Michael Augenbraun

A Randomized Trial of Enhanced Therapy for Early Syphilis in Patients with and without Human Immunodeficiency Virus Infection

BACKGROUND Reports of neurosyphilis and invasion of cerebrospinal fluid by Treponema pallidum in patients with human immunodeficiency virus (HIV) infection have led to doubts about the adequacy of the recommended penicillin G benzathine therapy for early syphilis. METHODS In a multicenter, randomized, double-blind trial, we assessed two treatments for early syphilis: 2.4 million units of penicillin G benzathine and that therapy enhanced with a 10-day course of amoxicillin and probenecid. The serologic and clinical responses of patients with and without HIV infection were studied during one year of follow-up. RESULTS From 1991 through 1994, 541 patients were enrolled, including 101 patients (19 percent) who had HIV infection but differed little from the uninfected patients in their clinical presentations. The rates at which chancres and rashes resolved did not differ significantly according to treatment assignment or HIV status. Serologically defined treatment failures were more common among the HIV-infected patients. The single clinically defined treatment failure was in an HIV-infected patient. Rates of serologically defined treatment failure did not differ according to treatment group (18 percent at six months with usual therapy; 17 percent with enhanced therapy). T. pallidum was found at enrollment in the cerebrospinal fluid of 32 of 131 patients (24 percent) and after therapy in 7 of 35 patients tested. None had clinically evident neurosyphilis, and the rate of detection of T. pallidum did not differ according to HIV status. CONCLUSIONS After treatment for primary or secondary syphilis, the HIV-infected patients responded less well serologically than the patients without HIV infection, but clinically defined failure was uncommon in both groups. Enhanced treatment with amoxicillin and probenecid did not improve the outcomes. Although T. pallidum was detected in cerebrospinal fluid before therapy in a quarter of the patients tested, such a finding did not predict treatment failure. The current recommendations for treating early syphilis appear adequate for most patients, whether or not they have HIV infection.

Impact of Highly Active Antiretroviral Therapy on Anemia and Relationship Between Anemia and Survival in a Large Cohort of Hiv-infected Women: Women’s Interagency Hiv Study

BackgroundAnemia is common in HIV-infected individuals and may be associated with decreased survival. ObjectiveTo ascertain the impact of highly active antiretroviral therapy (HAART) on anemia and the relationship between anemia and overall survival in HIV-infected women. MethodsA prospective multicenter study of HIV-1 infection in women. Visits occurred every 6 months, including a standardized history, physical examination, and comprehensive laboratory evaluation. The setting was a university-affiliated clinic at 6 sites in the United States. Participants were 2056 HIV-infected women from the Women’s Interagency HIV Study (WIHS). The outcome measure was anemia, defined as hemoglobin (Hb) <12 g/dL. Survival analysis was based on overall mortality during the follow-up period. ResultsAmong HIV-infected women who were not anemic at baseline, 47% became anemic by 3.5 years of follow-up. On multivariate analysis, the use of HAART was associated with resolution of anemia even when used for only 6 months (odds ratio [OR] = 1.45; P < 0.05). In the multivariate model, a CD4 cell count <200 cells/μL (OR = 0.56; P < 0.001); HIV-1 RNA level ≥50,000 copies/mL (OR = 0.65; P < 0.001), and mean corpuscular volume (MCV) value <80 fL (OR = 0.40; P < 0.001) were also associated with an inability to correct anemia. Similarly, use of HAART for 12 months or more was associated with a protective effect against development of anemia (OR = 0.71; P < 0.001). Among HIV-infected women, anemia was independently associated with decreased survival (hazard ratio [HR] = 2.58; P < 0.001). Other factors associated with decreased survival included a CD4 cell count <200 cells/μL (HR = 5.83; P < 0.001), HIV-1 RNA level ≥50,000 copies/mL (HR = 2.12; P < 0.001), and clinical diagnosis of AIDS (HR = 2.83; P < 0.001). ConclusionsAnemia is an independent risk factor for decreased survival among HIV-infected women. HAART therapy for as little as 6 months is associated with resolution of anemia.

Prevalence and correlates of anemia in a large cohort of HIV-infected women: Women's interagency HIV study

Summary: Anemia is a common manifestation of HIV infection, occurring in approximately 30% of patients with asymptomatic infection and in as many as 75% to 80% of those with AIDS. Anemia has been associated with decreased quality of life and decreased survival. We performed a cross‐sectional study nested within a multicenter prospective cohort study to describe the prevalence of anemia in 2056 HIVinfected and 569 HIV‐negative women as well as to define the demographic, clinical, immunologic, and virologic correlates of anemia among HIV‐infected women. A total of 37% of HIV‐positive women and 17% of HIV‐negative women had hemoglobin levels < 12 g/dl (p < .001). Factors associated with anemia in HIV‐positive and HIV‐negative women included mean corpuscular volume (MCV) < 80 fl (p < .001) and black race (p < .001). Among HIV‐infected women, multivariate logistic analyses revealed that African American race (p < .0001), MCV < 80 fl (p < .0001), CD4 count < 200 per microliter (p < .0001), higher HIV RNA in plasma (p = .02), current use of ZDV (p = .01), and history of clinical AIDS (p = .004) were all independent predictors of anemia. These data indicate that worsening parameters of HIV disease are associated with anemia among HIV‐infected women. Black women and women with low MCV values are at increased risk for anemia independent of HIV status.

Normalization of cerebrospinal fluid abnormalities after neurosyphilis therapy: does HIV status matter?

To identify factors that affect normalization of laboratory measures after treatment for neurosyphilis, 59 subjects with neurosyphilis underwent repeated lumbar punctures and venipunctures after completion of therapy. The median duration of follow-up was 6.9 months. Stepwise Cox regression models were used to determine the influence of clinical and laboratory features on normalization of cerebrospinal fluid (CSF), white blood cells (WBCs), CSF protein concentration, CSF Venereal Disease Research Laboratory (VDRL) reactivity, and serum rapid plasma reagin (RPR) titer. Human immunodeficiency virus (HIV)-infected subjects were 2.5 times less likely to normalize CSF-VDRL reactivity than were HIV-uninfected subjects. HIV-infected subjects with peripheral blood CD4+ T cell counts of < or =200 cells/ mu L were 3.7 times less likely to normalize CSF-VDRL reactivity than were those with CD4+ T cell counts of >200 cells/ mu L. CSF WBC count and serum RPR reactivity were more likely to normalize but CSF-VDRL reactivity was less likely to normalize with higher baseline values. Future studies should address whether more intensive therapy for neurosyphilis is warranted in HIV-infected individuals.

Activation of CD8 T Cells Predicts Progression of HIV Infection in Women Coinfected with Hepatitis C Virus

BACKGROUND Because activation of T cells is associated with human immunodeficiency virus (HIV) pathogenesis, CD4 and CD8 activation levels in patients coinfected with HIV and hepatitis C virus (HCV) may explain conflicting reports regarding effects of HCV on HIV disease progression. METHODS Kaplan-Meier and multivariate Cox regression models were used to study the risk of incident clinical AIDS and AIDS-related deaths among 813 HCV-negative women with HIV infection, 87 HCV-positive nonviremic women with HIV coinfection, and 407 HCV-positive viremic women with HIV coinfection (median follow-up time, 5.2 years). For 592 women, the percentages of activated CD4 and CD8 T cells expressing HLA-DR (DR) and/or CD38 were evaluated. RESULTS HCV-positive viremic women had a statistically significantly higher percentage of activated CD8 T cells (P < .001) and a statistically significantly higher incidence of AIDS compared with HCV-negative women (P < .001 [log-rank test]). The AIDS risk was greater among HCV-positive viremic women in the highest tertile compared with the lowest tertile (>43% vs <26%) of CD8(+)CD38(+)DR(+) T cells (hazard ratio, 2.94 [95% confidence interval, 1.50-5.77]; P = .001). This difference was not observed in the HCV-negative women (hazard ratio, 1.87 [95% confidence interval, 0.80-4.35]; P = .16). In contrast, CD4 activation predicted AIDS in both groups similarly. Increased percentages of CD8(+)CD38(-)DR(+), CD4(+)CD38(-)DR(-), and CD8(+)CD38(-)DR(-) T cells were associated with a >60% decreased risk of AIDS for HCV-positive viremic women and HCV-negative women. CONCLUSION HCV-positive viremic women with HIV coinfection who have high levels of T cell activation may have increased risk of AIDS. Earlier treatment of HIV and HCV infection may be beneficial.

Lower genital tract infections among HIV-infected and high-risk uninfected women: findings of the Women's Interagency HIV Study (WIHS).

BACKGROUND AND OBJECTIVES Few comparisons of factors associated with sexually transmitted diseases (STDs) and HIV are available for representative samples of American women. GOAL OF THE STUDY To compare factors associated with STDs in a large sample of women infected with HIV and women not infected with HIV. STUDY DESIGN A cross-sectional analysis of STDs in 2,058 women seropositive (HIV+) for HIV and 567 women seronegative (HIV-) for HIV. RESULTS HIV + women were more likely than HIV- women to report previous STDs, with the exceptions of chlamydia and bacterial vaginosis. Both HIV status and CD4 lymphocyte count were associated with evidence of genital ulcerations, warts, and vaginal candidiasis (p <0.001 for all). HIV- women were more apt to report recent vaginal intercourse (p <0.001), a factor that was independently associated with the occurrence of bacterial and protozoan infections. CD4 lymphocyte depletion was the factor most closely associated with the expression of chronic viral infections. CONCLUSIONS In this North American cohort, HIV+ women were more likely than HIV- women to report previous genital tract infections and symptoms. However, the HIV+ women reported less recent sexual activity and few gonococcal or chlamydial infections.

Factors associated with hepatitis C viremia in a large cohort of HIV-infected and - uninfected women

BACKGROUND Co-infection with hepatitis C virus (HCV) is common among HIV-infected women. OBJECTIVE To further our understanding of the risk factors for HCV viremia and the predictors of HCV viral load among women. STUDY DESIGN We investigated sociodemographic, immunologic, and virologic factors associated with presence and level of HCV viremia among 1049 HCV-seropositive women, 882 of whom were HIV-infected and 167 HIV-uninfected at their entry into the Womens Interagency HIV Study. RESULTS Plasma HCV RNA was detected in 852 (81%) of these 1049 women (range: 1.2-7.8 log(10)copies/ml). HCV-viremic women were more likely to have an HIV RNA level >100,000 copies/ml (P=0.0004), to have reported smoking (P=0.01), or to be Black (P=0.005). They were less likely to have current or resolved hepatitis B infection. HCV RNA levels were higher in women who were >35 years old, or HIV-infected. Current smoking and history of drug use (crack/freebase cocaine, marijuana, amphetamines, or heroin) were each associated with both presence and level of viremia. CONCLUSIONS Substance abuse counseling aimed at eliminating ongoing use of illicit drugs and tobacco may reduce clinical progression, improve response to treatment, and decrease HCV transmission by lowering levels of HCV viremia in women.

Chlamydia pneumoniae pneumonia with pleural effusion: Diagnosis by culture

A case of Chlamydia pneumoniae pneumonia with pleural effusion in an otherwise healthy 19-year-old man is described. Diagnosis was made by serologic means as well as by culture of both the nasopharynx and the pleural fluid.

Integrated plan to augment surge capacity.

INTRODUCTION Surge capacity is defined as a healthcare systems ability to rapidly expand beyond normal services to meet the increased demand for appropriate space, qualified personnel, medical care, and public health in the event ofbioterrorism, disaster, or other large-scale, public health emergencies. There are many individuals and agencies, including policy makers, planners, administrators, and staff at the federal, state, and local level, involved in the process of planning for and executing policy in respect to a surge in the medical requirements of a population. They are responsible to ensure there is sufficient surge capacity within their own jurisdiction. PROBLEM The [US] federal government has required New York State to create a system of hospital bed surge capacity that provides for 500 adult and pediatric patients per 1 million population, which has been estimated to be an increase of 15-20% in bed availability. In response, the New York City Department of Health and Mental Hygiene (NYC DOH) has requested that area hospitals take an inventory of available beds and set a goal to provide for a 20% surge capacity to be available during a mass-casualty event or other conditions calling for increased inpatient bed availability. METHODS In 2003, under the auspices of the NYC DOH, the New York Institute of All Hazard Preparedness (NYIHP) was formed from four unaffiliated, healthcare facilities in Central Brooklyn to address this and other goals. RESULTS The NYIHP hospitals have developed a surge capacity plan to provide necessary space and utilities. As these plans have been applied, a bed surge capacity of approximately 25% was identified and created for Central Brooklyn to provide for the increased demand on the medical care system that may accompany a disaster. Through the process of developing an integrated plan that would engage a public health incident, the facilities of NYIHP demonstrate that a model of cooperation may be applied to an inherently fractioned medical system.

The insulin-like growth factor axis and risk of liver disease in hepatitis C virus/HIV-co-infected women

Objective:Insulin-like growth factor (IGF) I stimulates the proliferation of hepatic stellate cells (HSC), the primary source of extracellular matrix accumulation in liver fibrosis. In contrast, insulin-like growth factor binding protein (IGFBP) 3, the most abundant IGFBP in circulation, negatively modulates HSC mitogenesis. To investigate the role of the IGF axis in hepatitis C virus (HCV)-related liver disease among high-risk patients, we prospectively evaluated HCV-viremic/HIV-positive women. Design:A cohort investigation. Methods:Total IGF-I and IGFBP-3 were measured in baseline serum specimens obtained from 472 HCV-viremic/HIV-positive subjects enrolled in the Womens Interagency HIV Study, a large multi-institutional cohort. The aspartate aminotransferase to platelet ratio index (APRI), a marker of liver fibrosis, was assessed annually. Results:Normal APRI levels (< 1.0) at baseline were detected in 374 of the 472 HCV-viremic/HIV-positive subjects tested, of whom 302 had complete liver function test data and were studied. IGF-I was positively associated [adjusted odds ratio comparing the highest and lowest quartiles (AORq4–q1), 5.83; 95% confidence interval (CI) 1.17–29.1; Ptrend = 0.03], and IGFBP-3 was inversely associated (AORq4–q1, 0.13; 95% CI 0.02–0.76; Ptrend = 0.04), with subsequent (incident) detection of an elevated APRI level (> 1.5), after adjustment for the CD4 T-cell count, alcohol consumption, and other risk factors. Conclusion:High IGF-I may be associated with increased risk and high IGFBP-3 with reduced risk of liver disease among HCV-viremic/HIV-positive women.