Jill Blumenthal

Comparative Effectiveness of Aminoglycosides, Polymyxin B, and Tigecycline for Clearance of Carbapenem-Resistant Klebsiella pneumoniae from Urine

ABSTRACT Carbapenem-resistant Klebsiella pneumoniae (CRKP) is an increasingly common cause of health care-associated urinary tract infections. Antimicrobials with in vitro activity against CRKP are typically limited to polymyxins, tigecycline, and often, aminoglycosides. We conducted a retrospective cohort study of cases of CRKP bacteriuria at New York-Presbyterian Hospital from January 2005 through June 2010 to compare microbiologic clearance rates based on the use of polymyxin B, tigecycline, or an aminoglycoside. We constructed three active antimicrobial cohorts based on the active agent used and an untreated cohort of cases that did not receive antimicrobial therapy with Gram-negative activity. Microbiologic clearance was defined as having a follow-up urine culture that did not yield CRKP. Cases without an appropriate follow-up culture or that received multiple active agents or less than 3 days of the active agent were excluded. Eighty-seven cases were included in the active antimicrobial cohorts, and 69 were included in the untreated cohort. The microbiologic clearance rate was 88% in the aminoglycoside cohort (n = 41), compared to 64% in the polymyxin B (P = 0.02; n = 25), 43% in the tigecycline (P < 0.001; n = 21), and 36% in the untreated (P < 0.001; n = 69) cohorts. Using multivariate analysis, the odds of clearance were lower for the polymyxin B (odds ratio [OR], 0.10; P = 0.003), tigecycline (OR, 0.08; P = 0.001), and untreated (OR, 0.14; P = 0.003) cohorts than for the aminoglycoside cohort. Treatment with an aminoglycoside, when active in vitro, was associated with a significantly higher rate of microbiologic clearance of CRKP bacteriuria than treatment with either polymyxin B or tigecycline.

Will risk compensation accompany pre-exposure prophylaxis for HIV?

As evidence for the success of new HIV prevention interventions increases, there is concern that users of these interventions may increase risky sexual behaviors.

Adolescent Understanding and Acceptance of the HPV Vaccination in an Underserved Population in New York City.

Background. HPV vaccination may prevent thousands of cases of cervical cancer. We aimed to evaluate the understanding and acceptance of the HPV vaccine among adolescents. Methods. A questionnaire was distributed to adolescents at health clinics affiliated with a large urban hospital system to determine knowledge pertaining to sexually transmitted diseases and acceptance of the HPV vaccine. Results. 223 adolescents completed the survey. 28% were male, and 70% were female. The mean age for respondents was 16 years old. Adolescents who had received the HPV vaccine were more likely to be female and to have heard of cervical cancer and Pap testing. Of the 143 adolescents who had not yet been vaccinated, only 4% believed that they were at risk of HPV infection and 52% were willing to be vaccinated. Conclusions. Surveyed adolescents demonstrated a marginal willingness to receive the HPV vaccine and a lack of awareness of personal risk for acquiring HPV.

Pre-exposure prophylaxis for HIV infection: how antiretroviral pharmacology helps to monitor and improve adherence

Introduction: Pre-exposure prophylaxis (PrEP) with antiretroviral drugs is a novel biomedical intervention that can prevent HIV transmission among high-risk populations. As findings from multiple PrEP studies have suggested that adherence is vital to achieve the full prevention benefits of PrEP, it is important to understand the clinical pharmacology and pharmacokinetic (PK) properties of PrEP antiretrovirals, the association of PK and PrEP efficacy, and the potential for drug concentration measurement to be used as a tool to monitor PrEP adherence. Areas covered: This review examines studies related to PrEP adherence with attention to the clinical pharmacology and PK of current and novel PrEP agents. Studies of animal models, PK, and clinical trials related to PrEP and adherence were reviewed. Expert opinion: In summary, when combined as part of a comprehensive prevention strategy that includes use of condoms and risk-reduction counseling, PrEP has tremendous promise as an adjunctive biomedical HIV prevention intervention, providing that adherence is maintained.

Factors Associated with High Transmission Risk and Detectable Plasma HIV RNA in HIV-infected MSM on ART

Summary HIV transmission risk is increased during antiretroviral therapy (ART) use if individuals are not virologically suppressed and engage in high risk transmission behaviour. Baseline data of HIV-infected men who have sex with men (MSM) with recent history of risky behaviour on ART for ≥3 months (n = 139) were evaluated to assess predictors of detectable viraemia and HIV transmission risk-taking behaviour. Twenty-four subjects had viral load (VL) >75 copies/mL and 12 had VL >1000 copies/mL. In multivariable regression analyses, subjects with VL >75 copies/mL were more likely to be Black (OR = 4.48, p = 0.007), have lower CD4 cell counts (OR = 0.727, p = 0.005) and have used methamphetamines in the last month (OR = 6.64, p = 0.019). Subjects with VL >1000 copies/mL were more likely to have lower CD4 cell counts (OR = 0.494, p = 0.004), report <90% adherence (OR = 7.94; p = 0.046) and have used methamphetamines in the last month (OR = 10.01, p = 0.034). Subjects with VL >75 copies/mL with the greatest transmission risk behaviour (n = 14) were more likely to be Black (OR = 8.00, p = 0.006), have lower CD4 cell counts (OR = 0.657, p = 0.009) and have used methamphetamines in the last month (OR = 5.20, p = 0.042). High risk HIV transmission behaviour with viraemia occurred in 10% of the cohort. Future efforts to reduce HIV transmission among MSM on ART will require combined interventions that target risk-taking behaviours and substance use.

Randomized Controlled Trial of Daily Text Messages to Support Adherence to Preexposure Prophylaxis in Individuals at Risk for Human Immunodeficiency Virus: The TAPIR Study

Background Adherence is critical for efficacy of tenofovir disoproxil fumarate/emtricitabine (FTC) as preexposure prophylaxis (PrEP). Methods Between February 2013 and February 2016, 398 men who have sex with men and transgender women were randomized 1:1 to receive individualized texting for adherence building (iTAB) or standard care (SoC) for 48 weeks. The primary endpoint was dried blood spot (DBS) tenofovir diphosphate (TFV-DP) concentrations at both week 12 and the last on-drug visit of >719 fmol/punch (ie, adequate adherence). Secondary outcomes included DBS TFV-DP concentrations of >1246 fmol/punch (ie, near-perfect adherence) and plasma FTC >350 ng/mL (consistent with dosing within the past 24 hours). Results Concentrations >719 fmol/punch of TFV-DP were found in 88.6% of participants at week 12 and 82.5% at week 48. For the primary endpoint, the study arms did not differ (72.0% in iTAB and 69.2% in SoC; P > .05). For the secondary composite endpoint of >1246 fmol/punch the iTAB arm was superior to SoC (33.5% vs 24.8%; P = .06), reaching statistical significance when adjusting for age (odds ratio, 1.56 [95% confidence interval, 1.00-2.42]; P < .05). At week 48, iTAB was superior to SoC for near-perfect adherence (51.0% vs 37.4%; P = .02). At week 12, iTAB was superior to SoC for dosing in past 24 hours by plasma FTC (47.5% vs 33.3%; P = .007), but not at weeks 24, 36, and 48 (all P > .05). Conclusions Automated text messaging is a low-burden tool that improves durability of near-perfect PrEP adherence. Clinical Trials Registration NCT01761643.

Recent HIV Risk Behavior and Partnership Type Predict PrEP Adherence in Men who have Sex with Men

Abstract Background Individuals engaging in higher risk behavior are often more adherent to PrEP but it is unclear if partnership type itself affects PrEP adherence. We examined the effect of recent HIV risk behaviors and partnership type on PrEP adherence in men who have sex with men (MSM) taking PrEP. Methods CCTG 595 is a 48-week PrEP demonstration study of 398 HIV− at-risk MSM. At baseline and week 48, HIV risk score was estimated as the probability of seroconversion over the next year based on number of condomless anal sex acts with HIV+/unknown partners in the last month and any STI diagnosed at study visit. HIV risk score was categorized as low (<0.12), moderate (0.12−0.59) and high (>0.59) risk based on population seroconversion probabilities. Partnership type was assigned as no/single HIV− partner, single HIV+ partner, or multiple partners of any serostatus in the past 3 months. PrEP adherence was estimated by intracellular tenofovir-diphosphate (TFV-DP) levels as a continuous variable at week 48. Statistical methods included McNemar’s test, Wilcoxon rank-sum test, and linear regression model where appropriate. Results Of 313 MSM who completed week 48, there was no significant change in HIV risk category from baseline to week 48 (low: 44 to 42%; moderate: 27 to 24%; high: 28 to 34%; P = 0.25). There was a significant change in partnership type, with the proportion of those with no or single HIV− partnerships increasing (1 to 9%, P < 0.001). In univariate analysis, moderate and high-risk groups had higher TFV-DP levels than the low-risk group at week 48 (P = 0.018). Participants with no/single HIV− partner had significantly lower TFV-DP levels than those with one HIV+ partner or multiple partners (P = 0.007). In a multivariable linear regression model, only low-risk partnerships remained significant where no/single HIV− partnerships were associated with lower TFV-DP levels (mean difference = −344fmol/punch [−617, −71], P = 0.014). Conclusion Although there was a shift in partnership type towards lower risk partnerships, objective HIV risk behavior remained stable over time. Individuals with higher HIV risk behaviors and risk partnerships had higher TFV-DP levels suggesting maintained strong motivation for PrEP adherence. Thus, recent sexual risk behavior and partnership type may be important predictors of PrEP adherence in MSM. Disclosures All authors: No reported disclosures.

Trajectories and Predictors of Longitudinal Preexposure Prophylaxis Adherence Among Men Who Have Sex With Men

Background Adherence is necessary for efficacy of preexposure prophylaxis (PrEP), and text-messaging methods are promising tools for both adherence assessment and support. Although PrEP adherence is variable, little research has examined patterns of variability or factors associated with longitudinal use. Methods In the context of a randomized controlled trial of text-messaging versus standard of care for PrEP adherence, 181 men who have sex with men received once-daily tenofovir disoproxil fumarate/emtricitabine and daily adherence texts for 48 weeks. Growth mixture modeling (GMM) was used to identify subgroups of individuals with similar trajectories of text-reported adherence. Between-group differences in pharmacologic measures of adherence (ie, tenofovir diphosphate and emtricitabine triphosphate levels), as well as predictors and study-end attitudes associated with group membership, were examined. Results GMM identified 4 trajectories of text-reported adherence. Classes with higher text-reported adherence had higher drug concentrations. Younger age and minority race were associated with lower adherence, and individuals in classes with lower adherence had greater baseline levels of depression, substance use concerns, and sexual risk. Differences in study satisfaction were also associated with adherence. Conclusions This study supports the use of text-reported PrEP adherence. Identifying factors associated with less-than-optimal adherence may aid clinicians in anticipating at-risk patients requiring augmented intervention. Clinical trials registration NCT01761643.

Effect of rectal douching/enema on rectal gonorrhoea and chlamydia among a cohort of men who have sex with men on HIV pre-exposure prophylaxis

Objectives Rectal douching/enema (RD) is a common practice among men who have sex with men (MSM) in preparation for sex. RD can break down the rectal mucosal barrier and potentially affect the rectal microbiome. The objective of this study was to understand if RD is associated with acquiring rectal infections (RI) with rectal gonorrhoea (NG) and/or chlamydia (CT). Methods From 2013 to 2015, 395 adult HIV-uninfected MSM were enrolled in a randomised controlled study for pre-exposure prophylaxis (PrEP) adherence with routine sexual risk survey and testing. Using data from this cohort, baseline differences by RI were assessed using Pearson’s χ² and Wilcoxon-Mann-Whitney test. Association between RD and RI was modelled using multivariable logistic regression adjusted for potential confounders (sexual behaviour, substance use and age) selected a priori. Effect modification by number of male partners and sensitivity analysis to rule out reverse causality were also conducted. Results Of 395 participants, 261 (66%) performed RD and 133 (33%) had at least one NG/CT RI over 48 weeks. Number of condomless anal receptive sex (med: 4, p<0.001), male partners (med:6, p<0.001) and substance use (any of methamphetamine/hallucinogens/dissociative/poppers) (p<0.001) were associated with increased odds of RI. Controlling for potential confounders, odds of prevalent RI were 3.59 (p<0.001, 95% CI 1.90 to 6.78) and incident RI 3.87 (p=0.001, 95% CI 1.78 to 8.39) when douching weekly or more compared with not douching. MSM with more than six male partners had 5.34 (p=0.002, 95% CI 1.87 to 15.31) increased odds of RI when douching weekly or more compared with not douching. Conclusion Rectal hygiene with RD is a common practice (66%) among HIV-uninfected MSM on PrEP in this study, which increases the odds of acquiring rectal NG and/or CT independent of sexual risk behaviour, substance use and other factors. This suggests interventional approaches targeting rectal hygiene products and practices could reduce sexually transmitted infections.

The Importance of Human Immunodeficiency Virus Research for Transgender and Gender-Nonbinary Individuals

Transgender and gender-nonbinary (trans/GNB) individuals are disproportionally affected by human immunodeficiency virus (HIV), yet they are not adequately represented in HIV research and often underserved in clinical care. By building on community strengths and addressing structural, psychological and biological challenges, we can improve the engagement of trans/GNB people in research and ultimately improve prevention, testing, and care for this population. Here, we review the current state of the science related to HIV for trans/GNB people and discuss next steps to expand research that aims to improve the lives and well-being of trans/GNB persons.