Jose G. Castro

Performance of the Cepheid CT/NG Xpert Rapid PCR Test for Detection of Chlamydia trachomatis and Neisseria gonorrhoeae

ABSTRACT Tests for Chlamydia trachomatis and Neisseria gonorrhoeae, which can provide results rapidly to guide therapeutic decision-making, offer patient care advantages over laboratory-based tests that require several days to provide results. We compared results from the Cepheid GeneXpert CT/NG (Xpert) assay to results from two currently approved nucleic acid amplification assays in 1,722 female and 1,387 male volunteers. Results for chlamydia in females demonstrated sensitivities for endocervical, vaginal, and urine samples of 97.4%, 98.7%, and 97.6%, respectively, and for urine samples from males, a sensitivity of 97.5%, with all specificity estimates being ≥99.4%. Results for gonorrhea in females demonstrated sensitivities for endocervical, vaginal, and urine samples of 100.0%, 100.0%, and 95.6%, respectively, and for urine samples from males, a sensitivity of 98.0%, with all estimates of specificity being ≥99.8%. These results indicate that this short-turnaround-time test can be used to accurately test patients and to possibly do so at the site of care, thus potentially improving chlamydia and gonorrhea control efforts.

High interest in preexposure prophylaxis among men who have sex with men at risk for HIV infection: baseline data from the US PrEP demonstration project.

Background:Preexposure prophylaxis (PrEP) is the first biomedical intervention with proven efficacy to reduce HIV acquisition in men who have sex with men (MSM) and transgender women. Little is known about levels of interest and characteristics of individuals who elect to take PrEP in real-world clinical settings. Methods:The US PrEP Demonstration Project is a prospective open-label cohort study assessing PrEP delivery in municipal sexually transmitted disease clinics in San Francisco and Miami and a community health center in Washington, DC. HIV-uninfected MSM and transgender women seeking sexual health services at participating clinics were assessed for eligibility and offered up to 48 weeks of emtricitabine/tenofovir for PrEP. Predictors of enrollment were assessed using a multivariable Poisson regression model, and characteristics of enrolled participants are described. Results:Of 1069 clients assessed for participation, 921 were potentially eligible and 557 (60.5%) enrolled. In multivariable analyses, participants from Miami (adjusted Relative Risk [aRR]: 1.53; 95% confidence interval [CI]: 1.33 to 1.75) or DC (aRR: 1.33; 95% CI: 1.2 to 1.47), those who were self-referred (aRR: 1.48; 95% CI: 1.32 to 1.66), those with previous PrEP awareness (aRR: 1.56; 95% CI: 1.05 to 2.33), and those reporting >1 episode of anal sex with an HIV-infected partner in the last 12 months (aRR: 1.20; 95% CI: 1.09 to 1.33) were more likely to enroll. Almost all (98%) enrolled participants were MSM, and at baseline, 63.5% reported condomless receptive anal sex in the previous 3 months. Conclusions:Interest in PrEP is high among a diverse population of MSM at risk for HIV infection when offered in sexually transmitted disease and community health clinics.

Effect of risk-reduction counseling with rapid HIV testing on risk of acquiring sexually transmitted infections: The AWARE randomized clinical trial

IMPORTANCE To increase human immunodeficiency virus (HIV) testing rates, many institutions and jurisdictions have revised policies to make the testing process rapid, simple, and routine. A major issue for testing scale-up efforts is the effectiveness of HIV risk-reduction counseling, which has historically been an integral part of the HIV testing process. OBJECTIVE To assess the effect of brief patient-centered risk-reduction counseling at the time of a rapid HIV test on the subsequent acquisition of sexually transmitted infections (STIs). DESIGN, SETTING, AND PARTICIPANTS From April to December 2010, Project AWARE randomized 5012 patients from 9 sexually transmitted disease (STD) clinics in the United States to receive either brief patient-centered HIV risk-reduction counseling with a rapid HIV test or the rapid HIV test with information only. Participants were assessed for multiple STIs at both baseline and 6-month follow-up. INTERVENTIONS Participants randomized to counseling received individual patient-centered risk-reduction counseling based on an evidence-based model. The core elements included a focus on the patients specific HIV/STI risk behavior and negotiation of realistic and achievable risk-reduction steps. All participants received a rapid HIV test. MAIN OUTCOMES AND MEASURES The prespecified outcome was a composite end point of cumulative incidence of any of the measured STIs over 6 months. All participants were tested for Neisseria gonorrhoeae, Chlamydia trachomatis, Treponema pallidum (syphilis), herpes simplex virus 2, and HIV. Women were also tested for Trichomonas vaginalis. RESULTS There was no significant difference in 6-month composite STI incidence by study group (adjusted risk ratio, 1.12; 95% CI, 0.94-1.33). There were 250 of 2039 incident cases (12.3%) in the counseling group and 226 of 2032 (11.1%) in the information-only group. CONCLUSION AND RELEVANCE Risk-reduction counseling in conjunction with a rapid HIV test did not significantly affect STI acquisition among STD clinic patients, suggesting no added benefit from brief patient-centered risk-reduction counseling. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01154296.

Rectal infections with chlamydia and gonorrhoea in women attending a multiethnic sexually transmitted diseases urban clinic

Sexually transmitted rectal infections with Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC) have been well documented in men who have sex with men (MSM). Few studies have described infections in women who engage in anal intercourse. We performed testing for rectal infections in women who reported ano-receptive intercourse at the Miami Dade Health Department Sexually Transmitted Diseases (STD) clinic and report the prevalence and characteristics of women with rectal CT or GC infections. Our results revealed a prevalence of 17.5% for rectal chlamydia and 13.4% for rectal gonorrhoea. Urine-based screening alone would have missed 6% of rectal chlamydia infections and 35% of rectal gonorrhoea infections. Anal symptoms were reported in 12.5% of women with rectal chlamydia infections. The only associated factor identified was an age less than 28 years. We conclude that rectal screening for CT and GC should be included in STD prevention strategies, especially in the younger population.

NGX-4010, a capsaicin 8% dermal patch, for the treatment of painful HIV-associated distal sensory polyneuropathy: Results of a 52-week open-label study

Objectives:To evaluate the efficacy, safety, and tolerability of repeated NGX-4010 treatments in the open-label extension phase of a 52-week study in patients with neuropathic pain due to HIV-associated distal sensory polyneuropathy (HIV-DSP). Methods:Patients completing the 12-week, randomized, double-blind phase of the study could enter a 40-week, open-label phase, and receive up to 3, 60-minute NGX-4010 treatments. Patients recorded their “average pain for the past 24 hours” daily using the Numeric Pain Rating Scale (NPRS). Efficacy assessment included the percentage NPRS score reduction from baseline to weeks 2 to 12 after the final treatment, and Patient Global Impression of Change (PGIC) and Clinician Global Impression of Change (CGIC) questionnaires at study termination. Results:Of 307 patients randomized, 272 entered the open-label phase; 81, 90, 55, and 46 received 0, 1, 2, and 3 retreatments, respectively. The mean percentage decrease in NPRS score from baseline to weeks 2 to 12 after the final treatment was similar in patients receiving single or multiple NGX-4010 treatments (−25.8%, −27.1%, −24.6%, and −22.7% for 1, 2, 3, and 4 NGX-4010 treatments, respectively). PGIC and CGIC results demonstrated a benefit of NGX-4010 treatment through to the end of the study regardless of the number of treatments received. Transient local application site reactions were the most frequently reported adverse events, and were mainly mild to moderate, nonserious, and did not increase with repeated treatment. Discussion:Repeated NGX-4010 treatments were generally well tolerated and resulted in consistent reductions in HIV-DSP-associated pain and improvement in patient-reported outcomes.

The implementation of an analgesia-based sedation protocol reduced deep sedation and proved to be safe and feasible in patients on mechanical ventilation

Introduction Deep sedation in critically ill patients is associated with a longer duration of mechanical ventilation and a prolonged length of stay in the intensive care unit. Several protocols have been used to improve these outcomes. We implement and evaluate an analgesia-based, goal-directed, nurse-driven sedation protocol used to treat critically ill patients who receive mechanical ventilation. Methods We performed a prospective, two-phase (before-after), non-randomized multicenter study that involved 13 intensive care units in Chile. After an observational phase (observational group, n=155), we designed, implemented and evaluated an analgesia-based, goal-directed, nurse-driven sedation protocol (intervention group, n=132) to treat patients who required mechanical ventilation for more than 48 hours. The primary outcome was to achieve ventilator-free days by day 28. Results The proportion of patients in deep sedation or in a coma decreased from 55.2% to 44.0% in the interventional group. Agitation did not change between the periods and remained approximately 7%. Ventilator-free days to day 28, length of stay in the intensive care unit and mortality were similar in both groups. At one year, post-traumatic stress disorder symptoms in survivors were similar in both groups. Conclusions We designed and implemented an analgesia-based, goal-directed, nurse-driven sedation protocol in Chile. Although there was no improvement in major outcomes, we observed that the present protocol was safe and feasible and that it resulted in decreased periods of deep sedation without increasing agitation.

Virologic Response, Early HIV-1 Decay, and Maraviroc Pharmacokinetics With the Nucleos(t)ide-Free Regimen of MaravIroc Plus Darunavir/Ritonavir in a Pilot Study

Objective:To address the need for nucleos(t)ide reverse transcriptase inhibitor (NRTI)–sparing regimens, we explored the virologic and pharmacokinetic characteristics of maraviroc plus ritonavir-boosted darunavir in a single-arm, open-label, 96-week study. Methods:Twenty-four antiretroviral-naive R5 HIV-1–infected participants received maraviroc 150 mg and darunavir/ritonavir (DRV/r) 800/100 mg (MVC/DRV/r) once daily. The primary outcome was virologic failure (VF) = confirmed viral load (VL) >50 copies per milliliter at week 24 in the modified intent-to-treat population. To determine viral dynamics, participant-specific first- and second-phase empirical Bayes estimates were compared with decay rates from efavirenz (EFV) plus lopinavir/ritonavir, lopinavir/ritonavir plus 2NRTIs, and EFV plus 2NRTIs. Maraviroc plasma concentrations were determined at weeks 2, 4, 12, 24, and 48. Results:Baseline median (Q1, Q3) CD4 count and VL were 455 (299, 607) cells per cubic millimeter and 4.62 (4.18, 4.80) log10 copies per milliliter, respectively. VF occurred in 3 of 24 participants {12.5% [95% confidence interval (CI): 2.7 to 32.4]} at week 24. One of these resuppressed, yielding a week 48 VF rate of 2/24 [8.3% (95% CI: 1.0 to 27.0)]. The week 48 failures were 2 of the 4 participants (50%) with baseline VL >100,000 copies per milliliter. Week 96 VF rate was 2/20 [10% (95% CI: 1.2 to 31.7)]. Phase 1 decay was faster with MVC/DRV/r than reported for ritonavir-boosted lopinavir plus 2NRTIs (P = 0.0063) and similar to EFV-based regimens. Individual maraviroc trough concentrations collected between 20 and 28 hours post dose (n = 59) was 13.7 to 130 ng/mL (Q1, 23.4 ng/mL; Q3, 46.5 ng/mL), and modeled steady-state concentration was 128 ng/mL. Conclusions:MVC/DRV/r 150/800/100 mg once daily has potential for treatment-naive patients with R5 HIV-1.

Management of Pneumocystis Jirovecii pneumonia in HIV infected patients: current options, challenges and future directions

The discovery of the Human Immunodeficiency Virus (HIV) was led by the merge of clustered cases of Pneumocystis jirovecii Pneumonia (PCP) in otherwise healthy people in the early 80’s.1,2 In the face of sophisticated treatment now available for HIV infection, life expectancy approaches normal limits. It has dramatically changed the natural course of HIV from a nearly fatal infection to a chronic disease.3–5 However, PCP still remains a relatively common presentation of uncontrolled HIV. Despite the knowledge and advances gained in the prevention and management of PCP infection, it continues to have high morbidity and mortality rates. Trimethoprim-sulfamethoxazole (TMP-SMZ) remains as the recommended first-line treatment. Alternatives include pentamidine, dapsone plus trimethoprim, clindamycin administered with primaquine, and atovaquone. For optimal management, clinicians need to be familiar with the advantages and disadvantages of the available drugs. The parameters used to classify severity of infection are also important, as it is well known that the adjunctive use of steroids in moderate to severe cases have been shown to significantly improve outcome. Evolving management practices, such as the successful institution of early antiretroviral therapy, may further enhance overall survival rates.

Making the Case for Circumcision as a Public Health Strategy: Opening the Dialogue

Hispanics in the United States have lower rates of male circumcision and higher rates of HIV. Although MC has been demonstrated to reduce the risk of acquisition of several sexual transmitted diseases such as HIV, human papilloma virus infection, and herpes simplex virus type 2, MC is only medically reimbursable by insurance for adults or children following recurrent infection, injury, or malformation of the penis. We conducted two studies of attitudes regarding MC among health care providers to Hispanic clients at Miami, Florida STD and Prenatal Clinics. This study presents qualitative data drawn from intensive interviews with 21 providers, including a mohel. Qualitative data was analyzed for dominant themes and collapsed into overarching themes. Thirteen themes emerged; acceptability, appearance, circumcision and children, circumcision and HIV, cost, cultural differences, health benefits, knowledge and personal experiences, pain and injury to the penis, perceived HIV risk, religion, sexual performance, and sexual pleasure. Except for the mohel, Hispanic male providers related MC acceptability to American Pediatric Association guidelines, personal circumcision status, and were skeptical regarding health benefits for sexually transmitted disease (STD)/HIV risk reduction. Female providers focused on the financial burden to parents, lack of information, and low acceptability among Hispanic men. This study illustrates the differing attitudes on circumcision held by providers, and suggests that gender, culture, cost, and providers themselves may limit MC acceptability among Hispanic clients. Results suggest that promotion of MC as an HIV risk reduction strategy must begin with the support of medical practitioners to promote the endorsement of MC as a prevention strategy.

Etravirine: the renaissance of non-nucleoside reverse transcriptase inhibitors

Background: Etravirine is the first non-nucleoside reverse transcriptase inhibitor (NNRTI) to be active against human immunodeficiency virus with NNRTI mutations. Objective: To understand the unique features of etravirine and to evaluate its safety, efficacy, and optimal use. Methods: The structure and the mechanism of action of etravirine in blocking the reverse transcriptase enzyme and the preclinical, pharmacokinetic and pharmacodynamic studies were reviewed. The DUET Phase III clinical trials and the resistance profile of etravirine were evaluated. Conclusions: Etravirine has unique activity against most HIV isolates that are resistant to other NNRTIs. Unlike other NNRTIs, it has a higher genetic barrier to developing high-grade resistance. In the DUET studies, etravirine demonstrated virological efficacy superior to the control arms with comparable rates of adverse events with the exception of rash. Because of its effect on the cytochrome P450 system, there are important drug interactions that will need to be taken into consideration with its use.