Philip A. Chan

Misclassification of First-Line Antiretroviral Treatment Failure Based on Immunological Monitoring of HIV Infection in Resource-Limited Settings

BACKGROUND The monitoring of patients with human immunodeficiency virus (HIV) infection who are treated with antiretroviral medications in resource-limited settings is typically performed by use of clinical and immunological criteria. The early identification of first-line antiretroviral treatment failure is critical to prevent morbidity, mortality, and drug resistance. Misclassification of failure may result in premature switching to second-line therapy. METHODS Adult patients in western Kenya had their viral loads (VLs) determined if they had adhered to first-line therapy for >6 months and were suspected of experiencing immunological failure (ie, their CD4 cell count decreased by 25% in 6 months). Misclassification of treatment failure was defined as a 25% decrease in CD4 cell count with a VL of <400 copies/mL. Logistic and tree regressions examined relationships between VL and 4 variables: CD4 T cell count (hereafter CD4 cell count), percentage of T cells expressing CD4 (hereafter CD4 cell percentage), percentage decrease in the CD4 T cell count (hereafter CD4 cell count percent decrease), and percentage decrease in the percentage of T cells expressing CD4 (hereafter CD4% percent decrease). RESULTS There were 149 patients who were treated for 23 months; they were identified as having a 25% decrease in CD4 cell count (from 375 to 216 cells/microL) and a CD4% percent decrease (from 19% to 15%); of these 149 patients, 86 (58%) were misclassified as having experienced treatment failure. Of 42 patients who had a 50% decrease in CD4 cell count, 18 (43%) were misclassified. In multivariate logistic regression, misclassification odds were associated with a higher CD4 cell count, a shorter duration of therapy, and a smaller CD4% percent decrease. By combining these variables, we may be able to improve our ability to predict treatment failure. CONCLUSIONS Immunological monitoring as a sole indicator of virological failure would lead to a premature switch to valuable second-line regimens for 58% of patients who experience a 25% decrease in CD4 cell count and for 43% patients who experience a 50% decrease in CD4 cell count, and therefore this type of monitoring should be reevaluated. Selective virological monitoring and the addition of indicators like trends CD4% percent decrease and duration of therapy may systematically improve the identification of treatment failure. VL testing is now mandatory for patients suspected of experiencing first-line treatment failure within the Academic Model Providing Access to Healthcare (AMPATH) in western Kenya, and should be considered in all resource-limited settings.

Peripheral Venous Catheter-Related Staphylococcus aureus Bacteremia

OBJECTIVE Better understand the incidence, risk factors, and outcomes of peripheral venous catheter (PVC)-related Staphylococcus aureus bacteremia. DESIGN Retrospective study of PVC-related S. aureus bacteremias in adult patients from July 2005 through March 2008. A point-prevalence survey was performed January 9, 2008, on adult inpatients to determine PVC utilization; patients with a PVC served as a cohort to assess risk factors for PVC-related S. aureus bacteremia. SETTING Tertiary care teaching hospital. RESULTS Twenty-four (18 definite and 6 probable) PVC-related S. aureus bacteremias were identified (estimated incidence density, 0.07 per 1,000 catheter-days), with a median duration of catheterization of 3 days (interquartile range, 2-6). Patients with PVC-related S. aureus bacteremia were significantly more likely to have a PVC in the antecubital fossa (odds ratio [OR], 6.5), a PVC placed in the emergency department (OR, 6.0), or a PVC placed at an outside hospital (P = .005), with a longer duration of catheterization (P < .001). These PVCs were significantly less likely to have been inserted in the hand (OR, 0.23) or placed on an inpatient medical unit (OR, 0.17). Mean duration of antibiotic treatment was 19 days (95% confidence interval, 15-23 days); 42% (10/24) of cases encountered complications. We estimate that there may be as many as 10,028 PVC-related S. aureus bacteremias yearly in US adult hospitalized inpatients. CONCLUSION PVC-related S. aureus bacteremia is an underrecognized complication. PVCs inserted in the emergency department or at outside institutions, PVCs placed in the antecubital fossa, and those with prolonged dwell times are associated with such infections.

UNPROTECTED SEX, UNDERESTIMATED RISK, UNDIAGNOSED HIV AND SEXUALLY TRANSMITTED DISEASES AMONG MEN WHO HAVE SEX WITH MEN ACCESSING TESTING SERVICES IN A NEW ENGLAND BATHHOUSE

Abstract:American men who have sex with men (MSM) continue to have increased rates of HIV and sexually transmitted diseases (STD). Between 2004 and 2010, 1155 MSM were tested for HIV and/or STDs at Providence, RI bathhouse. The prevalence of HIV was 2.3%; syphilis, 2.0%; urethral gonorrhea, 0.1%; urethral chlamydia, 1.3%; 2.2% of the men had hepatitis C antibodies. Although 43.2% of the men engaged in unprotected anal intercourse in the prior 2 months, the majority of the men thought that their behaviors did not put them at increased risk for HIV or STDs. Multivariate analyses found that men who engaged in unprotected anal intercourse were more likely to have had sex with unknown status or HIV-infected partners; have sex although under the influence of drugs; tended to find partners on the internet; and were more likely to have a primary male partner. Men who were newly diagnosed with HIV or syphilis tended to be older than 30 years; had sex with an HIV-infected partner; had a prior STD diagnosis; and met partners on the internet. For 10.5% of the men, bathhouse testing was the first time that they had ever been screened for HIV. Of 24 men who were newly diagnosed with HIV infection, only 1 was not successfully linked to care. These data suggest that offering HIV and STD testing in a bathhouse setting is effective in attracting MSM who are at increased risk for HIV and/or STD acquisition or transmission.

Extragenital Infections Caused by Chlamydia trachomatis and Neisseria gonorrhoeae: A Review of the Literature

In the United States, sexually transmitted diseases due to Chlamydia trachomatis and Neisseria gonorrhoeae continue to be a major public health burden. Screening of extragenital sites including the oropharynx and rectum is an emerging practice based on recent studies highlighting the prevalence of infection at these sites. We reviewed studies reporting the prevalence of extragenital infections in women, men who have sex with men (MSM), and men who have sex only with women (MSW), including distribution by anatomical site. Among women, prevalence was found to be 0.6–35.8% for rectal gonorrhea (median reported prevalence 1.9%), 0–29.6% for pharyngeal gonorrhea (median 2.1%), 2.0–77.3% for rectal chlamydia (median 8.7%), and 0.2–3.2% for pharyngeal chlamydia (median 1.7%). Among MSM, prevalence was found to be 0.2–24.0% for rectal gonorrhea (median 5.9%), 0.5–16.5% for pharyngeal gonorrhea (median 4.6%), 2.1–23.0% for rectal chlamydia (median 8.9%), and 0–3.6% for pharyngeal chlamydia (median 1.7%). Among MSW, the prevalence was found to be 0–5.7% for rectal gonorrhea (median 3.4%), 0.4–15.5% for pharyngeal gonorrhea (median 2.2%), 0–11.8% for rectal chlamydia (median 7.7%), and 0–22.0% for pharyngeal chlamydia (median 1.6%). Extragenital infections are often asymptomatic and found in the absence of reported risk behaviors, such as receptive anal and oral intercourse. We discuss current clinical recommendations and future directions for research.

Distinguishing characteristics between pandemic 2009-2010 influenza A (H1N1) and other viruses in patients hospitalized with respiratory illness.

Background Differences in clinical presentation and outcomes among patients infected with pandemic 2009 influenza A H1N1 (pH1N1) compared to other respiratory viruses have not been fully elucidated. Methodology/Principal Findings A retrospective study was performed of all hospitalized patients at the peak of the pH1N1 season in whom a single respiratory virus was detected by a molecular assay targeting 18 viruses/subtypes (RVP, Luminex xTAG). Fifty-two percent (615/1192) of patients from October, 2009 to December, 2009 had a single respiratory virus (291 pH1N1; 207 rhinovirus; 45 RSV A/B; 37 parainfluenza; 27 adenovirus; 6 coronavirus; and 2 metapneumovirus). No seasonal influenza A or B was detected. Individuals with pH1N1, compared to other viruses, were more likely to present with fever (92% & 70%), cough (92% & 86%), sore throat (32% & 16%), nausea (31% & 8%), vomiting (39% & 30%), abdominal pain (14% & 7%), and a lower white blood count (8,500/L & 13,600/L, all p-values<0.05). In patients with cough and gastrointestinal complaints, the presence of subjective fever/chills independently raised the likelihood of pH1N1 (OR 10). Fifty-five percent (336/615) of our cohort received antibacterial agents, 63% (385/615) received oseltamivir, and 41% (252/615) received steroids. The mortality rate of our cohort was 1% (7/615) and was higher in individuals with pH1N1 compared to other viruses (2.1% & 0.3%, respectively; p = 0.04). Conclusions/Significance During the peak pandemic 2009–2010 influenza season in Rhode Island, nearly half of patients admitted with influenza-like symptoms had respiratory viruses other than influenza A. A high proportion of patients were treated with antibiotics and pH1N1 infection had higher mortality compared to other respiratory viruses.

Risk factors for HIV infection in Males who have Sex with Males (MSM) in Bangladesh

BackgroundRecent surveillance data from Bangladesh indicate rising HIV infection among intravenous drug users (IDU) in the country. We suggest a likely association between HIV risk factors in this group and other groups, such as males who have sex with males (MSM).MethodsData on MSM in Bangladesh was collected and analyzed from numerous primary and secondary sources, including government ministries, non-profit health organizations, and personal communications.ResultsThe overall prevalence of HIV in Bangladesh is relatively low, but surveillance data indicate that infection has reached significant proportions in certain high-risk groups and may soon spread to other groups, specifically MSM.ConclusionThe epidemiology of HIV infection in other countries suggests that increasing rates of HIV in higher-risk populations can precede an epidemic in the general population. We review the data concerning MSM, IDU and HIV in Bangladesh from a variety of sources and propose ways to prevent HIV transmission.

Performing private database queries in a real-world environment using a quantum protocol.

In the well-studied cryptographic primitive 1-out-of-N oblivious transfer, a user retrieves a single element from a database of size N without the database learning which element was retrieved. While it has previously been shown that a secure implementation of 1-out-of-N oblivious transfer is impossible against arbitrarily powerful adversaries, recent research has revealed an interesting class of private query protocols based on quantum mechanics in a cheat sensitive model. Specifically, a practical protocol does not need to guarantee that the database provider cannot learn what element was retrieved if doing so carries the risk of detection. The latter is sufficient motivation to keep a database provider honest. However, none of the previously proposed protocols could cope with noisy channels. Here we present a fault-tolerant private query protocol, in which the novel error correction procedure is integral to the security of the protocol. Furthermore, we present a proof-of-concept demonstration of the protocol over a deployed fibre.

Clinical Characteristics and Outcomes in Hospitalized Patients with Respiratory Viral Co-Infection during the 2009 H1N1 Influenza Pandemic

Background The clinical consequences of co-infection with two or more respiratory viruses are poorly understood. We sought to determine if co-infection with pandemic 2009–2010 influenza A H1N1 (pH1N1) and another respiratory virus was associated with worse clinical outcomes. Methods A retrospective cohort study was performed of all hospitalized patients with a positive respiratory viral panel (RVP) for two or more viruses within 72 hours of admission at our institution from October 2009 to December 2009. We compared patients infected with one respiratory virus to those with respiratory viral co-infection. Results We identified 617 inpatients with a positive RVP sample with a single virus and 49 inpatients with a positive RVP sample for two viruses (i.e. co-infection). Co-infected patients were significantly younger, more often had fever/chills, tachypnea, and they more often demonstrated interstitial opacities suggestive of viral pneumonia on the presenting chest radiograph (OR 7.5, 95% CI 3.4–16.5). The likelihood of death, length of stay, and requirement for intensive care unit level of care were similar in both groups, but patients with any respiratory virus co-infection were more likely to experience complications, particularly treatment for a secondary bacterial pneumonia (OR 6.8, 95% CI 3.3–14.2). Patients co-infected with pH1N1 and another respiratory virus were more likely to present with chest radiograph changes suggestive of a viral pneumonia, compared to mono-infection with pH1N1 (OR 16.9, 95% CI 4.5–62.7). By logistic regression using mono-infection with non-PH1N1 viruses as the reference group, co-infection with pH1N1 was the strongest independent predictor of treatment for a secondary bacterial pneumonia (OR 17.8, 95% CI 6.7–47.1). Conclusion Patients with viral co-infection, particularly with pH1N1, were more likely to have chest radiograph features compatible with a viral pneumonia and complications during their hospital course, particularly treatment for secondary bacterial pneumonia. Despite this, co-infection was not associated with ICU admission.

Oseltamivir-resistant 2009–2010 pandemic influenza A (H1N1) in an immunocompromised patient

Although neuraminidase inhibitors are active against most 2009-2010 pandemic influenza A (H1N1) swine-origin strains, sporadic cases of oseltamivir resistance have been described. Since April 2009, 54 cases of oseltamivir-resistant H1N1 swine-origin have been reported in the USA (http://www.cdc.gov/flu/weekly/; accessed 1 February 2010). Approximately 1.4% of tested isolates are oseltamivir resistant. We report a patient with an underlying hematological malignancy who was hospitalized with influenza A (H1N1) swine-origin and whose strain developed oseltamivir resistance during therapy.

Implementation of Preexposure Prophylaxis for Human Immunodeficiency Virus Prevention Among Men Who Have Sex With Men at a New England Sexually Transmitted Diseases Clinic.

Background Preexposure prophylaxis (PrEP) is efficacious in preventing human immunodeficiency virus (HIV) among men who have sex with men (MSM). We assessed PrEP uptake among MSM presenting for services at a sexually transmitted diseases (STD) clinic. Methods Men who have sex with men presenting to the Rhode Island STD Clinic between October 2013 and November 2014 were educated about, and offered, PrEP. We categorized PrEP engagement using an implementation cascade to describe gaps in uptake which described MSM who: (1) were educated about PrEP, (2) indicated interest, (3) successfully received follow-up contact, (4) scheduled an appointment, (5) attended an appointment, and (6) initiated PrEP (ie, received a prescription). Bivariate and multivariable logistic regression models were used to examine predictors of PrEP initiation. Results A total of 234 MSM were educated about PrEP; of these, 56% expressed interest. Common reasons for lack of interest were low HIV risk perception (37%), wanting more time to consider (10%), concern about side effects (7%), and financial barriers (3%). Among those interested, 53% followed up. Of those, 51% scheduled an appointment. The most common reason patients did not schedule an appointment was low HIV risk perception (38%). Seventy-seven percent of those with an appointment attended the appointment; of those, 93% initiated PrEP. Patients with higher HIV-risk perception (adjusted odds ratios, 2.17; 95% confidence interval, 1.29–3.64) and a history of sex with an HIV-positive partner (adjusted odds ratios, 7.08; 95% confidence interval, 2.35–21.34) had significantly higher odds of initiating PrEP. Conclusions Low HIV-risk perception was the most significant barrier to PrEP uptake among MSM attending a public STD clinic.