Bisher AKIL, MD

Archive for February, 2013|Monthly archive page


In General Health, HIV, Immune System on February 28, 2013 at 6:55 pm

Earlier studies have suggested that HIV-infected individuals have an increased prevalence of nasal colonization with community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) and a greatly increased risk for CA-MRSA skin and soft-tissue infections. To explore the prevalence and colonization burden of CA-MRSA in HIV-infected and HIV-uninfected individuals, researchers studied patients admitted to a general medicine or HIV ward service at a Chicago hospital between March 2011 and April 2012.Patients were enrolled within 72 hours after admission and were swabbed for CA-MRSA at sites typical for colonization. Risk factors for CA-MRSA colonization were determined using a targeted questionnaire and review of medical records. Of the 745 participants (64% men; 63% black; mean age, 48), 374 were HIV infected. The overall prevalence of CA-MRSA colonization was 10% at the nares and 15% at extranasal sites. HIV-infected patients had a higher prevalence of colonization at any site than did HIV-uninfected patients (20% vs. 11%; P=0.002). Extranasal colonization was most frequent in perirectal and inguinal sites for HIV-infected patients, and in perirectal, inguinal, and throat sites for HIV-uninfected patients. In HIV-infected patients, mean CD4-cell count and median viral load did not differ between those who were and were not colonized with CA-MRSA. In multivariate analysis, factors associated with an increased colonization burden (number of sites colonized per patient) in HIV-infected patients were current or recent incarceration, male sex, and younger age; Hispanic ethnicity was associated with a decreased colonization burden. In HIV-uninfected patients, temporary housing was the only factor associated with a higher CA-MRSA colonization burden. Most of the CA-MRSA isolates (74%) were USA300. Predictors of this strain included HIV infection, male sex, younger age, and current or former illicit drug use.

Published in Journal Watch HIV/AIDS Clinical Care

Citation: Popovich KJ et al. Community-associated methicillin-resistant Staphylococcus aureus colonization burden in HIV-infected patients. Clin Infect Dis 2013 Feb 12;

Comments: The data is not new, but still important to emphasize: one out five HIV infected individuals carry MRSA and not in the usual places (so cultured the nasal area may not be revealing). This has diagnostic and treatment implication as well as public health change in policies_ BA


Why we use supplements?

In General Health on February 28, 2013 at 6:38 pm

Summary from the authors: Dietary supplements are used by more than half of adults, although to our knowledge, the reasons motivating use have not been previously examined in US adults using nationally representative data. The purpose of this analysis was to examine motivations for dietary supplement use, characterize the types of products used for the most commonly reported motivations, and to examine the role of physicians and health care practitioners in guiding choices about dietary supplements. Method: Data from adults (≥20 years; n = 11 956) were examined in the 2007-2010 National Health and Nutrition Examination Survey, a nationally representative, cross-sectional, population-based survey. Results:   The most commonly reported reasons for using supplements were to “improve” (45%) or “maintain” (33%) overall health. Women used calcium products for “bone health” (36%), whereas men were more likely to report supplement use for “heart health or to lower cholesterol” (18%). Older adults (≥60 years) were more likely than younger individuals to report motivations related to site-specific reasons like heart, bone and joint, and eye health. Only 23% of products were used based on recommendations of a health care provider. Multivitamin-mineral products were the most frequently reported type of supplement taken, followed by calcium and ω-3 or fish oil supplements. Supplement users are more likely to report very good or excellent health, have health insurance, use alcohol moderately, eschew cigarette smoking, and exercise more frequently than nonusers.

Citation: Bailey RL et al. Why US adults use dietary supplements. JAMA Intern Med 2013 Feb 4;

Comments: Large study with somewhat surprising results: the percentage of people using vitamins, characteristics of users and the reason(s) given for that use. In addition, the choice of the supplement is not done with consultation with a physician; actually, how many supplement users tell their physicians what they actually take? Not all supplements are harmless; some interaction with prescribed medications have been reported and then the “too much of a good thing” (see previous posting). The supplement business is a $28 billion a year_BA

Too much of a good thing,…

In General Health on February 28, 2013 at 6:23 pm

Calcium intake, both dietary and supplemental, is encouraged to improve bone health, and many older adults take calcium supplements. Recent randomized trials of supplementation suggest an association with cardiovascular disease (CVD), but the studies are heterogeneous, and results are mixed. In this prospective cohort study, U.S. researchers assessed baseline calcium intake — including dietary recall and calcium supplements and calcium-containing antacids and multivitamins — in 390,000 older adults (mean age, 61). About 50% of men and 70% of women used calcium-containing supplements. Median daily dietary intake of calcium in both men and women was 700 mg. During 12 years of follow-up, researchers identified 12,000 CVD-related deaths. In analyses adjusted for multiple CVD risk factors, supplemental calcium was associated significantly with CVD-related death in men but not in women: In men, daily calcium supplementation of >1000 mg, compared with no supplement use, was associated with 20% higher risk for CVD-related death, with the excess risk entirely attributable to heart disease. Calcium intake was not associated with death from cerebrovascular disease.

Published in Journal Watch

Comments: A large trial over a long period of time with convincing results, although somewhat puzzling Men but not women? Heart but not brain? How much is safe for men (should men take it? what age?) BA

Citation: Xiao Q et al. Dietary and supplemental calcium intake and cardiovascular disease mortality: The National Institutes of Health–AARP Diet and Health study. JAMA Intern Med 2013 Feb 4;

Eat, drink and be healthy

In General Health on February 25, 2013 at 8:51 pm

The New England Journal of Medicine (NEJM) published online a study from Spain, where they randomly assigned  7447 participants between the age of 55-80, both men and women (57%), who were at high cardiovascular risk, but with no cardiovascular disease at enrollment, to one of three diets: a Mediterranean diet supplemented with extra-virgin olive oil, a Mediterranean diet supplemented with mixed nuts, or a control diet (adviced to reduce dietary fat). Participants received quarterly individual and group educational sessions and  free provision of extra-virgin olive oil, mixed nuts, or small nonfood gifts. The primary end point was the rate of major cardiovascular events (myocardial infarction, stroke, or death from cardiovascular causes). On the basis of the results of an interim analysis, the trial was stopped after a median follow-up of 4.8 years.

Results: The two Mediterranean-diet groups had good adherence to the intervention, according to self-reported intake and biomarker analyses. A primary end-point event occurred in 288 participants. The multivariable-adjusted hazard ratios were 0.70 (95% confidence interval [CI], 0.54 to 0.92) and 0.72 (95% CI, 0.54 to 0.96) for the group assigned to a Mediterranean diet with extra-virgin olive oil (96 events) and the group assigned to a Mediterranean diet with nuts (83 events), respectively, versus the control group (109 events). No diet-related adverse effects were reported.

Conclusion: Among persons at high cardiovascular risk, a Mediterranean diet supplemented with extra-virgin olive oil or nuts reduced the incidence of major cardiovascular events.

Citation: N Engl J Med 2013. DOI: 10.1056/NEJMoa1200303; This article was published on February 25, 2013, at

Comments: this study is unique for several reasons: the participants did not have a CVD at the time of enrollment (preventative intervention), large number of women participants (57%), realistic diet that is not punishing (wine is fine), and the end points for the study were true life clinical events, and not laboratory biomarkers. This is a diet that one could adhere without feeling retribution for preventing CVD. The diet in this study, contained: Olive oil: ≥4 tbsp/day, Tree nuts and peanuts: ≥3 servings/wk, Fresh fruits: ≥3 servings/day, Vegetables: ≥2 servings/day, Fish (especially fatty fish), seafood: ≥3 servings/wk, Legumes: ≥3 servings/wk; Sofrito (sauce made with tomato and onion, often including garlic and aromatic herbs, and slowly simmered with olive oil.): ≥2 servings/wk; White meat Instead of red meat; Wine with meals (optionally,)≥7 glasses/wk – Discouraged: Soda drinks: <1 drink/day; Commercial bakery goods, sweets, and pastries:<3 servings/wk, Spread fats: <1 serving/day; Red and processed meats:<1 serving/day. For participants assigned to the Mediterranean diet with nuts, the recommended consumption was one daily serving (30 g, composed of 15 g of walnuts, 7.5 g of almonds, and 7.5 g of hazelnuts). [tbsp.= one table spoon;  United States Department of Agriculture (USDA) sets a serving size for fruit or vegetables to be equal to about one-half cup. Greens like spinach and lettuce have a serving size equal to one full cup. One serving of sliced fruit is equal to one-half cup; however a single piece of fruit, such as an apple or an orange counts as one serving; also note that amount of olive oil above includes oil used for cooking and salads and oil consumed in meals eaten outside the home. In the group assigned to the Mediterranean diet with extra-virgin olive oil, the goal was to consume 50 g (approximately 4 tbsp) or more per day of the polyphenol-rich olive oil – not the refined olive oil!] The results: an energy-unrestricted Mediterranean diet supplemented with either extra-virgin olive oil or nuts resulted in an absolute risk reduction of approximately 3 major cardiovascular events per 1000 person-years, for a relative risk reduction of approximately 30%, among high risk persons who were initially free of cardiovascular disease.

Deadlier than HIV?

In General Health, HIV on February 25, 2013 at 7:11 am

Smoking is extremely common among HIV-infected patients. To quantify the contribution of smoking to mortality in HIV patients, researchers analyzed a median of 4 years of follow-up data from 2921 patients (78% men, 77% on antiretroviral therapy at baseline) in a Danish national HIV cohort and from 10,642 matched controls in the Danish general population. Each patient’s smoking status — current (any weekly tobacco use), previous, or never — was assessed at time of enrollment and held constant for purposes of analysis. Duration of smoking was not considered. Outcomes data came from Danish national registries. In the HIV-infected cohort, analyses adjusted for HIV-related and other clinical variables revealed that all-cause mortality was more than fourfold higher, and non–AIDS-related mortality was more than fivefold higher, among current smokers than among never smokers. The population-attributable risk for death related to smoking was about 62% in the HIV cohort and 34% in the control group. Compared with controls, HIV patients had roughly triple the excess mortality and life-years lost from smoking. The relative risk for death associated with smoking did not differ significantly between the two groups.

Comment: Striking numbers: 12.3 life-years lost from smoking, compared with 5.1 lost from HIV infection!

CITATION: Helleberg M et al. Mortality attributable to smoking among HIV-1–infected individuals: A nationwide, population-based cohort study. Clin Infect Dis 2012 Dec 18.

Published in Journal Watch HIV/AIDS Clinical Care.

Obesity: Myths and Facts

In General Health on February 25, 2013 at 7:03 am

Researchers identify a variety of myths about obesity and deliver sometimes-unpleasant countervailing facts in the New England Journal of Medicine. Among them:

Myth: Sexual activity is a good form of exercise.

Fact: It may be intense, but it’s not long-lasting enough to be much better than watching television, calorically speaking.

Myth: Breast-feeding infants protects them from obesity later in life.

Fact: Studies that controlled for confounding found no evidence of a protective effect.

Myth: Patients should set realistic goals for weight loss. Otherwise they might become frustrated and not lose as much.

Fact: Studies have shown that patients who set more ambitious goals are likely to lose more weight.

Citation:Myths, Presumptions, and Facts about Obesity, N Engl J Med 2013; 368:446-454; DOI: 10.1056/NEJMsa1208051

KP-1461: A Novel Approach in treating HIV infection

In HIV on February 25, 2013 at 6:38 am

Most of the antiretrovirals in development represent additions to the currently available drug classes. KP-1461 belongs to a novel class of drugs — viral decay accelerators — that increase the mutation rate, with the goal of exceeding the virus’s error threshold and thereby decreasing replication. In a recent manufacturer-sponsored, phase IIa study, researchers evaluated the safety, tolerability, and efficacy of 4 months of oral KP-1461 (1600 mg twice daily).The study involved 24 HIV-infected patients who had not received antiretroviral therapy (ART) for 16 weeks (83% men; median age, 47.5; mean duration of HIV infection, 15 years; median baseline CD4 count, 429 cells/mm3; median viral load, 68,450 copies/mL). All had received nonsuppressive ART in the past or had documented HIV resistance to multiple ART classes, or both, and many had intolerance to available agents. Trough levels of KP-1461 during the study exceeded those previously shown in vitro to be associated with significant viral load declines. Twelve patients experienced possibly drug-related adverse events, most of them mild to moderate in severity. Two patients discontinued medications because of adverse events, and two died of causes unrelated to study medications. No significant effect on viral load, CD4-cell count, or drug-resistance pattern was seen among the 13 patients who completed 4 months of treatment. Comparison of viral sequences between 10 of these patients and controls revealed mutation-pattern changes consistent with the drug’s proposed mechanism of action.

Comment:These are small and early data; however, and despite some shortfalls (the choice of patients (not totally naive, and not typical experienced patients), unusual disposition of some of the study participants), these data should lead to larger studies to assess the true role of this treatment.

CITATION: Hicks C et al. Safety, tolerability, and efficacy of KP-1461 as monotherapy for 124 days in antiretroviral-experienced, HIV type-1 infected subjects. AIDS Res Hum Retroviruses 2013 Feb; 29:250.

Published in Journal Watch HIV/AIDS Clinical Care

Lersivirine: unfinished story

In HIV on February 25, 2013 at 6:28 am

Lersivirine — a next-generation nonnucleoside reverse transcriptase inhibitor (NNRTI) from the class of efavirenz (Sustiva®) nevirapine (Viramune®), rilpivirine (Edurant®)and etravirine (Intelence®)— has shown promise in early clinical trials, but its comparative efficacy has not been established. In a manufacturer-sponsored, placebo-controlled, double-blind, phase IIb, dose-seeking study, 195 HIV-infected adults with viral loads 1000 copies/mL and CD4 counts 200 cells/mm3 were randomized to receive tenofovir/FTC plus either lersivirine (500 or 750 mg once daily) or efavirenz (600 mg once daily). In a modified intent-to-treat analysis, the proportion of patients with viral loads <50 copies/mL at week 48 was 78.5% in both lersivirine arms and 85.7% in the efavirenz group. Virologic failure was somewhat more common with lersivirine, but efavirenz had a slightly higher adverse-event rate.

Comment: Lersivirine is a novel NNRTI with a unique resistance pattern, broad cross-clade activity, and a promising adverse-event profile. Although the current study was not adequately powered to assess noninferiority to efavirenz, the results in all three arms were similar enough to justify large-scale, appropriately powered studies of lersivirine. Unfortunately, the makers of the drug have decided not to pursue further development, so trials to determine the drug’s true safety and efficacy will not take place.

CITATION: Vernazza P et al. Efficacy and safety of lersivirine (UK-453,061) versus efavirenz in antiretroviral treatment–naive HIV-1–infected patients: Week 48 primary analysis results from an ongoing, multicenter, randomized, double-blind, phase IIb trial. J Acquir Immune Defic Syndr 2013 Feb 1; 62:171.

Published in Journal Watch HIV/AIDS Clinical Care

Medicine in bottles do not work.

In HIV on February 25, 2013 at 12:31 am

One of the greatest concerns about ever-expanding access to antiretroviral therapy (ART) is an increase in drug resistance. To assess trends in — and determinants of — such resistance in Western Europe, researchers examined HIV genotype data on samples obtained from ART-experienced patients in the U.K., Italy, Portugal, Germany, Sweden, Spain, and Belgium between 1997 and 2008.  Records for 20,323 samples were included in the analysis. Overall, 16,278 samples (80%) showed at least one resistance mutation. Resistance to nucleoside reverse transcriptase inhibitors (NRTIs) was most common (67%), followed by nonnucleoside reverse transcriptase inhibitors (NNRTIs; 51%) and protease inhibitors (PIs; 33%). Resistance to one, two, and three of these drug classes was seen in 26%, 38%, and 16% of the samples, respectively.  The proportion of samples with at least one resistance mutation declined over time, from 81% in 1997 to 71% in 2008; NRTI and PI mutations showed notable decreases. The proportion of sampled patients who exhausted available drug options dropped dramatically, from 32% in 2000 to 1% in 2008. During the sampling period, NRTI use decreased (from 98% of the patients in 1997 to 94% in 2008), NNRTI use increased (from 6% in 1997 to 41% in 2000, leveling off at 32% in 2008), unboosted PI use decreased (from 55% in 1997 to 7% in 2008), and boosted PI use increased (from 1% in 1997 to 48% in 2008). In multivariable analysis, factors associated with detection of resistance included being a man who has sex with men, non-B subtype virus, history of suboptimal therapy, failure of higher-line regimens, and longer duration of ART exposure.

Comment: The declining HIV drug resistance over time in this European meta-cohort retrospective analysis reflect adherence, but it also reflects better choices for cART, such as replacing PI-boosted for non boosted regimens, and better treatment options (new classes of medications). Interestingly, the European regimens that are NRTI sparing are on the rise as shown in this paper, which is not as widely used in the US where it has always been associated with skepticism. BA

CITATION: De Luca A et al. Declining prevalence of HIV-1 drug resistance in antiretroviral treatment-exposed individuals in Western Europe. J Infect Dis 2013 Jan 11.

Summary published in Journal Watch HIV/AIDS Clinical Care 

How effective is HPV vaccination?

In General Health, Immune System on February 25, 2013 at 12:18 am

The quadrivalent human papillomavirus (HPV) vaccine prevented genital wart acquisition among women in clinical trials , but its effect at the population level is just beginning to be evaluated. In Denmark, routine free HPV vaccination of 12-year-old girls was introduced in 2009, and the current estimated coverage is 80% for all three doses. Now, investigators have assessed the incidence of genital warts in 55% of the Danish population from 1996 to 2011. Annual incidence of genital warts rose in both women and men from 1996 to 2008, when a downward turn was noted among women but not men. This reduction was especially pronounced among 16- to 17-year-old women, in whom incidence fell 10-fold (from 382 per 100,000 to 40 per 100,000). During this period, prevalence of chlamydia and syphilis continued to rise.

Comment: The drop in prevalence of genital warts but not other sexually transmitted diseases suggests that the human papillomavirus vaccine — and not a behavioral change in the target population — was primarily responsible for this beneficial outcome. It also indicates the need to vaccinate both men and women. Such studies also demonstrate how countries with healthcare systems that allow for efficient delivery of preventive care as well as rapid assessment of the benefits at the national level. The U.S. would do well to learn from such successes.

CITATION: Baandrup L et al. Significant decrease in the incidence of genital warts in young Danish women after implementation of a national human papillomavirus vaccination program. Sex Transm Dis 2013 Feb; 40:130.

Published in Journal Watch Women’s Health