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Objective. The HIV Prevention Trials Network (HPTN) 065 trial sought to expand HIV screening of emergency department (ED) patients in Bronx, New York, and Washington, D.C. This study assessed the testing costs associated with different expansion processes and compared them with costs of a hypothetical optimized process. Methods. Micro-costing studies were conducted in two participating EDs in each city that switched from point-of-care (POC) to rapid-result laboratory testing. In three EDs, laboratory HIV testing was only conducted for patients having blood drawn for clinical reasons; in the other ED, all HIV testing was conducted with laboratory testing. Costs were estimated through direct observation and interviews to document process flows, time estimates, and labor and materials costs. A hypothetical optimized process flow used minimum time estimates for each process step. National wage and fringe rates and local reagent costs were used to determine the average cost (excluding overhead) per completed nonreactive and reactive test in 2013 U.S. dollars. Results. Laboratory HIV testing costs in the EDs ranged from $17.00 to $23.83 per completed nonreactive test, and POC testing costs ranged from $17.64 to $37.60; cost per completed reactive test ranged from $89.29 to $123.17. Costs of hypothetical optimized HIV testing with automated process steps were approximately 45% lower for nonreactive tests and 20% lower for reactive tests. The cost per ED visit to conduct expanded HIV testing in each hospital ranged from $1.21 to $3.96. Conclusion. An optimized process could achieve additional cost savings but would require an investment in electronic system interfaces to further automate testing processes.

BACKGROUND: Human immunodeficiency virus (HIV) testing is critical for both HIV treatment and prevention. Expanding testing in hospital settings can identify undiagnosed HIV infections. METHODS: To evaluate the feasibility of universally offering HIV testing during emergency department (ED) visits and inpatient admissions, 9 hospitals in the Bronx, New York and 7 in Washington, District of Columbia (DC) undertook efforts to offer HIV testing routinely. Outcomes included the percentage of encounters with an HIV test, the change from year 1 to year 3, and the percentages of tests that were HIV-positive and new diagnoses. RESULTS: From 1 February 2011 to 31 January 2014, HIV tests were conducted during 6.5% of 1621016 ED visits and 13.0% of 361745 inpatient admissions in Bronx hospitals and 13.8% of 729172 ED visits and 22.0% of 150655 inpatient admissions in DC. From year 1 to year 3, testing was stable in the Bronx (ED visits: 6.6% to 6.9%; inpatient admissions: 13.0% to 13.6%), but increased in DC (ED visits: 11.9% to 15.8%; inpatient admissions: 19.0% to 23.9%). In the Bronx, 0.4% (408) of ED HIV tests were positive and 0.3% (277) were new diagnoses; 1.8% (828) of inpatient tests were positive and 0.5% (244) were new diagnoses. In DC, 0.6% (618) of ED tests were positive and 0.4% (404) were new diagnoses; 4.9% (1349) of inpatient tests were positive and 0.7% (189) were new diagnoses. CONCLUSIONS: Hospitals consistently identified previously undiagnosed HIV infections, but universal offer of HIV testing proved elusive.

Background. We assessed factors associated with antiretroviral therapy (ART) adherence, including specific ART medications. Methods. The Strategies for Management of Antiretroviral Therapy study was an international antiretroviral therapy (ART) strategy trial that compared intermittent ART, using CD4+ T-cell count as a guide, to continuous ART. Adherence during the 7 days before each visit was measured using self-report. We defined high adherence as self-report of taking “all” pills for each prescribed ART medication; all other reports were defined as suboptimal adherence. Factors associated with adherence were assessed using logistic regression with generalized estimating equations. Results. Participants reported suboptimal adherence at 6016 of 35 695 study visits (17%). Factors independently associated with suboptimal adherence were black race, protease inhibitor–containing regimens, greater pill burden, higher maximum number of doses per day, and smoking. Factors independently associated with higher adherence were older age, higher education, region of residence, episodic treatment, higher latest (at the time of adherence) CD4+ T-cell count, and being prescribed concomitant drugs (ie, medications for comorbidities). Of specific drugs investigated, atazanavir, atazanavir/ritonavir, fosamprenavir, indinavir, indinavir/ritonavir, and lopinavir/ritonavir were associated with suboptimal adherence, and tenofovir disoproxil fumarate/emtricitabine was associated with higher adherence. Conclusions. In this, the largest analysis of ART adherence to date, some protease inhibitor–containing regimens and regimens with >1 dose per day were associated with suboptimal adherence.

Not the final published version, OBJECTIVE: To compare the HIV transmission risk among patients randomized to episodic versus continuous antiretroviral therapy. DESIGN: This was a substudy of the Strategies of Management of Antiretroviral Therapy study, in which patients were randomized to continuous versus CD4-guided episodic antiretroviral therapy. Participants were surveyed about sexual activity and needle sharing and had laboratory testing for gonorrhea, chlamydia, and syphilis. RESULTS: A total of 883 patients were enrolled in this study, the mean age of the patients was 45 years, 25% were women, and 78% were on antiretroviral therapy. At baseline, 136 participants (15.4%) had high-risk behavior (vaginal or anal sex without a condom, needle sharing, or incident bacterial sexually transmitted infection). After randomization, the proportion of participants reporting high-risk behavior was stable and did not differ by randomized arm (P = 0.39). Among participants off therapy at baseline, high-risk behavior was less common 4 months after randomization among those who were randomized to start antiretroviral therapy (P = 0.03). HIV transmission risk (high-risk behavior while HIV RNA level >1500 copies/mL) with partners perceived to be HIV uninfected was higher in the episodic therapy arm (P = 0.02). CONCLUSIONS: Patients on episodic antiretroviral therapy did not decrease high-risk behavior, and because HIV RNA levels were higher, this strategy may result in increased HIV transmission.

Symptoms and quality of life were assessed among human immunodeficiency virus (HIV)-infected individuals initiating their first course of antiretroviral therapy. Symptoms, which were mostly mild or moderate, were common in the first year and significantly affected the patients' quality of life. Quality of life was inversely related to the number of symptoms and in the change in the number of symptoms from baseline.

Background The Xpert MTB/RIF (Xpert) assay is a rapid nucleic acid amplification test widely used in settings of high tuberculosis prevalence to detect tuberculosis as well asrpoBmutations associated with rifampin resistance. Data are needed on the diagnostic performance of Xpert in lower-prevalence settings to inform appropriate use for both tuberculosis detection and the need for respiratory isolation. Methods Xpert was compared to 2 sputum samples, each evaluated with acid-fast bacilli (AFB) smear and mycobacterial culture using liquid and solid culture media, from participants with suspected pulmonary tuberculosis from the United States, Brazil, and South Africa. Results Of 992 participants enrolled with evaluable results, 22% had culture-confirmed tuberculosis. In 638 (64%) US participants, 1 Xpert result demonstrated sensitivity of 85.2% (96.7% in participants with AFB smear-positive [AFB(+)] sputum, 59.3% with AFB smear-negative [AFB(-)] sputum), specificity of 99.2%, negative predictive value (NPV) of 97.6%, and positive predictive value of 94.9%. Results did not differ between higher- and low-prevalence settings. A second Xpert assay increased overall sensitivity to 91.1% (100% if AFB(+), 71.4% if AFB(-)), with specificity of 98.9%. In US participants, a single negative Xpert result predicted the absence of AFB(+)/culture-positive tuberculosis with an NPV of 99.7%; NPV of 2 Xpert assays was 100%, suggesting a role in removing patients from airborne infection isolation. Xpert detected tuberculosis DNA and mutations associated with rifampin resistance in 5 of 7 participants with rifampin-resistant, culture-positive tuberculosis. Specificity for rifampin resistance was 99.5% and NPV was 98.9%. Conclusions In the United States, Xpert testing performed comparably to 2 higher-tuberculosis-prevalence settings. These data support the use of Xpert in the initial evaluation of tuberculosis suspects and in algorithms assessing need for respiratory isolation.

Treatment-naïve participants were randomized to three antiretroviral strategies (all with nucleoside reverse transcriptase inhibitor [NRTI] background): protease inhibitor (PI), non-nucleoside reverse transcriptase inhibitor (NNRTI), or PI+NNRTI. The strategies were compared for drug resistance at first virologic failure (VF; HIV RNA1000 copies/mL). The impact of resistance on AIDS or death was determined.Drug resistance was determined by genotype. Cox models were used to compare the strategies for VF with resistance and to determine the impact of resistance on AIDS or death.Of 1,360 participants, 866 experienced VF; 226 experienced AIDS or death (median follow-up 5 years). Rates (per 100 personyears) for VF with resistance were 14.9 (PI), 10.8 (NNRTI), and 11.5 (PI+NNRTI); hazard ratio (HR) was 0.78 (95% CI 0.61-0.99) for NNRTI versus PI. Compared to those with no VF, there was a significantly increased risk of AIDS or death for participants with solitary NNRTI resistance (HR 2.31, 95% CI 1.46-3.66) and for those failing with no known resistance (HR 1.78, 95% CI 1.18-2.68). Participants failing with solitary NNRTI resistance and with no resistance had the lowest percent of time on antiretroviral treatment (ART) and the lowest cumulative mean adherence scores.For treatment-naïve participants, the risk of AIDS or death is increased for those who failed virologically with solitary NNRTI resistance and those who failed with no known drug resistance compared to those with no virologic failure. Both the lack of ART exposure in nonadherent participants and the development of NNRTI resistance among those who take and fail their ART regimen predict poor clinical outcomes.

Rates of invasive disease caused by penicillin-resistant pneumococci are rising. Previous reports have found no association between resistant pneumococci and increased mortality. To evaluate the impact of penicillin resistance and other variables on mortality, we retrospectively studied all cases of pneumococcal bacteremia identified by our microbiology laboratory from 1 January 1992 through 31 December 1996. There were 462 cases of pneumococcal bacteremia in 432 patients. The mean age was 35 years; 55% of the cases occurred in male patients, 58% were in black patients, and 40% were in Hispanic patients. One-half of the cases occurred in patients with documented human immunodeficiency virus (HIV) infection. Penicillin resistance was first noted in 1994 and increased yearly, accounting for 17% of 1996 isolates. Of all resistant isolates, 65% were resistant to penicillin at a high level. The overall mortality was 17%. On multivariate analysis, high-level penicillin resistance, older age, severe disease, multilobar infiltrates and/or effusion(s) on chest roentgenogram, and Hispanic ethnicity were independent predictors of mortality in pneumococcal bacteremia. In HIV-infected patients, a CD4 cell count below the median just missed statistical significance. This is the first report demonstrating penicillin resistance as an independent predictor of mortality among patients with pneumococcal bacteremia.

OBJECTIVES To determine the seroprevalence of, and risk factors for, HTLV-I and HTLV-II infection among HIV-infected women and women at high risk for HIV infection. DESIGN Cross-sectional analysis of baseline data for women enrolled in the prospective Women's Interagency HIV Study (WIHS). METHODS From October 1994 through November 1995, 2657 women from five metropolitan areas in the United States (Chicago, Los Angeles, New York City [two sites], Northern California, and Washington DC) were enrolled in WIHS. An interview-based survey collected data on demographics, behavior, and medical history. HTLV-I and HTLV-II determinations were made using a combined HTLV-I/HTLV-II indirect immunofluorescent antibody (IFA) screening test, an IFA titration specificity test, and individual HTLV-I and HTLV-II confirmatory Western blots. Fisher's exact tests and logistic regression were used to determine univariate and multivariate independent predictors for HTLV-II infection. RESULTS Of 2625 women enrolled in WIHS with confirmed HIV results, 2487 (95%) were tested for HTLV-I and HTLV-II. Of these, 241 (10%) were HTLV-II-seropositive and 13 (0.5%) were HTLV-I-seropositive. On multivariate analysis, independent predictors of HTLV-II infection included injection drug use (OR = 5.2; p 35 years (OR = 3.3; p < .001) and a history of sex with a male injecting drug user (OR = 1.9; p < .001). Among women infected with HIV, the seroprevalence of HTLV-II was 11% compared with 6% for women at risk for HIV but not infected (p < .001). However, HIV was not an independent predictor of HTLV-II infection in multivariate analysis. CONCLUSIONS This cross-sectional analysis confirms that HTLV-II is found commonly in HIV-infected women and uninfected women at risk for HIV in major urban areas throughout the United States and that HTLV-II is far more common than HTLV-I in these populations. Although injecting drug use is most strongly associated with HTLV-II infection, sexual transmission likely contributes to the high HTLV-II seroprevalence in this cohort.

Initially recognized in 1982, acquired immunodeficiency syndrome (AIDS) has been the leading cause of death among young adults in the United States for much of this decade, and it has had a devastating impact on people in the developing world. It is estimated that 42 million people worldwide have been infected with human immunodeficiency virus (HIV), the virus that causes AIDS, and that almost 12 million people have died from AIDS-related diseases through 1997. Among these 12 million are 3 million children. Two thirds of the more than 30 million people with HIV or AIDS reside in sub-Saharan Africa. In the United States, 641,086 patients have been diagnosed with AIDS through 1997, and at least 385,000 have died. However, for the first time, new highly active antiretroviral therapies that include multiple drugs that attack the virus at several sites have slowed the progression from HIV to AIDS and from AIDS to death for those infected with HIV. The cumulative effect of these changes has been a reduction in both AIDS incident cases and AIDS deaths. Recent epidemiologic trends indicate that the proportion of AIDS incident cases and new HIV infections are increasing among women, African-Americans, and Hispanics, and the infections are more likely to be acquired through heterosexual transmission. The clinical management of HIV infection and AIDS has become increasingly complex in recent years. In addition to complete medical and social histories and physical examinations, hematologic, biochemical, serologic, and immunologic laboratory tests are required to predict the likelihood that patients will develop opportunistic infections and other complications related to HIV infection. Among the most important laboratory tests are measurements of HIV in plasma (viral load) in conjunction with peripheral blood CD4+ helper T lymphocyte counts. These tests are potent predictors of disease progression and their results have become markers for clinical response to therapy. The development of highly active antiretroviral therapy has had a profound impact on the epidemiology of AIDS and on the lives of individual patients. Through combinations of antiretroviral drugs, especially protease inhibitors, viral suppression can be achieved. However, adherence to these complex medical regimens and drug interactions have been problems for many patients. In addition, numerous questions remain unanswered, most importantly those regarding the timing of the initiation of treatment, the durability of viral suppression and clinical response, and the optimal "salvage" regimens for patients failing therapy either clinically or virologically.

This study examined whether adding levofloxacin to a standard four-drug regimen improved the 8-week culture response and compared effectiveness of 9 versus 6 months of intermittent therapy for human immunodeficiency virus-related pansusceptible pulmonary tuberculosis. Patients were randomized to receive either four or five drugs, the fifth being levofloxacin. Patients who completed induction therapy were randomized to complete 9 versus 6 months of intermittent therapy with isoniazid and rifampin. In the randomized induction phase, 97.3% of patients in the four-drug group and 95.8% in the five-drug group had sputum culture conversion at 8 weeks (P = 1.00). In the continuation phase, one patient (2%) assigned to 9 months and two patients (3.9%) assigned to 6 months of therapy had treatment failure/relapse (P = 1.00). In conclusion, this study showed that levofloxacin added no benefit to a highly effective, largely intermittent, four-drug induction regimen. Both 9 and 6 months of intermittent therapy were associated with low treatment failure/relapse rates.

Objective: To characterize the susceptibility to levofloxacin of clinical isolates of Mycobacterium tuberculosis (MTB) obtained from patients with HIV-related tuberculosis and to characterize the molecular genetics of levofloxacin resistance. Design and methods: Isolates from culture-positive patients in a United States multicenter trial of HIV-related TB were tested for susceptibility to levofloxacin by minimum inhibitory concentration (MIC) determinations in Bactec 7H12 broth. Automated sequencing of the resistance determining region of gyrA was performed. Results: Of the 135 baseline MTB isolates tested, 134 (99%; 95% exact binomial confidence interval, 95.9–99.9%) were susceptible to levofloxacin with an MIC ≤ 1.0 µg/ml. We identified a previously unrecognized mis-sense mutation occurring at codon 88 of gyrA in a levofloxacin mono-resistant MTB isolate obtained from a patient with AIDS who had received ofloxacin for 8 months prior to the diagnosis of tuberculosis. Conclusions: Clinical MTB isolates from HIV-infected patients were generally susceptible to levofloxacin. However, the identification of a clinical isolate with mono-resistance to levofloxacin highlights the need for circumspection in the use of fluoroquinolones in the setting of potential HIV-related tuberculosis and for monitoring of rates of resistance of MTB isolates to fluoroquinolones.

For hospitalized patients with smear-positive pulmonary or laryngeal tuberculosis, the Centers for Disease Control and Prevention recommends that three consecutive sputum samples be negative for acid-fast bacilli (AFB) before respiratory isolation is discontinued. Limited data are available to predict the length of time to obtain three negative sputum smears and cultures and to determine factors associated with a prolonged interval before sputum smear and culture conversion, especially among patients infected with human immunodeficiency virus (HIV). For 100 consecutive patients with smear-positive pulmonary tuberculosis, the mean and median numbers of days from the initiation of appropriate therapy to the first of three consecutive negative smears were calculated, and associated risk factors were determined. The mean number of days before the first of three consecutive negative sputum smears was 33 days; the median was 23 days. On stepwise multiple regression analysis, cavitary disease, numerous AFB on the initial smear, and no prior history of tuberculosis were the factors independently associated with an increased number of days for both smear and culture conversion. HIV does not prolong the period of infectiousness.

Our aim was to evaluate the effect of human immunodeficiency virus (HIV) disease stage on chest radiographic (CXR) findings among patients with HIV-related pulmonary tuberculosis (TB). Data are from a prospective multicenter treatment trial for HIV-related TB. Baseline CXR findings and CD4 / lymphocyte counts were compared among patients with HIV-related TB. Data from published studies describing CXR findings in HIV-infected patients were reviewed and a pooleddata analysis was conducted. Of 135 patients with culture-confirmed HIV-related TB, 128 had both CXR and CD4 / lymphocyte data. CD4 / lymphocyte counts ofo200/mm 3 (nA 98) were significantly associated with hilar/mediastinal adenopathy on CXR (30%, vs. 7% with counts ⁄200/mm 3 ; P A .01); counts of ⁄200/mm 3 (n A 30) more frequently were associated with cavitation (20% vs. 7%; PA .08). Analyses of these results, pooled with other published data, confirmed these findings. This study demonstrates associations of certain CXR findings with HIV disease stage. Knowledge of the degree of immunosuppression is important when evaluating CXR findings in HIV-infected patients.

Mycobacterium tuberculosis infects one third of the world's population, and tuberculosis remains one of the most common infectious diseases of humans. From a global perspective, tuberculosis may be one of the most common HIV-related opportunistic infections. HIV immunosuppression has had a dramatic influence on the epidemiology, natural history and clinical presentation of tuberculosis. Treatment is highly effective for drug susceptible tuberculosis and has been shown to have a significant impact on resistant, especially multidrug-resistant, tuberculosis if started promptly. Directly observed therapy and rigorous adherence to infection control principles have helped control the tuberculosis epidemic in the United States.

BACKGROUND Investigations of outbreaks of multidrug-resistant tuberculosis have found low rates of treatment response and very high mortality, and they have mainly involved patients with advanced human immunodeficiency virus (HIV) infection. For patients without HIV infection, one study reported an overall rate of response to treatment of 56 percent, and the mortality from tuberculosis was 22 percent. We investigated treatment response and mortality rates in 26 HIV-negative patients in New York with multidrug-resistant tuberculosis. METHODS We obtained detailed data from seven teaching hospitals in New York City on patients with multidrug-resistant tuberculosis--defined as tuberculosis resistant at least to isoniazid and rifampin--who were HIV-negative on serologic testing. Lengths of times from diagnosis to the initiation of appropriate therapy and from the initiation of appropriate therapy to conversion to negative cultures were assessed. Therapeutic responses were evaluated by both microbiologic and clinical criteria. RESULTS Between March 1991 and September 1994, 26 HIV-negative patients were identified and treated. Of the 25 patients for whom adequate data were available for analysis, 24 (96 percent) had clinical responses; all 17 patients for whom data on microbiologic response were available had such a response. The median times from diagnosis to the initiation of appropriate therapy and from the initiation of therapy to culture conversion were 44 days (range, 0 to 181) and 69 days (range, 2 to 705), respectively. Side effects requiring the discontinuation of medication occurred in 4 of 23 patients (17 percent) who were treated with second-line antituberculosis medications. The median follow-up for the 23 patients who responded and who received appropriate therapy was 91 weeks (range, 41 to 225). CONCLUSIONS In this report from New York City, HIV-negative patients with multidrug-resistant tuberculosis, contrary to previous reports, responded well to appropriate chemotherapy, both clinically and microbiologically.

The annual number of cases of tuberculosis in New York City has increased since 1978. In addition, in 1991 a 1-month survey of cases of tuberculosis in New York City found that 33% of all cases were resistant to at least one drug. To determine susceptibility trends from 1987 to 1991, a period during which an unprecedented rise in resistant tuberculosis occurred in New York City, we reviewed the microbiology records of 44 New York City hospitals (comprising > 14,000 cases). The percentage of cases resistant to at least one drug rose from 19% in 1987 to 28% in 1991, and the percentage of cases resistant to isoniazid rose from 13% in 1987 to 23% in 1991, while resistance to at least both isoniazid and rifampin rose from 6% to 14%. The rise of multidrug-resistant tuberculosis occurred in all four surveyed boroughs (counties) of New York City. These data demonstrate how rapidly multidrug-resistant tuberculosis can appear, and they suggest that initial empirical regimens should be broadened at certain hospitals.

To assess the association between adherence to antiretroviral therapy and the presence of class-specific antiretroviral medication resistance.Secondary analysis of prospective clinical trial data.Participants randomized to the protease inhibitor or nonnucleoside reverse transcriptase inhibitor (NNRTI) strategies of the Community Programs for Clinical Research on AIDS (CPCRA) Flexible Initial Retrovirus Suppressive Therapies (FIRST) Study were included. Adherence was measured by 7-day self-report. Virological failure was defined as an HIV-RNA more than 1000 at or after 4 months. The association between cumulative adherence and the development of class-specific genotypic resistance was assessed by Cox regression analysis.Included were 457 and 446 antiretroviral-naive participants on the protease inhibitor and NNRTI strategies, respectively. The median time to initial virological failure in the protease inhibitor strategy was 1.2 years; 135 (30%) individuals failed with resistance. The median time to initial virological failure in the NNRTI strategy was 3.0 years; 127 (28%) failed with resistance. No association was found between cumulative adherence and protease inhibitor resistance [hazard ratio 1.1, 95% confidence interval (CI) 0.9-1.4 per 10% lower adherence]. However, lower cumulative adherence was associated with an increased risk of NNRTI resistance at initial virological failure (hazard ratio 1.2, 95% CI 1.1-1.3 per 10% lower adherence). In both strategies, lower cumulative adherence was associated with an increased risk of nucleoside reverse transcriptase inhibitor (NRTI) resistance at initial virological failure.Adherence-resistance relationships are class-specific. For NRTIs and NNRTIs, initial virological failure with resistance is more likely at lower levels of cumulative adherence.

Infections due to Salmonella serotype enteritidis have increased markedly in the northeastern United States. Due to the potential severity of these infections, host risk factors for infection were determined in the largest nosocomial S. enteritidis outbreak to have occurred in the United States. In a case-control study, patients in a New York City hospital who developed infection after exposure to an S. enteritidis-contaminated meal were more likely to be medication-dependent diabetics than were those who did not develop infection (17/75 vs. 7/80, Mantel-Haenszel adjusted odds ratio = 3.1, 95% confidence interval = 1.1, 8.6). Proposed mechanisms for diabetes as a risk factor for infection include decreased gastric acidity in diabetic patients and an autonomic neuropathy of the small bowel that reduces intestinal motility and prolongs gastrointestinal transit time.

A study of risk factors for HIV-1 infection was conducted at a sexually transmitted disease clinic in an area of New York City where the cumulative incidence of AIDS in adults through mid-1990 was 9.1 per 1000 of the population and where the use of illicit drugs, including smokable freebase cocaine (crack), is common. The overall seroprevalence among volunteers was 12% (369 out of 3084), with 80% of those who were seropositive reporting risk behavior associated with HIV-1 infection, including male-to-male sexual contact, intravenous drug use and heterosexual contact with an intravenous drug user. The seroprevalence in individuals denying these risks was 3.6% (50 out of 1389) and 4.2% (22 out of 522) in men and women, respectively. Among these individuals, the behaviors significantly associated with infection were use of crack and prostitution in women, and history of syphilis and crack use in men. These results suggest that in areas where the level of HIV-1 infection in heterosexual intravenous drug users is high and the use of crack is common, increased sexual activity (including the exchange of drugs or money for sex) may result in increased heterosexual transmission of HIV-1.

The adequacy of treatment for syphilis has routinely been evaluated by the serological response, i.e. the rapid plasma reagin test (RPR). Since the description of AIDS and HIV aspects of both the natural history of syphilis and the response of Treponema pallidum to treatment have come under increased scrutiny. With concurrent epidemics of HIV and syphilis in New York City, a serological case-control study was done to determine whether HIV-infected individuals given treatment for primary or secondary syphilis have a modified serological response. All study participants had primary or secondary syphilis and paired specimens available for testing. Cases were defined as people who were HIV-positive and were compared with controls who were HIV-negative. HIV-infected patients with primary syphilis when compared with HIV-negative controls were less likely to have a fourfold or greater RPR decrease or seroreversion within 6 months of treatment [15 out of 28 versus 153 out of 210; odds ratio = 0.4, P less than 0.05]. Cases and controls with secondary syphilis had similar serological responses after treatment for syphilis. Although this study adds to the growing body of literature which suggests that HIV may alter the RPR response, prospective studies are needed to determine definitively whether HIV alters the serological response to therapy in patients with early syphilis.

Objectives—To investigate the occurrence of differential adherence to components of combination antiretroviral therapy and assess its predictors and association with virological failure and antiretroviral medication resistance. Design—A secondary analysis of prospective clinical trial data. Methods—The Flexible Initial Retrovirus Suppressive Therapies study (Community Programs for Clinical Research on AIDS 058) was a randomized trial comparing non-nucleoside reverse transcriptase inhibitor (NNRTI) versus protease inhibitor (PI) versus NNRTI plus PI-based (threeclass) antiretroviral therapy in treatment-naive HIV-1-infected individuals. Adherence was assessed at months 1 and 4, and then every 4 months. Differential adherence, defined as any difference in selfreported level of adherence to individual antiretroviral medications at the same timepoint, was evaluated as a binary time-updated variable in multivariate Cox regression analyses of time to initial virological failure (HIV-RNA >1000 copies/ml) and initial virological failure with genotypic antiretroviral resistance. Results—Differential adherence was reported at least once by 403 of 1379 participants (29%), over 60 months median follow-up. Differential adherence was more commonly reported by participants randomly assigned to the three-class strategy (35%) than the NNRTI (28%) or PI (25%) strategies (P = 0.005), but was not associated with demographic or baseline disease-specific factors. Of those reporting differential adherence, 146 (36%) reported it before initial virological failure. These participants had an increased risk of initial virological failure and initial virological failure with antiretroviral resistance compared with participants without differential adherence before initial virological failure. Conclusion—Differential adherence was commonly reported and was associated with an increased risk of initial virological failure and initial virological failure with antiretroviral resistance.

A decrease in the number of circulating CD4+ T-lymphocytes occurs in subjects infected with the human immunodeficiency virus (HIV). In those without HIV infection, depletion of T-lymphocytes in general and CD4+ cells in particular has been reported in association with many underlying conditions, including tuberculosis. A low CD4+ T-lymphocyte count at the time of diagnosis of tuberculosis does not clarify whether the low count is a predisposing factor for or a consequence of the disease. Our patients without HIV infection but with tuberculosis and CD4+ T-lymphocyte depletion on presentation normalized their CD4+ cell counts with tuberculosis treatment. This normalization strongly suggests that tuberculosis is a reversible cause of CD4+ lymphocytopenia.

Background. Zidovudine is a thymidine analogue that has been reported to have antiviral and antineoplastic activity in vitro. Methods. The case of a patient with acquired immune deficiency syndrome (AIDS) and a pulmonary non-Hodgkin lymphoma treated with zidovudine and no other treatment is presented. Results. The patient achieved a prolonged partial remission of a pulmonary non-Hodgkin lymphoma while receiving zidovudine alone. Conclusions. Zidovudine may have antitumor effects in AIDS-related lymphomas and should be evaluated for its antitumor potential.

Cases of multidrug-resistant tuberculosis (MDRTB), defined as resistance to at least isoniazid and rifampin, increased sharply in the early 1990s [1–3]. The rise in MDRTB was associated with previous treatment for tuberculosis, human immunodeficiency virus (HIV) infection, and in some inner city communities, recently transmitted disease [1,4,5]. Case fatality rates in early outbreak investigations often exceeded 80%, with a median survival of between 4 and 16 weeks [6–11]. Subsequent data documented a substantial decline in the number of new MDRTB cases and improvement in clinical outcomes, even among severely immunocompromised patients [12– 15]. Drug resistant tuberculosis, however, is not a new phenomenon. In fact, almost immediately after the introduction of streptomycin in 1944, streptomycin-resistant Mycobacterium tuberculosis was described [16,17]. Patients who initially had responded to treatment later relapsed as a result of streptomycin-resistant strains. The development of effective therapy followed by drug resistance and clinical failure is a recurrent theme in the history of tuberculosis. This chapter will focus specifically on studies that have provided data on the expected outcome of patients with MDRTB. The treatment of MDRTB in both the industrial and developing world, the pharmacology of second-line antituberculosis chemotherapy and new chemotherapeutic agents and strategies are discussed elsewhere in this volume [18–21].

The acceptance of highly active antiretroviral therapy (HAART) among patients and health care providers has had a dramatic impact on the epidemiology and clinical characteristics of many opportunistic infections associated with human immunodeficiency virus (HIV). Previously intractable opportunistic infections and syndromes are now far less common. In addition, effective antibiotic prophylactic therapies have had a profound impact on the risk of patients developing particular infections and on the incidence of these infections overall. Most notable among these are Pneumocystis carinii, disseminated Mycobacterium avium complex, tuberculosis, and toxoplasmosis. Nevertheless, infections continue to cause significant morbidity and mortality among patients who are infected with HIV. The role of HAART in many clinical situations is unquestioned. Compelling data from clinical trials support the use of these therapies during pregnancy to prevent perinatal transmission of HIV. HAART is also recommended for health care workers who have had a "significant" exposure to the blood of an HIV-infected patient. Both of these situations are discussed in detail in this article. In addition, although more controversial, increasing evidence supports the use of HAART during the acute HIV seroconversion syndrome. An "immune reconstitution syndrome" has been newly described for patients in the early phases of treatment with HAART who develop tuberculosis, M avium complex, and cytomegalovirus disease. Accumulating data support the use of hydroxyurea, an agent with a long history in the field of myeloproliferative disorders, for the treatment of HIV. Newer agents, particularly abacavir and adefovir dipivoxil, are available through expanded access protocols, and their roles are being defined and clarified.

The number of patients with methicillin-resistant Staphylococcus aureus (MRSA) before and after discontinuing placement of patients into private rooms was determined. The mean monthly number of patients with MRSA decreased from 34 to 22, and the proportion of S aureus isolates that were MRSA decreased from 34% to 20%. We found no evidence that failure to isolate patients with MRSA resulted in an increased prevalence of MRSA.

We conducted a retrospective study of patients with culture-confirmed multidrug-resistant tuberculosis (MDR-TB) at Bronx-Lebanon Hospital Center (South Bronx, NY) to determine what factors affected clinical and microbiological responses and survival. For the 38 patients with MDR-TB, reporting of first-line drug susceptibilities was relatively rapid (median time, 30 days). Thirty-four patients (89%) were infected with human immunodeficiency virus (HIV), and initial and overall response rates were 59% and 50%, respectively; the median survival was 315 days; and 50% of these patients died of tuberculosis. Bivariate analysis revealed that the following factors had a positive impact on response and survival: receiving > or = 2 consecutive weeks of appropriate therapy with at least two drugs to which the isolate was susceptible in vitro; starting appropriate therapy within 4 weeks of the diagnosis; and having tuberculosis that was limited to the lungs. Multivariate analysis revealed that the only variable associated with response was receipt of appropriate therapy for > or = 2 consecutive weeks. In contrast to findings in the published literature, our results indicate the outcome of MDR-TB can be improved, particularly for severely immunosuppressed HIV-infected patients. Rapid reporting of susceptibilities and prompt initiation and continuation of appropriate antituberculous therapy improved response and survival.

Objective: To evaluate the impact of a coordinated approach for the isolation, diagnosis, and treatment of patients with tuberculosis. Design: Retrospective cohort study. Setting: Bronx-Lebanon Hospital Center, an inner-city hospital in the South Bronx, New York City. Patients: Patients with smear-positive, culture-confirmed pulmonary tuberculosis. Interventions: Institution of a coordinated tuberculosis team. Results: Admissions of 46 patients before and 39 patients after the formation of a tuberculosis team were reviewed. Before institution of the tuberculosis team, 35% of patients were isolated within 24 hours of presentation, 41% never were isolated, and the mean number of days patients were not isolated was 19. After implementation of the tuberculosis team, 59% of patients were isolated within 24 hours, only 5% were never isolated, and the mean number of days patients were not isolated was 3.5. These differences were statistically significant. There also was a corresponding decrease in length of hospitalization. In addition, there were noticeable improvements in patient and staff morale and attitudes. Conclusions: The tuberculosis team likely has decreased the risk of nosocomial tuberculosis transmission by increasing the proportion of infectious tuberculosis patients admitted into AFB isolation and by reducing (by 780) the number of days out of isolation while smear positive. There also were concomitant financial savings.

To determine the relative risk for human immunodeficiency virus (HIV-1) seroconversion in patients with and without genital ulcers caused by chancroid, syphilis, and herpes.A prospective cohort study.An inner-city, sexually transmitted disease clinic.Patients seronegative for HIV-1 with and without genital ulcers who were followed for a minimum of 3 months.Questionnaire to obtain data on demographics, sexual behavior, and illicit drug use; testing for HIV-1 at entry and at a minimum of 3 months after entry; medical examination for the presence or absence of genital ulcer disease.Overall, 758 heterosexual men with no history of injection drug use completed the study; HIV-1 seroconversion occurred in 10 of 344 (2.9%; 95% CI, 1.4% to 5.3%) men with a genital ulcer and in 4 of 414 (1%; CI, 0.2% to 2.5%) without a genital ulcer (relative risk, 3.0; P = 0.05). In a multiple logistic regression analysis, those men with chancroid and a new sexually transmitted disease during follow-up each had about three times the risk for HIV-1 seroconversion (Por = 0.04).In this group of heterosexual men, chancroid and repeated acquisition of sexually transmitted diseases appeared to facilitate the sexual transmission of HIV-1.

Invasive aspergillosis is an uncommon infectious complication in patients with AIDS. Of the 972 patients with AIDS who were observed at our institution over a 10-year period, Aspergillus species were isolated from the respiratory sites of 45 patients before death. Invasive aspergillosis was documented at autopsy in four of these patients and was strongly suspected in an additional patient on whom an autopsy was not performed. A fifth case was documented at autopsy (no antemortem respiratory sample was obtained from this patient). Traditional risk factors for the development of invasive disease (neutropenia, hematologic malignancy, and/or corticosteroid use) were present in all of our patients with invasive aspergillosis. A review of the literature revealed reports of an additional 13 cases of invasive aspergillosis in patients with AIDS. Therapy with amphotericin B should be considered for neutropenic patients with AIDS who have pneumonia of uncertain etiology and from whom Aspergillus species have been isolated from a respiratory specimen.

To determine risk factors for the development of pneumothorax in patients with the acquired immunodeficiency syndrome (AIDS).Prospective cohort study.Tertiary care center.Of 1030 patients with AIDS who were followed at Memorial Sloan-Kettering Cancer Center between 1 January 1980 and 30 September 1989, 20 (2%) developed pneumothorax that was unrelated to trauma or a pulmonary procedure.Of 20 patients with AIDS who presented with pneumothorax, 19 had compelling evidence of concurrent Pneumocystis carinii pneumonia. Using bivariate analysis, patients receiving aerosol pentamidine prophylaxis (relative risk, 17.6) and those with a history of P. carinii pneumonia (relative risk, 14.5) were more likely to develop pneumothorax. By Mantel-Haenszel stratified analysis, aerosol pentamidine use was a statistically significant risk factor independent of a history of P. carinii pneumonia. The pneumothorax-related mortality rate was 10% and there was considerable morbidity.Patients with AIDS at the highest risk for developing pneumothorax are those with a history of P. carinii pneumonia who are receiving aerosol pentamidine prophylaxis but who nevertheless develop P. carinii pneumonia. The benefits of aerosol pentamidine prophylaxis in these patients far outweigh this risk. Pneumocystis carinii pneumonia should be considered as the most likely diagnosis in any patient with AIDS who develops a pneumothorax.

A case of disseminated infection with Pneumocystis carinii is presented, and the Englishlanguage literature is reviewed for cases of documented extrapulmonary infection with this organism. In this case- with P. carinii diffusely replacing the bone marrow and causing hepatic, adrenal, and glomerular tuft necrosis - the clinical illness and multiple-organ dysfunction attributed to disseminated P carinii were more severe than had previously been described. Because the rate of extrapulmonary R carinii infection found at autopsy in patients with AIDS is at least 2.5% at our institution, we caution against the routine use of aerosol rather than parenteral pentamidine for treatment of P carinii pneumonia until additional data are available. Pneumocystis carinii is the most common agent causing opportunistic infection in patients with AIDS. Over 60% of patients with AIDS reported to the Centers for Disease Control have presented with P carinii pneumonia (PCP) as their initial op

In October and November 1987, eight cases of type E botulism occurred in New York City and Israel. All eight patients had eaten uneviscerated, salted, air-dried whitefish known as kapchunka. Clostridium botulinum was isolated from samples of fish, and trypsinized portions of kapchunka contained type E toxin despite levels of salt that were far in excess of those considered adequate for safety. As C. botulinum has been found in the viscera of fish from the Great Lakes, possible explanations for the outbreak include multiplication of C. botulinum and production of toxin during shipping or during processing before the fish reached inhibitory salt levels. However, there was no evidence of mishandling of the fish. More likely, the viscera provided a relatively low salt "protective" environment for organism multiplication and toxin production. A major public health campaign was initiated and regulations were passed prohibiting the processing, distribution, and sale of raw, uneviscerated, salt-cured fish products within New York City.

Background Recurrent pneumococcal bacteremia receives infrequent mention in the literature, usually in association with patients who are immunocompromised. Objective To examine recurrent cases of pneumococcal bacteremia to determine risk factors and outcomes (mortality rates and emergence of resistance) associated with recurrences. Methods We retrospectively reviewed all cases of pneumococcal bacteremia identified by our microbiology laboratory from January 1, 1992, through December 31, 1996. Demographic, clinical, and laboratory data were abstracted. Results There were 462 bacteremic episodes in 432 patients; 23 of these patients had 30 recurrent episodes. The 5.3% recurrence rate (23/432) is greater than that previously described. The median time to recurrence was 200 days. The mean age of patients with recurrences was 34 years, 70% were women, all were black or Hispanic (in near equal numbers), and 87% were infected with the human immunodeficiency virus (HIV). Human immunodeficiency virus infection, coexistent cancer, and female sex were independent predictors of recurrence. Only patients who were HIV-infected had multiple recurrences. Isolates from recurrent bacteremias were more likely to be penicillin-resistant than were initial bacteremic isolates (relative risk, 2.0; P = .16). Patients with recurrences had a higher (although not statistically significant) mortality rate than those without recurrences (22% vs 16%; P = .33). There was an inverse relationship between severity of illness and likelihood of recurrence. Conclusions Rates of recurrent pneumococcal bacteremia may be higher than previously reported. In patients with recurrent pneumococcal bacteremia, the presence of an underlying immunodeficiency should be investigated.

Background: We conducted a trial to compare treatment with zidovudine or didanosine in patients with advanced human immunodeficiency virus type 1 (HIV-1) infection who had received little or no previous therapy with zidovudine. Methods: Six hundred seventeen patients with acquired immunodeficiency syndrome (AIDS), advanced AIDS-related complex (CD4 cell count, ≤0.30× 10 9 /L [300/μL]), or asymptomatic HIV (CD4 cell count, ≤0.20× 10 9 /L) received zidovudine, 500 mg/d of didanosine, or 750 mg/d of didanosine in a randomized, double-blind allocation, with cross-over to alternative medication after development of an end point or serious toxic effect. To be eligible, patients must have received either no or up to 16 weeks of zidovudine therapy before entry into the study. Primary end points were development of a new AIDS-defining event or death. Secondary clinical end points were new or recurrent AIDS-defining events, or death, and survival. Results: In the study as a whole, there were no differences in the relative risks (RRs) of the development of end points between treatment groups. However, there was a strong interaction between the relative efficacies of zidovudine and didanosine and previous experience with zidovudine. Among 380 patients with no previous zidovudine therapy, zidovudine was more effective than 750 mg/d of didanosine (RR, 1.43; 90% confidence interval [CI], 1.02 to 2.00), with a similar trend for zidovudine compared with 500 mg/d of didanosine (RR, 1.21; 90% CI, 0.86 to 1.71). However, among 118 patients with more than 8 weeks but no more than 16 weeks of previous zidovudine therapy, 500 mg/d of didanosine was more effective than zidovudine (RR, 0.48; 90% CI, 0.27 to 0.86); there was a similar trend for increased effectiveness of 750 mg/d of didanosine compared with zidovudine (RR, 0.61; 90% CI, 0.36 to 1.03). Among 119 patients who had some but no more than 8 weeks of previous zidovudine therapy, there were no significant differences among the treatment arms. Similar findings were noted in the analysis of the two secondary clinical end points. No significant differences were found in efficacy between the groups receiving 500 and 750 mg/d of didanosine. The major toxic effect associated with zidovudine was hematopoietic (granulocytopenia) and that associated with didanosine was pancreatitis (dosage, 750 mg/d). Conclusions: In patients with advanced HIV disease, zidovudine appears to be more effective than didanosine as initial therapy; however, some patients with advanced HIV disease may benefit from a change to didanosine therapy after as little as 8 to 16 weeks of therapy with zidovudine. (Arch Intern Med. 1995;155:961-974)