Norman Markowitz

Bacterial Pneumonia in Persons Infected with the Human Immunodeficiency Virus

BACKGROUND Patients with human immunodeficiency virus (HIV) infection are at increased risk for bacterial pneumonia in addition to opportunistic infection. However, the risk factors for bacterial pneumonia and its incidence in this population are not well defined. METHODS In a multicenter, prospective, observational study, we monitored 1130 HIV-positive and 167 HIV-negative participating adults for up to 64 months for pulmonary disease. The HIV-positive group comprised 814 homosexual or bisexual men, 261 injection-drug users, and 55 female partners of HIV-infected men. RESULTS There were 237 episodes of bacterial pneumonia among the HIV-positive participants (rate, 5.5 per 100 person-years), as compared with 6 episodes among the HIV-negative participants (rate, 0.9 per 100 person-years; P < 0.001). The rate of bacterial pneumonia increased with decreasing CD4 lymphocyte counts (2.3, 6.8, and 10.8 episodes per 100 person-years in the strata with more than 500, 200 to 500, and fewer than 200 cells per cubic millimeter, respectively; P < or = 0.022 for each comparison). Injection-drug users had a higher rate of bacterial pneumonia than did homosexual or bisexual men or female partners. In the stratum with the fewest CD4 lymphocytes, cigarette smoking was associated with an increased rate of pneumonia. Mortality was almost four times higher among participants with an episode of pneumonia than among the others. Prophylaxis with trimethoprim-sulfamethoxazole was associated with a 67 percent reduction in confirmed episodes of bacterial pneumonia (P = 0.007). CONCLUSIONS Bacterial pneumonia is more frequent in HIV-positive persons than in seronegative controls, and the risk is highest among those with CD4 lymphocyte counts below 200 per cubic millimeter and among injection-drug users.

Human Infection with Ehrlichia canis, a Leukocytic Rickettsia

RICKETTSIA that are pathogenic for humans include five main antigenic groups that cause, respectively, typhus, spotted fever, scrub typhus, Q fever, and trench fever.1 There is also a group of intr...

Trimethoprim-Sulfamethoxazole Compared with Vancomycin for the Treatment of Staphylococcus aureus Infection

OBJECTIVE To compare trimethoprim-sulfamethoxazole (TMP-SMZ) and vancomycin regarding efficacy and safety in the therapy of serious Staphylococcus aureus infections. DESIGN Randomized, double-blind comparative trial. SETTING A tertiary-care hospital. PATIENTS One hundred and one intravenous drug users hospitalized with S. aureus infection. MEASUREMENTS Cure and failure rates; blood and wound cultures; minimum inhibitory and bactericidal concentrations; serum inhibitory and bactericidal titers; temperature; leukocyte count; durations of treatment and hospitalization; and toxicity. RESULTS Of 228 intravenous drug users, 101 had S. aureus infection and were included in the efficacy analysis (43 received TMP-SMZ and 58 received vancomycin). Methicillin-resistant S. aureus (MRSA) accounted for 47% of S. aureus isolates, and 65% of patients were bacteremic. Infections were cured in 57 of 58 vancomycin recipients and in 37 of 43 TMP-SMZ recipients (P less than 0.02). Failure occurred mostly in patients with tricuspid valve endocarditis and only in those with infection caused by methicillin-sensitive S. aureus (MSSA). The mean duration of bacteremia was 6.7 days in TMP-SMZ recipients and 4.3 days in vancomycin recipients. Among 222 subjects hospitalized for at least 24 hours, toxicity rates were similar for TMP-SMZ (23%) and vancomycin (20%) recipients; nausea and vomiting were associated with TMP-SMZ and inflammation at the intravenous site was associated with vancomycin. Forty-four percent of TMP-SMZ recipients and 29% of vancomycin recipients experienced side effects in the efficacy cohort (P greater than 0.05). CONCLUSIONS Vancomycin is superior to TMP-SMZ in efficacy and safety when treating intravenous drug users who have staphylococcal infections. However, all treatment failures occurred in patients with MSSA infection at any site. Therefore, TMP-SMZ may be considered as an alternative to vancomycin in selected cases of MRSA infection.

Methicillin-resistant Staphylococcus aureus. epidemiologic observations during a community-acquired outbreak

Infection with strains of methicillin-resistant Staphylococcus aureus occurred in 40 patients at time of admission to a large urban hospital from March to December 1980. Community-acquired methicillin-resistant S. aureus infections occurred in 24 drug abusers and 16 nonabusers. Patients with infections had a longer mean hospitalization and previously had received antimicrobial therapy more frequently than control subjects. Drug abusers with infections had been treated with cephalosporins more often than control subjects (P less than 0.05). Phage typing of 32 isolates showed that 21 were linked by a common phage type (29/52/80/95). Transmission of methicillin-resistant S. aureus from community-acquired cases occurred in the hospital. By January 1981, methicillin-resistant S. aureus accounted for 30.6% of nosocomial S. aureus infections at Henry Ford Hospital. Methicillin-resistant S. aureus infection may arise in the community as well as in the hospital and has the potential to disseminate in both settings.

INCIDENCE OF TUBERCULOSIS IN THE UNITED STATES AMONG HIV-INFECTED PERSONS. THE PULMONARY COMPLICATIONS OF HIV INFECTION STUDY GROUP

Among opportunistic pathogens associated with the acquired immunodeficiency syndrome (AIDS), Mycobacterium tuberculosis is distinguished by its relative virulence and potential for person-to-person transmission. Persons infected with human immunodeficiency virus (HIV) are particularly susceptible to tuberculosis, both from the reactivation of latent infection and from new infection with rapid progression to active disease [1-4]. The annual incidence of tuberculosis in the United States was 8.7 per 100 000 persons in 1995 [5], but rates 1000-fold higher have been reported in some HIV-seropositive populations [6-14]. Most studies have been restricted by geography, HIV-risk group, or specific high-prevalence settings; such restrictions have resulted in an inaccurate assessment of the overall effect of the HIV epidemic on the incidence of tuberculosis in the United States [15, 16]. The Pulmonary Complications of HIV Infection Study (PCHIS) [17] prospectively followed HIV-seropositive patients who had demographic variables similar to those of patients with AIDS in the United States. Participants with asymptomatic or symptomatic HIV infection were recruited from sites in the eastern, midwestern, and western United States. A previous report on this cohort [18] identified determinants of delayed-type hypersensitivity response and risk factors for tuberculin reactivity. We examined the incidence of tuberculosis among patients enrolled in the PCHIS for a median observation period of approximately 4.5 years. Methods Patients and Study Design The PCHIS was a multicenter, prospective study of the frequency and spectrum of pulmonary disorders in persons infected with HIV. From November 1988 through February 1990, 1171 HIV-seropositive persons and 182 HIV-seronegative persons were enrolled at centers in six U.S. cities: New York; Newark, New Jersey; Detroit; Chicago; San Francisco; and Los Angeles. Participants were followed through 31 March 1994. We report on 1130 HIV-infected persons from the PCHIS who were followed past baseline. Participants were recruited to represent a range of severity of HIV disease. Approximately half of the participants at each center had CD4 lymphocyte counts of 400 cells/mm3 or more and no HIV-related symptoms, and half had CD4 lymphocyte counts of less than 400 cells/mm3 or symptomatic HIV infection. Both groups included persons from one of three HIV-transmission categories: homosexual men, male and female injection drug users, and women who had acquired HIV through heterosexual contact. Exclusion criteria were AIDS, as defined by the Centers for Disease Control and Prevention (CDC) [19]; acute pulmonary processes; use of immunosuppressive therapy in the past 6 months; and treatment of tuberculosis in the past 12 months. The study was approved by the institutional review board at each site, and participants gave informed consent. At baseline and at regular intervals, clinical monitoring (including T-lymphocyte subset analysis and chest roentgenography) was done, and participants were acutely evaluated if new pulmonary symptoms occurred. Centers used the same predetermined diagnostic algorithms that were initiated if specified criteria were met. Complete details of the study design have been described elsewhere [17]. Delayed hypersensitivity was tested at baseline and then annually using purified protein derivative (PPD) tuberculin at a strength of 5 TU per 0.1-mL dose and mumps antigen (Connaught Laboratories, Inc., Swiftwater, Pennsylvania). Tests were administered by intradermal injection of 0.1 mL of antigen by the Mantoux method and read by experienced nurses 48 to 72 hours later in most cases (the interval exceeded 4 days in 18 persons). A positive response to PPD was defined as an induration at least 5 mm in diameter. Any person who was not positive when first tested but who became positive on any subsequent test was considered to be a tuberculin converter. A positive response to mumps was defined as any degree of induration (>0 mm). The criteria for anergy was nonreactivity (0 mm) to both PPD and mumps antigen. Pulmonary tuberculosis was defined by the isolation of M. tuberculosis from a respiratory tract specimen or by improvement on chest radiography in response to specific multidrug antituberculous therapy. Patients who were diagnosed with extrapulmonary tuberculosis had clinically compatible disease and response to specific therapy, with or without the isolation of the organism from a site outside the lung. Patients who were considered to have both pulmonary and extrapulmonary tuberculosis met each set of criteria. These requirements are consistent with those of the CDC for reporting cases of tuberculosis [20], except that we did not require patients to be PPD positive if they had disease that was not mycobacteriologically confirmed. Statistical Analysis Tuberculosis rates were calculated as the number of cases divided by the number of years that patients were followed multiplied by 100. Except as noted below, the length of time that patients were followed was calculated for each person starting from enrollment and continuing until one of the following occurred: diagnosis of tuberculosis, death from any cause, the last study visit, or 31 March 1994. Statistical significance for comparison of rates was determined by tests for person-time data done on the basis of binomial distribution [21]. P values were determined by an exact test when sample sizes were insufficient and by an asymptotic test when sizes were sufficient. All tests were two-sided, and a P value of 0.05 was considered significant. Exact 95% CIs were calculated for rates by assuming the numerator to be a Poisson variable [22] and for rate ratios using a modified binomial model [21]. Adjusted rate ratios for comparisons among groups defined by demographic variables were calculated by using a Mantel-Haenszel type estimator for incidence-rate data with approximate 95% confidence limits based on the tests [21]. Seventy-three participants, including women who had acquired HIV through heterosexual contact and persons were not black, white, or Hispanic, were excluded from some calculations of adjusted rates because of small sample sizes. Distributions of time to death among patients with tuberculosis were estimated using the Kaplan-Meier method, and comparisons were made using the log-rank test. To calculate tuberculosis rates by immunologic status, we divided the time each participant was followed into the number of years during which CD4 lymphocyte counts were 200 cells/mm3 or greater and the number of years after CD4 lymphocyte counts were less than 200 cells/mm3. Time for these CD4 groups was then summed for all participants. Rates were calculated as the number of tuberculosis cases in each group divided by the number of years followed. One participant who did not have CD4 measurements was omitted from these calculations. Twenty-three participants who were never tested for PPD response were excluded from PPD conversion rates and calculations of tuberculosis rates by PPD status. Participants who were tested for PPD response at least once were classified into one of three groups: positive at entry, newly positive (converted), or negative. One hundred seventy-two of 1107 participants were assigned to groups on the basis of only one test. Baseline PPD status was assigned for 66 participants who were not tested at study entry by using the first reported test and time followed calculated from the date of that test. For participants who developed tuberculosis, only the results of PPD tests done before diagnosis were considered. Tuberculin converters were considered to be part of the negative group before becoming PPD positive and to be part of the newly positive group after converting. Persons who reported a history of isoniazid use or tuberculosis before the study or who received isoniazid for at least 6 months during follow-up were considered to have completed prophylactic therapy. All others were considered to have not been given prophylaxis. Time before completion of isoniazid therapy was included with time followed in the untreated group. Restricted tuberculosis rates were calculated by PPD status for those considered to have not received prophylaxis. Results Patient Characteristics at Baseline Overall, 1171 HIV-seropositive persons entered the study. Follow-up was completed for 1130 persons (96%), whose baseline characteristics are shown in Table 1. Approximately 1% of patients reported a history of tuberculosis, 8% reported a previous positive result on a PPD test, and 4% reported previous use of isoniazid. The median CD4 T-lymphocyte count among HIV-seropositive patients was 410 cells/mm3: Thirty-six percent of patients had counts of at least 500 cells/mm3, 44% had counts between 200 and 499 cells/mm3, and 19% had counts of less than 200 cells/mm3. At study entry, 6% of patients were PPD positive, 42% were reactive to mumps antigen, and 54% were anergic. A cross-sectional analysis of skin-test results at baseline in this cohort has been described in detail elsewhere [18]. Table 1. Baseline Characteristics of the Study Chart* Patient Follow-up The median duration of follow-up was 53 months. By the end of the study, 655 persons had survived after a median follow-up of 57 months (range, 31 to 64 months), 354 had died after a median follow-up of 31 months (range, 1 to 63 months), and 121 withdrew or were lost to follow-up after a median of 25 months (range, 1 to 61 months). Participants received PPD skin tests a median of three times, and 1107 (98%) participants were evaluated at least once. Sixty-six (6%) participants were PPD positive when first tested. Among the 1041 patients who were PPD negative at first testing, 29 subsequently became PPD positive (0.8 conversions per 100 person-years). During follow-up, isoniazid prophylaxis was prescribed for 110 persons (10%), but only 53 (5%) received therapy for 6 months or more. Inc

Tuberculin and Anergy Testing in HIV-Seropositive and HIV-Seronegative Persons

Human immunodeficiency virus (HIV) is playing a substantial role in the resurgence of tuberculosis in the United States. Particularly affected are people in urban areas, where there are large populations of HIV-infected persons [1-8]. Urban subpopulations with a high prevalence of HIV infection, such as intravenous drug users (a group already at increased risk for tuberculosis before the appearance of the acquired immunodeficiency syndrome [AIDS]), have the highest tuberculosis attack rates [3]. Unlike other AIDS-associated opportunistic pathogens, Mycobacterium tuberculosis is readily communicable among persons with all levels of immunity. Recently, tuberculosis outbreaks, some with multidrug-resistant strains, have occurred among HIV-positive patients with transmission to HIV-negative patients and health care workers [9-13]. Prevention strategies rely heavily on the use of tuberculin purified protein derivative (PPD) to identify persons harboring M. tuberculosis [14]. Anergy, a consequence of HIV infection, undermines these strategies in persons at the highest risk for tuberculosis infection and subsequent active disease [15-18]. A negative PPD test result in this setting could be attributable to a true lack of exposure to tuberculosis or simply to the incapacity of the patient to manifest an appropriate cell-mediated immune response. To reduce the measured prevalence of anergy and thereby increase the proportion of tuberculin nonreactors who can be considered truly PPD negative, the Centers for Disease Control and Prevention (CDC) has recommended the additional use of at least two delayed-type hypersensitivity control antigens (mumps antigen plus Candida antigen or tetanus toxoid) when screening HIV-infected patients. Thus, persons from populations with a prevalence of tuberculous infection of 10% or more and who are tuberculin negative but not anergic may be spared preventive therapy with isoniazid [19]. However, the ability of control antigens to predict the likelihood that a negative PPD test result is truly negative in this highly anergic population is unknown. To improve approaches to tuberculosis prophylaxis, more data are needed about the relations among delayed-type hypersensitivity responsiveness, the prevalence of tuberculosis, and the waning immunity associated with progressive HIV infection. In an ongoing multicenter study of the natural history of the pulmonary complications associated with HIV infection, we have been examining these factors prospectively in a cohort of 1353 persons in 6 U.S. geographic areas. Recently, we evaluated baseline delayed-type hypersensitivity responses in this cohort of HIV-seropositive and HIV-seronegative persons and identified variables associated with tuberculin reactivity and anergy. Methods Patients and Study Design The Pulmonary Complications of HIV Infection Study is a multicenter study designed to prospectively describe the frequency, types, and effect of pulmonary complications in HIV-infected persons, both before and after the development of AIDS. All diagnoses, treatments, and outcomes are recorded and monitored in a common database. Because our purpose was to evaluate longitudinally both the early and late pulmonary manifestations of HIV infection, each center attempted to recruit about 170 HIV-seropositive participants, half with CD4 lymphocyte counts of 400 cells/mm3 or more and no HIV-related symptoms and half with fewer than 400 CD4 cells/mm3 or symptomatic HIV-infection (defined by a temperature of 38 C or more for at least 2 weeks, involuntary weight loss of 10% or more from baseline, diarrhea of at least a 1-month duration, oral candidiasis, or oral hairy leukoplakia). Within each group, participants were drawn from one of three HIV transmission categories (homosexual men, male and female intravenous drug users, and women with heterosexually acquired HIV infection) to reflect their approximate distribution at each clinical site. About 30 HIV-seronegative homosexual men and intravenous drug users were also recruited at each site to serve as controls. Participants had to be willing and able to comply with the protocol and were required to give informed consent. The study was reviewed and approved by the institutional review board at each site. Exclusion criteria included Centers for Disease Control and Prevention (CDC)-defined AIDS [20], severe non-HIV-related disease likely to affect survival, lung disorders likely to interfere with the required evaluations, acute pulmonary processes, immunosuppressive therapies within the previous 6 months, and treatment for active tuberculosis within the past 12 months. From November 1988 through February 1990, we enrolled 1353 persons in the study, of whom 1171 were HIV seropositive and 182 were HIV seronegative. Human immunodeficiency virus serologic status was confirmed at study entry using a licensed enzyme-linked immunosorbent assay and a Western blot assay. Further baseline evaluation included a complete medical history, a physical examination, hematologic and biochemical studies, T-lymphocyte subset analysis, delayed-type hypersensitivity testing, a chest roentgenogram, and pulmonary function measurements. Measurement of Delayed-Type Hypersensitivity Response We tested delayed-type hypersensitivity with the following antigens: mumps antigen (Connaught Laboratories, Inc., Swiftwater, Pennsylvania); Dermatophytin 0 (Candida) at 1:100 dilution (Hollister-Stier, Spokane, Washington); Dermatophytin (trichophytin) at 1:100 dilution (Hollister-Stier); and tuberculin PPD at a strength of 5 tuberculin units per 0.1-mL dose (Connaught Laboratories, Ltd., Willowdale, Ontario, Canada). Tests were administered by intradermal injection of 0.1 mL of antigen (Mantoux method) and read by a trained observer 48 to 72 hours after application in most participants (the interval exceeded 4 days in 18 persons). Response was recorded as the greatest diameter of induration. We used the current standard operational criteria for a positive response: induration of at least 5 mm for all antigens except PPD, for which an induration of 10 mm was required among HIV-uninfected persons [19]. Anergy was defined as 0 mm of induration for all delayed-type hypersensitivity antigens administered in a given panel. Unless otherwise specified, a test battery of tuberculin PPD, mumps antigen, and Candida antigen was used to define anergy. At one site, however, the investigators did not distinguish between induration and erythema for the mumps, Candida, and trichophytin tests, documenting reactions to these antigens in terms of millimeters of erythema. When examined by zone diameter, their measurements were generally consistent with those from the other centers. Furthermore, the results of multivariate analyses with and without the data from this site were similar. Other investigators have shown a high degree of correlation between induration and erythema with these antigens [21]. Thus, for the purposes of our analysis, responses were recorded in millimeters of induration. Because trichophytin elicited a positive reaction in only 14.0% of those tested, it was dropped from the delayed-type hypersensitivity battery midway through the enrollment period. Although lot numbers varied, the skin tests used at the centers were supplied by the same manufacturers, with a single exception: At one site, investigators used a different Candida preparation. The Candida test results for this center (247 participants) were excluded from all analyses involving this antigen. Determination of Lymphocyte Subsets Lymphocyte subsets were determined for CD3, CD4, and CD8 receptor-bearing cells by the same laboratory at each site. All laboratories participated in the flow cytometry quality control program sponsored by the National Institute of Allergy and Infectious Diseases [22]. Statistical Analysis All analyses are based on data collected during the baseline evaluation. Statistical significance for comparisons of proportions was determined by chi-square or Fisher exact test [23]. For comparisons among nonindependent groups, repeated-measures analysis for categorical outcomes was used to determine statistical significance [24, 25]. Logistic regression models were used to study the relation between PPD positivity or anergy and potential risk factors [26]. Risk factors considered were HIV status; CD4 count among HIV-seropositive persons; intravenous drug use; race or ethnicity; a history of a positive PPD test result, tuberculosis, or BCG vaccination; age; gender; and socioeconomic status. Seventy-seven participants, including women with heterosexually acquired infection and persons who were not white, black, or Hispanic, were excluded from all multivariate analyses because of small sample sizes. Initial models included HIV status (positive or negative), intravenous drug use (presence or absence), race or ethnicity (white, black, or Hispanic), a history of a positive PPD test result, and age, as well as interaction terms, to determine whether the effect of HIV positivity varied among these groups or whether the effect of drug use varied by race. No statistically significant interactions were observed. All odds ratios presented were derived from subsequent models containing main effects only. A dichotomous variable indicating the 12% of the cohort who did not have a high school diploma was used as an index of socioeconomic status and was included in all final models. All tests were two sided. A P value of 0.05 was considered statistically significant. Ninety-five percent CIs are given when appropriate. Results Patient Characteristics During the 16-month enrollment period, 1171 HIV-seropositive and 182 HIV-seronegative persons entered the study. The two groups were similar with regard to age, sex, race, transmission category, and tuberculosis-associated history (Table 1). Of the 1165 men, 966 (82.9%) were homosexual; of the 188 women, 132 (70.2%) were intravenous drug users.

A Comparative Trial of Didanosine or Zalcitabine after Treatment with Zidovudine in Patients with Human Immunodeficiency Virus Infection

BACKGROUND Both didanosine and zalcitabine are commonly used to treat patients with human immunodeficiency virus (HIV) infection who cannot tolerate zidovudine treatment or who have had disease progression despite it. The relative efficacy and safety of these second-line therapies are not well defined. METHODS In this multicenter, open-label trial we randomly assigned 467 patients who previously received zidovudine and had 300 or fewer CD4 cells per cubic millimeter or a diagnosis of the acquired immunodeficiency syndrome (AIDS) to treatment with either didanosine (500 mg per day) or zalcitabine (2.25 mg per day). RESULTS After a median follow-up of 16 months, disease progression or death occurred in 157 of 230 patients assigned to didanosine and 152 of 237 patients assigned to zalcitabine, for a relative risk of 0.93 for the zalcitabine group as compared with the didanosine group (P = 0.56), which decreased to 0.84 (P = 0.15) after adjustment for the CD4 count, Karnofsky score, and presence of AIDS at base line. There were 100 deaths in the didanosine group and 88 in the zalcitabine group, for a relative risk of 0.78 (P = 0.09) and an adjusted relative risk of 0.63 (P = 0.003). A majority of patients in each group (66 percent) had at least one adverse event during treatment (153 patients taking didanosine and 157 taking zalcitabine). Peripheral neuropathy and stomatitis occurred more often with zalcitabine and diarrhea and abdominal pain more frequently with didanosine. CONCLUSIONS For patients with HIV infection who have not responded to treatment with zidovudine, zalcitabine is at least as efficacious as didanosine in delaying disease progression and death.

Zidovudine alone or in combination with didanosine or zalcitabine in HIV-infected patients with the acquired immunodeficiency syndrome or fewer than 200 CD4 cells per cubic millimeter

BACKGROUND We compared two combinations of nucleosides with zidovudine alone in patients with advanced human immunodeficiency virus (HIV) infection. METHODS A total of 1102 patients with the acquired immunodeficiency syndrome or fewer than 200 CD4 cells per cubic millimeter were randomly assigned to receive zidovudine alone or zidovudine combined with either didanosine or zalcitabine. Disease progression, survival, toxic effects, and the CD4 cell response were assessed. RESULTS After a median follow-up of 35 months, disease progression or death occurred in 62 percent of the 363 patients assigned to zidovudine plus didanosine, 63 percent of the 367 assigned to zidovudine plus zalcitabine, and 66 percent of the 372 assigned to zidovudine only (P=0.24). As compared with zidovudine therapy, treatment with zidovudine plus didanosine was associated with a relative risk of disease progression or death of 0.86 (95 percent confidence interval, 0.71 to 1.03), and treatment with zidovudine plus zalcitabine was associated with a relative risk of 0.92 (95 percent confidence interval, 0.76 to 1.10). Survival was similar in the three groups. In a subgroup analysis, combination therapy delayed disease progression or death in patients who had previously received zidovudine for 12 months or less. Therapy with zidovudine plus didanosine resulted in more gastrointestinal adverse effects, and treatment with zidovudine plus zalcitabine, more neuropathy. The mean increases in CD4 cell counts at two months were higher with combination therapy than with zidovudine alone. CONCLUSIONS In patients with advanced HIV infection, combination therapy with zidovudine and either didanosine or zalcitabine is not superior to zidovudine therapy alone. However, these combinations may be more effective than zidovudine monotherapy in patients with little or no previous zidovudine treatment.

A study of HIV RNA viral load in AIDS patients with bacterial pneumonia.

We examined the effect of bacterial pneumonia on the magnitude of circulating plasma HIV RNA in HIV-infected patients. Serum samples from 13 adult HIV-infected patients (median CD4 count = 83 cells/microl) were assayed for HIV RNA using the reverse transcriptase polymerase chain reaction assay (a) before bacterial pneumonia, (b) during the acute phase, and (c) after the recovery from the disease. Patients remained on constant antiretroviral therapy: HIV RNA was detected in all samples tested. The medians before, during, and after bacterial pneumonia were 60,000 copies per ml, 245,000 copies per ml, and 84,000 copies per ml, respectively. All 13 patients had increased HIV RNA levels on developing pneumonia. There was a decline in the level of HIV RNA with recovery from pneumonia in 12 of 13 patients. The difference between the HIV RNA levels before and after pneumonia was not significant, nor was there significant difference in the CD4 counts before and after pneumonia. In conclusion, bacterial pneumonia is associated with a consistent, transient increase in HIV RNA of variable magnitude in AIDS patients. Interpretation of HIV RNA changes for clinical management of AIDS patients must take into account this reversible elevation during infections.

The urological manifestations of the acquired immunodeficiency syndrome

Between 1984 and March 1987, 120 patients with either the acquired immunodeficiency syndrome or its related complex seen at our hospital were studied retrospectively for urological signs and/or symptoms. Autopsy findings also were reviewed. Of the patients 84 per cent had no complaints referable to the urinary system, 2 per cent had gross hematuria (all with a negative diagnostic evaluation) and 14 per cent had urinary infections. We conclude that only a small percentage of patients with the acquired immunodeficiency syndrome suffer from significant urological manifestations and that a full urological evaluation of such patients generally is not warranted. If the patient presents with gross hematuria excretory urography should be performed if there is no infectious etiology, and cytoscopy should be performed only if the hematuria is life-threatening or prolonged and possibly to confirm significant urographic findings.