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Factors related to virologic failure among HIV-positive injecting drug users treated with combination antiretroviral therapy including two nucleoside reverse transcriptase inhibitors and nevirapine.

Treatment strategies in human immunodeficiency virus (HIV)-positive active injecting drug users (IDUs) must take into account their lifestyles, that often result in low adherence to therapy. The nonnucleoside reverse transcriptase inhibitors (NNRTI) offer simpler treatment regimens, but the appearance of drug resistance during treatment failure may cause high levels of cross-resistance to all NNRTIs. We adopted a combination therapy of two NRTIs and nevirapine (NVP) for treatment of IDU patients to evaluate its feasibility in such patients. From October 1998 to December 1999, demographic, clinical, and laboratory data from 80 IDUs on this regimen were collected. Fisher's exact test, Kaplan Meier method, and Cox model were used for statistical analysis. Overall, 20 IDUs discontinued the treatment because of side effects and 20 IDUs experienced treatment failure. Considering the treatment failure as an end point, 55.6% (95% confidence interval [CI]: 37.9%-72.6%) of patients was still undergoing treatment after 12 months compared to 44.6% (31.8%-58.6%) when discontinuation was also taken into account. An increasing trend over time was observed in the CD4+ lymphocyte count, among failing and nonfailing IDUs. By multivariate analysis, baseline HIV-RNA, treatment breaks and low adherence and active injecting drug use turned out to be significantly associated with treatment failure. Our results show that continuing injecting drug use and treatment breaks are the main factors that can lead to treatment failure in IDUs and easily to NNRTI class resistance.

Adult↗

A randomized, double-blind, phase I/II trial of tumor necrosis factor and interferon-gamma for treatment of AIDS-related complex (Protocol 025 from the AIDS Clinical Trials Group).

To determine safety and efficacy of tumor necrosis factor (TNF) and interferon-gamma (IFN gamma) in the treatment of patients with acquired immunodeficiency syndrome (AIDS)-related complex, a randomized, double-blind study was conducted. Twenty-five patients with AIDS-related complex and CD4 lymphocytes less than or equal to 500 x 10(6)/L attended an AIDS Clinical Trials Unit of a tertiary referral center. Patients were administered tumor necrosis factor (TNF) (10 micrograms/m2) or IFN gamma (10 micrograms/m2), or both intramuscularly three times weekly for 16 weeks. Side effects from all three preparations included fever, constitutional symptoms, and local reactions. No significant hematologic, hepatic, renal, or coagulation abnormalities were observed. CD4 lymphocyte counts, beta 2-microglobulin, p24 antigen levels, and anti-p24 antibody did not change significantly during therapy. Similarly, no significant change was noted in rates of HIV isolation from peripheral blood mononuclear cells or plasma. TNF and IFN gamma were tolerable after premedication with acetaminophen; however, no significant change in markers of human immunodeficiency virus infection was demonstrated. These cytokines alone do not appear to be of benefit, nor do they appear to hasten the progression of HIV infection.

AIDS-Related Complex↗

Psychological adjustment and suicidal ideation in patients with AIDS.

This article assesses the psychosocial adjustment to illness and examines the relationship between adjustment and psychosocial and medical variables in 91 ambulatory HIV-infected patients. The 91 subjects were receiving ambulatory medical care in hospitals (Memorial Hospital, New York Hospital, and St. Vincent's Hospital) and in private medical consult (Gay Men's Health Crisis) in New York. The majority (74.5%) of subjects had AIDS. The sample was composed principally of white Roman Catholic homosexual men living alone. However, 49.5% were black or hispanic, 31.9% had intravenous drug use as their HIV risk behavior, 54.9% had past psychiatric history (including illegal drug use), and 22% had previous suicide attempts. Self-report measures of psychological adjustment (Psychological Adjustment to Illness Scale), mood (Brief Symptom Inventory), physical (PHYS) and psychological (PSYCH) symptoms from the Memorial Symptom Assessment Scale-Short Form (MSAS-SF), social support (Social Support Questionnaire-Short Report), suicidal ideation (Scale for Suicide Ideation Self-Report), and measures of disease status (Karnofsky Performance Rating Scale, HIV CDC Classification, and Absolute CD4+ Lymphocyte Count) were used in the study. The average age of subjects was 40 years (SD = 6.80). fifty-two (63.4%) subjects acknowledged some indication of suicidal ideation. Variables that correlated with poor medical adjustment (health-care posture) were current suicide ideation (0.32, p = 0.003), number of psychological symptoms (0.45, p = 0.0001), physical symptoms (0.31, p = 0.006), social support (-0.24, p = 0.03), and satisfaction with the social support received (-0.36, p = 0.001). Poor sexual adjustment was related to current suicide ideation (0.39, p = 0.0004), number of psychological symptoms (0.40, p = 0.0003), satisfaction with the social support received (-0.28, p = 0.01), and number of physical symptoms (0.35, p = 0.002). In patients with a diagnosis of AIDS, the number of psychological symptoms (Beta = 0.29, R2 = 0.07, p = 0.02) and the satisfaction with the social support received (Beta = -0.38, R2 = 0.14, p = 0.003) were clear predictors of poor medical adjustment (health-care posture). Likewise, the predictors of poor sexual adjustment were psychological symptoms (Beta = 0.33, R2 = 0.10, p = 0.003) and suicidal ideation (Beta = 0.40, R2 = 0.10, p = 0.002). The results suggest that suicide ideation is associated with poor adjustment, rather than serving as an adaptive function, as has been suggested by others.

Acquired Immunodeficiency Syndrome↗

A controlled, Phase 1 clinical trial to evaluate the safety and effects in HIV-1 infected humans of autologous lymphocytes transduced with a ribozyme that cleaves HIV-1 RNA.

This Phase I study, "Ribozyme Gene Therapy of HIV-1 Infection" (UCSD HSC #971072, FDA BB-IND 6405), is a prospective, open-label trial of infusion of autologous gene-altered cells into asymptomatic HIV-1 seropositive individuals. The objectives of this trial are to test the safety, feasibility, and potential efficacy of T-cell ribozyme gene therapy of HIV-1 infection. To accomplish this, autologous CD8-depleted mononuclear cells are transduced with ribozyme expressing or control murine retroviral vectors, expanded ex vivo, and and infused. Subjects are monitored intensively to determine effects of infusion on HIV burden and replication. In addition, in vivo survival of control and ribozyme transduced cells is followed in an effort to obtain evidence of proof of concept. A unique strategy of sample blinding is introduced in this protocol, wherein both subject and control specimens are supplied to the research laboratory as coded samples, spiking blood from HIV seropositive volunteers matched for CD4 lymphocyte count with known but varying numbers of cells transduced with each vector. While this study is still in progress, preliminary results indicate that infusion of gene-altered, activated T-cells in HIV infected patients is safe, and that transduced cells can persist for long intervals in HIV-infected subjects. Results also suggest ribozyme transduced cells may possess a survival advantage in vivo.

Clinical Protocols↗

Changing trends in clinical AIDS presentations and survival among HIV-1-infected women.

OBJECTIVES: To profile trends of clinical AIDS-defining illness (ADI) among a cohort of human immunodeficiency virus (HIV)-infected women over a 12-year period. METHODS: In a prospective evaluation of AIDS clinical presentation in the Women and Infants Transmission Study (WITS), 2255 subjects were enrolled and followed between December 1989 and June 2002 (total, 4993 person-years). Data on clinical AIDS presentation of 140 (6.2%) HIV-seropositive subjects were evaluated across three calendar periods corresponding to the use of different therapy regimens. Incidence rates (per 1000 woman-years) for AIDS and specific ADIs were compared between periods using Poisson regression methods. RESULTS: Incidence rates of AIDS, Mycobacterium tuberculosis, recurrent bacterial pneumonia, herpes simplex disease, esophageal/bronchial candidiasis, wasting syndrome, and neurological diseases have showed significant downward trends. Among women with ADI, the frequency of either esophageal or bronchial candidiasis as initial ADI showed an increasing trend (p(trend) = 0.03), whereas a decrease in proportion of cases with nontuberculosis mycobacterial infection (P(trend) = 0.05) was observed over the same periods. In the multivariate analysis, both the CD4+ lymphocyte count and HIV-1 RNA at the time of diagnosis were independently associated with survival after AIDS. Highly active antiretroviral therapy (HAART) was associated with a 70% reduction in progression to death following AIDS. CONCLUSIONS: Temporal changes in the incidence and clinical presentations in HIV-positive women in our cohort reflect an increased use of HAART that may have a differential effect on reduction in the risk of ADIs. These illnesses, although considerably less frequent in recent years, are still important contributors to morbidity in HIV-positive women.

AIDS-Related Opportunistic Infections↗

Changes in the cytotoxic T-cell repertoire of HIV-1-infected individuals: relationship to disease progression.

The repertoire of antigen-specific receptors expressed on T lymphocytes is shaped by fixed genetic and variable environmental selective pressures. Recent technological advances have enabled the analysis of T-cell receptor (TCR) expression in the context of selective pressures arising through normal immune system development and also through pathological features of disease. The pathological features of acquired immune deficiency syndrome (AIDS) are reflected by selective depletion of particular T lymphocyte subsets and expansion of others. An important question concerning the immunopathogenesis of AIDS is whether or not the perturbation of the CD4+ and CD8+ T-cell subsets following infection with human immunodeficiency virus (HIV) is selective based on TCR variable (V) region gene expression. To address this question, we have functionally analyzed TCR V gene expression on CD8+ cytotoxic T lymphocytes from HIV-1-infected individuals. This was done using monoclonal antibodies against individual TCR V regions to trigger redirected cytolysis in 51Cr release assays. The percent specific lysis induced by each antibody functionally measures the representation of the TCR V region gene product it is specific for. Relative to non-HIV-infected controls and asymptomatic HIV-infected individuals with only moderate CD4 lymphocyte depletion, HIV-infected individuals with low CD4 lymphocyte counts exhibited skewed patterns of TCR V region representation. Therefore, the perturbation within the CD8+ cytotoxic T lymphocyte repertoire in HIV infection appears to be selective based on TCR V region usage, increasingly so as disease progresses. The TCR V genes affected varied between different HIV-infected individuals and skewing detected in functional assays was not always apparent by flow cytometric analysis. These results suggest that HIV infection causes generalized effects on the T-cell repertoire, which are reflected in the relative TCR V gene representation of the CD8+ cytotoxic T lymphocyte population in peripheral blood.

Acquired Immunodeficiency Syndrome↗

Presence of HLA-C-restricted cytotoxic T-lymphocyte responses in long-term nonprogressors infected with human immunodeficiency virus.

Approximately 5% of people with human immunodeficiency virus type 1 (HIV-1) infection remain free of disease for 10 or more years. These long-term nonprogressors (LTNPs) exhibit lower viral loads and stable CD4+ lymphocyte counts. The immunologic basis for this disease-free condition is not known. Because cytotoxic T lymphocytes (CTLs) constitute a major immune defense mechanism for sustained recovery from viral infections, we analyzed HIV-specific CTL responses in three asymptomatic LTNPs. We observed the presence of HIV-1 envelope-specific CTL responses mediated by HLA class I C-restricted CD8+ cells in these individuals. Using autologous target cells and a panel of HLA-matching and -mismatching B-cell lines as targets, we determined that HLA-Cw7 is the restricting element for the observed CTL activity. Additionally, we identified three peptides, one previously not reported, from conserved regions in the envelope protein as CTL epitopes. We previously reported these peptides to be efficient in inducing HIV-specific cellular immune responses in murine and nonhuman primate models. Our results support the role of the HLA-C locus in generating CTL responses and constitute the first report of an HLA-Cw7-restricted HIV-1 envelope-specific CTL response in HIV+ LTNPs, which may be important in the control of HIV replication in vivo.

Amino Acid Sequence↗

Effect of maternal and neonatal vitamin A supplementation and other postnatal factors on anemia in Zimbabwean infants: a prospective, randomized study.

BACKGROUND: Anemia is prevalent in infants in developing countries. Its etiology is multifactorial and includes vitamin A deficiency. OBJECTIVE: Our primary aim was to measure the effect of maternal or neonatal vitamin A supplementation (or both) on hemoglobin and anemia in Zimbabwean infants. Our secondary aim was to identify the underlying causes of postnatal anemia. DESIGN: A randomized, placebo-controlled trial was conducted in 14 110 mothers and their infants; 2854 infants were randomly selected for the anemia substudy, of whom 1592 were successfully observed for 8-14 mo and formed the study sample. Infants were randomly assigned within 96 h of delivery to 1 of 4 treatment groups: mothers and infants received vitamin A; mothers received vitamin A and infants received placebo; mothers received placebo and infants received vitamin A; and mothers and infants received placebo. The vitamin A doses were 400,000 and 50,000 IU in the mothers and infants, respectively. RESULTS: Vitamin A supplementation had no effect on hemoglobin or anemia (hemoglobin <105 g/L) in unadjusted or adjusted analyses. Infant HIV infection independently increased anemia risk >6-fold. Additional predictors of anemia in HIV-negative and -positive infants were male sex and lower total body iron at birth. In addition, in HIV-positive infants, the risk of anemia increased with early infection, low maternal CD4+ lymphocyte count at recruitment, and frequent morbidity. Six-month plasma ferritin concentrations <12 microg/L were a risk factor in HIV-negative but not in HIV-positive infants. Maternal HIV infection alone did not cause anemia. CONCLUSION: Prevention of infantile anemia should include efforts to increase the birth endowment of iron and prevent HIV infection.

Adult↗

AIDS-related Burkitt's lymphoma. Morphologic and immunophenotypic study of biopsy specimens.

In patients infected with HIV, high-grade B-cell non-Hodgkin's lymphomas (NHL), including the small noncleaved cell (SNCC) category, exhibit pleomorphic features, which makes precise definition difficult. Sixty-nine pathologic specimens with HIV-related systemic lymphomas, including 42 SNCC, 20 immunoblastic lymphomas (IBL), and 7 cases with features "intermediate" between SNCC and IBL were morphologically and immunophenotypically investigated. The host immune status was also analyzed in 57 of 69 patients. In 29 representative SNCC lymphomas, in 9 IBL cases, and an additional 3 intermediate lymphomas, both p53 protein overexpression and the association of Epstein-Barr virus (EBV) genetic information were assessed. Small noncleaved cell lymphomas included tumors exhibiting features of the 2 established subtypes (27 Burkitt's and 15 non-Burkitt's). In the seven intermediate cases, cells showed features intermediate between SNCC with plasmablastic differentiation and immunoblasts plasmacytoid. Immunoblast-like cells were also present. p53 protein overexpression and EBV association were found in a proportion of SNCC (14 of 29; 7 of 29) and intermediate (3 of 3; 2 of 3) lymphomas. Conversely, IBL cases were consistently p53 negative, but showed a high EBV association (7 of 9). All the evaluated patients with intermediate lymphomas had a considerably lower mean (76.6 per mm3 +/- 77.4 SD) and median (54 per mm3) number of CD4+ lymphocyte count than SNCC patients (mean 227.9 per mm3 +/- 186.9 SD, median 193 per mm3), thus mirroring IBL patients (mean 95.3 per mm3 +/- 82.8 SD, median 81 per mm3). All data provide evidence that lymphomas showing intermediate features constitute a distinct subgroup from either SNCC or IBL.

Biopsy↗

Human immunodeficiency virus infection in children.

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.

AIDS-Related Opportunistic Infections↗

Protease inhibitors for the treatment of human immunodeficiency virus infection.

The pharmacology, pharmacokinetics, efficacy, adverse effects, drug interactions, and dosage and administration of protease inhibitors are reviewed. Protease inhibitors are a novel class of drugs used for the treatment of human immunodeficiency virus (HIV) infection. Saquinavir, ritonavir, indinavir, and nelfinavir have been approved in the United States; several other agents are under development. Protease inhibitors selectively block HIV protease, an enzyme involved in the later stages of HIV replication. Various pharmacokinetic differences exist among these agents, including differences in bioavailability, protein binding, and drug interactions. The drugs undergo extensive hepatic metabolism; dosage adjustments should be considered for patients with hepatic dysfunction. Clinical trials have shown protease inhibitors to be effective in reducing HIV RNA levels and increasing CD4+ lymphocyte counts. When protease inhibitors are used in combination with other antiretroviral agents, an additional beneficial effect on these markers occurs. Adverse effects of saquinavir and nelfinavir include mild gastrointestinal disturbances such as diarrhea. Ritonavir is less well tolerated because of gastrointestinal disturbances and circumoral and peripheral paresthesia. Indinavir has been associated with nephrolithiasis and asymptomatic hyperbilirubinemia. The development of resistance to protease inhibitors may be related to suboptimal dosages, noncompliance, or partial compliance. Protease inhibitors are potent and highly selective agents that block a critical step in HIV replication. They are effective and relatively well tolerated, but they are expensive, have extensive drug interaction profiles, and require careful compliance with the prescribed regimen.

Adult↗

Caspofungin acetate: an antifungal agent.

The pharmacology, bioavailability and pharmacokinetics, clinical efficacy, and adverse effects of caspofungin acetate are reviewed. Caspofungin acetate is an echinocandin with fungicidal activity against a wide range of pathogens, including Candida spp., Aspergillus spp., and Histoplasma spp. It is active against fluconazole-resistant and fluconazole-susceptible strains of Candida albicans. Caspofungin acetate irreversibly inhibits the enzyme 1,3-beta-D-glucan synthase, preventing the formation of glucan polymers and disrupting the integrity of the fungal cell wall. Caspofungin acetate has an elimination half-life of 9-10 hours and is suitable for once-daily regimens. Data from animal and human studies demonstrate that the drug is 80-96% protein bound. Less than 3% of the dose is eliminated unchanged in the urine, and the proposed route of elimination is hepatic. In a trial of 128 patients with Candida esophagitis, clinical response rates were higher with caspofungin acetate 50 or 70 mg/day (85%) than with amphotericin B 0.5 mg/kg/day (67%). Most enrolled patients had HIV infection, and almost half had CD4+ lymphocyte counts of less than 50 cells/microL in another study, 56 immunocompromised patients with aspergillosis were treated with one 70-mg dose of caspofungin acetate, then 50 mg once a day. All patients had refractory invasive aspergillosis or were intolerant of amphotericin B, liposomal amphotericin B, or azole therapy. In patients who received at least one dose of caspofungin acetate, a favorable response was reported in 41%. In 128 patients who received either caspofungin acetate or amphotericin B, fewer caspofungin acetate recipients (1.4%) had elevated serum creatinine levels and discontinued therapy because of adverse effects (4%) than amphotericin B recipients (15% and 22%, respectively). The manufacturer's recommended dose for infections caused by Candida or Aspergillus spp. has not been determined. Caspofungin acetate appears to be fungicidal, with a wide spectrum of antifungal activity and a good safety profile. The lack of adequate efficacy and safety data in humans makes a recommendation to add this drug to the formulary premature. Pending advanced clinical trials and cost information, caspofungin acetate may be a reasonable addition to the formulary, particularly in hospitals with large immunocompromised patient populations.

Adult↗

Pharmaceutical services in an HIV clinic.

Pharmaceutical-related interventions in a pharmacist-directed human immunodeficiency virus (HIV) clinic were characterized. Intervention types, clinical significance, and expected outcomes were adapted from the literature. Pharmacists' interventions were recorded on a spreadsheet, and two pharmacists came into agreement to ensure the consistency of categorization. Intervention types, clinical significance, expected outcomes, and types of therapy precipitating interventions were summarized. The number of patients seen was totaled, and the number of interventions per patient per visit was calculated. The average number of medications and CD4+ lymphocyte counts throughout the study were obtained through the Veterans Affairs Medical Center computer patient record system. A total of 70 patients received pharmaceutical services during the four-year period. Each patient received an average of seven medications and two interventions. The most common interventions were medication counseling (39%), recommendations of monitoring parameters (17%), and prescription processing (9%). The majority of interventions were clinically significant (89%) and enhanced treatment efficacy (62%). The percentage of antiretroviral therapy-related and HIV-related interventions fluctuated over the study period, while the percentage of non-HIV-related interventions increased. Pharmacists' interventions and direct patient care at an HIV clinic effectively ensured patient adherence to treatment and provided clinical benefits for patients.

Anti-HIV Agents↗

Atazanavir: a new protease inhibitor to treat HIV infection.

PURPOSE: The pharmacology, pharmacokinetics, and clinical trials of and drug interactions and formulary considerations associated with atazanavir, the newest protease inhibitor (PI) to treat human immunodeficiency virus (HIV) infection, are evaluated. SUMMARY: Clinical and pharmacokinetic trials were identified through a MEDLINE search. In addition, all available literature citations and meeting abstracts were obtained from the drug's manufacturer. All articles identified from the data sources were evaluated, and all information deemed relevant was included in this review. Data on atazanavir for the treatment of HIV infection are limited to several phase II and III trials, one of which is still ongoing. Atazanavir has shown efficacy comparable with other PIs and the nonnucleoside reverse-transcriptase inhibitor efavirenz in reducing HIV RNA levels, increasing CD4+ lymphocyte counts, and increasing the percentage of patients achieving clinically undetectable HIV RNA levels when given as the sole PI in treatment-naive patients, in combination with saquinavir in treatment-experienced patients, and with ritonavir-boosting regimens in highly treatment-experienced patients. Treatment-naive patients receiving atazanavir commonly develop a protease enzyme mutation on codon 50, which decreases HIV's susceptibility to atazanavir but may increase the susceptibility of the virus to other PIs. When atazanavir is given to patients with preexisting PI-related mutations, the virus's susceptibility to atazanavir is greatly reduced. The occurrence of lipid abnormalities, which has been a major concern with previous PIs, has not been shown to be troublesome in patients receiving atazanavir. CONCLUSION: Atazanavir may be used alone as a first-line PI, with saquinavir in treatment-experienced patients, or in combination with a ritonavir-boosting regimen in highly treatment-experienced patients as part of a salvage regimen.

Atazanavir Sulfate↗

Intramuscular pentamidine for the prevention of Pneumocystis carinii pneumonia in patients infected with human immunodeficiency virus.

We retrospectively reviewed the charts of 96 patients infected with human immunodeficiency virus (HIV) who received intramuscular pentamidine for the prevention of Pneumocystis carinii pneumonia (PCP). These patients, all of whom had either a history of PCP or a CD4 lymphocyte count of < or = 0.2 x 10(9)/L, were intolerant of sulfa drugs, neutropenic, or intolerant of aerosolized treatment. Intramuscular pentamidine was given monthly by the Z-track technique at a dosage of 300 mg (4 mg/kg if the patient weighed < 50 kg). During a total of 350 months of primary prophylaxis in 47 patients and 426 months of secondary prophylaxis in 49 patients, only three cases of PCP occurred. More than 73% of the patients were receiving zidovudine concomitantly. Adverse reactions to intramuscular pentamidine included two episodes of hypotension, three of sterile abscess, two of glucose intolerance, and one of asymptomatic hypoglycemia. The administration of intramuscular pentamidine by the Z-track technique for PCP prophylaxis appears to be highly effective and minimally toxic.

AIDS-Related Opportunistic Infections↗

Symptomatic primary infection due to human immunodeficiency virus type 1: review of 31 cases.

In this series of 31 patients with acute infection due to human immunodeficiency virus (HIV) type 1, the male-to-female ratio was 3.4:1 and the mean age was 31.3 years. Sexual transmission accounted for 83.9% of cases; 45.2% of the patients were homosexual and 38.7% were heterosexual. The mean duration of symptoms and signs was 21 days (range, 5-60 days). Fever (87.1%) and skin rash (67.7%) were most commonly reported. Physical examination findings were abnormal for 96% of the patients; the oral cavity (76.7%) and the skin (73.3%) were the most frequently involved sites. Thirteen of 25 patients with sexually acquired infection had genital or oral ulcers, whereas five intravenous drug users had none (P = .052). Thrombocytopenia was the most common hematologic abnormality and was detected in 17 of 23 patients tested. P24 antigenemia, an initially negative screening test for HIV antibody, and a low CD4+ lymphocyte count were noted in 23 of 29, 23 of 30, and 14 of 21 tested patients, respectively.

Adult↗

Intestinal coinfection with Enterocytozoon bieneusi and Cryptosporidium in a human immunodeficiency virus-infected child with chronic diarrhea.

The microsporidian Enterocytozoon bieneusi has been recognized as an important cause of chronic diarrhea in severely immunodeficient adults infected with human immunodeficiency virus (HIV). We report the first case of intestinal E. bieneusi infection in a child. The 9-year-old boy with connatal HIV infection presented with failure to thrive, chronic diarrhea, and intermittent abdominal pain. His CD4 lymphocyte count was 0.05 x 10(9)/L and dropped to 0.01 x 10(9)/L. No HIV-associated opportunistic infection other than oral hairy leukoplakia and oral candidiasis had been found before microsporidia were detected. Treatment of microsporidiosis with albendazole was of no benefit. During follow-up, the boy also developed intestinal cryptosporidiosis. Evaluation of chronic diarrhea in severely immunodeficient HIV-infected children should include examination for intestinal microsporidia. We recommend the use of a new coprodiagnostic technique that allows detection of microsporidial spores in stool specimens. Furthermore, consideration of dual or even multiple parasitic infections in the differential diagnosis of chronic diarrhea may have both important clinical and epidemiological implications.

AIDS-Related Opportunistic Infections↗

Nocardiosis in 30 patients with advanced human immunodeficiency virus infection: clinical features and outcome.

A total of 30 patients (aged 6-56 years) with nocardiosis and infection due to human immunodeficiency virus type 1 (HIV-1) were identified in our institution between January 1985 and June 1989. Eighteen patients had an AIDS-defining illness before or concurrently with nocardiosis. The mean CD4 lymphocyte count was 109/mm3. Pulmonary nocardiosis in 21 patients, extra-pulmonary nocardiosis in 8, and pulmonary and extrapulmonary nocardiosis in 1 patient was diagnosed. Chest radiographs showed alveolar patterns of infiltrates in 14 patients, reticulonodular patterns in 2, mixed alveolar and reticulonodular patterns in 6, cavitation in 4, and pleural effusion in 3. Of 27 patients treated, the conditions of 22 improved, but the extensive disease in 5 progressed. For 14 patients, recurrence was rapid after their treatment was discontinued. Nocardiosis caused or contributed to the death of 19 patients; in six patients, there was no evidence of nocardial infection at death. Nocardiosis can be a fatal complication of advanced HIV-1 disease. Delayed diagnosis, extensive disease, and early discontinuation of treatment were associated with poor outcome.

AIDS-Related Opportunistic Infections↗