobacterium and also altered PPD reactivity to Mycobacterium avium in patients with IFN-γR defect.

Disseminated Mycobacterium avium complex infection in a renal transplant patient

Organ transplant recipients are at an increased risk of developing opportunistic infections due to prolonged immunosuppression. We present the case of a renal transplant recipient with severe CD4 lymphopenia who developed disseminated Mycobacterium avium complex infection. Recovery from infection was paralleled by a progressive increase in CD4 lymphocytes. T lymphocyte subsets are not monitored routinely in organ transplants but may identify patients at risk of developing serious infectious complications.

肺&lt;I&gt;Mycobacterium avium&lt;/I&gt; complex (MAC) 症の3姉妹例

We reported three sisters of pulmonary Mycobacterium avium complex (MAC) disease. The oldest sister was complaining of bloody sputum, and cultures were positive for M. avium. By monotherapy with clarithromycin, symptom and imaging findings had shown no progression for six years. The second sister was complaining of productive cough, and cultures were positive for M. intracellulare. Her symptom and imaging findings had shown no progression for seven years without any treatment. The third sister had rheumatoid arthritis and diabetes mellitus, and cultures were positive for M. intracellulare. Although she received chemotherapy with rifampicin, clarithromycin, ethambutol, and kanamycin, symptom and imaging findings had progressed gradually. She died of respiratory failure four years later. Autopsy findings revealed no disseminated MAC disease. The results which three cases showed different isolate patterns and clinical courses suggest the importance of underlying anti-mycobacterial immunological impairment and defects of local host defense rather than virulence of infected strains as the pathogenesis of pulmonary MAC disease.

Unusual Presentation of Chronic Myelogenous Leukemia Concomitant with Mycobacterium Avium Complex Infection.

Only rare cases of patients with chronic myelogenous leukemia (CML) with disseminated Mycobacterium avium complex (MAC) infection are reported in the literature. In the majority of those cases, MAC infection was diagnosed after at least 12 months and following busulfan or high dose steroids therapy. In many of those cases, disseminated MAC infection was preceded by clinically evident pulmonary disease, including interstitial pneumonia and/or pulmonary alveolar proteinosis. We report a highly unusual case of CML presenting with concomitant disseminated MAC infection in a HIV-negative host with no known preexisting active pulmonary disease.A 41-year-old Caucasian male without significant past medical history presented to the emergency department with a ten-day history of progressively worsening abdominal pain. He reported generalized weakness, fever, chills, night sweats, decreased appetite and weight loss. His laboratory data were significant for thrombocytosis of 992,000/uL, mild anemia, and a normal white blood cell count of 10,000/uL. He had marked splenomegaly, hepatomegaly, and lymphadenopathy. Bone marrow aspiration was markedly hypercellular with normal myeloid to erythroid ratio, no increase in blasts, mild eosinophilia, moderate fibrosis, and focal necrosis. Routine cytogenetic study revealed t(9;22)(q34;q11). Acid fast bacillus (AFB) culture was positive for MAC, confirmed by DNA probe. Flow cytometry revealed normal CD4:CD8 ratio of T-lymphocytes. There was no evidence of HIV infection by serologic and molecular studies. Therapy with ethambutol and azythromycin was initiated. The patient's course was complicated by severe pancytopenia, bleeding episodes, and dyspnea. A repeat bone marrow examination revealed severe myelofibrosis with decrease of cellularity and foamy macrophages positive for AFB. Bronchioalveolar lavage demonstrated AFB positive for MAC DNA probe. He required multiple blood product transfusions. Rifampin, Amikacin, Levaquin, imatinib and GM-CSF were added to his therapy. Five months after his initial presentation the patient developed a new lung infiltrate on chest radiography and subsequently underwent video-assisted thoracoscopy with lung biopsy, reveling Aspergillus fumigatus infection. Voriconazole therapy was added. The patient continued to decline and expired six months after his initial presentation.In summary, this was an atypical presentation of CML without leukocytosis or granulocytic hyperplasia in the bone marrow. While the bone marrow findings were consistent with a chronic myeloproliferative disease, they were more typical of chronic idiopathic myelofibrosis rather than CML. Yet, the cytogenetic study documented the presence of Philadelphia chromosome, diagnostic for CML. It is possible that the underlying MAC infection was responsible for the atypical features. This case illustrates the fact that patients with CML can be at risk for MAC or other atypical mycobacterial infections even prior to chemotherapy. The mechanism of immunosuppression in CML has not been satisfactory explained.

Nontuberculous Mycobacterial Infections: A Clinical Review

Nontuberculous mycobacteria (NTM) are important environmental pathogens that can cause a broad spectrum of diseases. The last few years brought several changes in this expanding field: The number of infections that can be associated with specific species as well as the number of new species as etiological agents has exploded due to the development of new diagnostic tools. The incidence of disseminated Mycobacterium avium complex (MAC) infections in HIV patients is decreasing with more potent anti-HIV treatments, while the rate of pulmonary NTM infection and disease as well as the prevalence of Buruli ulcer, a chronic, necrotizing, progressive ulcerous disease caused by Mycobacterium ulcerans, is increasing. The disease manifestations depend on the interaction between the specific mycobacterial pathogen and the host's immune system. This article presents an update of the epidemiology, diagnosis, and treatment of NTM-associated pulmonary disease, lymphadenitis, skin and soft tissue disease, skeletal infection and foreign body- and catheter-related NTM infections.

Successful HLA-identical bone marrow transplantation in a patient with interferon-γ receptor 2 deficiency and disseminated Mycobacterium avium complex infection

Interferon gamma receptor-2 (IFNγR2) deficiency is characterized by increased susceptibility to nontuberculous mycobacteria and intracellular pathogens. We report successful HLA-identical bone marrow transplantation (BMT) of a patient with this defect. A Qatari male born to consanguineous parents presented with a CMV positive urine culture, while blood and urine mycobacterial cultures were initially negative. Bacille-Calmette-Guerin (BCG) vaccine was not administered due to a history of IFN-γ R2 deficiency in his deceased older sister. The patient was found to have the same defect. Parents initially refused BMT. He received prophylactic azithromycin but developed disseminated Mycobacterium avium complex (MAC) infection requiring an aggressive regimen including amikacin, azithromycin, ethambutol, linezolid, rifampin and moxifloxacin. CMV infection was treated with ganciclovir, foscarnet, and CMV immune globulin. Splenectomy was performed at age 9 months, due to massive hypersplenism with subsequent growth of MAC. CMV DNA was positive until age 11 months, while mycobacterial blood cultures were positive until age 10 months. At age 13 months, he underwent bone marrow transplantation from his HLA-identical father. Pre-transplant conditioning included busulfan, cyclophosphamide, and antithymocyte globulin (ATG). Post-transplant graft vs. host disease prophylaxis included methotrexate and cyclosporine. RFLP analysis revealed 98% donor cells on day +32 post-transplant. Transplant course was complicated by Clostridium difficile infection, fevers, hypertension and thrombocytopenia, but he is stable 94 days post-transplantation. Conclusions Our case is the only living patient who has undergone successful BMT for a defect in the IFNγR2. We conclude that bone marrow transplantation for IFNγR2 deficiency is an effective means of correcting this immunodeficiency.

MAC Infection: 3 Drugs Better Than 2?

Disseminated Mycobacterium avium complex (MAC) disease occurs frequently during late-stage HIV infection. Current guidelines propose therapy with

Defective antigen processing associated with familial disseminated mycobacteriosis.

To gain insights into a possible immune defect predisposing to disseminated mycobacteria infection, we studied three of six surviving children with disseminated Mycobacterium avium complex infection, who had no recognized form of immunodeficiency. We used mycobacteria isolated from the patients and diphtheria, tetanus and pertussis vaccine (DTP) to study antigen-specific T lymphocyte responses. We observed that interferon-gamma (IFN-gamma) production by T cells in response to antigens (both mycobacteria and DTP) in these patients with disseminated infection was greatly impaired. This defect did not seem to be the result of T cell unresponsiveness, as phytohaemagglutinin (PHA) stimulation was able to induce high levels of IFN-gamma comparable to those seen in control patients with localized infection. Further experiments showed that peripheral blood mononuclear cells (PBMC) from patients with disseminated infection were able to present influenza haemagglutinin (HA) peptides to specific T cell clones. However, this ability was lost when the whole HA protein was used as source of antigen. Taken together, these observations support the notion that the primary immune defect in these patients with disseminated mycobacterial infection rests in the antigen-processing functions of their antigen-presenting cells (APC). These findings may provide clues to the wider problem of susceptibility to mycobacteria and other intracellular pathogens and have implications in designing therapy for these patients.

The complexity of HLA class II (DRB1, DQB1, DM) associations with disseminated Mycobacterium avium complex infection among HIV-1-seropositive whites.

Earlier associations of polymorphism in classic HLA class II (DRB1 and DQB1) genes have been extended to include the accessory genes DMA and DMB as determinants of disseminated Mycobacterium avium complex (DMAC) infection among HIV-1-seropositive whites. From the Multicenter AIDS Cohort study, 176 DMAC cases were matched with 176 controls in a nested case-control study. PCR-based HLA genotyping techniques were used to resolve variants of DRB1 and DQB1 to their four-digit or five-digit alleles, and single-strand conformation polymorphism was used to resolve sequences in exon 3 at each DM locus. The DMA*0102 allele occurred less frequently among DMAC cases than among controls (OR = 0.46, p =.02). Combinations of DRB1 alleles with or without specific DMA and DMB variants showed significant differences in distributions between the cases and controls, but both of the previously associated class II alleles (DRB1*1501 and DRB1*0701) showed stronger positive associations with DMAC in the absence than in the presence of DMA*0102. Apparent joint effects of DRB1 and DM allelic combinations on occurrence and timing of DMAC suggest that class II disease relationships may be better predicted by biologically plausible interactive combinations than by polymorphisms in individual genes.

Efficacy of clofazimine–modified cyclodextrin against Mycobacterium avium complex in human macrophages

Clofazimine, a water insoluble substituted iminophenazine derivative with anti-mycobacterial and anti-inflammatory activity, is recommended by the WHO for the treatment of leprosy. It is also active against disseminated Mycobacterium avium complex (MAC) disease in HIV-infected patients. Recently, we achieved a 4000-fold increase of clofazimine water solubility using a novel modified clofazimine–cyclodextrin complex synthesized and patented by our group [Wasserlösliche, Iminiophenazinderivate enthaltende pharmazeutische Zusammensetzungen, deren Herstellung und Verwendung, German Patent, DE19814814C2]. In this paper we examine the activity of this complex against MAC in human macrophages, and evaluate its cytotoxicity. MAC-infected macrophages were treated for 24 h with free or complexed clofazimine. The in vitro minimum inhibitory concentrations of both free and complexed clofazimine were 0.1 μg/ml. Free and complexed clofazimine inhibited the growth of MAC inside macrophages to a similar extent, while modified cyclodextrin alone had no observable effects on MAC or macrophages. Complexed clofazimine was not toxic to cells at concentrations effective against MAC. The TD 50 of the modified cyclodextrin in THP-1 cell line was 297 μg/ml.

Disseminated Mycobacterium avium complex (MAC) in a patient with acquired immunodeficiency syndrome (AIDS).

Disseminated Mycobacterium avium complex (MAC) in a patient with acquired immunodeficiency syndrome (AIDS).

Successful discontinuation of therapy for disseminated Mycobacterium avium complex infection after effective antiretroviral therapy.

Highly active antiretroviral therapy (HAART) is associated with improvement or resolution of several HIV-associated opportunistic infections. Although prophylaxis against disseminated Mycobacterium avium complex infection may be successfully discontinued after a favorable response to HAART, the 1999 guidelines from the U.S. Public Health Service/Infectious Diseases Society of America recommend continuing therapy for disseminated M. avium complex infection, regardless of the response to HAART. To examine the outcome among patients with disseminated M. avium complex infection whose antimycobacterial therapy was discontinued after a favorable response to HAART. Retrospective chart review between May 2000 and May 2001. 13 Canadian HIV clinics. 52 HIV-infected adults (43 men; mean age, 37.3 years) in whom successful antimycobacterial therapy for disseminated M. avium complex infection was discontinued after a favorable virologic response to HAART. Survival, survival free of disseminated M. avium complex infection, and CD4(+) cell count responses. At the time of diagnosis of disseminated M. avium complex infection, the median CD4(+) cell count was 0.016 x 10(9) cells/L, and the median plasma HIV RNA level was 90 000 copies/mL (plasma HIV RNA levels were available for only 21 patients). The patients received a median of 32 months of antimycobacterial therapy that included ethambutol plus either clarithromycin or azithromycin. When antimycobacterial therapy was discontinued, the median CD4(+) cell count was 0.23 x 10(9) cells/L and the median plasma HIV RNA level was less than 50 copies/mL. A median of 20 months after discontinuation of antimycobacterial therapy, only 1 patient had developed recurrent M. avium complex disease (37 months after stopping antimycobacterial therapy). This patient had stopped HAART 2 months earlier because of uncontrolled HIV viremia. Twenty months after stopping antimycobacterial therapy, the other 51 patients had a median CD4(+) cell count of 0.288 x 10(9) cells/L; 34 (67%) had undetectable plasma HIV RNA levels, and 8 (15%) had plasma HIV RNA levels of 50 to 1000 copies/mL. Discontinuation of successful disseminated M. avium complex therapy after a successful response to HAART is safe and reduces patients' pill burdens, potential drug adverse effects, drug interactions, and costs of therapy.

Low incidence of colonization and no cases of disseminated Mycobacterium avium complex infection (DMAC) in Brazilian AIDS patients in the HAART era.

Evaluate the incidence of mycobacterial disease and the colonization of the respiratory and gastrointestinal tracts by Mycobacterium avium complex (MAC) bacteria in AIDS patients. HIV-positive individuals with at least one CD(4)(+) count < 100 cells/mm(3). Mycobacterial disease and MAC prophylaxis. Stool, sputum, and blood cultures were prospectively obtained every month from September, 1997, to December, 1999. The incidence was calculated using Poisson regression. Survival was estimated by the Kaplan Meier method and the Cox proportional hazard model. We followed-up 79 patients during a median period of 428 days. Blood cultures (n = 742) were negative for all mycobacteria. Positive cultures (25 samples) were obtained from non-sterile sites: Stools (19/703 specimens = 2.7%) and sputum (14/742 specimens = 1.9%). MAC was isolated in 7/703 stool samples (1%) and 1/32 sputum specimens (0.1%). The incidence of patient colonization with MAC was 0.09 /year (CI=0.05-0.18). CD4 counts in patients colonized with MAC were below 100 cells/mm(3) in only 2 out of 8 cases. Restoration of CD(4)(+) counts >100 cells/mm(3) (HR = 0.18; CI = 0.05-0.70) predicted a lower risk of death (P<0.05) but was not protective for MAC colonization (HR=0.52;CI =0.62-4.35, P=0.55). The absence of DMAC infection in colonized individuals argues in favor of a HAART protective effect against; DMAC; however, restoration of CD(4) counts did not protect patients against MAC colonization.

Safe interruption of maintenance therapy against previous infection with four common HIV-associated opportunistic pathogens during potent antiretroviral therapy.

The safety of interrupting maintenance therapy for previous opportunistic infections other than Pneumocystis carinii pneumonia among patients with HIV infection who respond to potent antiretroviral therapy has not been well documented. To assess the safety of interrupting maintenance therapy for cytomegalovirus (CMV) end-organ disease, disseminated Mycobacterium avium complex (MAC) infection, cerebral toxoplasmosis, and extrapulmonary cryptococcosis in patients receiving antiretroviral therapy. Observational study. Seven European HIV cohorts. 358 patients taking potent antiretroviral therapy (> or =3 drugs) who interrupted maintenance therapy at a CD4 lymphocyte count greater than 50 x 10(6) cells/L. Recurrence of opportunistic infection after interruption of maintenance therapy. 379 interruptions of maintenance therapy were identified: 162 for CMV disease, 103 for MAC infection, 75 for toxoplasmosis, and 39 for cryptococcosis. During 781 person-years of follow-up, five patients had relapse. Two relapses (one of CMV disease and one of MAC infection) were diagnosed after maintenance therapy was interrupted when the CD4 lymphocyte count was less than 100 x 10(6) cells/L or when only one recent measurement exceeded this value. Two relapses (one of CMV disease and one of MAC infection) were diagnosed after maintenance therapy was interrupted once CD4 counts were greater than 100 x 10(6) cells/L for 10 and 8 months, respectively. One relapse (toxoplasmosis) was diagnosed after maintenance therapy interruption at a CD4 lymphocyte count greater than 200 x 10(6) cells/L for 15 months. The overall incidences of recurrent CMV disease, MAC infection, toxoplasmosis, and cryptococcosis were 0.54 per 100 person-years (95% CI, 0.07 to 1.95 per 100 person-years), 0.90 per 100 person-years (CI, 0.11 to 3.25 per 100 person-years), 0.84 per 100 person-years (CI, 0.02 to 4.68 per 100 person-years), and 0.00 per 100 person-years (CI, 0.00 to 5.27 per 100 person-years), respectively. Maintenance therapy against previous infection with CMV, MAC, Toxoplasma gondii, or Cryptococcus neoformans in patients with HIV infection can be interrupted after sustained CD4 count increases to greater than 200 (or possibly 100 to 200) x 10(6) cells/L for at least 6 months after the start of potent antiretroviral therapy.