Showing papers by "Henry Masur published in 2009"

Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America.

Abstract: This report updates and combines earlier versions of guidelines for the prevention and treatment of opportunistic infections (OIs) in HIV-infected adults (i.e., persons aged >/=18 years) and adolescents (i.e., persons aged 13--17 years), last published in 2002 and 2004, respectively. It has been prepared by the Centers for Disease Control and Prevention (CDC), the National Institutes of Health (NIH), and the HIV Medicine Association (HIVMA) of the Infectious Diseases Society of America (IDSA). The guidelines are intended for use by clinicians and other health-care providers, HIV-infected patients, and policy makers in the United States. These guidelines address several OIs that occur in the United States and five OIs that might be acquired during international travel. Topic areas covered for each OI include epidemiology, clinical manifestations, diagnosis, prevention of exposure; prevention of disease by chemoprophylaxis and vaccination; discontinuation of primary prophylaxis after immune reconstitution; treatment of disease; monitoring for adverse effects during treatment; management of treatment failure; prevention of disease recurrence; discontinuation of secondary prophylaxis after immune reconstitution; and special considerations during pregnancy. These guidelines were developed by a panel of specialists from the United States government and academic institutions. For each OI, a small group of specialists with content-matter expertise reviewed the literature for new information since the guidelines were last published; they then proposed revised recommendations at a meeting held at NIH in June 2007. After these presentations and discussion, the revised guidelines were further reviewed by the co-editors; by the Office of AIDS Research, NIH; by specialists at CDC; and by HIVMA of IDSA before final approval and publication. The recommendations are rated by a letter that indicates the strength of the recommendation and a Roman numeral that indicates the quality of evidence supporting the recommendation, so that readers can ascertain how best to apply the recommendations in their practice environments. Major changes in the guidelines include 1) greater emphasis on the importance of antiretroviral therapy for the prevention and treatment of OIs, especially those OIs for which no specific therapy exists; 2) information regarding the diagnosis and management of immune reconstitution inflammatory syndromes; 3) information regarding the use of interferon-gamma release assays for the diagnosis of latent Mycobacterium tuberculosis (TB) infection; 4) updated information concerning drug interactions that affect the use of rifamycin drugs for prevention and treatment of TB; 5) the addition of a section on hepatitis B virus infection; and 6) the addition of malaria to the list of OIs that might be acquired during international travel. This report includes eleven tables pertinent to the prevention and treatment of OIs, a figure that pertains to the diagnois of tuberculosis, a figure that describes immunization recommendations, and an appendix that summarizes recommendations for prevention of exposure to opportunistic pathogens.

Evolving health effects of Pneumocystis: one hundred years of progress in diagnosis and treatment.

Abstract: 2009 marks the 100th anniversary of the first description of Pneumocystis, an organism that was ignored for much of its first 50 years but that has subsequently been recognized as an important pathogen of immunocompromised patients, especially patients infected with human immunodeficiency virus (HIV). We present a patient with chronic lymphocytic leukemia who died from Pneumocystis pneumonia (PCP) despite appropriate anti-Pneumocystis therapy. Although substantial advances in diagnosis, treatment, and prevention of PCP have decreased its frequency and improved prognosis, PCP continues to be seen in both HIV-infected patients and patients receiving immunosuppressive medications. Pneumocystis species comprise a family of fungi, each of which appears to be able to infect only 1 host species. Pneumocystis has a worldwide distribution. Immunocompetent hosts clear infection without obvious clinical consequences. Pneumocystis has been identified in patients with other diseases such as chronic obstructive pulmonary disease, although its clinical impact is uncertain. Immunocompromised patients develop disease as a consequence of reinfection and possibly reactivation of latent infection. In patients with HIV infection, the CD4 count is predictive of the risk for developing PCP, but such reliable markers are not available for other immunocompromised populations. In the majority of patients with PCP, multiple Pneumocystis strains can be identified using recently developed typing techniques. Because Pneumocystis cannot be cultured, diagnosis relies on detection of the organism by colorimetric or immunofluorescent stains or by polymerase chain reaction. Trimethoprim-sulfamethoxazole is the preferred drug regimen for both treatment and prevention of PCP, although a number of alternatives are also available. Corticosteroids are an important adjunct for hypoxemic patients.

HIV-Associated Opportunistic Infections—Going, Going, But Not Gone: The Continued Need for Prevention and Treatment Guidelines

Abstract: In the United States, the incidence of HIVassociated opportunistic infections (OIs) has decreased dramatically. The trend observed in the Centers for Disease Control and Prevention (CDC)-sponsored HIV Outpatient Study—a prospective, observational cohort study involving 18500 HIV-infected persons in 9 US cities who have received routine outpatient care (figure 1)—is typical of trends seen in many other clinical and research cohorts and medical practices. These reductions have resulted, in part, from improvements in and the diffusion of effective OI prophylaxis, but most importantly, they have resulted from the advent of combination antiretroviral therapy. It is not uncommon now for some medical residents and infectious diseases fellows to have never seen a case of cytomegalovirus retinitis or cryptosporidial diarrhea in an HIV-infected patient. As antiretroviral therapy becomes simpler, more potent, and less toxic, and

Fighting HIV/AIDS In Washington, D.C.

Abstract: Washington, D.C., is the capital of the United States and is a major center for public health and health policy expertise. Yet the District of Columbia has an HIV prevalence rate among adults of 3 percent, on par with some sub-Saharan African countries. To date, the local public health response has not controlled the epidemic. The ways in which that response has been galvanized in recent years—through collaboration among the capital’s public health agencies, community and faith organizations, and research institutions—may be instructive to other jurisdictions combating HIV/AIDS.

High Sensitivity and Specificity of Acid-Fast Microscopy for Diagnosis of Pulmonary Tuberculosis in an African Population with a High Prevalence of Human Immunodeficiency Virus

Abstract: Laboratories in low-income countries report that acid-fast microscopy is insensitive and nonspecific. We demonstrate that for a Ugandan population with high prevalences of tuberculosis and human immunodeficiency virus infection, acid-fast microscopy is highly sensitive (93.1%) and specific (100%) when performed by trained technologists in a carefully controlled manner using established techniques.

Polymerase Chain Reaction of secA1 on Sputum or Oral Wash Samples for the Diagnosis of Pulmonary Tuberculosis

Abstract: Background Nucleic acid amplification tests are sensitive and specific for identifying Mycobacterium tuberculosis in sputum smear-positive populations, but they are less sensitive in sputum smear-negative populations. Few studies have assessed their performance among patients infected with HIV, and no studies have assessed their performance with oral wash specimens, which may be easier to obtain than sputum samples. Methods We performed a prospective study involving 127 adults from 2 populations who were undergoing evaluation for respiratory complaints at Mulago Hospital in Kampala, Uganda. We obtained and tested sputum samples for Mycobacterium tuberculosis, and we simultaneously obtained oral wash specimens to test for M. tuberculosis DNA by polymerase chain reaction (PCR) amplification of a novel locus, the secA1 gene. A positive mycobacterial culture of sputum was used to define cases of tuberculosis; we calculated the sensitivity and specificity of the PCR assay with sputum or oral wash specimens in reference to the standard of sputum culture results. Results Tuberculosis (75 [59%] of 127 patients) and HIV infection (58 [46%] of 126 patients) were both common in the study population. PCR of sputum samples was highly sensitive (sensitivity, 99%; 95% confidence interval, 93%-100%) and specific (specificity, 88%; 95% confidence interval, 77%-96%) for detection of pulmonary tuberculosis and performed well among HIV-infected patients and among patients with negative sputum smear results. PCR of oral wash specimens was less sensitive (sensitivity, 73%; 95% confidence interval, 62%-83%) but also detected a substantial proportion of tuberculosis cases. Conclusions PCR targeting the secA1 gene was highly sensitive and specific for identifying M. tuberculosis in sputum samples, independent of smear or HIV infection status. Oral washes showed promise as an easily obtained respiratory specimen for tuberculosis diagnosis. PCR of sputum for detection of the secA1 gene could be a rapid, effective diagnostic tool for tuberculosis referral centers.

Hepatitis C viral kinetics during treatment with peg IFN-alpha-2b in HIV/HCV coinfected patients as a function of baseline CD4+ T-cell counts.

Abstract: Background:HIV/hepatitis C virus (HCV) coinfected patients are known to have lower sustained viral response (SVR) rates than HCV monoinfected patients. However, the role of CD4+ T-cell counts on viral kinetics and outcome is not fully understood.Methods:HCV RNA kinetics (bDNA v3, lower limit of dete

Therapeutic response to peg-IFN-alpha-2b and ribavirin in HIV/HCV co-infected African-American and Caucasian patients as a function of HCV viral kinetics and interferon pharmacodynamics.

Abstract: In this study we sought to characterize the relationship between several pharmacokinetic (PK) and pharmacodynamic (PD) parameters and virologic responses among HIV/HCV genotype-1 co-infected patients receiving pegylated interferon-alpha-2b (peg-IFN2b) and ribavirin. We also tried to establish the underlying mechanisms that lead to poor SVR rates observed with African Americans (AA) against Caucasians and compared their results with those observed in a cohort of HCV mono-infected patients. Among our studied population, a viral decline of more than 1.0 log at day 3 combined with viral load of less than 5.0 log IU/ml at day 28 predicted SVR with NPV=100% and PPV=100%. AA had significantly (P<0.01) slower HCV VK as compared to Caucasians. However, peg-IFN2b concentrations and PK parameters, peg-IFN2b max and peg-IFN2b half-life, were similar in both groups and did not predict SVR. Nevertheless, the PD parameter Ec50, estimated from non-linear fitting of the viral kinetics together with peg-IFN2b concentration data, showed that HIV/HCV co-infected AA have lower sensitivity to interferon-alpha thus giving rise to slower viral decline. The combined PK/PD parameter IFNmax/Ec90 was excellent predictor of SVR, thus showing the importance to maintain peg-IFN2b levels above Ec90 to achieve successful treatment. Further studies are needed to evaluate whether these pharmacodynamical predictions are a result of differential host response to peg-IFN2b or other viral factors conferring relative resistance to peg-IFN2b.

Rapid development of advanced liver fibrosis after acquisition of hepatitis C infection during primary HIV infection.

Abstract: We report the first reported case of a 61-year-old MSM who was diagnosed with syphilis, primary HIV infection, and acute hepatitis C (HCV) within the same time period who rapidly developed significant liver fibrosis within 6 months of acquisition of both infections. It has been well described that individuals with primary HIV infection have an increase in activated CD8+ T cells, which causes a state of immune activation as was evident in this patient. Acquisition of HCV during this time could have further skewed this response resulting in massive hepatocyte destruction, inflammation, and subsequent liver fibrosis. Recent literature suggest that MSM with primary HIV infection have higher rates of acquisition of HCV than other HIV-positive cohorts and HCV acquisition can occur very soon after acquiring HIV. This case of rapid hepatic fibrosis progression coupled with the increasing incidence of HCV in individuals with primary HIV infection demonstrates a need for this phenomenon to be studied more extensively.

Fighting HIV/AIDS In Washington, D.C. With an HIV prevalence rate comparable to some resource-limited countries, the District mounts a broad response.

Abstract: Washington, D.C., is the capital of the United States and is a major center for public health and health policy expertise. Yet the District of Columbia has an HIV preva- lence rate among adults of 3 percent, on par with some sub-Saharan African countries. To date, the local public health response has not controlled the epidemic. The ways in which that response has been galvanized in recent years—through collaboration among the capi- tal's public health agencies, community and faith organizations, and research institutions— may be instructive to other jurisdictions combating HIV/AIDS. (Health Aff (Millwood). 2009;

Drug Resistance in Pneumocystis jirovecii

Abstract: Pneumocystis jirovecii is a fungus that appears to be transmitted from human to human by aerosol spread. There is no animal reservoir and probably no environmental reservoir for the species which infects humans. Trimethoprim-sulfamethoxazole is the drug of choice for both treatment and prevention of disease in humans. The enzymes targeted by trimethoprim and by sulfamethoxazole have been identified and sequenced. In spite of the inability to culture the organisms, it is now clear that mutations involved in sulfa and atovaquone drug resistance have emerged in P. jirovecii as a result of selective pressure by the widespread use of PCP prophylaxis. Currently the clinical effect of the described mutations appears to be modest. DHPS mutations at codon 55 and 57 are implicated in failure of low-dose sulfa prophylaxis, but there is so far no firm evidence that DHPS mutations result in significant resistance to high-dose sulfa therapy. It is possible that if additional mutations arise, then high-level sulfa resistance could emerge and lead to diminished efficacy of TMP-SMX. This would lead to the loss of the most efficient and inexpensive therapy for PCP. Sequencing of the genomes of Pneumocystis species, especially P. jirovecii, will be crucial for further understanding of the infection and will enable identification of new polymorphic regions and drug targets and may eventually also lead to the development of a culture system.