D. Schürmann

Efficacy of pyrimethamine/sulfadoxine in the prevention of toxoplasmic encephalitis relapses and Pneumocystis carinii pneumonia in HIV-infected patients.

The efficacy and safety of 25 mg pyrimethamine plus 500 mg sulfadoxine given twice a week in preventing relapses of AIDS-related toxoplasmic encephalitis was evaluated in an open study. The 56 HIV-infected patients evaluated had responded to intensive treatment with pyrimethamine/clindamycin prior to starting the present prophylactic regimen. Four patients (7 %) experienced relapse while on pyrimethamine/sulfadoxine. The probability of freedom from relapse was >90 % for 12 months and >80 % for 24 months. Side effects comprised mild or moderate allergic reactions which occurred in 23 patients (41 %), leading to discontinuation in four patients (7%). Forty-nine of the 56 patients did not have a history ofPneumocystis carinii pneumonia and did not receive antiparasitic prophylaxis other than pyrimethamine/sulfadoxine; two of them (4 %) developed pneumocystosis. The probability of freedom from pneumocystosis was about 90 % for 24 months. Pyrimethamine/sulfadoxine twice a week appears to be a promising regimen for prevention of toxoplasmic encephalitis, and also appears to provide protection againstPneumocystis carinii pneumonia. Although allergic reactions are usually mild and disappear on continuation, they may limit the value of this regimen.

Effectiveness of the macrolide clarithromycin in the treatment ofMycobacterium avium complex infection in HIV-infected patients

SummaryIn a randomized double-blind study, nine mycobacteremic patients with AIDS-related disseminatedMycobacterium avium complex (MAC) infection received clarithromycin or placebo in addition to a basic regimen that included isoniazid, ethambutol and clofazimine. All four patients receiving clarithromycin showed blood culture conversion and clinical response. Of the five patients treated without clarithromycin, two showed resolution of mycobacteremia and clinical reponse, while another two died without having shown response. The remaining patient deteriorated until a switch from placebo to clarithromycin led to blood culture conversion and rapid clinical improvement. After finishing six weeks of intensive treatment, clarithromycin was given in an open maintenance phase to all patients, initially in combination with rifabutin for 24 weeks and then alone. One patient had a relapse of MAC infection while receiving clarithromycin alone. The relapse was associated with acquired resistance to the drug. Clarithromycin appears to be a promising component of multi-drug therapy for patients with MAC infection. Monotherapy can lead to drug resistance.ZusammenfassungNeun AIDS-Patienten mit disseminierterMycobacterium avium complex (MAC)-Infektion wurden in einer randomisierten Doppelblind-Studie mit Clarithromycin oder Plazebo behandelt, die zu einer Basiskombination aus Isoniazid, Ethambutol und Clofazimine hinzugegeben wurden. Alle vier mit Clarithromycin behandelten Patienten sprachen auf die Therapie an. Von fünf ohne Clarithromycin behandelten Patienten sprachen zwei auf die Therapie an, während zwei andere ohne Therapieeffekt verstarben. Ein Patient verschlechterte sich kontinuierlich, bis der Austausch von Plazebo gegen Clarithromycin zur Blutkultur-Konversion und Rückbildung von Krankheitserscheinungen führte. Nach einer sechswöchigen Akuttherapie-Phase erhielten alle Patienten Clarithromycin in einer offenen Studie zur Rezidiv-Prophylaxe, zunächst in Kombination mit Rifabutin für 24 Wochen und anschließend als Monotherapie. Ein Patient hatte ein Rezidiv der MAC-Infektion, das in der Monotherapie-Phase auftrat und mit einer erworbenen Resistenz gegen das Medikament assoziiert war. Clarithromycin ist eine vielversprechende Substanz für ein Kombinationsregime zur Behandlung der MAC-Infektion. Eine Monotherapie kann zur Resistenz-Entwicklung führen.

Immunosuppression and mycobacteria other than Mycobacterium tuberculosis: results from patients with and without HIV infection

Infections caused by mycobacteria other than Mycobacterium tuberculosis (MOTT) have often been described as common in AIDS patients. To evaluate whether infections with MOTT are specific for HIV related immunosuppression or are also frequent in patients with immunosuppression of different aetiology, data on the frequency of isolation from immunosuppressed patients with HIV infection are important. Blood, stool and urine specimens from 134 patients with non-HIV related immunosuppression, and from 55 immunocompetent subjects were examined for mycobacteria. MOTT have been isolated from one immunocompetent person but from none of the immunosuppressed patients. Since in AIDS patients an initial colonization of the gastrointestinal tract (GI-tract) with MOTT is common, GI-tract biopsy specimens from an additional 80 patients were examined microscopically and histologically for mycobacteria. Mycobacteria were not isolated from these specimens. In the same period of time 72 AIDS patients have been examined; 7 (10%) had infections with M. tuberculosis whereas MOTT have been isolated from 16 (22%) of these patients. Mycobacteria have been found only rarely in immunocompetent patients and have not been isolated from patients with non-HIV related immunosuppression. The isolation of MOTT is highly correlated with an HIV-related immunosuppression.

Combined and alternating ganciclovir and foscarnet in acute and maintenance therapy of human immunodeficiency virus-related cytomegalovirus encephalitis refractory to ganciclovir alone

SummaryCytomegalovirus (CMV) causes life-threatening disseminated infections and in particular vision-threatening infections of the retina in patients with the acquired immunodeficiency syndrome. Ganciclovir currently represents the most frequently used therapy for CMV retinitis. However, cases of ganciclovir-resistant CMV strains have been described, in which foscarnet seems to be an effective alternative. Both drugs have serious toxicities, and relapses frequently occur during maintenance therapy. In a patient with CMV encephalitis, we administered a 3-week combination ganciclovir/foscarnet induction therapy (ganciclovir 5 mg/kg every 12 h; foscarnet 60 mg/kg every 8 h), followed by an alternating maintenance administration of both drugs every other day (ganciclovir 5 mg/kg, foscarnet 120 mg/kg) to reduce toxicity and resistance. This regimen was tolerated well and seemed to be more effective than ganciclovir alone in a patient with CMV encephalitis.

Intensive treatment of AIDS-related non-Hodgkin's lymphomas with the MACOP-B protocol

Abstract: The usefulness of intensive chemotherapy with the MACOP‐B protocol was evaluated in 8 patients with AIDS‐related non‐Hodgkins lymphoma (NHL). Four patients had a prior AIDS diagnosis. The median CD4+ lymphocyte count was 0.079 cells × 109/1 (range 0.016–0.330). All patients responded to treatment. Four patients finished chemotherapy, all with complete remission, while another 3 patients deteriorated prior to finishing treatment and died. The median survival was 4 months (range 1 to 86 months). Major causes of the poor outcome were AIDS‐related opportunistic infections and meningeal CNS involvement by NHL developing during or after chemotherapy. Patients with AIDS‐related NHL usually do not appear to benefit from treatment with MACOP‐B protocol. Advanced immunodeficiency is associated with poor tolerance to treatment and inability to finish this chemotherapy protocol. MACOP‐B chemotherapy does not prevent meningeal spread of lymphoma in spite of using repeatedly systemic methotrexate crossing the blood‐brain barrier. CNS prophylaxis with repeated application of intrathecal methotrexate may lower the risk of meningeal spread of lymphoma, which developed in 1 of 5 patients given CNS prophylaxis as compared to 2 of 3 patients without CNS prophylaxis.

Acute and long-term efficacy of antituberculous treatment in HIV-seropositive patients with tuberculosis: A study of 36 cases

Thirty-six consecutively observed HIV-seropositive patients with tuberculosis, including 31 patients with AIDS, who received antituberculous treatment, were followed up to evaluate its efficacy. Treatment with standard antituberculous regimens was intended except when an individuals condition required a modified therapeutic approach. Therapeutic failure occurred in five patients (14%) while on treatment, one also had a post-treatment relapse. Treatment failure was associated with drug resistance and non-compliance in three patients and in another two, both of whom died early in the course of their disease, with HIV-related conditions other than tuberculosis. The median relapse-free post-treatment follow-up time in 24 patients in whom treatment did not fail was 13 months (range 4-67). Standard antituberculous treatment is highly effective in the immediate and long-term treatment of HIV-related tuberculosis provided that drug susceptibility and treatment compliance are confirmed.

MYCOBACTEREMIA IN AIDS PATIENTS. RESULTS OF A PROSPECTIVE STUDY

SummaryThe importance of blood cultures in diagnosing disseminated mycobacteriosis in AIDS patients was evaluated. Blood samples were screened for mycobacteria by culture and microscopic techniques. Mycobacteremia was proven in 20/136 (14.7%) AIDS patients, the agent being M. avium-M. intracellulare (MAI) in 16 cases and M. tuberculosis in four cases. The rate of cases with positive blood samples in disseminated MAI infection was 59.3% (16/27 cases) and in disseminated tuberculosis 57.1% (4/7 cases). To detect mycobacteria buffy-coat was slightly superior to lysated cell pellets, obtained by a lysis-centrifugation technique. In 4/16 cases with MAI bacteremia, the agent was proven by positive blood smears for acid-fast bacilli only; in these four patients MAI was demonstrated at other body sites. These results illustrate the diagnostic role of blood culture and its use in early diagnosis of disseminated mycobacteriosis, with microscopic examination of blood smears being an important adjunct.

Safety of alternating ganciclovir and foscarnet maintenance therapy in human immunodeficiency virus (HIV)-related cytomegalovirus infections. An open-labeled pilot study.

In the treatment of cytomegalovirus (CMV) disease in patients with AIDS, a life-long suppression therapy following an induction therapy consisting of ganciclovir or foscarnet is essential. Due to drug-related toxicities, anti-CMV therapy frequently has to be discontinued. To determine whether toxicities and side effects may be reduced with an alternating combination therapy consisting of ganciclovir and foscarnet (ganciclovir: 5 mg/kg every other day; foscarnet: 120 mg/kg every other day), 10 AIDS patients with CMV disease received this maintenance therapy for a median time of 18.5 weeks (5-51 weeks). Side effects were reported from 5 patients (nausea 5, malaise/fatigue 2, penile ulcers 1). Hematological or renal toxicities were mild, 1-week discontinuation of therapy due to neutropenia was necessary in 1 patient. Progression of CMV disease was observed in 3 patients at 2, 6, and 30 weeks of maintenance therapy. Median relapse-free interval for all patients was 105 days. We conclude that combination therapy with ganciclovir and foscarnet can be used safely for induction and maintenance therapy. Therefore, this regimen should be assessed in further trials to evaluate safety, efficacy, and the development of resistance in comparison to ganciclovir or foscarnet monotherapy.