levoleucovorin and AIDS-Related-Opportunistic-Infections

The increased resistance, intolerance, or allergy to trimethoprim/sulfamethoxazole (TMP/SMX) has brought much attention to alternative treatment of pneumonia caused by Pneumocystis carinii (PCP). Pentamidine is considered when there is documented allergy or intolerance to TMP/SMX. Similarly, either dapsone/trimethoprim or clindamycin/primaquine is effective in the treatment of mild to moderate PCP, but both regimens are contraindicated in glucose 6-phosphate dehydrogenase (G6PD) deficiency. For this purpose, atovaquone should be used in patients who are deficient in G6PD or who are unable to be on TMP/SMX or pentamidine. On the other hand, in severe disease, adjunctive corticosteroids can enhance the efficacy of either TMP/SMX or pentamidine. If these therapies yield no response, trimetrexate with leucovorin has been approved as initial and salvage therapy in severe PCP. We review alternative treatment to TMP/SMX and propose ideal and practical therapeutic and prophylactic guidelines in the treatment and prevention of PCP.

Topics: Adrenal Cortex Hormones; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antifungal Agents; Atovaquone; Clindamycin; Dapsone; Drug Combinations; Drug Hypersensitivity; Drug Resistance, Microbial; Humans; Leucovorin; Naphthoquinones; Pentamidine; Pneumonia, Pneumocystis; Primaquine; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Trimetrexate

We report a case of watery diarrhea due to duodenal toxoplasmosis in a patient with the acquired immunodeficiency syndrome. Treatment with pyrimethamine, clindamycin, and folinic acid decreased the diarrhea as well as the duodenal toxoplasma cyst load. Hepatic toxoplasmosis was also present, associated with an elevated serum alkaline phosphatase activity and a minimally elevated lactate dehydrogenase level.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Clindamycin; Diarrhea; Duodenal Diseases; Humans; Intestinal Diseases, Parasitic; Leucovorin; Liver Diseases, Parasitic; Male; Prevalence; Pyrimethamine; Toxoplasmosis

Toxoplasmic encephalitis (TE) is the second most common AIDS-related opportunistic infection of the CNS. It occurs in 10%-50% of patients with AIDS who are seropositive for antibodies to Toxoplasma gondii and have CD4+ T lymphocyte counts of < 100/mm3. Primary toxoplasmic infection usually is acquired by ingestion of T. gondii oocysts from soil contaminated by cat feces or by ingestion of tissue cysts present in undercooked red meats. In patients with AIDS, TE probably results from the reactivation of Toxoplasma tissue cysts that remained latent after the primary infection. Detection of IgG antibodies to Toxoplasma indicates prior infection and the possible presence of tissue cysts and, thus, risk for developing TE. A regimen of trimethoprim-sulfamethoxazole or dapsone plus pyrimethamine with leucovorin is recommended for persons infected with the human immunodeficiency virus (HIV) and who are seropositive for IgG to Toxoplasma after their CD4+ T lymphocyte counts fall to < 100/mm3. HIV-infected persons who are seronegative for IgG to Toxoplasma should be counseled to protect themselves from primary toxoplasmic infection by eating only well-cooked meats and washing their hands after outdoor activities involving soil contact; if they have a cat, they should feed it only commercial or well-cooked foods, keep it indoors, and make sure that the litter box is changed daily. HIV-infected persons who are Toxoplasma seropositive may also be advised about these preventive behavioral practices.

Topics: AIDS-Related Opportunistic Infections; Animals; Anti-Infective Agents; Cats; Dapsone; Drug Therapy, Combination; Encephalitis; Humans; Incidence; Leucovorin; Pyrimethamine; Recurrence; Risk Factors; Toxoplasmosis, Animal; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination; United States

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

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

Pyrimethamine (50 mg) with folinic acid (15 mg) given three times weekly was assessed as primary prophylaxis for toxoplasmic encephalitis (TE) in 554 human immunodeficiency virus-infected patients seropositive for Toxoplasma gondii and with < 200 CD4 cells/mm3. At 1 year, the incidence of TE was similar in pyrimethamine, 12%, and placebo, 13%, groups (relative risk [RR], 0.9; 95% confidence interval [CI], 0.6-1.4), and the survival rate was also similar, 85% and 80%, respectively (RR, 0.9; 95% CI, 0.7-1.2). Rash was the only adverse event that appeared significantly more frequently in the pyrimethamine arm (7% vs. 1%). In the on-treatment analysis, the incidence of TE was lower in the pyrimethamine arm, 4%, than in the placebo arm, 12% (P < .006). Thus, pyrimethamine cannot be recommended as a first-line regimen for primary prophylaxis of TE if the patient can take cotrimoxazole. However, it should be considered for patients who are intolerant to cotrimoxazole, especially in high-risk patients with < 100 CD4 cells/mm3.

Topics: Adult; AIDS-Related Opportunistic Infections; Animals; Anti-Infective Agents; Antibodies, Protozoan; Double-Blind Method; Drug Therapy, Combination; Encephalitis; Female; Follow-Up Studies; Humans; Leucovorin; Male; Multivariate Analysis; Pyrimethamine; Survival Rate; Toxoplasma; Toxoplasmosis; Toxoplasmosis, Cerebral

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

Ninety-two AIDS patients with Pneumocystis carinii pneumonia (PCP) were randomized to receive folinic acid or matching placebo in conjunction with trimethoprim-sulfamethoxazole in a prospective, double-blind trial. Neither frequency of dose-limiting toxicity (26% vs. 37%; P = .4) nor time to occurrence (P = .7) was associated with folinic acid use. Although incidence of neutropenia was lower in patients receiving folinic acid (23% vs. 47%; P = .03), time to occurrence of neutropenia did not differ (P = .4). Seven (7.6%) of 92 patients with confirmed PCP met criteria for therapeutic failure, and 5 (6%) died during therapy. Surprisingly, folinic acid use was associated with a higher rate of both therapeutic failure (15% vs. 0; P = .01) and death (11% vs. 0; P = .06). Time to therapeutic failure was shorter and probability of death greater in patients receiving folinic acid (P = .005, P = .02, respectively), even when adjusted for baseline arterial oxygen pressure, serum lactate dehydrogenase, respiratory rate, CD4 cell count, and peak serum level of trimethoprim or sulfamethoxazole.

Topics: Adolescent; Adult; AIDS-Related Opportunistic Infections; Female; Humans; Incidence; Leucovorin; Male; Middle Aged; Neutropenia; Placebos; Pneumonia, Pneumocystis; Probability; Risk Factors; Treatment Failure; Trimethoprim, Sulfamethoxazole Drug Combination

Trimetrexate is a powerful inhibitor of the dihydrofolate reductase of Pneumocystis carinii. AIDS patients (n = 215) with moderate to severe P. carinii pneumonia were enrolled in a double-blind study of trimetrexate plus leucovorin versus trimethoprim-sulfamethoxazole (TMP-SMZ) for 21 days. By study day 10, study therapy failed because of lack of efficacy in 16% of patients assigned to TMP-SMZ and 27% assigned to trimetrexate (P = .064), and the PAO2-PaO2 improved significantly faster with TMP-SMZ. By study day 21, failure rates were 20% with TMP-SMZ and 38% with trimetrexate (P = .008), with respective mortality rates of 12% and 20% (P = .088). By study day 49, the difference in mortality (16% vs. 31%) was significant (P = .028). The cumulative incidence of serious and treatment-terminating adverse events including hematologic toxicities was less with trimetrexate (P < .001). Thus, trimetrexate plus leucovorin was effective, albeit inferior to TMP-SMZ, for moderately severe P. carinii pneumonia but was better tolerated than TMP-SMZ.

Topics: Adolescent; Adult; AIDS-Related Opportunistic Infections; Child; Clinical Protocols; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Leucovorin; Male; Middle Aged; Multicenter Studies as Topic; Pneumonia, Pneumocystis; Prospective Studies; Sulfamethoxazole; Treatment Outcome; Trimethoprim; Trimetrexate

Cerebral toxoplasmosis is the most frequent opportunistic infection in patients with acquired immune deficiency syndrome in France. We evaluated the effect of adding folic acid to the standard treatment (including pyrimethamine) on preventing induced cytopenia in order to determine the optimal dose.. From January to September 1990, pyrimethamine (50 mg 3 times per week) was given as primary prophylaxis against toxoplasmosis to 30 patients who were positive for human immunodeficiency virus (CDC classes II or II, CD4 counts < 200/mm3). The patients were randomly divided into three groups given 5, 25 and 0 mg folic acid 3 times per week. Associated treatments were the same in all patients (zidovudine 600 mg/d, pentamidine isethionate aerosol, 300 mg, once a month). Blood cell counts and lymphocyte subset counts were made on days 0, 30, 90 and 180.. Two patients were lost to follow-up and between day 90 and 180, 3 were excluded due to other opportunist infection and 1 due to zidovudine induced anaemia. Between the groups, there was no difference in haemoglobin level or cell counts on day 0. No haematologic toxicity was observed at day 90. Haemoglobin was significantly reduced in the control group (0 mg folic acid) on day 180 (mean haemoglobin on day 180, 13.8, 13.1 and 12.1 g/dl in groups 1, 2 and 3 respectively). No variation in polynuclear neutrophil counts was observed.. These findings suggest that folic acid has a moderate beneficial effect on preventing haematologic disease in patients treated with pyrimethamine. There was no observed dose effect.

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Blood Cell Count; Hemoglobin A; Humans; Leucovorin; Prospective Studies; Pyrimethamine; Thrombocytopenia; Toxoplasmosis, Cerebral

We measured the urine concentrations of sulfamethoxazole, sulfamethoxazole hydroxylamine, and N-sulfamethoxazole on days 3 and 10 in 15 patients with acquired immunodeficiency syndrome treated with a combination product of trimethoprim (15 mg/kg/day) and sulfamethoxazole (75 mg/kg/day). The percentage of sulfamethoxazole and metabolites excreted on days 3 and 10, respectively, were sulfamethoxazole 17.2% +/- 11.3% versus 15.6% +/- 8.2%; sulfamethoxazole hydroxylamine 2.6% +/- 2.0% versus 5.0% +/- 5.2% (p < 0.05); N-acetylsulfamethoxazole 80.0% +/- 12.9% versus 79.8% +/- 11.8%. The percentage of sulfamethoxazole hydroxylamine excreted was similar between the eight patients who discontinued therapy because of toxicity and the seven patients who did not (2.9% +/- 2.3% versus 2.3% +/- 2.0%, p = 0.7). In two patients who had major liver toxicity the percentage of sulfamethoxazole hydroxylamine excreted was significantly lower than that of the 13 patients who did not (0.8% +/- 0.1% versus 2.9% +/- 2.0%, p < 0.05). This is the first report of the formation and excretion of sulfamethoxazole hydroxylamine in patients with acquired immunodeficiency syndrome. With 15 patients we were unable to show a significant correlation between the percentage of sulfamethoxazole hydroxylamine excreted and adverse reactions. However, patients with liver toxicity excreted less sulfamethoxazole hydroxylamine.

Topics: Administration, Oral; Adult; AIDS-Related Opportunistic Infections; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Injections, Intravenous; Leucovorin; Male; Middle Aged; Pneumonia, Pneumocystis; Sulfamethoxazole; Trimethoprim, Sulfamethoxazole Drug Combination

The use of full-dose intensive regimens of chemotherapy in patients with HIV-associated lymphoma has often resulted in severe toxicity, treatment delay, and reduced subsequent dosing. We conducted a Phase I trial to evaluate the toxicity of the combination of m-BACOD (methotrexate, Bleomycin, doxorubicin, cyclophosphamide, vincristine, dexamethasone) with granulocyte-macrophage colony stimulating factor (GMCSF) in these patients. A total of 17 patients were entered and treated at three dose levels of m-BACOD in combination with a fixed dose of GMCSF. Eight patients received standard dose m-BACOD plus GMCSF without experiencing dose-limiting hematologic toxicity, although significant nonhematologic toxicity was seen. We conclude that it is feasible to treat patients with HIV-associated lymphoma using standard dose m-BACOD plus GMCSF, but further study is needed to determine whether full-dose regimens improve survival when compared with reduced dose regimens in these individuals.

Topics: Adult; AIDS-Related Opportunistic Infections; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Dexamethasone; Doxorubicin; Granulocyte-Macrophage Colony-Stimulating Factor; HIV Core Protein p24; Humans; Kidney; Leucovorin; Leukocyte Count; Lung; Lymphoma, AIDS-Related; Lymphoma, Non-Hodgkin; Male; Methotrexate; Neutropenia; Remission Induction; Vincristine

Current treatment options for acquired-immunodeficiency syndrome (AIDS)-related non-Hodgkin's lymphoma (NHL) are unsatisfactory because of excessive toxicity rates and frequent recurrence of lymphoma. In this phase II study, we evaluated a novel 12 week chemotherapy program with respect to feasibility, toxicity and therapeutic results. Thirty HIV-seropositive patients with intermediate grade or small non-cleaved cell NHL received a 12 week program of weekly intravenous and oral chemotherapy consisting of etoposide, adriamycin, cyclophosphamide, bleomycin, vincristine, methotrexate and prednisone as well as biweekly intrathecal cytosine arabinoside. Prophylaxis against Pneumocystis carinii pneumonia (PCP) and candida were given routinely. The overall objective response rate was 73% with 33% complete responders. The time to progression for those stable or responding was 9.4 months. Five of 10 complete responders are well and free of disease 13.2 to 24.5 months from diagnosis. Median survival for the 30 patients was 8.1 months. NHL was the most common cause of death (13/22); opportunistic infection caused only one death (cryptococcal meningitis). Only 1 case of PCP occurred. The major toxicity was neutropenia. In conclusion this regimen resulted in response rates similar to other reports with acceptable toxicity and a very low incidence of PCP. Relapse of NHL remains a major challenge, however, and further studies are needed. Routine PCP prophylaxis should be incorporated into new trials of therapy for AIDS-related NHL.

Topics: Adult; Aged; AIDS-Related Opportunistic Infections; Antineoplastic Combined Chemotherapy Protocols; Bacterial Infections; Bleomycin; Cyclophosphamide; Doxorubicin; Feasibility Studies; Female; Humans; Incidence; Leucovorin; Life Tables; Lymphoma, AIDS-Related; Male; Methotrexate; Middle Aged; Neutropenia; Pentamidine; Pneumonia, Pneumocystis; Prednisone; Remission Induction; Survival Analysis; Treatment Outcome; Vincristine

Toxoplasmosis is an important cause of enhancing brain lesions in patients with acquired immunodeficiency syndrome (AIDS), and it is typically associated with low CD4-lymphocyte counts. Extensive toxoplasma encephalitis when the CD4-lymphocyte count is above 100 cells/µl is unusual. Cavitary lung lesions are also not typically associated with toxoplasmosis. Here, we present a case of toxoplasmosis associated with extensive brain masses and cavitary lung lesions, both of which improved with directed toxoplasmosis therapy, in an AIDS patient with a CD4 cell count of 120 cells/µl.

Topics: Acquired Immunodeficiency Syndrome; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antibodies, Protozoan; Antiprotozoal Agents; Brain; CD4 Lymphocyte Count; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Heterocyclic Compounds, 3-Ring; Humans; Leucovorin; Magnetic Resonance Imaging; Male; Middle Aged; Oxazines; Piperazines; Polymerase Chain Reaction; Pyridones; Toxoplasma; Toxoplasmosis, Cerebral; Treatment Outcome

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Antiprotozoal Agents; Antiretroviral Therapy, Highly Active; Cerebral Hemorrhage; Headache; Hemianopsia; Humans; Leucovorin; Magnetic Resonance Imaging; Male; Paresis; Pyrimethamine; Sulfadiazine; Tomography, X-Ray Computed; Toxoplasmosis, Cerebral

The best management strategy for HIV patients who fail to respond to first-line therapy for Pneumocystis jirovecii pneumonia is currently unclear. We identified all patients who were treated with trimetrexate and folinic acid who failed 7 or more days of cotrimoxazole, clindamycin-primaquine or dapsone-trimethoprim between 1996 and 2006. Trimetrexate was tolerated in 100% of cases with no treatment termination secondary to adverse drug reactions. Despite severe disease, 71% of patients were alive after 12 weeks.

Topics: Adult; AIDS-Related Opportunistic Infections; Antifungal Agents; Drug Evaluation; Drug Therapy, Combination; Female; HIV-1; Humans; Leucovorin; Male; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Retrospective Studies; Salvage Therapy; Treatment Outcome; Trimetrexate

To report a case of toxoplasmosis with optic nerve and orbital involvement as the initial presentation of HIV infection.. Case report.. A 46-year-old zookeeper, who had had right central retinal vein occlusion (CRVO) 2 weeks previously, presented with painless lid and conjunctival swelling and profound visual loss in his right eye (RE). Examination revealed no light perception (NLP) RE with axial proptosis and ocular motility restriction; fundal examination revealed a clinical picture of an ischaemic CRVO. MRI of the brain and orbit showed ring-enhancing targetoid lesions in the brain and inflammatory changes in the right optic nerve, extraocular muscles and orbital fat. He was subsequently found to be HIV positive and had positive toxoplasma IgG serology.. Immunocompromised individuals have an increased likelihood for more severe and atypical presentations; this highlights the need for increased index of suspicion for HIV infection as ocular or orbital disease may be the first manifestation of life-threatening systemic toxoplasmosis.

Topics: AIDS-Related Opportunistic Infections; Anti-Retroviral Agents; Blepharitis; CD4 Lymphocyte Count; Conjunctivitis; Drug Therapy, Combination; HIV Seropositivity; Humans; Leucovorin; Magnetic Resonance Imaging; Male; Methylprednisolone; Middle Aged; Optic Nerve Diseases; Orbital Pseudotumor; Pyrimethamine; Retinal Vein Occlusion; Sulfadiazine; Toxoplasmosis, Ocular

Pneumocystis carinii is a common cause of pneumonia in patients with AIDS, however, the incidence has dropped with the availability of effective prophylactic regimens. First-line treatment for both acute Pneumocystis pneumonia and chronic prophylaxis is trimethoprim/sulfamethoxazole (TMP/SMX). This combination can cause hypersensitivity reactions as well as myelosuppression. The simultaneous administration of leucovorin during acute treatment has been shown to reduce the incidence of neutropenia, but may interfere with the efficacy of TMP/SMX. We report a case of P. carinii pneumonia in a patient with AIDS who failed TMP/SMX prophylaxis while taking leucovorin.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Drug Therapy, Combination; Humans; Leucovorin; Male; Pneumocystis; Pneumonia, Pneumocystis; Treatment Failure; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Anti-Infective Agents; Antiprotozoal Agents; Antitubercular Agents; Antiviral Agents; Clarithromycin; Cytomegalovirus Infections; Drug Therapy, Combination; Ethambutol; Ganciclovir; Humans; Leucovorin; Mycobacterium avium-intracellulare Infection; Pneumonia, Pneumocystis; Pyrimethamine; Recurrence; Rifabutin; Sulfadiazine; Sulfamethoxazole; Toxoplasmosis; Trimethoprim

Topics: Adult; AIDS-Related Opportunistic Infections; Anemia, Megaloblastic; Antifungal Agents; Humans; Leucovorin; Male; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

As more drugs are approved for the prevention of opportunistic infections, concerns regarding the benefits and potential risks of these therapies are arising. A synopsis of the data for prophylaxis against opportunistic infections is provided for the following: Pneumocystis carinii pneumonia, fungal infections, Mycobacterium avium complex, cytomegalovirus infections, and toxoplasmosis. General precautions in using preventive medications for people with fewer than 100 CD4 plus cells are highlighted.

Topics: Acyclovir; AIDS-Related Opportunistic Infections; Clarithromycin; Clindamycin; Clinical Trials as Topic; Clotrimazole; Cytomegalovirus Infections; Dapsone; Fluconazole; Ganciclovir; Humans; Itraconazole; Leucovorin; Mycobacterium avium-intracellulare Infection; Mycoses; Pentamidine; Pneumonia, Pneumocystis; Pyrimethamine; Rifabutin; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination; Valacyclovir; Valine

Topics: Adult; AIDS-Related Opportunistic Infections; Drug Therapy, Combination; Female; Humans; Kidney Calculi; Leucovorin; Male; Pyrimethamine; Sulfadiazine; Toxoplasmosis, Cerebral

A presumptive diagnosis of toxoplasmic encephalitis was made in 73 of the 428 AIDS patients followed in the Bordeaux Regional Hospital between 1985 and 1990. The sex ratio (M:F) was 2.8:1. The mean age was 36.2 years. Forty-three percent were homosexuals, 30 percent intravenous drug abusers. The encephalitis revealed the HIV infection in 10 percent of the cases; it was the first opportunistic infection in 27 percent. The clinical manifestations were: focal neurologic deficit (62 percent), fever (58 percent), headaches (47 percent), altered consciousness (45 percent), seizures (18 percent). The CT scan findings were focal lesions with (60 percent) or without (40 percent) ring enhancement. Oedema was present in 58 percent of the lesions, and multiple lesions in 59 percent. At the time of diagnosis, the mean CD4 lymphocyte count was 72 per mm3. The initial therapeutic regimens were: pyrimethamine (P) plus sulfadiazine (n = 57), P plus clindamycin (n = 11) and P plus clarithromycin (n = 5). Following acute therapy the patients had a complete (64 percent) or partial (18 percent) response, and 18 percent died. Adverse reactions were noticed in 53 percent. Sixty patients received a maintenance therapy; after a mean follow-up of 8 months, 12 relapsed and died of toxoplasmic encephalitis; 17 died of another cause. The median survival after toxoplasmosis was diagnosed was 7.5 months.

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Clarithromycin; Clindamycin; Drug Therapy, Combination; Female; France; Humans; Leucovorin; Male; Middle Aged; Pyrimethamine; Recurrence; Retrospective Studies; Sulfadiazine; Tomography, X-Ray Computed; Toxoplasmosis, Cerebral