Edward E. Telzak

Heterosexual transmission of HIV-1 associated with the use of smokable freebase cocaine (crack)

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.

Quality of life in HIV-infected individuals receiving antiretroviral therapy is related to adherence

This study assesses changes in quality of life (QoL) over time among HIV-infected individuals receiving antiretroviral therapy (ART) and evaluates how this relates to ART adherence. Prospective, longitudinal data were examined from 1050 participants in two large, randomized, multi-centre antiretroviral clinical trials. QoL was assessed by the SF-12; adherence by the Terry Beirn Community Programs for Clinical Research on AIDS Antiretroviral Medication Self-report. Participants included 20% women, 53% African Americans, 16% Latinos; mean age was 39 years; mean baseline CD4+ cell count 230 cells/mm3; 89% were ART-naïve at entry. Baseline physical and mental health summary QoL scores were 45.4 and 42.9, comparable to scores reported in other advanced HIV populations. Significant improvements in mean QoL scores were seen for the group as a whole after 1 to 4 months on new ART regimens, and persisted for 12 months. Participants reporting 100% ART adherence achieved significantly higher QoL scores at 12 months compared to those with poorer adherence, particularly if 100% adherence was consistent (p<0.001). Those with at least 80% ART adherence had smaller gains in QoL at 12 months when compared to baseline, while those with <80% adherence had worsening of QoL. In this analysis, ART adherence was associated with improved QoL, particularly if adherence was sustained.

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.

Multidrug-Resistant Tuberculosis in Patients without HIV Infection

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.

Penicillin Resistance and Other Predictors of Mortality in Pneumococcal Bacteremia in a Population with High Human Immunodeficiency Virus Seroprevalence

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.

HIV-1 Seroconversion in Patients with and without Genital Ulcer Disease: A Prospective Study

Since the beginning of the acquired immunodeficiency syndrome (AIDS) epidemic, two predominant and distinct epidemiologic patterns of human immunodeficiency virus (HIV-1) transmission have been reported. In North America and Western Europe, although heterosexual transmission has been increasing [1], men exposed to HIV-1 through sexual contact with other men and injection drug users (users of illicit drugs) are the predominant groups at risk for development of AIDS [2]. The second pattern, prevalent in Africa and parts of Asia and the Caribbean, is predominantly characterized by heterosexual transmission, with a nearly equal male-to-female ratio of patients [3, 4]. The reasons for these different patterns of transmission have not been fully identified, but studies have addressed the possibility that the presence of genital ulcers, especially chancroid, has enhanced heterosexual transmission [5, 6]. Sexually transmitted diseases that result in a disrupted genital epithelium, such as syphilis, chancroid, and herpes, have been associated with heterosexual transmission of HIV-1 using retrospective studies in the United States [7-10] and both retrospective [11] and prospective studies in sub-Saharan Africa [12, 13]. In New York City, an ongoing epidemic of genital ulcer disease has occurred in communities where HIV-1 infection related to injection drug use is well documented [10, 14]. The number of cases of primary and secondary syphilis reported to the New York City Department of Health increased from 2157 in 1985 to 4231 in 1990. The number of reported cases of chancroid increased from 1323 in 1985 to 2277 in 1989. Consequently, a prospective study of HIV-1 seroconversion was initiated to further characterize the relation between genital ulcer disease and HIV-1 transmission in primarily heterosexual persons in the United States. Methods Study Population This study was done in 1 of the 12 inner-city, sexually transmitted disease clinics operated by the New York City Department of Health. The study site is located in an area of New York City where the cumulative incidence of AIDS in adults through 1990 was 1 per 100 persons (New York City AIDS Case Surveillance data) and illicit drug use, including crack (smokable freebase cocaine) use, is common. In 1990, this clinic provided care to 14 243 persons: 9589 (67%) were men and 4654 were women. Primary or secondary syphilis was diagnosed in 226 patients, and 113 were found to have chancroid. From 1988 to 1989, the HIV-1 prevalence in this clinic was 7.8%, estimated by a serosurvey that was done without using patient identifiers (Weisfuse I. Personal communication). Study Population Recruitment into the study consisted of two phases. In the first phase, all of the approximately 28 000 persons attending the clinic for diagnosis or treatment of a sexually transmitted disease during the study period were asked to participate in a study of the prevalence of HIV-1 infection and associated risk factors. Those who agreed (n = 2893) received HIV-1 pretest counseling and were given a return appointment to receive test results and post-test counseling. Those with a diagnosis of genital ulcer were recruited more intensively. Thus, approximately 700 (24%) of the 2893 participants recruited into phase 1 had genital ulcers. These 700 participants with genital ulcer disease represented more than 80% of all patients seen in the clinic with ulcers during the study period. Study interviewers administered standardized questionnaires in either English or Spanish. Information on demographic characteristics, socioeconomic status, and risk behavior associated with HIV-1 transmission was collected, as previously described [14]. Of the 2543 participants who were HIV negative, 1679 returned for post-test counseling 3 weeks after initial study enrollment and were asked to participate in the prospective component (or phase 2) of the study. For those who agreed, an additional questionnaire was administered to identify potential HIV-1-related high-risk behavior during three periods of interest: the 6 months before the initial clinic visit, the 10 days before the symptom developed that resulted in the clinic visit, and the period while the symptoms were present. The questioning focused on intravenous drug use and the number of sexual contacts and the type of sexual activities with intravenous drug users, homosexual or bisexual men, prostitutes, and others. The regularity of condom use was determined using the following scale: always, usually (>50%), sometimes (approximately 50%), rarely (<50%), and never. Anonymous HIV-1 testing was available for patients who did not want to participate in the study or who did not have a sexually transmitted disease. At the time of enrollment in phase 2, participants were asked to return to the clinic for a third time, approximately 3 months after the initial clinic visit. For the participants who returned for the final follow-up visit, a repeated serum sample for HIV-1 testing was obtained, and a questionnaire similar to that described above was administered to identify high-risk behavior for the period between the two HIV-1 antibody tests. Informed consent was obtained for both phases of the study, and the study was approved by the institutional review boards of the New York City Department of Health and the Centers for Disease Control and Prevention. Laboratory Methods Patients with a genital ulcer had the following diagnostic tests: syphilis serology, dark-field examination of ulcer exudate for Treponema pallidum, Gram stain of ulcer exudate, microbiologic culture for Haemophilus ducreyi using blood and chocolate media, and Tzanck smear for herpes virus. Testing for syphilis was done using the rapid plasma reagin card test (Hynson, Wescott, and Dunning; Baltimore, Maryland) and the microhemagglutination assay for T. pallidum (Fujirebio Inc., Tokyo, Japan, and Ames Division, Miles Laboratory, Elkhart, Indiana). Haemophilus ducreyi was isolated using previously described methods [15]. Antibody testing for HIV-1 was done by an enzyme-linked immunosorbent assay (DuPont, Wilmington, Delaware), followed by a confirmatory Western blot analysis of all reactive samples using reagents prepared by the Laboratory of Retrovirology and Immunobiology of the New York City Department of Health [16]. Diagnosis of Genital Ulcer Disease Primary syphilis was diagnosed when a genital ulcer was present and the ulcer exudate was dark-field positive, the rapid plasma reagin card test was positive, or the patient had recent contact with a person known to have syphilis. A diagnosis of chancroid was made when a positive culture occurred for H. ducreyi, if Gram stain of the ulcer exudate showed pleomorphic gram-negative rods, or if clinical findings suggested chancroid (tender or multiple ulcers, painful inguinal adenitis) with a negative dark-field examination as well as a negative syphilis serologic test result and a negative Tzanck smear. Genital herpes was diagnosed when the lesions were vesicular or recurrent or an ulcer had a positive Tzanck smear. In the absence of, or with negative, microbiologic and serologic data, the clinical diagnosis was made by the supervising physician in the clinic and not by study personnel. Statistical Analysis Analysis was done using the SAS statistical software system, version 6.06 (SAS Institute, Inc., Cary, North Carolina). The strength of the association between individual categorical variables or continuous variables grouped categorically and HIV-1 seroconversion was evaluated by the relative risk, and 95% direct precision-based CIs were obtained. Statistical relations were tested by the chi-square test or the Fisher exact test (two-tailed). Differences between continuous variables were analyzed by the Student t-test (two-tailed), the Wilcoxon rank-sum test, or the median test. The SAS LOGIST procedure was used to fit the multiple logistic regression model to the single binary outcome variable (HIV seroconversion or no seroconversion). The adjusted odds ratios obtained in this model approximated the adjusted relative risk. Measurement of Risk Index For heterosexual men, a summary measure was constructed of the risk for HIV-1 transmission attributable to a combination of the probability of encountering and the frequency of exposure to an HIV-1-infected partner. The sexual risk index was generated for the period from 6 months before the clinic visit through the second HIV test. Indices were computed by taking the sum of the products of the number of sexual contacts with partners in each of four risk groups (prostitutes, female intravenous drug users, women with chancroid, and women with no risk) and the estimated HIV-1 seroprevalence among the members of that group. Prevalence estimates for risk groups were determined from among our own study participants during phase 1, unblinded risk-factor serosurvey because sexual contacts were likely to occur in the local geographic area. The overall seroprevalence for the 644 women with no risk in phase 1 was 6%, for the 88 injection drug users it was 44%, for the 167 female prostitutes it was 29%, and for the 26 women with chancroid it was 19%. Using these values, risk indices were generated for four groups of male study participants: those with chancroid who did and did not seroconvert and those without chancroid who did and did not seroconvert. The risk indices were scaled proportionately from 0 to 100 for graphic presentation. Statistical comparisons were done between the Sexual Risk Index medians of the patients with chancroid and those without chancroid who seroconverted; between those without chancroid who seroconverted and those without chancroid who did not seroconvert; and between patients with chancroid who seroconverted and all patients who did not seroconvert using the median test. Results Of the 2543 seronegative persons identified in the cross-sectional component (phase 1) of the study, 1679 (62%) r

Pneumothorax in AIDS

Objective: To determine risk factors for the development of pneumothorax in patients with the acquired immunodeficiency syndrome (AIDS). Design: Prospective cohort study. Setting: Tertiary care cen...

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.

Factors Influencing Time to Sputum Conversion Among Patients with Smear-Positive Pulmonary Tuberculosis

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.

Differential adherence to combination antiretroviral therapy is associated with virological failure with resistance

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 (three-class) 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 self-reported 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.