David C. Perlman

Variation of Chest Radiographic Patterns in Pulmonary Tuberculosis by Degree of Human Immunodeficiency Virus-Related Immunosuppression

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 pooled-data analysis was conducted. Of 135 patients with culture-confirmed HIV-related TB, 128 had both CXR and CD4+ lymphocyte data. CD4+ lymphocyte counts of < 200/mm3 (n = 98) were significantly associated with hilar/mediastinal adenopathy on CXR (30%, vs. 7% with counts > or = 200/mm3; P = .01); counts of > or = 200/mm3 (n = 30) more frequently were associated with cavitation (20% vs. 7%; P = .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.

Evaluation of an Intensive Intermittent-Induction Regimen and Duration of Short-Course Treatment for Human Immunodeficiency Virus-Related Pulmonary Tuberculosis

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.

Informed altruism and "partner restriction" in the reduction of HIV infection in injecting drug users entering detoxification treatment in New York City, 1990-2001.

ObjectiveTo assess recent developments in the HIV epidemic in injecting drug users (IDUs) in New York City. With >50,000 cases of AIDS in IDUs, New York has experienced the largest HIV/AIDS epidemic in IDUs of any city in the world. MethodsSerial cross-sectional surveys conducted continuously from 1990 to 2001 of IDUs entering the Beth Israel Medical Center (BIMC) drug detoxification program in New York City. HIV serostatus, use of prevention services, and risk behaviors were measured. Individuals were permitted to participate multiple times in the surveys but not more than once in any year. ResultsTwo thousand eight hundred eighty-seven individuals contributed 3100 observations from 1990 to 2001. There was a substantial and consistent decline in the prevalence of HIV infection among IDUs entering the BIMC detoxification program, from 54% (165/304) in 1991 to 13% (39/303) in 2001 (P < 0.0001). The decline was highly linear, with r2 = 0.92 and a slope of −3.7% in seroprevalence per year. The decline occurred for both males and females, both short and long-term IDUs, and the three largest racial/ethnic subgroups (all P < 0.001 by Cochran–Armitage testing). Use of HIV prevention services increased substantially, particularly syringe exchange and voluntary HIV counseling and testing. General reductions in injection risk behaviors occurred, but substantial numbers of IDUs continued to engage in both receptive and distributive syringe sharing. Two conditional types of risk reduction not currently recommended by health authorities were reported: “informed altruism,” in which persons who knew that they were HIV seropositive reduced transmission behavior, and “partner restriction,” in which persons who shared needles and syringes primarily confined this sharing within small social networks. ConclusionsHIV infection continues to decline in this population of IDUs in New York City, suggesting the possibility of bringing very high prevalence epidemics under control. Risk elimination may not be required; rather, multiple forms of risk reduction may be effective in reducing HIV transmission within a local population of IDUs.

A Review of Efficacy Studies of 6-Month Short-Course Therapy for Tuberculosis among Patients Infected with Human Immunodeficiency Virus: Differences in Study Outcomes

Six-month regimens that include rifampin for the treatment of tuberculosis in patients without human immunodeficiency virus (HIV) infection are recommended because of low percentage of relapses. Whether a similar duration of therapy should be used to treat tuberculosis in HIV-infected patients is unclear. Six studies of patients with HIV-infection and 3 of patients without HIV infection were reviewed and compared. The studies differed in terms of design, eligibility criteria, site of disease, frequency of dosing, dose administration methods, and outcome definitions. Among HIV-infected patients, the following percentages were found: cure, 59.4%--97.1%; treatment success, 34.0%--100%; effective treatment, 29.4%--88.2%; and relapse, 0%--10%. In those without HIV infection, percentages were as follows: cure, 62.3%--88.0%; treatment success, 91.2%--98.8%; effective treatment, 70.6%--83.8%; and relapse, 0%--3.4%. Although the rate of relapse appeared to be higher in some studies of HIV-infected patients with tuberculosis, this review demonstrates the limitation in the use of relapse as the exclusive outcome of interest when comparing studies.

Providing hepatitis B vaccination to injection drug users: referral to health clinics vs on-site vaccination at a syringe exchange program.

Injection drug users (IDUs) are at very high risk for infection with hepatitis B virus (HBV) through multiperson use of injection equipment and through unprotected sexual contact. Although a safe and efficacious vaccine exists for hepatitis B, there are multiple problems in vaccinating IDUs in the United States, including (1) discrimination against drug users by health care providers, (2) the need to reach IDUs before they are exposed to HBV, (3) paying for the vaccinations, and (4) difficulties in completing the 3-injection vaccination series. We compared 2 methods for delivering free hepatitis B vaccination to IDUs: (1) referral by research staff to local health care providers and (2) on-site vaccination at a syringe exchange program.

A Focus of Rocky Mountain Spotted Fever within New York City

In the spring and summer of 1987, four persons acquired Rocky Mountain spotted fever within New York City, an area in which the disease had not previously been known to be endemic. Three of the four patients were residents of the Soundview area of the Bronx. All diagnoses were confirmed by indirect fluorescent-antibody tests. Environmental investigation revealed that the tick vector for Rickettsia rickettsii, Dermacentor variabilis, was present in a local park. Of the 66 specimens of D. variabilis collected, 5 (8 percent) were positive for rickettsiae from the spotted fever group. Of an additional 96 specimens of D. variabilis, 5 (5 percent) were found positive for rickettsiae by a more specific monoclonal antibody assay. Eight additional New York City parks in all five boroughs were searched for ticks. D. variabilis was found in only one other park; of the 147 ticks collected there, none were positive for rickettsiae. These findings emphasize the focal nature of Rocky Mountain spotted fever and the need to consider that disease in the differential diagnosis of any obscure acute febrile illness, even in the absence of a history of travel to known endemic areas.

Isospora belli Infection: Treatment with Pyrimethamine

Isosporiasis is an uncommon but important diarrheal disease of humans that, like cryptosporidiosis, is life-threatening in patients with the acquired immunodeficiency syndrome (AIDS). Isospora belli infection responds rapidly to therapy with trimethoprim-sulfamethoxazole, but patients with AIDS have a high rate of adverse reactions to this therapy. The cases of two patients with AIDS, sulfonamide allergy, and I. belli infection are reported. They were treated successfully with pyrimethamine alone, 75 mg/d, and recurrence was prevented with daily pyrimethamine therapy, 25 mg/d. In patients with AIDS with sulfonamide allergy or intolerance, pyrimethamine alone seems to be a reasonable alternative therapy for I. belli infection.

The Clinical Pharmacokinetics of Rifampin and Ethambutol in HIV-Infected Persons with Tuberculosis

BACKGROUND The pharmacokinetics of rifampin and ethambutol in HIV-infected patients with tuberculosis (TB) are incompletely characterized. We examined the pharmacokinetics of rifampin and ethambutol in a cohort of patients with HIV-related TB who were treated in the United States. METHODS Serum drug concentrations were determined 2, 6, and 10 h after dosing in 36 HIV-infected patients with TB who were taking rifampin and in 49 who were taking ethambutol. Observed serum concentrations were compared with published normal ranges and published data. RESULTS With daily dosing of rifampin (600 mg), 26 (77%) of 34 patients (95% confidence interval [CI], 59%-89%]) had a low maximum concentration of rifampin (<8 microg/mL), and 12 (35%; 95% CI, 20%-54%) had a very low maximum concentration (<4 microg/mL). With intermittent rifampin dosing (600 mg), 13 (68%) of 19 patients (95% CI, 44%-85%) had a low maximum concentration of rifampin, and 5 (26%; 95% CI, 11%-50%) had a very low maximum concentration. With daily ethambutol dosing (20 mg/kg), 33 (69%) of 48 patients (95% CI, 55%-81%) had a low maximum concentration of ethambutol (<2 microg/mL), and 18 (38%; 95% CI, 24%-53%) had a very low maximum concentration (<1 microg/mL). With intermittent ethambutol dosing (50 mg/kg twice weekly or 30 mg/kg thrice weekly), 13 (72%) of 18 patients (95% CI, 47%-88%) had a low maximum concentration of ethambutol (<4 microg/mL), and 5 (28%; 95% CI, 12%-54%]) had a very low maximum concentration (<2 microg/mL). CONCLUSIONS In HIV-infected patients with TB who are receiving rifampin and ethambutol, low maximum concentrations of rifampin and ethambutol were common. For patients with HIV-related TB, therapeutic monitoring of rifampin and ethambutol levels may help clinicians achieve target serum concentrations.

A Randomized Trial of a Hepatitis Care Coordination Model in Methadone Maintenance Treatment

OBJECTIVES We evaluated the efficacy of a hepatitis care coordination intervention to improve linkage to hepatitis A virus (HAV) and hepatitis B virus (HBV) vaccination and clinical evaluation of hepatitis C virus (HCV) infection among methadone maintenance patients. METHODS We conducted a randomized controlled trial of 489 participants from methadone maintenance treatment programs in San Francisco, California, and New York City from February 2008 through June 2011. We randomized participants to a control arm (n = 245) and an intervention arm (n = 244), which included on-site screening, motivational-enhanced education and counseling, on-site vaccination, and case management services. RESULTS Compared with the control group, intervention group participants were significantly more likely (odds ratio [OR] = 41.8; 95% confidence interval [CI] = 19.4, 90.0) to receive their first vaccine dose within 30 days and to receive an HCV evaluation within 6 months (OR = 4.10; 95% CI = 2.35, 7.17). A combined intervention adherence outcome that measured adherence to HAV-HBV vaccination, HCV evaluation, or both strongly favored the intervention group (OR = 8.70; 95% CI = 5.56, 13.61). CONCLUSIONS Hepatitis care coordination was efficacious in increasing adherence to HAV-HBV vaccination and HCV clinical evaluation among methadone patients.

Persistence and Change in Disparities in HIV Infection Among Injection Drug Users in New York City After Large-Scale Syringe Exchange Programs

OBJECTIVES We examined racial/ethnic disparities in HIV infection among injection drug users (IDUs) before and after implementation of large-scale syringe exchange programs in New York City. METHODS Participants were recruited from IDUs entering the Beth Israel drug detoxification program in New York City. Participants (n = 1203) recruited from 1990 through 1994, prior to large-scale syringe exchange programs (pre-exchange), were compared with 1109 participants who began injecting in 1995 or later and were interviewed in 1995 through 2008 (post-exchange). RESULTS There were large differences in HIV prevalence among pre-exchange vs post-exchange participants (African Americans, 57% vs 15%; Hispanics, 53% vs 5%; Whites, 27% vs 3%). Pre- and post-exchange relative disparities of HIV prevalence were similar for African Americans vs Whites (adjusted odds ratio [AOR] = 3.46, 95% confidence interval [CI] = 2.41, 4.96 and AOR = 4.02, 95% CI = 1.67, 9.69, respectively) and Hispanics vs Whites (AOR = 1.76, 95% CI = 1.49, 2.09 and AOR = 1.49, 95% CI = 1.02, 2.17). Racial/ethnic group differences in risk behavior did not explain differences in HIV prevalence. CONCLUSIONS New interventions are needed to address continuing disparities in HIV infection among IDUs, but self-reported risk behaviors by themselves may not be adequate outcome measures for evaluating interventions to reduce racial/ethnic disparities in HIV infection.