Abstract
HIV
Rilpivirine Receives FDA Approval
On May 20, the U.S. Food and Drug Administration granted approval to rilpivirine (Edurant®, Centocor Ortho Biotech, Horsham, PA), a non-nucleoside reverse transcriptase inhibitor (NNRTI), for use in highly active antiretroviral therapy (HAART) drug regimens to treat HIV-1 infection in treatment-naïve adults. Dosing is once-a-day with food. Phase 3 clinical trials showed rilpivirine to be as effective as efavirenz in lowering viral load; 83% and 80% of patients, respectively, had undetectable HIV levels in their blood after 48 weeks of treatment. The most commonly reported side effects with rilpivirine included depression, insomnia, headache, and rash. Further testing is ongoing to determine whether rilpivirine can be combined with Truvada® (Gilead Sciences, Foster City, CA) in a one-pill-a-day treatment format, similar to Atripla® (Bristol Myers-Squib, New York, NY).
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Benefits of Raltegravir Over Efavirenz
SWITCH-ER, a randomized, double-blinded, crossover study designed to compare the non-nucleoside reverse transcriptase inhibitor efavirenz (EFV) to raltegravir (RAL) showed significant differences between the two treatment groups in favor of RAL for measures of anxiety, stress, and blood lipid levels, as well as an overall patient preference for RAL. EFV is associated with central nervous system side effects in as many as half of patients, including reduced sleep quality, irritability, and nervousness, and an unfavorable blood lipid profile. In SWITCH-ER, patients who tolerated EFV on previous use received either RAL (400 mg twice daily) plus EFV-placebo, or EFV (600 mg once daily) plus RAL-placebo during the first 2 weeks of the study. Each treatment group then switched to the alternate regimen for the next 2 weeks.
At the end of the 4-week study period, 51% of patients previously on a stable EFV regiment chose to switch to RAL. The RAL treatment group had significant improvement in several blood lipid measures compared to EFV: median plasma cholesterol levels decreased by 0.4 mmol/L; triglycerides by 0.2 mmol/L; and low-density lipoprotein (LDL) by 0.2 mmol/L.
Source: Nguyen et al. A randomized cross-over study to compare raltegravir and efavirnez (SWITCH-ER study). AIDS May 17, 2011; DOI: 10.1097/QAD.0b013e328348dab0
Early Use of ART Reduces Transmission to Uninfected Partners
An early end to the phase 3 HPTN 052 trial, scheduled to run until 2015, is good news, because the results to date demonstrate unequivocally that early HIV treatment with oral antiretroviral therapy (ART) offers substantial protection against HIV acquisition by uninfected partners and has health benefits for HIV-infected patients as well. The HIV Prevention Trials Network reported that initiation of ART provided a 96% reduction in risk of HIV transmission in the randomized HPTN 052 study. The HIV-infected individuals who participated in the trial had CD4 cell counts of 350–550/mm3 at enrollment and did not require ART. One group of subjects began immediate treatment with ART, while the other group delayed initiation of ART until CD4 cell counts fell below 250/mm3 or an AIDS-related illness developed. Both groups received ongoing HIV-related care, evaluation, counseling, and treatment for HIV complications.
In the delayed ART group, HIV transmission occurred among 27 couples, while only one transmission occurred in the immediate ART group. The trial results indicated a health benefit of early ART initiation for the HIV-infected study participants: whereas 17 cases of extrapulmonary tuberculosis occurred in the delayed ART group, three cases occurred in the immediate ART group. “The HPTN 052 study provides compelling evidence for a new HIV prevention approach that links prevention and care efforts,” said Quarraisha Abdool Karim, an HPTN co-principal investigator.
Source: HIV Medicine Association, Center for Global Health Policy, May 12, 2011.
Expanding ART for All HIV-Infected MSM Would Reduce New Infection Rate
A simulation model for expanded HIV testing and treatment among men who have sex with men (MSM) in San Francisco led to the prediction that providing ART to all HIV-infected MSM (with any CD4 cell count) or to those with CD4 cell counts less tham 500 cells/mm3 could significantly reduce future HIV infections. The model assessed three expanded ART strategies: treatment of all HIV-infected individuals receiving care; treatment of patients with CD4 counts less than 500 cells/mm3; or intensified annual HIV testing and treatment of all HIV-infected MSM. All three strategies led to predicted decreases in new HIV infections compared with the current strategy of initiating ART when a patient's CD4 cell count falls below 350 cells/mm3. The largest effect would be achieved with the intensive test-and-treat strategy, with a reduction in HIV infection prevalence by more than half (26.2% to 12.8%) after 20 years. The two other expanded treatment strategies would also lead to significant reductions in new HIV infection according to the model.
Source: Charlebois ED, et al. The effect of expanded antiretroviral treatment strategies on the HIV epidemic among men who have sex with men in San Francisco. Clin Infect Dis 2011;52:1046–1049.
HIV Testing Laws in All But Five States Meet CDC Recommendations
With the exception of Maine, New York, Nebraska, Pennsylvania, and Rhode Island, the remaining 46 states (including the District of Columbia) have modified their HIV testing law to be compatible with the 2006 Centers for Disease Control and Prevention (CDC) recommendation that HIV screening be part of standard medical care offered in health care settings to all patients 13 to 64 years of age. The recommendation was part of an effort to streamline HIV diagnosis and pretest and posttest counseling. In Maine, patients must request an HIV test. Both Maine and Nebraska require separate consent for HIV testing, and together with New York and Pennsylvania, consent must be written and not oral. New York allows oral consent for rapid HIV testing. Counseling requirements in Pennsylvania and Rhode Island are not fully compatible with the CDC recommendations.
Source: CDC HIV/Hepatitis/STD/TB Prevention News Update and Neff S, Goldschmidt R. Centers for Disease Control and Prevention 2006 human immunodeficiency virus testing recommendations and state testing laws. JAMA 2011;305:1767–1768.
Lower Mortality with Earlier Initiation of ART in China
Zhang and colleagues evaluated overall mortality rates among HIV-infected adults in China who were eligible for highly active antiretroviral treatment between 1985 and 2009. As treatment coverage increased from almost zero in 2002 to 63.4% in 2009, there was a concomitant decrease in overall mortality from 39.3% per 100 person-years to 14.2%. Treatment coverage was higher and mortality lower for individuals infected through plasma donation or blood transfusion (80.2% coverage and 6.7 deaths per 100 person-years) compared to persons infected via intravenous drug use (42.7% coverage and 15.9 deaths per 100 person-years) or sexual intercourse (61.7% coverage and 17.5 deaths per 100 person-years). In China, HIV-infected intravenous drug users tend to be identified earlier in the course of the disease than individuals infected sexually because of routine testing performed on entry in detoxification centers and methadone maintenance treatment clinics. The authors concluded that treatment coverage and late treatment initiation (lower CD4 cell count (<50 cells/mm3) when determined to be treatment-eligible) are the two main risk factors for HIV-related mortality in China.
Source: Zhang F, et al. Effect of earlier initiation of antiretroviral treatment and increased treatment coverage on HIV-related mortality in China: A national observational cohort study. The Lancet; May 19, 2011; doi:10.1016/S1473-3099(11)70097-4
ART Failure Rate Over Time Among Children with HIV
Failure of triple-class antiretroviral drug regimens may occur sooner in children infected with HIV perinatally compared to adults with heterosexually transmitted HIV, according to the COHERE study. Children born with HIV infection will require long-term viral suppression. Whereas resistance to commonly used HIV drugs appears to develop slowly in adults, the study showed that among 1,007 children less than 16 years of age followed for a median of 4.2 years, 24% of whom were receiving ART, triple-class virologic failure had developed in 10%. The incidence of triple-class virologic failure increased with time following ART initiation and rose to 12% after 5 years. The authors emphasized the importance of early identification of children not responding to ART, as well as adherence support, and ART simplification strategies to optimize efforts to achieve and sustain virologic suppression.
Source: Pursuing Later Treatment Options II (PLATO II) project team for the Collaboration of Observational HIV Epidemiological Research Europe (COHERE)
Hepatitis C Virus
FDA Approves Boceprevir
On May 13, the FDA approved the antiviral drug boceprevir (Victrelis™, Merck, Whitehouse Station, NJ) to treat adults with chronic hepatitis C infection (HCV) who maintain some liver function and are either treatment-naïve or have failed previous HCV treatment. Boceprevir received approval for use in combination with peginterferon alfa and ribavirin. Two thirds of patients receiving this three-drug combination in two phase 3 clinical trials had a significantly increased sustained virologic response—no detectable HCV in the blood 24 weeks after cessation of treatment—compared to treatment with pegylated interferon and ribavirin alone. Dosing of boceprevir is three times a day with food. The most commonly reported side effects of the three-drug regimen are fatigue. Anemia, nausea, headache, and taste distortion.
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Sexually Transmitted Diseases
Testing Female Teens for STIs in the Emergency Department
To determine how common sexually transmitted infections (STIs) are in symptomatic adolescent females, researchers at the Children's Hospital of Philadelphia, University of Pennsylvania, tested females 14–19 years of age who came to the hospital's emergency department with symptoms of lower abdominal, pelvic, or flank pain and/or genitourinary complaints for Neisseria gonorrhoeae, Chlamydia trachomatis, and Trichomonas vaginalis. More than a quarter (26.3%) of the patients tested had an STI: 20% had a chlamydia infection: 10% trichomoniasis; and 3.5% gonorrhea. Additionally, 19% of the patients that tested positive for chlamydia also had trichomoniasis, and 6.7% of the teens with chlamydia also had gonorrhea.
These findings were presented at the Pediatric Academic Societies annual meeting, April 30, 2011, in Denver, Colorado. The authors of the study recommend routine STI testing for adolescent females presenting to the ED with the symptoms described above, as adolescents represent a high-risk group for STIs and failure to identify and treat these infections can have serious long-term health and reproductive consequences and can increased the likelihood of acquiring HIV.
STD Rates Rise Among Seniors
A recent article in the Orlando Sentinel Tribune reported a dramatic increase in the number of reported cases of syphilis and chlamydia among seniors aged 55 and older in Florida between 2005 and 2009. Compared to the 43% increase among seniors nationwide reported by the CDC for that time period, Florida recorded a 62% rise in the two sexually transmitted diseases (STDs), and Central Florida led the state with a 71% increase over those 5 years. A major factor contributing to this increase is the availability and aggressive marketing of sex-enhancing pharmaceuticals, according to Julia Gill, director of the Florida Department of Health's division of disease control. Medications such as Viagra and hormone replacements, including testosterone and progesterone and estrogen creams are helping seniors remain sexually active longer. The national trend of increasing STD rates among seniors has led Medicare to consider providing coverage for STD screening and for behavioral counseling for sexually active seniors.
Source: Orlando Sentinel Tribune, April 16, 2011.
Source: American Academy of Pediatrics;
Tuberculosis
Simpler Regimen as Effective for Treatment Latent TB Infection
The results of a 10-year randomized study that included more than 8000 persons with latent tuberculosis (TB) infection demonstrate that a 12-dose, once-weekly treatment regimen of existing drugs was safe and as effective at preventing new cases of TB as the current standard of care, which required 270 daily medication doses. Furthermore, more patients completed the simpler regimen (82%) than the standard course of therapy (69%). These findings were presented at the recent American Thoracic Society International Conference in Denver, Colorado, by Timothy Sterling, M.D., of Vanderbilt University, principal investigator of the study.
Approximately 11 million people in the United States (4% of the population) are infected with the TB bacterium. Patients with latent TB infection carry the bacterium but do not have symptoms and cannot transmit the bacterium to others. They are, however, at increased risk of progression to active TB infection.
The study compared two preventive treatment regimens: 3 months of once-weekly rifapentine (900 mg) and isoniazid (900 mg) administered under observation; or the current standard regimen, comprising 9 months of unsupervised, self-administered isoniazid (300 mg). Both regimens were associated with the development of few new cases of TB—seven with the 3-month regimen and 15 with standard treatment.
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