levoleucovorin and HIV-Infections

Colorectal cancers are rare in developing countries, but are the second most frequent malignancy in the affluent world. Data on colorectal cancer in HIV-positive patients are limited. Up to now, there are no published data on treatment patterns, response to therapy, or survival in this setting. Oxaliplatin is an antineoplastic agent currently indicated, concomitantly to fluorouracil and leucovorin, for the treatment of advanced colorectal cancer. The FOLFOX-4 regimen (oxaliplatin 85 mg/m(2) as a two-hour infusion on day 1; leucovorin 200 mg/m(2) as a two-hour infusion on days 1 and 2, fluorouracil as a bolus infusion on days 1 and 2, followed by a fluorouracil 22-hour infusion 600 mg/m(2) for two consecutive days every two weeks), with concomitant highly active antiretroviral therapy (HAART) is feasible and active, while the HIV infection is not a limiting factor for its use. Moreover, the concomitant use of HAART does not seem to increase the toxicity of the FOLFOX-4 regimen.

Topics: Adenocarcinoma; Adult; Antineoplastic Combined Chemotherapy Protocols; Antiretroviral Therapy, Highly Active; Colorectal Neoplasms; Female; Fluorouracil; HIV Infections; Humans; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Organoplatinum Compounds; Treatment Outcome

Burkitt's lymphoma and small noncleaved Burkitt's-like lymphoma are rare and are highly aggressive forms of non-Hodgkin's lymphoma that are characterized by dysregulation of the c-myc oncogene. Patients with human immunodeficiency virus (HIV) also appear to be at risk for developing Burkitt's lymphomas. Treatment options for Burkitt's lymphoma involve complex chemotherapy regimens that contain as many as 10 cytotoxic agents. Approximately 50%-80% of adult patients with Burkitt's lymphoma or small, noncleaved lymphoma can be cured with these intensive chemotherapy regimens, and in pediatric populations, the cure rate is even higher. However, a number of factors often compromise the outcome of patients with Burkitt's lymphoma. For instance, the high proliferation rate of Burkitt's lymphoma enhances the risk for tumor lysis syndrome, which results from metabolic imbalances, such as hyperuricemia, that occur as large numbers of malignant cells are lysed during cytotoxic chemotherapy. Standard treatment for tumor lysis syndrome includes adjustments in the chemotherapy regimen, vigorous hydration, administration of a uric acid synthesis inhibitor like allopurinol, and alkalinization. The administration of recombinant urate oxidase (rasburicase) also has been shown to provide effective prophylaxis against hyperuricemia in pediatric and adult patients with hematologic malignancies. The lifetime risk of developing central nervous system disease is 20%-30% for Burkitt's lymphoma. Consequently all chemotherapy regimens with activity in Burkitt's lymphoma utilize some form of central nervous system prophylaxis, such as systemic or intrathecal methotrexate or cytarabine. In the past, patients with HIV who developed Burkitt's lymphoma often received inadequate chemotherapy doses because of their immunosuppression. With the discovery of highly active antiretroviral therapy, the ability to treat and control Burkitt's lymphoma in patients with HIV has improved.

Topics: Adult; Allopurinol; Antineoplastic Combined Chemotherapy Protocols; Antiretroviral Therapy, Highly Active; Bleomycin; Burkitt Lymphoma; Clinical Trials as Topic; Cyclophosphamide; Cytarabine; Dexamethasone; Doxorubicin; Enzyme Inhibitors; Etoposide; HIV Infections; Humans; Ifosfamide; Leucovorin; Methotrexate; Time Factors; Treatment Outcome; Urate Oxidase; Vincristine

An increased frequency of toxoplasma encephalitis, caused by Toxoplasma gondii, has been reported in AIDS patients, especially in those with CD4+ T cell counts <100 cells/μL. Several guidelines recommend the combination of pyrimethamine, sulfadiazine, and leucovorin as the preferred regimen for AIDS-associated toxoplasma encephalitis. However, it is not commonly used in China due to limited access to pyrimethamine and sulfadiazine. The synergistic sulfonamides tablet formulation is a combination of trimethoprim (TMP), sulfadiazine and sulfamethoxazole (SMX), and is readily available in China. Considering its constituent components, we hypothesize that this drug may be used as a substitute for sulfadiazine and TMP-SMX. We have therefore designed the present trial, and propose to investigate the efficacy and safety of synergistic sulfonamides combined with clindamycin for the treatment of toxoplasma encephalitis.. This study will be an open-labeled, multi-center, prospective, randomized, and controlled trial. A total of 200 patients will be randomized into TMP-SMX plus azithromycin group, and synergistic sulfonamides plus clindamycin group at a ratio of 1:1. All participants will be invited to participate in a 48-week follow-up schedule once enrolled. The primary outcomes will be clinical response rate and all-cause mortality at 12 weeks. The secondary outcomes will be clinical response rate and all-cause mortality at 48 weeks, and adverse events at each visit during the follow-up period.. We hope that the results of this study will be able to provide reliable evidence for the efficacy and safety of synergistic sulfonamides for its use in AIDS patients with toxoplasma encephalitis.. This study was registered as one of 12 clinical trials under the name of a general project at chictr.gov on February 1, 2019, and the registration number of the general project is ChiCTR1900021195. This study is still recruiting now, and the first patient was screened on March 22, 2019.

Topics: Acquired Immunodeficiency Syndrome; Adolescent; Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antiprotozoal Agents; China; Clindamycin; Drug Therapy, Combination; Female; HIV Infections; Humans; Leucovorin; Male; Prospective Studies; Pyrimethamine; Sulfadiazine; Sulfamethoxazole; Sulfonamides; T-Lymphocytopenia, Idiopathic CD4-Positive; Toxoplasma; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination; Vitamin B Complex

HIV-infected individuals present a cluster of conditions that activate or injure the vascular endothelium. The administration of folates may exert beneficial effects on endothelial function in different populations at risk for cardiovascular disease. The aim of this study was to determine the effects of 4 wk of folinic acid supplementation on forearm vascular responses during reactive hyperemia in HIV-infected patients under highly active antiretroviral therapy.. This was a prospective, randomized, double-blind, placebo-controlled trial to compare the effects of 4 wk of daily ingestion of 5 mg of folinic acid (n = 15) or placebo (n = 15). Participants had to have been on antiretroviral therapy (ART) for at least 6 mo before enrollment, with undetectable viral load, and CD4 cell count >200 cells/mm(3). Vascular function was evaluated with venous occlusion plethysmography at baseline and after 4 wk, for the determination of brachial artery reactive hyperemia, and after isosorbide dinitrate administration.. The groups were comparable. The mean age of patients was 45 y; there were eight women in each group. There was no difference regarding ART regimen. The supplementation of folinic acid produced a significant improvement in reactive hyperemia (from 14.9 to 21.2 mL•min•100 mL). The same was not observed in placebo group (from 15.3 to 14.6 mL•min•100 mL; group P, 0.017; time P < 0.001; interaction P < 0.001). Endothelium-independent responses remained unchanged.. Short-term folinic acid supplementation improved vascular reactivity in HIV-infected individuals enrolled in the studied. As folate supplementation is safe and relatively inexpensive, long-term clinical trials should be conducted.

Topics: Adult; Antiretroviral Therapy, Highly Active; Blood Pressure; Brachial Artery; Brazil; CD4 Lymphocyte Count; Dietary Supplements; Double-Blind Method; Endothelium, Vascular; Female; Forearm; HIV Infections; Humans; Leucovorin; Male; Middle Aged; Prospective Studies; Regional Blood Flow; Vasodilation; Viral Load

The safety and efficacy of a fixed 25 mg pyrimethamine-500 mg sulfadoxine combination supplemented with 15 mg folinic acid twice a week as primary prophylaxis of Pneumocystis carinii pneumonia (PCP) and toxoplasmic encephalitis was evaluated in 106 patients infected with the human immunodeficiency virus. All patients had a CD4+ T-lymphocyte count of less than 100 cells/microl at study entry. Efficacy in this single-arm open-label prospective study was analyzed on an as-treated basis. No patient received highly active antiretroviral treatment, including protease inhibitors or non-nucleoside reverse transcriptase inhibitors, while on study medication. PCP developed in four patients, one of whom had been noncompliant. No PCP episode occurred in the first year. Probabilities of freedom from PCP were 0.97 (95%CI, 0.92-1) after 24 months and 0.93 (95%CI, 0.84-1) after 36 months. Of 74 (69.8%) patients positive for anti-toxoplasma IgG antibodies, one noncompliant patient developed toxoplasmic encephalitis after 24 months. Allergic reactions were observed in 18 (17%) patients and resulted in permanent discontinuation in 7 (6.6%) patients. One (0.9%) patient who had continued prophylaxis despite progressive hypersensitivity reactions developed a serious adverse reaction (Stevens-Johnson syndrome). The median survival of study participants was 29 months, with relentless progression of AIDS accounting for most deaths. The prophylaxis regimen studied appeared safe and effective for primary prophylaxis of PCP and toxoplasmic encephalitis. Severe adverse events can likely be prevented by discontinuation of prophylaxis at the time allergic reactions are noted. Rechallenge frequently results in tolerance. Efficacy and safety compare favorably with previously studied regimens. This simple prophylactic regimen may provide a convenient alternative for patients failing or intolerant to approved regimens.

Topics: Adult; Aged; AIDS-Related Opportunistic Infections; Animals; Anti-Infective Agents; Antiretroviral Therapy, Highly Active; Drug Administration Schedule; Drug Combinations; Female; HIV Infections; Humans; Leucovorin; Male; Middle Aged; Pneumocystis; Pneumonia, Pneumocystis; Pyrimethamine; Sulfadoxine; Toxoplasma; Toxoplasmosis, Cerebral

A prospective, randomized study was conducted to evaluate the role of vitamin B12 and folinic acid supplementation in preventing zidovudine (ZDV)-induced bone marrow suppression. Seventy-five human immunodeficiency virus (HIV)-infected patients with CD4+ cell counts < 500/mm3 were randomized to receive either ZDV (500 mg daily) alone (group I, n = 38) or in combination with folinic acid (15 mg daily) and intramascular vitamin B12 (1000 micrograms monthly) (group II, n = 37). Finally, 15 patients were excluded from the study (noncompliance 14, death 1); thus, 60 patients (31 in group I and 29 in group II) were eligible for analysis. No significant differences between groups were found at enrollment. During the study, vitamin B12 and folate levels were significantly higher in group II patients; however, no differences in hemoglobin, hematocrit, mean corpuscular volume, and white-cell, neutrophil and platelet counts were observed between groups at 3, 6, 9 and 12 months. Severe hematologic toxicity (neutrophil count < 1000/mm3 and/or hemoglobin < 8 g/dl) occurred in 4 patients assigned to group I and 7 assigned to group II. There was no correlation between vitamin B12 or folate levels and development of myelosuppression. Vitamin B12 and folinic acid supplementation of ZDV therapy does not seem useful in preventing or reducing ZDV-induced myelotoxicity in the overall treated population, although a beneficial effect in certain subgroups of patients cannot be excluded.

Topics: Adult; Anemia; Bone Marrow Diseases; CD4 Lymphocyte Count; Female; Folic Acid; Hematologic Diseases; HIV Infections; Humans; Leucovorin; Male; Neutropenia; Prospective Studies; Vitamin B 12; Zidovudine

Trimethoprim-sulfamethoxazole (TMP/SMX) is the preferred agent for prophylaxis of Pneumocystis carinii pneumonia (PCP) in patients with HIV infection, but frequent adverse events limit its usefulness. Intermittent dosing and supplementation with leucovorin have been tried in attempts to improve tolerance. We evaluated these strategies in persons with advanced HIV disease.. One hundred seven patients were enrolled. All had HIV infection, < 200 CD4+ lymphocytes per mm3, and no history of PCP. Fifty-two were randomized to TMP/SMX twice daily (BID); of these, 26 were randomized to leucovorin with each dose. Fifty-five patients were randomized to TMP/SMX (BID) 3 times per week; of these, 27 were randomized to leucovorin with each dose. All patients took zidovudine concurrently.. The 24-week risk of discontinuation due to protocol-defined limiting toxicity was 24% with thrice-weekly TMP/SMX versus 42% with daily TMP/SMX (risk ratio 0.4; 95% CI 0.2 to 1.0). The risks of discontinuation for any reason were 41% and 59% (risk ratio 0.4; 95% CI 0.2 to 0.8). Clinical toxicity, such as headache and gastrointestinal distress, accounted for the observed difference in tolerance between dosing regimens. The 24-week risk of discontinuation due to protocol-defined toxicity was 33% in both the leucovorin and non-leucovorin groups (risk ratio 1.1; 95% CI 0.5 to 2.5). The risks of discontinuation for any reason were 53% and 47% (risk ratio 0.8; 95% CI 0.3 to 1.7).. Intermittent therapy with TMP/SMX BID thrice weekly is better tolerated than daily BID therapy. Leucovorin use does not improve tolerance for chronic TMP/SMX dosing in AIDS, even among patients taking tablets daily.

Topics: Adolescent; Adult; AIDS-Related Opportunistic Infections; Bone Marrow Diseases; Drug Administration Schedule; Drug Therapy, Combination; Female; HIV Infections; Humans; Leucovorin; Male; Pneumonia, Pneumocystis; Proportional Hazards Models; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Zidovudine

We conducted an open prospective clinical trial to evaluate the efficacy and toxicity of trimethoprim-sulfamethoxazole given as one double-strength tablet thrice weekly for primary and secondary prophylaxis of Pneumocystis carinii pneumonia (PCP) in human immunodeficiency virus-infected (HIV+) patients. A total of 104 HIV+ patients were evaluated, with 74 being in the primary prophylaxis group and 30 being in the secondary prophylaxis group. All except six patients received concomitant zidovudine; five patients on primary prophylaxis and one patient on secondary prophylaxis refused zidovudine. There were 70 patients evaluated for the efficacy of primary prophylaxis. The mean CD4 count was 124.4 +/- 110.1 cells per microliter. The mean follow-up time was 11.8 +/- 5.8 months (median, 12 months; range, 1 to 32 months). Two noncompliant patients developed PCP after 1 and 3 months of chemoprophylaxis. The failure rate (under the intention to treat principle) was 2 of 70 patients (2.9%; 95% confidence interval, 0.35 to 10%), or 1 per 413 patient-months of observation. There were 27 patients evaluated for the efficacy of secondary prophylaxis. The mean follow-up time was 12.4 +/- 7.2 months (median, 11 months; range, 1 to 29 months). Two patients, one of whom was noncompliant, were treatment failures, developing PCP after 14 and 15 months of chemoprophylaxis; this gave a failure rate of 2 of 27 patients (7.4%; 95% confidence interval, 0.9 to 24.3%), or 1 per 167 patient-months of observation. Adverse reactions sufficient to permanently terminate therapy occurred in 9 of 104 patients (8.7%; 95% confidence interval, 4 to 15.7%) overall. The serum trimethoprim, sulfamethoxazole, and N4-acetyl-sulfamethoxazole concentrations measured by high-pressure liquid chromatography were uniformly low. One double-strength tablet of trimethoprim-sulfamethoxazole taken weekly on Monday, Wednesday, and Friday appeared to be well tolerated and efficacious for the prophylaxis of PCP in HIV+ patients at high risk and deserves further investigation.

Topics: Adult; Chromatography, High Pressure Liquid; Complement C4; Drug Administration Schedule; Female; HIV Infections; Humans; Leucovorin; Male; Pneumonia, Pneumocystis; Prospective Studies; Sulfamethoxazole; Trimethoprim; Zidovudine

To report on a unique combination of cerebral toxoplasmosis and ocular toxoplasmosis in an HIV-positive patient in Slovakia.. A 35-year-old heterosexual patient who presented with headache and major seizures underwent computed tomography (CT) and magnetic resonance imaging (MRI). Based on clinical findings, serological tests for toxoplasmosis were performed on serum and ocular fluid specimens. PCR was also used to detect Toxoplasma gondii and cytomegalovirus DNA. Goldmann and Witmer coefficient calculation was applied to demonstrate the synthesis of intraocular IgG antibodies.. CT and MRI revealed cystic lesions suspected of metastasis in the occipital and temporal regions, and we searched for the primary tumor. After vision loss in the left eye, which rapidly progressed to complete blindness, an eye examination detected macular edema. Anti-edema treatment was initiated. HIV positivity with a very low CD4 T-cell count (20/μL) was found, and the viral load was 100 400 HIV-RNA copies/ml. The serum was positive for anti-Toxoplasma IgG antibodies (> 200 IU/mL), IgM negative, and IgA borderline. As toxoplasmic encephalitis and retinitis were suspected, antitoxoplasmic therapy with pyrimethamine, spiramycin, and folinic acid was started. The ophthalmologist considered cytomegalovirus retinitis, which was not confirmed by serology or PCR. In contrast, the presence of IgG antibodies in ocular fluid and serum with the calculation of the Goldmann-Witmer coefficient (GW = 32) as well as PCR DNA positivity pointed to Toxoplasma gondii as the etiological agent. Follow-up MRI scan confirmed regression of the pathological lesions, neurological deficit also improved, CD4 T-lymphocytes increased above 200/μL, but blindness of the left eye persisted.. CT and MRI scans offered no clue as to Toxoplasma etiology of the brain and eye involvement in an HIV-positive patient, which was only confirmed by laboratory tests. Due to the delay in the diagnosis of toxoplasmosis, time from the epileptic seizure to treatment initiation was 16 days, which assumedly caused irreversible blindness in the patient.

Topics: Adult; Antibodies, Protozoan; Blindness; Central Nervous System; HIV Infections; Humans; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Leucovorin; Pyrimethamine; RNA; Spiramycin; Toxoplasma; Toxoplasmosis

Although FOLFOX4 is considered the standard chemotherapy regimen for colorectal cancer (CRC), few data are available on its results in human immunodeficiency (HIV)-related CRC. The results were analyzed to evaluate feasibility and activity of FOLFOX4 plus highly active antiretroviral therapy (HAART) in metastatic CRC (mCRC) HIV-seropositive patients.. From January 2002 to March 2007, 24 patients were selected among the CRC HIV-seropositive patients treated with FOLFOX4 and concomitant HAART within the Italian Cooperative Group on AIDS and Tumors (GICAT).. Four median cycles of chemotherapy were administered; the most common severe toxicity was neutropenia (37.5%). An overall response rate of 50% was observed; 4.2% of patients achieved complete response and 45.8% partial response. No opportunistic infections occurred during or immediately after chemotherapy. The median CD4+ count was 380 (range 220-570) at diagnosis.. To our knowledge, this is the largest study describing activity and tolerability of FOLFOX4 and HAART, in this setting. FOLFOX4 plus concomitant HAART resulted feasible and active also in HIV-seropositive patients. Moreover, the concomitant use of HAART did not to seem to increase the FOLFOX4 toxicity. This study suggests the good tolerability of the FOLFOX4, making it a reasonable option for combination with HAART.

Topics: Adult; Anti-HIV Agents; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Antiretroviral Therapy, Highly Active; Colorectal Neoplasms; Drug Therapy; Drug-Related Side Effects and Adverse Reactions; Female; Fluorouracil; HIV Infections; Humans; Italy; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Treatment Outcome

In the era of highly active antiretroviral therapy (HAART), malignancies are the primary cause of increased mortality in patients with human immunodeficiency virus (HIV) infection, hence representing a new challenge for oncologists. To date, there is little evidence in the English literature about chemotherapy treatment in HIV-positive patients with metastatic colorectal cancer.. We describe the case of an HIV-positive 48-year-old male patient with metastatic colorectal cancer, treated with a bevacizumab, irinotecan, fluorouracil, and leucovorin regimen, with concomitant HAART. No opportunistic infections and grade 3-4 haematological and non-haematological toxicity were reported. The HIV infection was kept under control during the bevacizumab chemotherapy treatment.. This case suggests that, in the HAART era, the best multidisciplinary approaches can be offered to HIV-positive patients with metastatic colorectal cancer, who have a good performance status and a well controlled HIV infection. An HIV infection should not preclude the use of the best available chemotherapy treatment in this particular group of patients, including targeted/biological drugs.

Topics: Anti-HIV Agents; Antineoplastic Combined Chemotherapy Protocols; Antiretroviral Therapy, Highly Active; Camptothecin; Colorectal Neoplasms; Fluorouracil; HIV Infections; Humans; Irinotecan; Leucovorin; Male; Middle Aged; Treatment Outcome

Recent data have shown the efficacy of cetuximab/Folfiri regimen in patients with chemotherapy-resistant metastatic colorectal cancer. In the literature there are no data about this treatment in HIV-positive patients with metastatic colorectal cancer. At the Aviano Cancer Center, we used the cetuximab/Folfiri regimen and concomitant HAART in an HIV-positive patient with metastatic colorectal cancer. The patient experienced acceptable non-hematological toxicity, without any opportunistic infection and his HIV infection was kept under control. This case suggests that, in the HAART era, a multidisciplinary approach can be offered to HIV patients with advanced cancer when they have good performance status, resulting in efficacious control of the HIV infection.

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Antiretroviral Therapy, Highly Active; Camptothecin; Cetuximab; Colorectal Neoplasms; Female; Fluorouracil; HIV Infections; Humans; Leucovorin; Middle Aged; Neoplasm Metastasis

Congenital toxoplasmosis usually results from acquired infection in non-immune pregnant women. However, severely HIV-infected women with a latent Toxoplasma infection can transmit the parasite as a result of reactivation. We report a case of toxoplasmic reactivation in an HIV-infected woman with moderate immunosuppression resulting in a severe congenital toxoplasmosis.

Topics: Adult; Animals; Antibodies, Protozoan; Antiprotozoal Agents; Female; Fetal Blood; HIV Infections; Humans; Immunocompromised Host; Infant, Newborn; Infectious Disease Transmission, Vertical; Leucovorin; Male; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Complications, Parasitic; Pyrimethamine; Recurrence; Toxoplasma; Toxoplasmosis; Toxoplasmosis, Congenital; Vitamin B Complex

The introduction of triple antiretroviral therapy has led to reductions in opportunistic diseases in HIV-infected patients. However, little is known of the effect of this therapy on the clinical and pathological features and the outcome of patients with AIDS-related systemic non-Hodgkin's lymphoma (NHL). We examined the incidence and clinical manifestations of HIV-infected patients with systemic NHL at the Harris County Hospital District and Veterans Affairs Medical Center (Houston, TX). Between January 1996 and December 2000, 76 cases of systemic NHL were diagnosed in 3655 HIV-infected patients. Three groups of patients diagnosed with systemic NHL were identified according to their history of antiretroviral therapy: treatment naive (n = 20), dual nucleoside (n = 22), and triple antiretroviral drug-treated patients (n = 34). The median duration of antiretroviral therapy before the diagnosis of systemic NHL in the triple antiretroviral and dual nucleoside treatment groups was 12 versus 8 months (p < 0.0004). Thirty-five percent of patients (12 of 34) in the triple treatment group had an HIV RNA viral load of <400 copies/ml and their median CD4+ cell count was 301 cells/mm(3) (range, 46 to 667 cells/mm(3)) at the time of diagnosis of systemic NHL. More patients treated with triple antiretroviral therapy received complete courses of chemotherapy as compared with the other two groups (p = 0.013). However, the overall survival did not differ significantly among the three groups of patients. These data suggest that AIDS-related systemic NHL continues to occur even in patients treated with triple antiretroviral therapy. In addition, this opportunistic malignancy is associated with significant mortality. Therefore, it is necessary to develop a better understanding of the pathogenesis of this disease.

Topics: Adult; Anti-HIV Agents; Antineoplastic Combined Chemotherapy Protocols; Base Sequence; Bleomycin; CD4 Lymphocyte Count; Cyclophosphamide; Dexamethasone; DNA Primers; Doxorubicin; Female; HIV Infections; Humans; Incidence; Leucovorin; Lymphoma, AIDS-Related; Male; Methotrexate; Middle Aged; Prednisone; Texas; Treatment Outcome; Vincristine; Viral Load

The penetration of 3'-amino-3'-deoxythymidine (AMT) into the cerebrospinal fluid (CSF) of HIV-1-infected patients has been investigated. In 23 patients who used zidovudine (ZDV) chronically, CSF and plasma samples were assayed for AMT and ZDV. The influences of time between ZDV oral administration and lumbar puncture, of ZDV dose, and of the medical indication for lumbar puncture based on the concentration of AMT in CSF and on the CSF-plasma concentration ratio were investigated. AMT can be detected in the CSF after oral administration of ZDV; concentrations of AMT in CSF ranged from 0.75 to 4.8 ng/ml (median, 1.7 ng/ml). The median CSF-plasma concentration ratio was 1, and equaled that for ZDV. CSF and plasma concentrations of AMT were approximately threefold higher in patients with cerebral toxoplasmosis; the CSF-plasma concentration ratio remained equal to unity in these cases. This phenomenon might be caused by a pharmacokinetic interaction between AMT and pyrimethamine, sulfadiazine, folinic acid, or a combination of these. The clinical relevance of AMT, especially the possibility of decreased efficacy of ZDV, throughout the body and in the central nervous system, and the involvement of this metabolite in ZDV-induced myelosuppression, remains to be established.

Topics: Administration, Oral; Adult; Anti-HIV Agents; Anti-Infective Agents; Antidotes; Dideoxynucleosides; Drug Interactions; Drug Therapy, Combination; Female; HIV Infections; HIV-1; Humans; Leucovorin; Male; Middle Aged; Pyrimethamine; Spinal Puncture; Sulfadiazine; Time Factors; Toxoplasmosis, Cerebral; Zidovudine

To determine how men infected with the human immunodeficiency virus (HIV) tolerate and respond to treatment for malignant germ cell tumors (GCTs), and how GCT histology and stage compare among HIV-infected versus non-HIV-infected men.. Two hundred ninety-four cases of GCT diagnosed or treated from 1980 to 1993 were reviewed. Nine new cases among HIV-infected men were identified; these were analyzed together with six cases previously reported from our institution.. Low-stage tumors (stages I and IIA) comprised 67% of HIV-infected and 63% of non-HIV-infected cases. Sixty-seven percent of HIV-infected cases were seminomas versus 51% of non-HIV-infected cases. Ten patients had AIDS at the time of GCT diagnosis. Five patients underwent radiation therapy and one patient underwent retroperitoneal lymphadenectomy without complications. Seven patients received chemotherapy with four cycles of cisplatin, etoposide, and bleomycin (PEB) or cisplatin, vinblastine, and bleomycin (PVB) without excess cytopenias or new opportunistic infections. Of seven patients treated for advanced disease, there were five complete and two partial responses. Six patients have died of AIDS at a median of 20 months after diagnosis of GCT. The median follow-up time for surviving patients has been 42 months (range, 8 to 87) and all but one remain without evidence of active disease. In no case was a patient's HIV disease classification altered by antitumor therapy.. The natural history of GCTs is comparable in HIV-infected and non-HIV-infected men and standard therapy including orchiectomy, retroperitoneal lymph node dissection, radiation therapy, and chemotherapy is well tolerated.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Dexamethasone; Doxorubicin; Follow-Up Studies; Germinoma; HIV Infections; Humans; Leucovorin; Male; Methotrexate; Neoplasm Staging; Retrospective Studies; Seminoma; Testicular Neoplasms; Vincristine

The occurrence of HIV associated non-Hodgkin's lymphoma (NHL) is a well recognized event. HIV associated Hodgkin's disease (HD) has also been observed. A unique patient with both entities is described. The patient was a 29 year old homosexual male who developed clinical IIA nodular sclerosis HD in 1985. He was HIV + with CD4/CD8 = 0.2 and his sister had HD 20 years earlier. He received MOPP and had a complete response. In October 1988 he developed weight loss with an abdominal mass and biopsy revealed diffuse small non-cleaved NHL, with bone marrow involvement. This was his first AIDS associated illness. Probes identified clonally rearranged DNA fragments in the J region of IgH chains and clonal rearrangements in the c-myc gene were also observed but EBV sequences could not be demonstrated. He was treated with m-BACOD but died in March 1989. His course was not complicated by opportunistic infection. Possible etiologies for the HD include his HIV status or shared sibling environment. The development of the NHL may have resulted from HIV infection and/or secondary to his treatment for HD. The relationship between the two lymphomas is uncertain and factors other than HIV exposure and its immune dysfunction may have been causal.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Child; Cyclophosphamide; Dexamethasone; DNA, Neoplasm; Doxorubicin; Environmental Exposure; Female; Gene Rearrangement, B-Lymphocyte, Heavy Chain; Herpesvirus 4, Human; HIV Infections; Hodgkin Disease; Humans; Incidence; Leucovorin; Lymphoma, AIDS-Related; Lymphoma, Non-Hodgkin; Male; Mechlorethamine; Methotrexate; Neoplasms, Multiple Primary; Neoplasms, Second Primary; Prednisone; Procarbazine; Remission Induction; Vincristine