Anal intraepithelial neoplasia in heterosexual and homosexual HIV-positive men with access to antiretroviral therapy.

BACKGROUND: Studies of human immunodeficiency virus (HIV)-positive men have demonstrated high rates of anal intraepithelial neoplasia (AIN), a precursor to anal carcinoma, mostly in white homosexual men and men not receiving effective antiretroviral therapy (ART). METHODS: Ninety-two participants--53% Latino, 36% African American, and 40% without a history of receptive anal intercourse (RAI)--were evaluated with a behavioral questionnaire, liquid-based anal cytological testing, Hybrid Capture 2 human papillomavirus (HPV) DNA assay and polymerase chain reaction, and anal colposcopy with biopsy of lesions. RESULTS: High-risk HPV DNA was identified in 61%, and this was associated with a history of RAI (78% vs. 33%; P<.001); 47% had abnormal cytological results, and 40% had AIN on biopsy. In multivariate analysis, both were associated with a history of RAI (odds ratio [OR], 10 [P<.001] and OR, 3.6 [P=.02], respectively) and lower nadir CD4(+) cell counts (P=.06 and P=.01). Current ART use was protective (OR, 0.09; P<.01 and OR, 0.18; P=.02). CONCLUSIONS: Although anal infections with high-risk HPV and AIN in HIV-positive men are associated with a history of RAI, both conditions are commonly identified in HIV-positive men without this history. Both lower nadir CD4(+) cell counts and lack of current ART were associated with AIN but not with the detection of anal HPV.

Incidence of cervical squamous intraepithelial lesions in HIV-infected women.

CONTEXT: Women infected with human immunodeficiency virus (HIV) are at increased risk for cervical squamous intraepithelial lesions (SILs), the precursors to invasive cervical cancer. However, little is known about the causes of this association. OBJECTIVES: To compare the incidence of SILs in HIV-infected vs uninfected women and to determine the role of risk factors in the pathogenesis of such lesions. DESIGN: Prospective cohort study conducted from October 1,1991, to June 30, 1996. SETTING: Urban clinics for sexually transmitted diseases, HIV infection, and methadone maintenance. PARTICIPANTS: A total of 328 HIV-infected and 325 uninfected women with no evidence of SILs by Papanicolaou test or colposcopy at study entry. MAIN OUTCOME MEASURE: Incident SILs confirmed by biopsy, compared by HIV status and risk factors. RESULTS: During about 30 months of follow-up, 67 (20%) HIV-infected and 16 (5%) uninfected women developed a SIL (incidence of 8.3 and 1.8 cases per 100 person-years in sociodemographically similar infected and uninfected women, respectively [P<.001]). Of incident SILs, 91% were low grade in HIV-infected women vs 75% in uninfected women. No invasive cervical cancers were identified. By multivariate analysis, significant risk factors for incident SILs were HIV infection (relative risk [RR], 3.2; 95% confidence interval [CI], 1.7-6.1), transient human papillomavirus (HPV) DNA detection (RR, 5.5; 95% CI, 1.4-21.9), persistent HPV DNA types other than 16 or 18 (RR, 7.6; 95% CI, 1.9-30.3), persistent HPV DNA types 16 and 18 (RR, 11.6; 95% CI, 2.7-50.7), and younger age (<37.5 years; RR, 2.1; 95% CI, 1.3-3.4). CONCLUSIONS: In our study, 1 in 5 HIV-infected women with no evidence of cervical disease developed biopsy-confirmed SILs within 3 years, highlighting the importance of cervical cancer screening programs in this population.

Purified protein derivative testing and tuberculosis preventive therapy for HIV-infected patients in New York City.

OBJECTIVE: To determine whether Centers for Disease Control and Prevention recommendations for purified protein derivative (PPD) testing and tuberculosis (TB) preventive therapy for PPD-positive patients are implemented in HIV clinics. DESIGN: Retrospective medical chart review. SETTING: Ten hospital-based HIV clinics in New York City. PARTICIPANTS: A total of 2397 patients with a first clinic visit in 1995. OUTCOME MEASURES: PPD testing of eligible patients, and recommendation of preventive therapy and completion of regimen in PPD-positive patients. METHOD: Outpatient medical records were abstracted for TB history, PPD testing, TB preventive therapy, and patient demographic, social and clinical characteristics. Multivariate analyses were performed using logistic regression. RESULTS: Of 1342 patients with an indication for a PPD test, 865 (64%) were PPD tested in the clinic and 757 (88%) returned to have it read. Factors strongly associated with PPD testing in the clinic were number of visits, same sex behavior with men, and CD4+ lymphocyte count above 200 x 10(6)/l. Preventive therapy was recommended for 80% of newly identified PPD-positive patients and 22% of previously identified PPD-positive patients. Of 119 patients on preventive therapy in the clinic, 49 (41%) completed the regimen, 50 (42%) were lost to follow-up, and 20 (17%) discontinued therapy or their status could not be determined. CONCLUSION: A significant number of missed opportunities to implement TB prevention practices were identified in HIV clinics. Focused attention in HIV clinics, and increased collaboration between HIV clinics and TB control programs may be needed to increase adherence to prevention guidelines.

A city-wide outbreak of a multiple-drug-resistant strain of Mycobacterium tuberculosis in New York.

SETTING: Incident patients with active tuberculosis (TB) resistant to two or more drugs in New York City hospitals in 1992. OBJECTIVE: To examine the New York-wide distribution of Public Health Research Institute (PHRI) strain W of Mycobacterium tuberculosis, an extremely drug-resistant strain identified by a 17-band Southern hybridization pattern using IS6110, during the peak tuberculosis year of 1992. We also compared strain W with other strains frequently observed in New York. DESIGN: Blinded retrospective study of stored M. tuberculosis cultures by restriction fragment length polymorphism (RFLP) DNA fingerprinting, and chart review. RESULTS: We found 112 cultures with the strain W fingerprint and 8 variants in 21 hospitals among incident patients hospitalized in 1992. Almost all isolates were resistant to four first-line drugs and kanamycin. This single strain made up at least 22% of New York City multiple-drug-resistant (MDR) TB in 1992, far more than any other strain. Almost all W-strain cases were acquired immune deficiency syndrome (AIDS) patients. The cluster is the most drug-resistant cluster identified in New York and the largest IS6110 fingerprint cluster identified anywhere to date. CONCLUSION: Because recommended four-drug therapy will not sterilise this very resistant strain, there was a city-wide nosocomial outbreak of W-strain TB in the early 1990s among New York AIDS patients. Other frequently seen strains were either also very resistant, or, surprisingly, pansusceptible. Individual MDR strains can be spread widely in situations where AIDS and TB are both common.

A multi-institutional outbreak of highly drug-resistant tuberculosis: epidemiology and clinical outcomes.

OBJECTIVE: To investigate a multi-institutional outbreak of highly resistant tuberculosis and evaluate patient outcome. DESIGN: Epidemiologic investigation of every tuberculosis case reported in New York City. SETTING: Patients cared for at all public and nonpublic institutions from January 1, 1990, to August 1, 1993 (43 months). PATIENTS: We reviewed medical and public health records and conducted clinical, epidemiologic, drug susceptibility, and restriction fragment length polymorphism (RFLP) analyses. A case was defined as tuberculosis in a patient with an isolate resistant to isoniazid, rifampin, ethambutol hydrochloride, and streptomycin (and rifabutin, if sensitivity testing included it), and, if RFLP testing was done, a pattern identical to or closely related to strain W. MAIN OUTCOME MEASURES: Patient survival and the conversion of sputum cultures from positive to negative. RESULTS: Of the 357 patients who met the case definition, 267 had identical or nearly identical RFLP patterns; isolates from the other 90 patients were not available for RFLP testing. Among these 267 patients, 86% were human immunodeficiency virus (HIV)-infected, 7% were HIV-negative, and 7% had unknown HIV status. All-cause mortality was 83%. Epidemiologic linkages were identified for 70% of patients, of whom 96% likely had nosocomially acquired disease at 11 hospitals. Survival was prolonged among patients who received medications to which their isolate was susceptible, especially capreomycin sulfate, and among patients with a CD4+ T-lymphocyte count greater than 0.200 x 10(9)/L (200/microL). Treatment with isoniazid and a fluoroquinolone antibiotic was also independently associated with longer survival. CONCLUSIONS: This outbreak accounted for nearly one fourth of the cases of multidrug-resistant tuberculosis in the United States during a 43-month period. Most patients had nosocomially acquired disease, were infected with HIV, and unless promptly and appropriately treated, died rapidly. With appropriate directly observed treatment, especially combinations including an injectable medication, even severely immunocompromised patients had culture conversion and prolonged, tuberculosis-free survival.

Low antituberculosis drug concentrations in patients with AIDS.

OBJECTIVE: To determine the frequency and magnitude of below normal apparent peak serum concentrations for antituberculosis drugs in patients with AIDS and CD4 cell counts less than 200 cells/mm3. We also explored the data for potential relationships between response variables and patient characteristics. DESIGN: Prospective study of consecutive patients seen in tuberculosis clinics. SETTING: Five urban tuberculosis clinics in four major metropolitan areas. PARTICIPANTS: Twenty-six patients diagnosed with HIV infection and receiving treatment for active tuberculosis were eligible. MAIN OUTCOME MEASURES: After 2 weeks or more of therapy, blood was collected 2 hours after observed doses of the antituberculosis drugs. Serum samples were frozen, shipped to National Jewish Center in Denver, and analyzed by HPLC or GC. Serum concentrations were compared with the proposed normal ranges. Data were analyzed to determine correlations between antituberculosis drug serum concentrations and patient characteristics. RESULTS: Low-2-hour serum concentrations were common for antituberculosis drugs, particularly rifampin and ethambutol. Absorption of isoniazid was generally high. Potential drug-drug interactions were found between rifampin and fluconazole (fluconazole appears to increase rifampin concentrations) and between pyrazinamide and zidovudine (zidovudine may lower pyrazinamide concentrations). Patients receiving pyrazinamide had lower rifampin concentrations than those not receiving pyrazinamide. CONCLUSIONS: Low antituberculosis drug serum concentrations occur frequently during the treatment of tuberculosis in patients with AIDS. Additional research is required for patients with drug-resistant tuberculosis, and to clarify the nature of the potential drug-drug interactions.

Characteristics of menstruation in women infected with human immunodeficiency virus.

OBJECTIVE: To determine the characteristics of menstruation in women infected with human immunodeficiency virus (HIV) and the impact of immunosuppression on menstruation in HIV-infected women. METHODS: In this cross-sectional study, 197 HIV-infected and 189 HIV-uninfected women were interviewed about menstruation and abnormal vaginal bleeding during the previous 12 months. Information was also obtained about CD4+ T-lymphocyte levels of HIV-infected women and other factors, including drug use and weight loss, that might affect menstruation. RESULTS: The number and duration of menses in HIV-infected women were not significantly different from those of uninfected women. During a 12-month period, 154 (78%) of 197 HIV-infected women and 150 (80%) of 188 uninfected women had 10-14 menses (P = .74). The proportions of women in the two groups with intermenstrual bleeding, postcoital bleeding, or no bleeding were also similar. In HIV-infected women, menstruation and the prevalence of abnormal vaginal bleeding were not significantly different by CD4+ T-lymphocyte level. By multiple logistic regression analysis, neither HIV infection nor CD4+ T-lymphocyte level less than 200 cells/microL was associated with intermenstrual bleeding, postcoital bleeding, or no bleeding. CONCLUSION: The results of this study suggest that neither HIV infection nor immunosuppression has a clinically relevant effect on menstruation or other vaginal bleeding. Most HIV-infected women menstruate about every 25-35 days, suggesting monthly ovulation and an intact hypothalamic-pituitary-ovarian axis.

Independent origin of mono-rifampin-resistant Mycobacterium tuberculosis in patients with AIDS.

Historically, infections caused by Mycobacterium tuberculosis have been treated simultaneously with isoniazid and rifampin. As a consequence of this combined therapy, strains resistant only to rifampin were rarely recovered. However, recently there has been an increasing number of reports describing HIV-positive patients infected with mono-rifampin-resistant M. tuberculosis strains. Organisms cultured from seven patients (including six with AIDS) with infections caused by mono-rifampin-resistant M. tuberculosis, and seen at one New York City hospital, were analyzed by molecular techniques to test the hypothesis that dissemination of a single clone had occurred. IS6110 DNA fingerprinting and automated DNA sequencing of a region of the RNA polymerase beta subunit structural gene (rpoB) containing mutations that confer rifampin resistance showed that all organisms independently acquired the mono-rifampin-resistant phenotype. Molecular analysis of mono-rifampin-resistant organisms cultured from 13 additional patients in New York City confirmed independent strain origin. The data rule out the possibility of person-to-person strain transmission among these patients, and they suggest that host factors such as poor compliance with antituberculosis medications or decreased absorption of rifampin have been a driving force in the origin of these strains.

A tale of two cities: tuberculosis control in Nicaragua and New York City.

The tuberculosis (TB) control programs in Managua, Nicaragua, and New York City are compared, including their methods of case finding, treatment, follow-up, data collection, and cure rate. In all areas, Managua's program has proven more successful than New York City's, despite the enormously greater resources available in the latter. Nicaragua's TB program concentrated on active cases, had immediately available diagnosis with a microscope in each clinic, had nearly 100% directly observed therapy during at least the first 2 months, and sent its workers into the field immediately after a patient broke an appointment. New York City's program has fewer than 2% of its patients under directly observed therapy, operates a laboratory and clinic system in which obtaining sputum smear results requires 10 to 20 days, and has delays of weeks to months in returning patients to supervision after a broken appointment. The numbers speak for themselves: the Nicaraguan TB program cured nearly 80% of the patients enrolled in the mid-to late 1980s, whereas New York City's program rarely cured 50% and in some areas cured less than 15%.

Resurgent tuberculosis in New York City. Human immunodeficiency virus, homelessness, and the decline of tuberculosis control programs.

The resurgence of tuberculosis in New York City has been largely attributed to the acquired immune deficiency syndrome (AIDS) epidemic. However, historical events predating the advent of AIDS and worsening economic and social conditions, including a rise in homelessness, have contributed significantly to the increase. We prospectively studied 224 consecutive patients with tuberculosis admitted to a large public hospital in New York over the first 9 months of 1988. Initial assessment included medical status, human immunodeficiency virus (HIV) risk factors, and detailed social information, including substance abuse history and housing status. All patients were tracked after discharge to determine compliance and cure rates. Tuberculosis patients were predominantly male (79%), with high rates of alcohol use (53%), intravenous drug and/or "crack" cocaine use (64%), and homelessness or unstable housing (68%). Half the patients had AIDS or AIDS-related complex (ARC) or were HIV antibody positive. A total of 178 patients were discharged on tuberculosis treatment, but 89% of these were lost to follow-up and failed to complete therapy. Of the 178 discharged patients, 48(27%) were readmitted within 12 months with confirmed active tuberculosis. Of these patients, 40 were discharged on treatment and at least 35 were again lost to follow-up. In a multivariate regression model noncompliance was significantly associated with the absence of AIDS or ARC (p less than 0.001), homelessness (p less than 0.005), and alcoholism (p less than 0.05). Because HIV infection and tuberculosis converge in a subpopulation with high rates of substance abuse and homelessness, the problem of ensuring treatment compliance may grow considerably in the future.(ABSTRACT TRUNCATED AT 250 WORDS)