Faculty Bibliography

OBJECTIVE: To define the contributions of human immunodeficiency virus (HIV) and hepatitis C virus infections to the development of porphyria cutanea tarda. DESIGN: Analysis of serum porphyrin levels in a cohort of 167 subjects. Serum samples were divided into 4 groups corresponding to the status of HIV and hepatitis C virus infections: positive-positive, positive-negative, negative-positive, and negative-negative. SETTING: Serum samples positive for HIV were obtained from the serum bank of an acquired immunodeficiency syndrome-HIV research center, and HIV-negative samples were obtained from a regional blood center. MAIN OUTCOME MEASURES: Spectrofluorometric measurement of serum porphyrin levels. RESULTS: The median values of porphyrin were 2.31 nmol/L (interquartile range [difference between the 25th and 75th percentiles]: 4.55) in the positive-positive group, 1.99 nmol/L (interquartile range: 1.63) in the positive-negative group, 1.31 nmol/L (interquartile range: 1.58) in the negative-positive group, and 1.14 nmol/L (interquartile range: 0.92) in the negative-negative group. The fluorescence emission spectra of samples with elevated porphyrin levels were identical with that reported for porphyria cutanea tarda. Elevated porphyrin levels were significantly associated with HIV infection (P < .001) and were observed in patients with an elevated level of alanine aminotransferase (P = .03). Infection with hepatitis C virus was also associated with an elevation in porphyrin levels, although the increase was not statistically significant (P = .16). Porphyrin levels in patients positive for HIV were not correlated with serum urea nitrogen or creatinine levels. None of the patients had symptomatic porphyria cutanea tarda. CONCLUSIONS: Factors associated with increased serum porphyrin levels included HIV infection, elevated alanine aminotransferase levels, and, to a lesser extent, hepatitis C virus infection. These findings suggest that patients with the above risk factors are potentially predisposed to the development of symptomatic porphyria cutanea tarda on further exposure to hepatotoxic agents

Pneumonia is an important cause of morbidity and mortality in the United States. The provision of effective prophylaxis for pneumonia has become a major goal for both public health officials and individual physicians. Prophylaxis for community-acquired pneumonia is pathogen-specific and is directed toward the most common microorganisms that cause it. The 23-valent pneumococcal polysaccharide vaccine; the trivalent influenza vaccine; the Haemophilus b conjugate vaccine; and either trimethoprim-sulfamethoxazole, dapsone, or aerosolized pentamidine are recommended to prevent Streptococcus pneumoniae, influenza viruses, H. influenzae type b, and Pneumocystis carinii respectively. Except for the microorganisms listed above, the prevention of nosocomial pneumonia is not pathogen-specific. Rather, prevention of nosocomial pneumonia requires the use of infection control procedures, including patient and staff education; isolation of patients with highly contagious respiratory pathogens; vigorous hand washing; cleaning and sterilizaton of respiratory equipment; and use of sterile water in nebulizers and humidifiers. It also requires procedures to limit pooling and aspiration of secretions, such as positioning and rotation of the bed-bound patient; frequent suctioning of respiratory secretions using gloves and sterile suction catheters; and limiting enteral alimentation. Finally, selective decontamination of the digestive tract may be considered for intubated patients

BACKGROUND. Clinical trials of antiretroviral drugs can take years to complete because the outcomes measured are progression to the acquired immunodeficiency syndrome (AIDS) or death. Trials could be accelerated by the use of end points such as changes in CD4+ lymphocyte counts and plasma levels of human immunodeficiency virus type 1 (HIV-1) RNA and beta 2-microglobulin, but there is uncertainty about whether these surrogate measures are valid predictors of disease progression. METHODS. We analyzed data from the Veterans Affairs Cooperative Study on AIDS, which compared immediate with deferred zidovudine therapy. Patients' plasma levels of HIV-1 RNA and beta 2-microglobulin were measured in stored plasma. RESULTS. Among the 129 patients in the immediate-treatment group, 34 had disease that progressed to AIDS, as compared with 57 of the 141 patients in the deferred-treatment group (P = 0.03). Progression to AIDS correlated strongly with base-line CD4+ lymphocyte counts (P = 0.001) and plasma levels of HIV-1 RNA (P < 0.001), but not with base-line levels of beta 2-microglobulin (P = 0.14). A decrease of at least 75 percent in the plasma level of HIV-1 RNA over the first six months of zidovudine therapy accounted for 59 percent of the benefit of treatment, defined as the absence of progression to AIDS (95 percent confidence interval, 13 to 112 percent). Plasma beta 2-microglobulin levels and CD4+ lymphocyte counts explained less of the effect of treatment. A 75 percent decrease in the plasma HIV-1 RNA level plus a 10 percent increase in the CD4+ lymphocyte count could explain 79 percent of the treatment effect (95 percent confidence interval, 27 to 145 percent). CONCLUSIONS. Treatment-induced changes in the plasma HIV-1 RNA level and the CD4+ lymphocyte count, taken together, are valid predictors of the clinical progression of HIV-related disease and can be used to assess the efficacy of zidovudine and possibly other antiretroviral drugs as well

Following a 4-year controlled trial comparing early and later zidovudine treatment, we conducted an additional 3-year follow-up. Of the original 338 patients, 275 participated. Clinical outcome measures were AIDS and death. In the early therapy group (n = 170), 67 patients progressed to AIDS compared with 85 in the later therapy group (n = 168); the relative risk (RR) comparing early with later therapy was 0.72% (95% confidence interval [CI] 0.52-0.99; p = 0.044). The early therapy group had 74 deaths compared with 73 in the later therapy (RR = 0.98; 95% CI, 0.71-1.36; p = 0.91). The early group had a peak CD4+ count increase at 1-2 months and a delay of 1 year before CD4+ counts fell below baseline. For patients who received zidovudine for more than the median duration (20.3 months) before their first AIDS diagnosis, the RR for death was 2.08 (95% CI, 1.36-3.19, p = 0.001). Additional factors independently associated with poor prognosis following AIDS were a CD4+ count of < 100 cells/mm3 and increased severity of the first AIDS diagnosis, whereas use of another antiretroviral agent was associated with improved survival. We conclude that early zidovudine therapy delays progression to AIDS but does not affect survival. Patients who progress to AIDS while on prolonged zidovudine monotherapy many benefit from a change to other antiretroviral therapy(ies)

The study objective was to obtain preliminary information regarding the safety and efficacy of amphotericin B (AmB) lipid complex (ABLC) in the treatment of AIDS-associated cryptococcal meningitis. Of 55 patients randomly assigned to 6 weeks of therapy with ABLC (1.2-5.0 mg/[kg.d], with ascending doses for three sequential cohorts) or AmB (0.7-1.2 mg/[kg.d]), 46 received > or = 12 doses. Transfusion requirements, mean decreases in hemoglobin level, and mean increases in creatinine level were significantly greater with AmB than with ABLC. The total number of adverse events, infusion-related events, and occurrences of hypomagnesemia and hypokalemia associated with each form of therapy were similar. Among 21 recipients of ABLC at a dosage of 5 mg/kg (daily for 2 weeks and then thrice weekly for 4 weeks), symptoms and signs resolved for 18 (86%). Of those receiving > or = 12 doses of ABLC, cultures converted to negative for 8 (42%), were undeterminable for 3 (16%), and remained positive for 8 (42%) despite resolution of symptoms. Although preliminary, these data suggest ABLC has significant activity in patients with AIDS-associated cryptococcal meningitis. Because this formulation has less hematologic and renal toxicity than does AmB, further evaluation of ABLC is warranted

Background: While strategies for medical care for human immunodeficiency virus-related Pneumocystis carinii pneumonia (PCP) are well established, racial variations in care have not been evaluated. Objective: To determine whether sociodemographic characteristics influence patterns of care and patient outcomes, by analyzing the use of diagnostic tests and anti-PCP medications and in-hospital mortality rates for persons who were hospitalized with human immunodeficiency virus-related PCP. Methods: Retrospective chart review of a cohort of 627 Veterans Administration (VA) patients and 1547 non-VA patients with empirically treated or cytologically confirmed PCP who were hospitalized from 1987 to 1990. Outcomes included representative aspects of the process of care for PCP and short-term mortality rates. Results: Among VA patients, black and Hispanic patients were not significantly different from white patients with regard to in-hospital mortality rates, use and timing of a bronchoscopy, or receipt of timely anti-PCP medications. Among non-VA patients, black and Hispanic patients were more likely to die in the hospital and less likely to undergo a diagnostic bronchoscopy in the first 2 days of hospitalization. These racial and ethnic group differences in the use of a bronchoscopy and in-hospital mortality among non-VA patients were almost fully accounted for by differences in health insurance status and hospital characteristics. Conclusions: Racial factors do not appear to be an important determinant of the intensity of diagnostic or therapeutic care among patients who are hospitalized with PCP. Variations in care are largely attributable to differences in health insurance and admitting hospital characteristics

Structured interviews measuring tuberculosis knowledge were administered to 494 New York City injection drug users, 31% of whom reported a history of having a reactive tuberculin skin test. Medical records review of a subsample confirmed the validity of self-reported data. Most respondents understood the mechanisms of tuberculosis transmission. Three fourths of the subjects did not fully understand the distinction between a reactive skin test and active tuberculosis, but those who reported a history of skin test reactivity were twice as likely to understand this distinction. Forty percent of subjects did not understand the importance of medication adherence. Misunderstandings, based on a recent lack of tuberculosis education, may contribute to the fear and confusion that interfere with efforts to control tuberculosis

Many patients infected with the human immunodeficiency virus (HIV) with symptoms suggestive of pneumonia are treated empirically for Pneumocystis carinii pneumonia (PCP), although other bacterial infections (e.g., tuberculosis) and pulmonary Kaposi's sarcoma may cause identical symptoms. Empiric treatment for PCP may result in misdiagnosis and mistreatment. When the outcomes of cytologically confirmed versus empirically treated PCP cases were evaluated, the most important predictors of in-hospital mortality were severity of illness and use of bronchoscopy. Persons who did not undergo bronchoscopy had higher mortality rates than patients negative by bronchoscopy or cytologically confirmed as positive for PCP (22% vs. 11% vs. 14%, P < .01), although severity of illness and timing of anti-PCP medications did not differ significantly. Compared with cytologically confirmed cases, persons who did not have bronchoscopy were more likely to die than were bronchoscopy-negative patients (P < .05), after adjusting for severity of illness. Bronchoscopy use may have contributed to better outcomes for persons treated for HIV-related PCP