Keith Chirgwin

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.

Neurological outcomes in late HIV infection: Adverse impact of neurological impairment on survival and protective effect of antiviral therapy

OBJECTIVE In a large multi-center clinical trial of combination reverse transcriptase inhibitors (RTIs), we assessed the impact of antiretroviral therapy on neurological function, the relationship between neurological and systemic benefit, and the prognostic value of neurological performance in late HIV-1 infection. DESIGN Neurological evaluations incorporated in a randomized, multi-center trial of combination antiretroviral therapy. SETTING Forty-two AIDS Clinical Trials Group sites and seven National Hemophilia Foundation sites. PATIENTS Adult HIV-infected patients (n = 1313) with CD4 counts < 50 x 10(6) cells/l. INTERVENTIONS Four combinations of reverse transcriptase inhibitors consisting of zidovudine (ZDV), alternating monthly with didanosine (ddl), or in combination with zalcitabine (ddC), ddl or ddl and nevirapine. MAIN OUTCOME MEASURES Mean change from baseline of a four-item quantitative neurological performance battery score, the QNPZ-4, administered to 1031 subjects. RESULTS Triple therapy and ZDV/ddl combination preserved or improved neurological performance over time compared with the alternating ZDV/ddl and ZDV/ddC regimens (P < 0.001), paralleling their impact on survival in the same trial as previously reported. QNPZ-4 scores were predictive of survival (P < 0.001), after adjusting for CD4 counts and HIV-1 plasma RNA concentrations. CONCLUSIONS Combination antiretroviral therapy can have a salutary effect on preserving or improving neurological function. Superior systemic treatments may likewise better preserve neurological function. The significant association of poor neurological performance with mortality, independent of CD4 counts and HIV-1 RNA levels indicates that neurological dysfunction is an important cause or a strong marker of poor prognosis in late HIV-1 infection. This study demonstrates the value of adjunctive neurological measures in large therapeutic trials of late HIV-1 infection.

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.

Hiv prevalence, immunosuppression, and drug resistance in patients with tuberculosis in an area endemic for Aids

From October 1987 to June 1988, we attempted to determine the prevalence of HIV infection among patients hospitalized with tuberculosis and the extent of immunosuppression among those tuberculosis patients infected with HIV. Of 178 consecutive patients, 18–65 years of age, who were hospitalized with newly diagnosed, previously untreated tuberculosis, 46% (82 out of 178) had clinical or serological evidence of HIV infection, 30% (54 out of 178) were HIV-seronegative, and 24% (42 out of 178) could not be assessed for the presence of HIV infection. Among the HIV-seropositive patients without an AIDS-defining diagnosis by non-tuberculous criteria, the median CD4 lymphocyte (CD4) count was 133 ± 106 cells/l (range: 11–677 ± 106); among the HIV-seronegative patients, the median CD4 count was 613 ± 106 cells/l (range: 238–1614 ± 106; P < 0.001). Among the HIV-seropositive patients, those with disseminated tuberculosis (median CD4 = 79 ± 106 cells/l) and those with pulmonary tuberculosis who had radiographic evidence of mediastinal or hilar adenopathy (median CD4 = 45 ± 106 cells/l) had the most severe CD4 depletion, whereas those with localized extrapulmonary tuberculosis (median CD4 = 242 ± 106 cells/l) and those with pulmonary tuberculosis without adenopathy (median CD4 = 299 ± 106 cells/l) were less severely immunosuppressed. Of the 178 patients, 6% (11 out of 178) were infected with strains of Mycobacterium tuberculosis resistant to both isoniazid and rifampin.

Menstrual function in human immunodeficiency virus-infected women without acquired immunodeficiency syndrome

To assess whether HIV infection is associated with menstrual abnormalities in HIV-infected women without AIDS, we evaluated 248 premenopausal HIV-infected women without AIDS and 82 HIV-negative women. Detailed medical, drug use, and menstrual histories (using menstrual calendars) were obtained. Complete physical and pelvic examinations and CD4 counts were performed. HIV-infected women were more likely to experience intervals > 6 weeks without menstrual bleeding [8 vs. 0%, odds ratio (OR) = 10.8, 95% confidence interval (CI) 1.8-1,000) and amenorrhea > 3 months (5 vs. 0%, OR = 7.1, 95% CI 1.1-1,000) (after adjustment for drug use, age, and race). Premenstrual breast swelling (p = 0.01), tenderness (p = 0.01), and dysmenorrhea (p = 0.04) were less common in HIV-infected women. There were no differences in intermenstrual bleeding or irregular menstrual cycles. Among HIV-infected women, only a past history of substance abuse was significantly associated with menstrual irregularities in a logistic regression model adjusting for age, current and past drug use, alcohol use, cigarette smoking, CD4 count, and category B conditions [1993 Centers for Disease Control (CDC) classification system]. The increase in amenorrhea (> 3 months) and in menstrual cycle intervals > 6 weeks and the lower rates of premenstrual breast symptoms in HIV-positive women suggest the possibility of disturbances in menstrual function that do not appear to be attributable to clinically apparent secondary complications of HIV. Changes in menstrual function were also significantly associated with a past history of, but not current, substance abuse, suggesting the possibility that socioeconomic factors rather than biologic effects of drugs may be responsible.

Susceptibility to levofloxacin of mycobacterium tuberculosis isolates from patients with Hiv-related tuberculosis and characterization of a strain with levofloxacin monoresistance

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.

Incidence and risk factors for heterosexually acquired HIV in an inner-city cohort of women : Temporal association with pregnancy

BACKGROUND A growing proportion of AIDS cases in the United States are due to heterosexual transmission of HIV, particularly in women. The risk of heterosexually acquired HIV was prospectively studied in a cohort of inner-city women with no history of parenteral drug use. METHODS Study participants were evaluated at 6-month intervals for the presence of HIV antibody, sexually transmitted diseases, self-reported sexual behavior, and drug use by self-report and urine screening. RESULTS Of 449 initially HIV-negative women who were seen at least once in follow-up, 4 seroconverted to HIV, with a cumulative incidence of 2.4% at 30 months. Risk factors for HIV seroconversion included nonparenteral drug use (p < .02) and anal intercourse (p < .01). Sexually transmitted diseases were not associated with HIV, although the power to detect such an association was limited. In addition, 3 of 4 seroconverters became pregnant, yielding a rate of 55.5 pregnancies/100 person-years of follow-up compared with a rate of 11.1 pregnancies/100 person-years of follow-up in nonseroconverters (p < .03). CONCLUSION The incident rate of heterosexually acquired HIV in this inner-city U.S. cohort of women who were not using parenteral drugs is comparable with that reported in some developing countries where heterosexually acquired HIV is endemic. Most seroconversions appeared related to risk behavior seen in association with nonparenteral drug use. The previously unreported association of incident HIV infection with pregnancy in this cohort may be related to either behavioral or biologic factors.