didanosine and Pneumonia--Pneumocystis

The transmission, diagnosis, and clinical manifestations of human immunodeficiency virus (HIV) infection in children up to 13 years of age are reviewed, and maintenance and prophylactic drug therapies for these patients are discussed. HIV can be transmitted from mother to infant in utero, during delivery, or through breast milk. Perinatal transmission accounts for almost 90% of all pediatric HIV infections. HIV infection can be diagnosed with HIV culturing, polymerase chain reaction testing, the enzyme-linked immunosorbent assay, the Western blot antibody assay, or the p24 core-antigen assay. Testing should begin as soon as possible after the at-risk child reaches one month of age. CD4+ lymphocyte counts are also used in diagnosis and monitoring. The median age at diagnosis of AIDS in children with perinatally acquired HIV infection is 12-24 months. Among the many possible clinical features are Pneumocystis carinii pneumonia (PCP), cytomegalovirus infection, failure to thrive, encephalopathy, recurrent bacterial infection, thrush, lymphoid interstitial pneumonitis, lymphadenopathy, pancreatis, hepatitis, anemia, and thrombocytopenia. Zidovudine is considered the drug of choice for initial therapy in HIV-infected children and is indicated for asymptomatic infection, early symptomatic disease, and advanced disease. However, new research is questioning the role of zidovudine monotherapy. Didanosine is the only agent with FDA-approved labeling for use as second-line therapy in children who do not respond to or become resistant to zidovudine. Agents under investigation for pediatric use are zalcitabine, stavudine, lamivudine, and nevirapine. Drug combinations, such as zidovudine plus didanosine, are also being examined. Zidovudine appears to reduce the rate of maternal transmission of HIV. Agents used prophylactically against PCP in children are trimethoprim-sulfamethoxazole, dapsone, and inhaled or i.v. pentamidine. HIV-infected children should also received prophylaxis against recurrent bacterial infections. The standard pediatric immunization schedule is used, but inactivated injectable poliovirus vaccine must be given instead of the live oral vaccine. Zidovudine remains the first-line agent for treating HIV infection in children. Alternatives are available for those who do not respond to zidovudine.

Topics: Adolescent; AIDS-Related Opportunistic Infections; Child; Child, Preschool; Dapsone; Didanosine; Drug Interactions; Drug Therapy, Combination; Female; HIV Infections; Humans; Male; Pentamidine; Pneumonia, Pneumocystis; Pregnancy; Pregnancy Complications, Infectious; Recurrence; Stavudine; Trimethoprim, Sulfamethoxazole Drug Combination; Zalcitabine; Zidovudine

Topics: CD4-Positive T-Lymphocytes; Clinical Protocols; Clinical Trials as Topic; Didanosine; Drug Monitoring; HIV Infections; HIV-1; Humans; Immunization; Leukocyte Count; Pneumonia, Pneumocystis; Primary Health Care; Sex Counseling; Zidovudine

Clinical trials often assess therapeutic benefit on the basis of an event such as death or the diagnosis of disease. Usually, there are several additional longitudinal measures of clinical status which are collected to be used in the treatment comparison. This paper proposes a simple non-parametric test which combines a time to event measure and a longitudinal measure so that a substantial treatment difference on either of the measures will reject the null hypothesis. The test is applied on AIDS prophylaxis and paediatric trials.

Topics: Acquired Immunodeficiency Syndrome; Anti-HIV Agents; Anti-Infective Agents; Antifungal Agents; Candidiasis; Child; Child, Preschool; Clinical Trials as Topic; Clotrimazole; Dapsone; Didanosine; Drug Therapy, Combination; Fluconazole; Head; Humans; Longitudinal Studies; Pentamidine; Pneumonia, Pneumocystis; Statistics, Nonparametric; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Zidovudine

The pattern of the development of opportunistic infections (OIs) in HIV-infected patients was evaluated, based on a cohort of 1,530 patients enrolled in two AIDS Clinical Trials Group anti-retroviral studies. We quantified the increase in risk of OIs associated with the occurrence of a previous OI. This assessment was based on the observed event rates of the more common AIDS-defining OIs: Pneumocystis carinii pneumonia (PCP), Mycobacterium avium complex (MAC), cytomegalovirus (CMV), and a systemic mycosis. Additionally, for each OI, we assessed the relative risks associated with a history of prior OIs, changes in CD4 levels, and baseline prognostic factors. We found that the occurrence of each of these OIs increased the risk of subsequent OIs, even after adjusting for the CD4 count. Specifically, the occurrence of PCP significantly increased the risk of MAC and CMV, and somewhat increased the risk of systemic mycoses. Diagnosis with MAC was associated with an increased risk of subsequent CMV, whereas the occurrence of CMV increased the risk of MAC. Finally, once patients were diagnosed with a systemic mycosis, they were at a somewhat increased risk of subsequently developing MAC or CMV. Although current practice for determining the timing and initiation of prophylactic therapies relies chiefly on CD4 count, the occurrence of specific AIDS-defining OIs in patients with HIV infection should also be taken into account in making decisions regarding prophylaxis strategies.

Topics: Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; CD4 Lymphocyte Count; Cohort Studies; Cytomegalovirus Infections; Didanosine; Double-Blind Method; Female; HIV Infections; HIV-1; Humans; Male; Mycobacterium avium-intracellulare Infection; Mycoses; Pneumonia, Pneumocystis; Prospective Studies; Retrospective Studies; Risk Factors; Survival Rate; Zidovudine

Drug therapies for patients with human immunodeficiency virus (HIV) infection are associated with adverse events that can potentially limit their effectiveness. We sought to quantify the incidence of these events in clinical practice and determine whether there were demographic and clinical differences in adverse event rates for these drugs.. We calculated specific and overall adverse event rates from use of zidovudine, didanosine, zalcitabine, cotrimoxazole, and dapsone in an observational urban cohort of 1,450 HIV-infected patients with a CD4+ count of 500 cells/mm3 or less. We compared adverse event rates by gender, race, age, injecting drug use, and CD4+ count.. Overall adverse event rates in order of incidence were dapsone, 16.2 per 100 person-years (PY); didanosine, 24.1 per 100 PY; zidovudine, 26.3 per 100 PY; cotrimoxazole, 26.3 per 100 PY; and zalcitabine, 37.0 per 100 PY. Rates increased significantly with decline in CD4+ count from > 200 to < 100 cells/mm3 for all drugs but dapsone. In addition, women were more likely than men to have an adverse event for didanosine (relative risk [RR] = 2.7, P = 0.03) and from cotrimoxazole (RR 1.5; P = 0.05). Whites were at greater risk than blacks for adverse events from cotrimoxazole (RR = 1.6, P = 0.03). Only 22 of 357 total events (6%) required hospitalization, and there were no deaths.. Adverse events from antiretroviral drugs and Pneumocystis carinii pneumonia prophylaxis that interrupt therapy are relatively common, although serious events requiring hospitalization are rare. Adverse event rates increase progressively with decline in CD4+ count. The gender and race of the patient modify the risk of adverse events for some drugs.

Topics: Adult; Antiviral Agents; CD4 Lymphocyte Count; Dapsone; Didanosine; Female; HIV Infections; Humans; Male; Pneumonia, Pneumocystis; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination; Urban Health; Zalcitabine; Zidovudine

Topics: Acquired Immunodeficiency Syndrome; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Antiprotozoal Agents; Antiviral Agents; Atovaquone; Candidiasis, Oral; Clindamycin; Clotrimazole; Cryptosporidiosis; Cytomegalovirus Infections; Dapsone; Didanosine; Drug Combinations; Drug Therapy, Combination; Fluconazole; Flucytosine; Folic Acid Antagonists; Foscarnet; Glucuronates; Herpes Simplex; Herpes Zoster; Humans; Isoniazid; Itraconazole; Ketoconazole; Lamivudine; Mycobacterium avium-intracellulare Infection; Naphthoquinones; Nystatin; Pentamidine; Pneumocystis Infections; Pneumonia, Pneumocystis; Prednisone; Primaquine; Reverse Transcriptase Inhibitors; Stavudine; Syphilis; Toxoplasmosis; Trimetrexate; Tuberculosis; Zalcitabine; Zidovudine

NIAID's AIDS Clinical Trials Group (ACTG) has completed several studies and their findings are reported. Findings from two studies, ACTG 081, involving three therapies for pneumonia prevention, and ACTG 981, examining fluconazole for preventing fungal infections, are reported in The New England Journal of Medicine (March 16, 1995). Other studies reviewed include ACTG 152, using AZT alone and in combination in children, and ACTG 204, examining the effectiveness of valacyclovir and two different doses of acyclovir in preventing cytomegalovirus end stage-organ disease and survival extension.

Topics: Acyclovir; Child; Clinical Trials as Topic; Cytomegalovirus Infections; Didanosine; Drug Therapy, Combination; Fluconazole; HIV Infections; Humans; Mycoses; Pneumonia, Pneumocystis; Valacyclovir; Valine; Zidovudine

To report a case of an HIV-positive man who received sequential didanosine and pentamidine treatment and subsequently developed acute clinical pancreatitis.. In June 1992 didanosine 200 mg po bid was initiated in a 30-year-old man with AIDS. After a 22-week course of didanosine, the patient was hospitalized and didanosine was discontinued on day 4. The patient then received 8 days of treatment for a presumed Pneumocystis carinii pneumonia (PCP) with pentamidine 4 mg/kg/d iv. As the patient responded clinically to therapy, he was discharged home to complete a 21-day course of pentamidine. On day 14 of therapy, the patient experienced nausea, vomiting, diarrhea, fatigue, and was hypotensive. The dosage of pentamidine was reduced by 50 percent. After receiving 18 doses of pentamidine, treatment was discontinued, as symptoms had worsened and serum amylase and lipase concentrations were elevated. The patient was hospitalized and the diagnosis of acute clinical pancreatitis was made. After a 21-day hospitalization, the patient was discharged home in fair condition on hyperalimentation.. Potential causes of pancreatitis, including opportunistic infections, neoplasms, and drugs, are discussed. The most probable factors associated with pancreatitis in our patient are didanosine and pentamidine therapy.. As our patient developed pancreatitis following sequential administration of didanosine and pentamidine, it would be prudent to monitor for signs and symptoms of pancreatitis in similar cases. In addition, didanosine should be discontinued during and for one week following treatment of PCP when pentamidine is used.

Topics: Acquired Immunodeficiency Syndrome; Acute Disease; Adult; Didanosine; Humans; Infusions, Intravenous; Male; Pancreatitis; Pentamidine; Pneumonia, Pneumocystis

We studied the association between socioeconomic status and survival in a prospective study of 364 HIV-infected homosexual men who were recruited during 1982-84. The participants were divided by annual income; those earning above Canadian $10,000 (high-income; n = 274) and those below $10,000 (low-income; n = 90) at recruitment. The latter threshold closely approximated to the poverty level for this population. Low income men were significantly younger than high income men but the groups were similar with respect to baseline CD4 counts, subsequent use of anti-retrovirals and prophylaxis against Pneumocystis carinii pneumonia (PCP), and number of visits attended during follow-up. Subjects were followed for a median of 9.5 years (range 1.8-13.1). By Dec 31, 1993, there were 135 deaths yielding a cumulative mortality rate of mean 45% (SD 4.0) at 11.5 years. Men aged 30 or more at infection had poorer survival than those under 30 (mortality risk ratio 1.56; 95% CI 1.09-2.24; p = 0.015), and longer survival was significantly associated with a higher CD4 count at the earliest seropositive visit. The age-adjusted mortality risk ratio for low income men compared with high income men was significantly increased at 1.63 (95% CI 1.11-2.40; p = 0.013). The significant risk of death for low income men persisted despite adjustment for age at infection, CD4 count, use of zidovudine, dideoxyinosine, and dideoxycytidine, use of PCP prophylaxis, and year of infection. We cannot attribute our findings to income loss as a result of more rapid HIV progression because the same effect was present in people who provided income data before seroconversion. Similarly, our findings are not due to differential access to care because the study was done within the context of a universal health care system, and the two income groups received treatments equally. This finding is consistent with the association of lower socioeconomic status with increased morbidity and mortality observed within large populations and in other diseases.

Topics: Acquired Immunodeficiency Syndrome; Adult; British Columbia; CD4 Lymphocyte Count; Cohort Studies; Didanosine; Health Services; HIV Infections; HIV Seropositivity; Homosexuality, Male; Humans; Income; Male; Pneumonia, Pneumocystis; Regression Analysis; Socioeconomic Factors; Survival Rate; Zalcitabine; Zidovudine

Topics: Dapsone; Didanosine; Drug Interactions; HIV Infections; Humans; Pneumonia, Pneumocystis; Retrospective Studies; Rifampin

Topics: Accidents, Occupational; Adjuvants, Immunologic; AIDS-Related Opportunistic Infections; Animals; Carrier State; Didanosine; Female; HIV Infections; Humans; Immunologic Factors; Male; Needles; Pneumonia, Pneumocystis; Zidovudine

Using data from the San Francisco Men's Health Study and the San Francisco General Hospital Cohort, we derived partially population-based estimates of human immunodeficiency virus (HIV) antiretroviral therapy and Pneumocystis carinii prophylaxis use in HIV-infected men in 1991. Zidovudine, didanosine, and dideoxycytidine were the antiretroviral therapies and aerosolized pentamidine, trimethoprim-sulfamethoxazole, and dapsone were the Pneumocystis prophylaxis evaluated. Among 81 men (29 of whom had AIDS) with < or = 200 CD4 cells, 76 (94%) had ever used and 56 (69%) were currently using an antiretroviral drug; 73 (90%) had ever used and 61 (75%) were currently using Pneumocystis prophylaxis. Among 127 men with 201-499 CD4 cells, 95 (75%) had ever used and 81 (64%) were currently using antiretroviral therapy; 49 (39%) had ever used and 36 (28%) were currently using Pneumocystis prophylaxis. Among 122 men with > or = 500 CD4 cells, 29 (24%) were currently receiving antiretroviral therapy. Forty-three men had discontinued antiretroviral therapy, 29 (67%) because of side effects. Thirty-seven men with < or = 500 CD4 cells had never used antiretroviral drugs: 48% because of feeling well and 28% because of possible side effects. Compared with 1987-1989, there were substantial increases in both antiretroviral therapy and anti-Pneumocystis prophylaxis use.

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antiviral Agents; Cohort Studies; Dapsone; Didanosine; Drug Combinations; Follow-Up Studies; HIV Infections; Humans; Male; Pentamidine; Pneumonia, Pneumocystis; San Francisco; Sulfamethizole; Trimethoprim; Zalcitabine; Zidovudine

Topics: Dapsone; Didanosine; Humans; Pneumonia, Pneumocystis