AIDS Clinical Trials Group

About: AIDS Clinical Trials Group is a nonprofit organization based out in Boston, Massachusetts, United States. It is known for research contribution in the topics: Zidovudine & Didanosine. The organization has 90 authors who have published 66 publications receiving 4099 citations.

The prevalence of rectal, urethral, and pharyngeal Neisseria gonorrheae and Chlamydia trachomatis among asymptomatic men who have sex with men in a prospective cohort in Washington, D.C.

Abstract: Dear Editor: Studies in sexually transmitted disease (STD) and HIV clinics show that the cumulative prevalences (for all anatomic sites—pharynx, rectum, and urine) of Neisseria gonorrhea (GC) and Chlamydia trachomatis (CT) among men who have sex with men (MSM), regardless of symptoms, range from 6%–25% and 2%–12%, respectively.1,2 The prevalence (for both organisms and all anatomic sites) in studies of predominantly asymptomatic samples of HIV-positive MSM (the most recently published of which reported a combined GC, CT, and syphilis prevalence of 14% among a sample composed entirely of asymptomatic, HIV-positive MSm3) has been 4%–11%.4,5 Since GC and CT infections may be asymptomatic, the Centers for Disease Control and Prevention (CDC) recommends screening MSM for both organisms.6 The majority of GC/CT prevalence studies among MSM have occurred at STD/HIV clinics among younger men, many of whom were symptomatic; furthermore, the 20- to 24-year-old age group has the highest prevalence of GC/CT infection in men.7 Evidence suggests there is an increasing incidence of HIV among older MSM,8,9 and because nonulcerative sexually transmitted infections (STIs) increase risk of HIV transmission10,11 more data are needed from community-based, asymptomatic cohorts of older MSM to evaluate GC/CT screening strategies. To address this paucity of data, we performed a pilot study to evaluate the prevalence of rectal, urethral and pharyngeal GC/CT in the pharynx, rectum and urethra among 147 asymptomatic MSM in the Multicenter AIDS Cohort Study (MACS), a long-standing cohort of aging MSM, whose average age is 51 years. Each DC MACS participant is seen semiannually at the Whitman Walker Clinic (WWC) for a detailed interview, a physical examination, and phlebotomy. The study questionnaires are available at www.statepi.jhsph.edu/macs/forms.html. One urine, rectal, and pharyngeal sample were collected from participants in the Washington, D.C. MACS who attended at least one of their visits from December 2006 to December 2007. Testing was performed at the WWC laboratory using a validated nucleic acid amplification technique (NAAT), the ProbeTec Strand Displacement Assay (Becton Dickinson, Franklin Lakes, NJ) the average sensitivity/specificity of which in the pharynx is 71.9%/99.5% for GC and 66.7%/100% for CT, and in the rectum 100%/99.5% for GC and 63.2%/100% for CT.12 The study protocol was approved by the Institutional Review Boards of Johns Hopkins University and Whitman Walker Clinic. Written informed consent was obtained from each participant. Comparisons between patients with “ever” versus “never” positive tests were performed using the χ2 method and exact p values for all outcomes except age, which was compared using a t test. Prevalence estimates were calculated using the number of participant screening visits. Descriptive statistics and t test results were calculated using SAS version 9.1 (SAS Institute, Inc., Cary, NC), while χ2 tests and 95% exact Casella-Blythe-Still confidence intervals were computed in StatXact version 4 (Cytel Inc., Cambridge, MA) to accommodate the small numbers of positive tests. Of the 160 active Washington, D.C. MACS participants, 156 attended at least one visit from December 2006 to December 2007, and 147 (94%) of these were enrolled. Of the 9 not enrolled, 8 declined, and 1 was excluded because he had deferred the physical examination. There were 242 participant screening visits (65% screened twice). The participants were predominantly white and middle-aged (mean, 50.9 years) and all were asymptomatic; 45% were HIV positive (Table 1). Of 242 sets of specimens tested, 14 tested positive, yielding a GC/CT prevalence from all anatomic sites of 5.8% (Table 2). In the pharynx, 7 samples (2.9%) were positive for GC and 1 (0.4%) for CT. In the rectum, 2 samples were positive for GC (0.8%) and 4 for CT (1.7%). All urine samples tested were negative for both organisms. The average age of those with positive GC/CT results was 49.6 ± 8.3. Meeting sexual partners on the internet was the only statistically significant correlate of GC/CT infection (p < 0.01, Table 2). Table 1. Sociodemographic, Substance use, and Sexual Practice Characteristics of the Washington, D.C. MACS/SHARE Participants who Underwent GC/CT Testing (n = 147) Table 2. Prevalence of GC/CT by Anatomic Site Among this sample of aging MACS participants, of whom 45% were HIV positive, we found the prevalence of asymptomatic GC/CT infection (5.8%) to be similar to that found among predominantly HIV-infected, asymptomatic MSM tested at STD/HIV clinics (4%–11% for both organisms and all anatomic sites).3–5 Our results were also similar to those found from urine and rectal GC/CT screening of asymptomatic participants from the Pittsburgh MACS site.1 The lower prevalence of pharyngeal GC in our study compared to the 9.2% found by Kent et al.2 in San Francisco is probably explained by the fact that the latter study included symptomatic patients. The lower GC/CT prevalence in our study compared to the approximately 11% found by Rieg et al.3 in Los Angeles could be due to demographic differences between the study populations (the latter being 100% HIV positive, predominantly Hispanic, and younger). It is also important to note that the GC/CT prevalence from our sample of asymptomatic MSM in Washington, D.C. may not be representative of MSM countrywide because the prevalence of these organisms in the Northeast has been consistently lower than other regions of the United States, particularly the South and the Midwest.13,14 Evidence suggests there is an increasing incidence of HIV among older MSM, but the role GC/CT infection plays in HIV transmission in this aging population remains unclear. Our results further suggest that older MSM continue to engage in high-risk sexual behavior; therefore, increased vigilance with GC/CT screening among older MSM is warranted. We are aware that the sample size is quite small, nevertheless our findings offer a thought provoking glimpse of what seems to be a percolating problem among older MSM, particularly those who are HIV positive who practice high-risk sex. We expected that the prevalence would be low since these men should have been intrinsically educated about preventing the spread of HIV and other STIs by participating in this cohort study, however it was not. Taken together with the recommended CDC testing guidelines, the intersection of the increasing U.S. incidence of HIV infection and STI infection rate shown here among older MSM should not be ignored.

Impact of minocycline on cerebrospinal fluid markers of oxidative stress, neuronal injury, and inflammation in HIV-seropositive individuals with cognitive impairment.

Abstract: Elevated cerebrospinal fluid (CSF) levels of markers of oxidative stress, neuronal injury, and inflammation and decreased neurotransmitter levels have been reported in HIV-associated neurocognitive disorders (HAND). Minocycline may have a neuroprotective effect by inhibiting inducible nitric oxide synthase, which produces nitric oxide, a compound that induces oxygen free radical production. In A5235, "Phase II, Randomized, Placebo-Controlled, Double-Blind Study of Minocycline in the Treatment of HIV-Associated Cognitive Impairment," minocycline was not associated with cognitive improvement, but the effect on the above CSF measures was not examined previously. The objective of this study was to examine the effect of minocycline on markers of oxidative stress, neuronal injury, neurotransmitter levels, and inflammation from CSF in participants in A5235. One hundred seven HIV+ individuals received either minocycline 100 mg or placebo orally every 12 h for 24 weeks. Twenty-one HIV+ individuals received the optional lumbar punctures. Lipid and protein markers of oxidative stress (e.g., ceramides and protein carbonyls), glutamate, neurotransmitter precursors, kynurenine metabolites, neurofilament heavy chain, and inflammatory cytokines were measured in the CSF before and after treatment. The 24-week change in ceramides was larger in a beneficial direction in the minocycline group compared to the placebo group. The two groups did not differ in the 24-week changes for other markers.These results suggest that minocycline may decrease lipid markers of oxidative stress (ceramides) in individuals with HAND; however, an effect of minocycline on other CSF markers was not observed. A larger sample size is needed to further validate these results.

Assessment of Hepatic Impairment and Implications for Pharmacokinetics of Substance Use Treatment

Abstract: Although the liver is the primary site of metabolism and biliary excretion for many medications, data are limited on the liver's pharmacokinetic abilities in cirrhosis. Cirrhosis develops through collagen deposition, eventually culminating in end-stage liver disease that compromises hepatic drug metabolism. Consequently, the US Food and Drug Administration (FDA) recommends evaluating the pharmacokinetics of medications in subjects with hepatic impairment if hepatic metabolism constitutes more than 20% of their elimination or if they have a narrow therapeutic range. A variety of noninvasive indices and radiologic procedures can be employed to assess hepatic drug metabolism and excretion. The Child-Pugh score is the most commonly used scale for assessing hepatic impairment among drugs submitted for US FDA approval. The score, originally developed to guide operative mortality in patients undergoing hepatic resection, has not been modified since its inception 5 decades ago. Furthermore, the score was not originally intended to be a guide for potential dose modification in patients with hepatic impairment. These reasons, in combination with the availability of a variety of new imaging modalities and an enhanced understanding of hepatic biology, should foster the development of novel methods to assess the effect of hepatic impairment on liver drug metabolism.

Mycobacterium Tuberculosis and Interactions with the Host Immune System: Opportunities for Nanoparticle Based Immunotherapeutics and Vaccines

Abstract: Tuberculosis (TB) caused by Mycobacterium tuberculosis remains a deadly infectious disease. The thin pipeline of new drugs for TB, the ineffectiveness in adults of the only vaccine available, i.e. the Bacillus Calmette-Guerin vaccine, and increasing global antimicrobial resistance, has reinvigorated interest in immunotherapies. Nanoparticles (NPs) potentiate the effect of immune modulating compounds (IMC), enabling cell targeting, improved transfection of antigens, enhanced compound stability and provide opportunities for synergistic action, via delivery of multiple IMCs. In this review we describe work performed in the application of NPs towards achieving immune modulation for TB treatment and vaccination. Firstly, we present a comprehensive review of M. tuberculosis and how the bacterium modulates the host immune system. We find that current work suggest great promise of NP based immunotherapeutics as novel treatments and vaccination systems. There is need to intensify research efforts in this field, and rationally design novel NP immunotherapeutics based on current knowledge of the mycobacteriology and immune escape mechanisms employed by M. tuberculosis.