Showing papers by "Myron S. Cohen published in 2000"

Potent antiretroviral treatment of HIV-infection results in suppression of the seminal shedding of HIV

Abstract: Objective: The amount of HIV in semen likely influences infectiousness. Antiretroviral therapy decreases HIV-RNA in semen, but data on HIV concentrations in semen in a large cohort of men with suppressed HIV-RNA in blood is unavailable. Methods: Male patients with a treatment-induced reduction of HIV-RNA load in plasma below 400 copies/ml were asked to donate a semen and blood sample. Blood and seminal plasma were tested for the presence of HIV-RNA by the NucliSens method (detection limit 400 copies/ml). Seminal cell samples from 67 patients were further analysed for the presence of HIV-DNA using a nested DNA-polymerase chain reaction. Results of RNA and DNA testing in semen were compared with 55 HIV-positive antiretroviral therapy-naive men. Results: A total of 114 patients participated in the study. Seminal plasma HIV-RNA was detectable in only two patients [1.8%, 95% confidence ratio (CI), 0-4.2%] compared with a detection frequency of 67% in untreated controls [Odds ratio (OR), 0.01; 95% CI, 0-0.03]. Detection of cell-associated HIV-DNA in semen was significantly less frequent (16 versus 38%) in patients receiving suppressive therapy compared with untreated controls (OR, 0.32; 95% Cl, 0.12-0.80). Conclusion: In patients with treatment-induced suppression of blood viral load the likelihood of having detectable HIV in semen is very low (< 4%). In addition, seminal shedding of cell-free and cell-associated HIV is significantly lower than in an untreated population of HlV-infected asymptomatic men. On a population basis, this effect of therapy may help to reduce sexual transmission of HIV. However, individual patients may still be infected as evidenced by continued shedding of cells harbouring the HIV provirus.

Breakthrough Pneumococcal Bacteremia in Patients Being Treated with Azithromycin and Clarithromycin

Abstract: Streptococcus pneumoniae strains have exhibited decreasing susceptibility to penicillins and macrolides during the past several years. We reviewed the medical charts of all patients with pneumococcal bacteremia who were admitted to a university hospital over a period of 1 year, to identify failures of outpatient therapy. Of 41 patients admitted with pneumococcal bacteremia, 4 had previously taken either azithromycin or clarithromycin for 3-5 days. All 4 had pneumococcal strains that exhibited low-level resistance to macrolide antibiotics. Among pneumococci, low-level resistance to macrolides can lead to clinical failure, and resistance to macrolides should be considered during the selection of empiric therapy for patients with presumed pneumococcal infections.

Antiretroviral-Drug Concentrations in Semen: Implications for Sexual Transmission of Human Immunodeficiency Virus Type 1

Abstract: The majority of human immunodeficiency virus type 1 (HIV-1) infections result from seminal transmission (17, 104). The size of the viral innoculum in seminal fluid is likely the major determinant of transmissibility. Current HIV prevention strategies include comprehensive population interventions promoting condom use, early diagnosis and treatment of sexually transmitted diseases, and education programs to decrease the rate of sexual-partner change and other high-risk sexual behavior (17, 18, 40, 76, 115). However, antiretroviral therapy targeted to reduce viral shedding in genital secretions may also assist in preventing transmission (17, 86). Although the HIV-1 pandemic continues to be driven by transmission of virus in genital fluids, little is known about the pharmacokinetics and pharmacodynamics of antiretroviral drugs in the genital tract (46). Similarly to the effect of antiretroviral therapy on viral burden in blood and lymphoid tissue (6, 14, 41, 42, 120, 132), potent combinations of HIV-1 reverse transcriptase and protease inhibitors which concentrate in semen may lead to marked viral suppression in this compartment (2, 21, 30, 37, 38, 41–43, 58–60, 84, 117, 118, 124, 138). This article reviews the biology of HIV-1 in the male genital tract, the impact of antiretroviral therapy on seminal shedding, and the emergence of drug-resistant variants. Major determinants of drug distribution into semen are discussed, and strategies for using this information to predict antiretroviral concentrations in this compartment are suggested. Finally, a discussion of animal models critical to investigating correlations between seminal antiretroviral concentrations and viral transmission is included.

Quantitation of human immunodeficiency virus type 1 RNA in different biological compartments

Abstract: Little information is available describing viral loads in body fluids other than blood. In addition, the suitability of commercially available assays for human immunodeficiency virus type 1 (HIV-1) RNA quantitation has not been evaluated in most nonblood fluids. We compared Organon Teknika's nucleic acid sequence-based amplification method (NASBA) and Roche's Amplicor HIV-1 Monitor (reverse transcriptase PCR [RT-PCR]) for quantitating HIV-1 RNA in cerebrospinal fluid (CSF), saliva, breast milk, seminal plasma, and cervical-vaginal lavage fluid (CVL). Saliva and breast milk frequently demonstrated some inhibition in the RT-PCR assay, similar to the inhibition previously described in seminal plasma. Inhibition of the RT-PCR assay was not observed with CSF or CVL, nor in any of the NASBA assays. When fluids from HIV-infected individuals were tested by RT-PCR and NASBA, 73 and 27% of CSF samples and 60 and 40% of breast milk specimens had detectable RNA, respectively. These differences were not statistically significant. In cross-sectional studies using RT-PCR to measure viral RNA in paired blood plasma and CSF samples, 71% of blood plasma samples and 42% of CSF samples were positive. A similar analysis using NASBA with paired blood plasma and CVL, saliva, or seminal plasma samples revealed 91% were blood plasma positive and 55% were CVL positive, 76% were blood plasma positive and 46% were saliva positive, and 83% were blood plasma positive and 63% were seminal plasma positive. NASBA worked fairly well to quantitate HIV-1 RNA from all fluids without apparent inhibition. RT-PCR performed well on CVL and CSF, frequently with greater sensitivity, although its use in other fluids appears limited due to the presence of inhibitors. These studies demonstrate that viral loads in nonblood fluids were generally lower than in blood.

Effects of Genital Tract Inflammation on Human Immunodeficiency Virus Type 1 V3 Populations in Blood and Semen

Abstract: We have examined cell-free viral populations in the blood plasma and seminal plasma compartments of men infected with subtype C human immunodeficiency virus type 1 (HIV-1) using the V3-specific heteroduplex tracking assay (V3-HTA). We studied two cohorts of subjects who had visited either a sexually transmitted disease (STD) clinic for genital tract inflammation in the form of urethritis (n = 43) or a dermatology clinic (controls, n = 14) in Malawi. We have previously shown that the presence of urethritis is associated with an eightfold increase in virus load in the seminal plasma compartment (M. S. Cohen et al., Lancet 349:1868–1873, 1997). The purpose of this study was to determine whether genital tract inflammation and its treatment caused genetic instability in cell-free HIV-1 populations. In a cross-sectional analysis at study entry, three-fourths of the STD and control subjects had multiple V3 populations in their blood while 60% of the STD subjects and 79% of the control subjects had multiple V3 populations in their semen. Overall, one-fourth of all of the subjects showed discordance between results with blood and semen specimens when samples were compared for the presence and absence of subpopulations. When differences in the relative levels of abundance of bands were also taken into account, two-fifths of all of the subjects showed discordance between the compartments. Among the subset of subjects in whom multiple virus populations could be detected, half showed discordance between the compartments. There were no differences between STD and control cohorts for these comparisons of the compartments in this cross-sectional analysis at study entry. Longitudinal analysis of the viral populations from two separate clinic visits over 1 to 4 weeks showed that the complexity of each V3 population as measured by Shannon entropy was different in blood and semen at the two time points, indicating that the blood and semen constitute different compartments for HIV-1. The seminal plasma compartment was more dynamic than the blood plasma compartment for the STD subjects who were treated for urethritis, with changes being noted in the presence or absence of V3-HTA bands in the semen of 29% of these subjects but in the blood of only 9% of these subjects. However, the changes were generally small. Overall, our results suggest that 40% of male subjects show discordance between seminal and blood viral populations and that the complexity of each V3 population was different between the two compartments. Both of these results point to the partial independence of the seminal compartment as a viral niche within the body.

Trends of Gonorrhea and Chlamydial Infection during 1985–1996 among Active-Duty Soldiers at a United States Army Installation

Abstract: High rates of sexually transmitted diseases (STDs) have been reported in military populations. However, it remains uncertain whether the incidence of STDs is higher among military personnel than in the civilian population. The annual incidence of gonorrhea and chlamydia from 1985 through 1996 at Fort Bragg, North Carolina, was determined by use of a clinic database and demographic information for the entire installation. A direct standardization for age, sex, and race/ethnicity was performed, and the adjusted annual rates among active duty soldiers were compared with rates among men and women in North Carolina and the United States. Results showed that the adjusted incidence of gonorrhea and chlamydia among Fort Bragg soldiers remained higher overall than comparable state and national rates during the period of analyses. The 1996 adjusted chlamydia rates for male and female active duty soldiers were 3-fold to 6-fold higher than rates for males and females in North Carolina and in the United States as a whole. STDs continue to lead to significant morbidity in this representative military population.

Preventing Sexual Transmission of HIV — New Ideas from Sub-Saharan Africa

Abstract: When human immunodeficiency virus type 1 (HIV-1) was identified as the cause of AIDS more than 15 years ago, it seemed possible that an end to the epidemic would follow. However, the control of com...

Features of urethritis in a cohort of male soldiers.

Abstract: Of 400 cases of urethritis in male soldiers enrolled in a behavioral intervention project, the etiology of 69% was defined at study enrollment, as well as the etiology of 72% of 25 repeated episodes involving 21 men during the first 78 days of active follow-up (5% of the cohort). Chlamydia trachomatis (36%), Neisseria gonorrhoeae (34%), and Ureaplasma urealyticum (19%) were the most common causes of infection identified at enrollment and during subsequent visits (44%, 28%, and 12%, respectively). By univariate analysis, patients with repeated infection ("repeaters") were significantly more likely to report a history of sexually transmitted disease (STD; relative risk [RR], 3) and sex with sex workers (RR, 4) than were nonrepeaters. By multivariate analysis, only STD history was significant (RR, 2.8). Characteristics of repeaters in this cohort suggest that specific patterns may be used to establish screening "profiles" of potential repeaters, by which such individuals might be targeted for aggressive intervention at the time of the initial diagnosis.

Prevalence of hepatitis C infection in Malawi and lack of association with sexually transmitted diseases.

Abstract: To investigate the role of sexual transmission for Hepatitis C virus (HCV) we studied its prevalence in sub-Saharan Africa where sexually transmitted diseases (STDs) are prevalent. Overall, HCV prevalence was 3.9% and similar in 206 STD patients, 127 dermatology patients, and 100 blood donors. No association with HIV or syphilis was observed. Despite high prevalence of STDs, sexual transmission does not appear to significantly contribute to HCV transmission in Malawi.

Sexually transmitted diseases in the Peoples Republic of China in Y2K. Back to the future [editorial]

Abstract: Cultural and governmental forces have a critical impact on the control of sexually transmitted diseases (STDs) in China. As the Chinese people face a resurgence of STDs and a new HIV epidemic development of new approaches to disease prevention seems inevitable. By 1950 over 10 million Chinese suffered from venereal diseases and 6.2% of the total hospital admissions were attributed to STDs. Poverty drug abuse commercial sex work and polygamous sexual practices all contribute to the spread of STDs in Chinese communities. Despite the success of earlier efforts to curb the epidemic the situation changed rapidly when China opened its door to the West in the 1980s showing a dramatic increase in STDs particularly syphilis and gonorrhea. This re-emergence of STDs is described in relation to the rise in commercial sex work as well as certain social forces that favor the spread of STDs such as increased cultural focus on personal wealth and consumer goods and unhappy marriages that favor extramarital affairs. Critical to the prominence of these social forces has been the loosening of government control over population movement. In addition to its reproductive consequences the re-emergence of STDs is expected to amplify transmission of HIV. It has been estimated that 10000000 Chinese will suffer from HIV infection by 2010 in the absence of an effective intervention. However China is clearly intent on developing new resources and policies to reduce HIV and STD transmission among its people.