Tuesday, March 13, 2012

Fw: Hot Topics at The Body's "Ask the Experts" Forums



From: "News at The Body" <update@news.thebody.com>
Date: 13 Mar 2012 16:38:33 -0400
To: <nelsonvergel@yahoo.com>
ReplyTo: "News at The Body" <update@news.thebody.com>
Subject: Hot Topics at The Body's "Ask the Experts" Forums

If you have trouble reading this e-mail, you can see the online version at: www.thebody.com/topics.html

March 13, 2012
Visit the Forums
"Hot Topics" Library
Change/Update Subscription


LIVING WITH HIV/AIDS


 How Can I Make a Difference With My Life?
As a person living with HIV I feel like I'm wasting my life. Despite being a college graduate, I have not had any form of employment for the last seven years. But I know I can make a difference. How can I share my knowledge on HIV/AIDS and help raise funds for the community?

Jacques Chambers, C.L.U., responds in the "Workplace and Insurance Issues" forum


 Dear Nelson: Am I Taking a Risk Every Time I Eat Sushi?
You advised against eating raw fish, in a previous response about what type of fish to avoid. Does that mean no sushi? I eat sushi about once a month. What are the risks?

Nelson Vergel responds in the "Nutrition and Exercise" forum


Visual AIDS: Art from HIV-Positive Artists

Image from the February 2012 Visual AIDS gallery Detail from:
"Fan Earrings," 1998
Jerome Walker

Visit the March 2012 Visual AIDS Web Gallery to view our latest collection of art by HIV-positive artists! This month's gallery, "From Arches to Earrings," is curated by Glynnis McDaris and Julia Trotta.

INSURANCE, WORKPLACE & LEGAL CONCERNS


 Can My Niece Press Charges Against a Boyfriend Who May Have Exposed Her to HIV?
I have a niece who was dating and sleeping with a guy for about three months. They had an argument and he admitted he was HIV positive. If he is indeed HIV positive, are there actions that can be taken against him, like charging him with attempted murder, because they did have unprotected sex?

Christa Douaihy, Esq., responds in the "Legal Issues and HIV" forum


 Should HIV-Positive Health Professionals Inform Their Employers About Their Status?
Is disclosing required in order for a health professional to practice? Where can I find more information?

Jacques Chambers, C.L.U., responds in the "Workplace and Insurance Issues" forum


More Questions About Insurance, Workplace & Legal Concerns:


HIV/AIDS TREATMENT


 Could My Med Switch Be Causing My Fatigue?
I was on Truvada (tenofovir/FTC), Reyataz (atazanavir) and Norvir (ritonavir) for over five years. But because of stomach issues, I had to switch out the Reyataz for Prezista (darunavir, TMC114) for about six weeks. I started getting terrible headaches, so my doctor switched me to Truvada and Isentress (raltegravir). But now I am feeling extremely tired, more than usual. Is it because of the new regimen?

Keith Henry, M.D., responds in the "Managing Side Effects of HIV Treatment" forum


 Can I Take Hallucinogenic Mushrooms With My HIV Meds?
I'm HIV positive and want to know if I can take hallucinogenic mushrooms. What are the risks? Will it affect my immune system or my health?

David Fawcett, Ph.D., L.C.S.W., responds in the "Substance Use and HIV" forum


 Is Resistance to a Regimen Inevitable?
If a person is adherent and does not get reinfected, can they still become resistant to their regimen? What have you seen in your clinical experience?

Benjamin Young, M.D., Ph.D., responds in the "Choosing Your Meds" forum


OTHER HEALTH ISSUES & HIV/AIDS


 Living With Tuberculous Meningitis: Can I Get My Concentration Back?
I have been living with HIV for 12 years, maintaining a CD4 count of 600 to 900. However, I contracted tuberculous meningitis and it has made my personality flip 180 degrees. Prior to this, I was seen as very sensible, considerate and polite. Now I have no reservations about speaking to a person I may have just met, and even go on for too long. Moreover, my attention span is shorter than ever. I used to devour books, but have only read one in the four years following my diagnosis. What can I do about this?

David Fawcett, Ph.D., L.C.S.W., responds in the "Mental Health and HIV" forum


 Lost Sex Drive: How Can I Regain My Mojo?
I am an HIV-positive 54-year-old male in a mixed-status relationship. My CD4 count is around 575 to 650 and my viral load is undetectable. But where is my sex drive? I used to love sex, but now I have little interest in it. Could it be because of my HIV meds? I am in good shape and work out three times a week. What else can I try?

Nelson Vergel responds in the "Aging With HIV" forum


Connect With Others

My Boyfriend Recently Tested Positive: Should I Stay or Go Now?
(A recent post from the "My Loved One Has HIV/AIDS" board)

Two months ago, my boyfriend of four years, father of my 2-year-old daughter, was diagnosed HIV positive. After starting treatment, he is feeling great. I am negative and test regularly, but will get another test next month just to confirm.

However, I am really confused and don't know if I can continue my life with him, knowing he is HIV positive. As for now, I love him and want to support him. Some days he feels like he should walk away and let me find someone else. I consider this sometimes, but we have a good relationship and do have a child together. Yet I'm scared to have sex even with protection. Any advice? -- Obvious1

Click here to join this discussion, or to start your own!

To do this, you'll need to register with TheBody.com's bulletin boards if you're a new user. Registration is quick and anonymous (all you need is an e-mail address) -- click here to get started!



UNDERSTANDING HIV/AIDS LABS


 What Does My CD4 Percentage of 6 Mean?
I have been off of HIV meds for over a year and just got my lab numbers back. My CD4 percentage is 6. Is this good or bad?

Benjamin Young, M.D., Ph.D., responds in the "Choosing Your Meds" forum


More Questions About Understanding HIV/AIDS Labs:


HIV & HEPATITIS TRANSMISSION


 Which HIV Meds Are Recommended as PEP?
This is the third day on my PEP (post-exposure prophylaxis) regimen, but I noticed that my doctor only prescribed me Truvada (tenofovir/FTC). Is this good enough? What are the usual PEP regimens?

Benjamin Young, M.D., Ph.D., responds in the "Choosing Your Meds" forum


 Are You Sure Hepatitis B and C Can't Be Transmitted Through Food?
If hepatitis B and C can be transmitted through sharing razors and toothbrushes, why is it OK to share food and eating utensils? Aren't they just as capable of transporting blood from one person to another?

Barbara McGovern, M.D., responds in the "Hepatitis and HIV Coinfection" forum


STRANGE BUT TRUE


 Can I Get HIV if There's None To Begin With?
Can I contract HIV even though my partner is HIV negative?

Shannon R. Southall responds in the "Safe Sex and HIV Prevention" forum



Worried Your Spam Filter Might Trash Our Mailings?

The Body's e-mail updates are especially prone to being caught up in spam filters, since our newsletters tend to refer frequently to sex, drugs, the human anatomy and so forth.

To make sure you never miss one of our mailings because anti-spam software labeled it as junk mail, add update@news.thebody.com to your address book, talk to the person who manages your e-mail security or check your anti-spam program's instructions for more information.

About This E-mail

This e-mail update has been sent to nelsonvergel@yahoo.com.

Want to change your subscription? Click here or send us a message at updates@thebody.com.

Missed an update? Our archive of past updates will keep you in the loop.

Have any other questions or comments, and don't want to send an e-mail? Feel free to snail-mail us at:

The Body's E-Mail Updates
Remedy Health Media, LLC
250 West 57th Street
New York, NY 10107


Advertisement


Follow Us
Facebook  Twitter



Activist Central

 Tell Gilead to Reduce the Cost of HIV Medications Now!


 Under Attack: Your Health Care Rights


 Ohioans Living With HIV/AIDS Need Our Help!


 Activists Launch New Survey to Help Speed HIV Cure Research


 Demand Hershey Reverse Decision on HIV+ Student and Dismiss School Officials


 Count HIV+ Women In! PWN Launches National Campaign on World AIDS Day


Monday, March 12, 2012

Best HIV Cure Lecture at CROI 2012


I highly recommend watching Dr Sharon Lewin's talk ( first one after the introduction).  In my opinion, it is the best talk I have seen on the current status of HIV cure research

http://bit.ly/xpT8re

Getting HIV Out of its Hiding Places - Reports from CROI 2012



 NATAP/CROI: HIV Eradication Study by DMargolis with Cancer Drug

Here is link to webcast of the oral session at CROI called HIV Persistence, Latency, and Eradication where Dr David Margolis presented the results of the study he conducted which is discussed below:

from Jules Levin: The drug Zolinza used in this study appears to have been able to "disrupt HIV latency, a signifucant step in eradication", flush out HIV RNA from latently infected resting CD4 cells, which is considered perhaps the major HIV reservoir that remains after successful HAART reduces & sustains HIV viral load to below 50 copies. This study has been a while in the making, years in fact, previously another drug was tried but unsuccessfully, and this drug & experiment appears to be successful, at least at first blush. It remains to be seen what the ultimate success will be in controlling HIV with this approach as well as with other approaches. So this appears to be a hopeful & successful step, but with more steps to go.

Zolinza May Help Reduce Latent HIV Reservoirs In People With HIV (CROI 2012)

aidsbeacon.com
Published: Mar 9, 2012 7:14 pm
Results from a recent small study indicate that Zolinza, a drug currently approved to treat a certain type of lymphoma, may successfully reduce the size of the latent HIV reservoir in HIV-positive adults taking antiretrovirals.
“This is a proof of concept demonstrating that latency can be targeted. This is a significant step towards eradication of HIV infection,” said Dr. David Margolis, a professor of medicine at the University of North Carolina at Chapel Hill and lead author of the study.
“The ability of this drug to deplete latent infection remains to be established and would be the next immediate goal of our work,” he added.
Dr. Margolis urged more research into the ability of Zolinza and other drugs to eliminate or reduce the latent HIV reservoir as a regular part of HIV infection management.
The results were presented yesterday at the 19th Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle.
Latent HIV is HIV that is not actively replicating. Instead, it lies dormant, often in immune system cells with long lifespans, such as memory cells (cells that “remember” bacteria and viruses from past infections so they can be effectively fought again). Since antiretroviral drugs usually work by blocking replication, they do not work on latent HIV.
Eradicating latent HIV is a top priority for scientists attempting to cure HIV, and several drugs are currently being tested for their ability to reduce or eliminate this hidden reserve of the virus.
Zolinza (vorinostat) is a histone deacetylase (HDAC) inhibitor, a type of drug currently used as mood stabilizers and anti-epileptic treatments. More recently, HDAC inhibitors have been investigated as anti-cancer agents, and Zolinza is approved to treat a type of lymphoma.
Research has shown that Zolinza successfully activates latent HIV in infected cells in the laboratory. Once latent HIV is activated and begins replicating, scientists hope it will become susceptible to elimination with antiretroviral therapy (see related AIDS Beacon news).
In this study, researchers investigated whether the drug is capable of activating latent HIV in adults whose HIV is well-controlled with antiretroviral therapy.
The study included six HIV-positive participants, each of whom received a single dose of 400 mg Zolinza. All participants had undetectable amounts of HIV in the blood.
Researchers measured the amount of HIV RNA, a marker of latent HIV, in resting CD4 (white blood) cells, a type of immune cell that is targeted by HIV and is thought to be a major source of latent HIV. The researchers measured the HIV RNA both before and within eight hours after giving the participants Zolinza.
Results showed that the amount of HIV RNA measured in participants’ resting CD4 cells increased an average of five-fold after they took Zolinza. According to the study authors, this indicates that Zolinza successfully reactivated the latent HIV in these cells.
There was no increase in the amount of HIV in participants’ blood due to the treatment.
Participants reported no serious side effects, and none of the side effects were attributed to taking Zolinza.
-------------------
CROI ABSTRACT

Administration of Vorinostat Disrupts HIV-1 Latency in Patients on ART
N Archin1, A Liberty1, A Kashuba1, S Choudhary1, J Kuruc1, M Hudgens1, M Kearney2, J Eron1, D Hazuda3, and David Margolis*1
1Univ of North Carolina at Chapel Hill, US; 2HIV Drug Resistance Prgm, NCI-Frederick, MD, US; and 3Merck Res Labs, West Point, PA, US
Background:  Despite ART, proviral latency of HIV-1 remains a principal obstacle to curing the infection. Inducing the expression of latent genomes within resting CD4+ T cells is a primary strategy to clear this reservoir. While histone deacetylase (HDAC) inhibitors such as suberoylanilide hydroxamic acid (SAHA or vorinostat [VOR]) can disrupt HIV-1 latency in vitro, the utility of this approach has never been directly proven in a study of HIV-infected patients.
Methods:  HIV+ participants on ART, stably <50 copies/mL, maintained ART, and resting CD4+ T cells are obtained via leukapheresis. If an increase in the frequency of HIV RNA expression was observed following ex vivo exposure of resting CD4+ T cells to VOR, patients received 400 mg VOR at separate visits. First, VOR pharmacokinetics were measured. Then biomarker measures of HDAC inhibition in peripheral blood mononuclear cells (PBMC), and measurements of unspliced HIV gag RNA in pools of 1 million resting CD4+ T cells were quantified during VOR exposure.
Results:  Five men have been studied (medians: age 45; CD4 count 562 cells/µL; 4 years of ART). VOR has been well tolerated with no adverse events greater than Grade I, and no adverse events attributable to VOR. Measures of PBMC cellular histone acetylation, and chromatin-bound histone acetylation at the human p21 gene promoter increased more than 2-fold within 8 hours of VOR dosing. VOR PK was comparable to oncology studies with Cmax 263 ng/mL (range 204 to 301) and Tmax 2 hours (range 1 to 4). In each participant, HIV RNA levels increased significantly in pools of resting CD4+ cells obtained after VOR dosing compared to baseline measurements (mean 5-fold, range 3- to 10-fold).
Conclusions:  We measured HIV RNA expression directly within circulating resting CD4+ T cells of patients in whom viremia was fully suppressed by ART. In all patients studied thus far, a single dose of VOR rapidly increased both biomarkers of cellular acetylation, and simultaneously induced up to a 10-fold increase in HIV RNA expression in resting CD4+cells. This is the first demonstration that a molecular mechanism known to enforce HIV latency can be specifically and successfully targeted in man, resulting in readily measureable HIV RNA expression in highly purified, resting CD4+ T cells. Our study provides proof-of-concept for HDAC inhibitors as a therapeutic class to directly attack and potentially eradicate latent HIV infection, and defines a precise approach for evaluating such strategies.


Thursday, March 08, 2012

Frailty & Muscle Loss Increase Mortality & Are Common in HIV+



Subject: NATAP/CROI: Frailty/Muscle Loss in HIV Increases Mortality & is Common

NATAP http://natap.org/
_______________________________________________



Frailty & Muscle Loss Increase Mortality & Are Common in HIV+

from Jules Levin at CROI Live in Seattle. This poster session is a
breakthrough in that it is identifying that muscle loss & frailty are
fairly common in HIV+ persons & they increase mortality. AND HCV & HBV
contribute to frailty in one study below.read this:

"Frailty is a significant predictor of mortality among both HIV+ and
at-risk IDU....... Impaired functional capacity is strongly associated
with lower bone density and lower muscle mass in middle-aged HIV-1+
persons......Co-morbidity Is Predictive of Muscle Strength in HIV+
Veterans: Results from the VACS Index....
Overall, 40% of SUN study participants aged ≤50 years with
well-controlled HIV infection were pre-frail or frail. The significant
association of pre-frailty and frailty with a history of opportunistic
infection suggests earlier diagnosis of HIV infection and prevention of
opportunistic infections may reduce risk for frailty.......Prevalence
of low muscle mass increases with age. The highest prevalence was found
in the 41- to 50-year age group. Predictors of FFMi change appear to be
associated with age, lipoatrophy recovery, and time. FFMi is associated
with all-cause mortality in HIV+ patients, suggesting that this
biological entity can provide prognostic information, in HIV+
patients..........We have recently demonstrated that patients with
prior exposure to nucleoside analog ARV, which inhibit DNA
polymerase-γ, accumulate acquired mitochondrial DNA (mtDNA) mutations
in skeletal muscle, in an apparent acceleration of the process seen in
normal aging. Here we explore an in vivo functional correlate in aging
HIV+ patients. Abnormalities of resting muscle pH handling have been
associated with fatigue and may contribute to functional decline in
this patient group."




Frailty and Pre-frailty in a Contemporary Cohort of HIV+ Adults

Nur Onen*1, P Patel2, J Baker3, L Conley2, J Brooks2, T Bush2, M
Kojic4, J Hammer5, E Overton6, and SUN Study Investigators

1Washington Univ Sch of Med in St Louis, MO, US; 2CDC, Atlanta, GA, US;
3Hennepin County Med Ctr, Univ of Minnesota, Minneapolis, US; 4Miriam
Hosp, Providence, RI, US; 5Denver Infectious Disease Consultants, CO,
US; and 6Univ of Alabama at Birmingham, US

Background:  HIV+ persons can become prematurely pre-frail and frail;
however, pre-frailty prevalence and risk factors for both frail and
pre-frail states have not been fully elucidated.

Methods:  Using data from a contemporary prospective observational
cohort of HIV+ adults (SUN Study), we determined the percentages of
non-frail, pre-frail, and frail participants at the most recent study
visit by the respective presence of 0, 1 to 2, and ≥3 of 5 established
frailty criteria as shown in the table. We evaluated associations with
pre-frailty/frailty using logistic regression analysis.

Results:  Of 308 SUN Study participants assessed—79% men, 58%
non-Hispanic white, median age 47 years (interquartile range 41 to 53),
95% on combination ART, median CD4 cell count 650 cells/mm3 (IQR 467 to
799), and 93% HIV RNA <400 copies/mL—57% were non-frail, 38% pre-frail,
and 5% frail 
(61%, 36%, and 4%, respectively, among the 199 [65%]
participants aged ≤50 years). Prevalence of frailty criteria are
presented in the table; exhaustion and physical inactivity
predominated.
 In multivariate analysis, pre-frail/frail vs non-frail
participants were more likely of non-white race/ethnicity (54% vs 33%;
adjusted odds ratio 3.24; 95% confidence interval 1.78 to 5.91), to
have had an AIDS-defining opportunistic infection (35% vs 15%; aOR
2.55, 95%CI 1.29 to 5.02), to have poorer median perceived health
scores on the SF-12 health survey
 (1, IQR 1 to 2 vs 2, IQR 1 to 3; aOR
2.12, 95%CI 1.49 to 3.03), to have higher median PHQ-9 depression
scores (6, IQR 2 to 11 vs 3, IQR 0 to 5; aOR 1.11, 95%CI 1.04 to 1.18)
and to be older (median age 48 years, IQR 44 to 54 vs 46 years, IQR 40
to 52; aOR 1.04, 95%CI 1.01 to 1.07). Lower CD4 cell count nadir,
female sex, and unemployment were not independently associated with
pre-frailty/frailty.

Conclusions:  Overall, 40% of SUN study participants aged ≤50 years
with well-controlled HIV infection were pre-frail or frail.
 The
significant association of pre-frailty and frailty with a history of
opportunistic infection suggests earlier diagnosis of HIV infection and
prevention of opportunistic infections may reduce risk for frailty.
Racial disparities warrant further investigation.
-------------------

Low Muscle Mass in HIV+ Patients: Prevalence, Predictors, and Clinical
Implication


Giovanni Guaraldi*1, S Zona1, A Silva2, G Orlando1, F Carli1, A
Santoro1, N Crupi2, G Ligabue1, C Mussi1, and L Ferruci3

1Univ of Modena and Reggio Emilia, Italy; 2Hosp de Joaquim Urbano,
Porto, Portugal; and 3Natl Inst on Aging, NIH, Baltimore, MD, US

Background:  In HIV+ patients, muscle mass measured as fat free mass
index (FFMi = FFM/h2) in DXA has never been characterized in large
epidemiological cohorts. We aimed:  to describe the prevalence of low
muscle mass using t- and z-score, per age decades, defined as <–2 SD
from the mean FFMi for an Italian Caucasian population, respectively,
for the same age or in the age strata 30 to 39 years; to identify
predictors of FFMi change; and to assess the association between FFMi
and all-cause mortality in a large HIV+ cohort.

Methods:  This observational prospective study included all consecutive
patients from 2005 to 2011 who underwent at least 2 DXA scans,
performed 1 year apart. Univariate and multivariable longitudinal
linear regressions were built to evaluate FFMI change-associated
factors. Co-variates included in the models were:  age, sex, body mass
index (BMI), physical activity; change in leg fat percentage (assessed
with DXA), in visceral adipose tissue (VAT), and in total adipose
tissue of the abdomen (TAT) (assessed with abdominal CT); NRTI, NNRTI,
and PI cumulative exposure; CD4 nadir and recovery; vitamin D plasma
level; and time between DXA scans. A Cox model was built to predict the
impact of FFMi on all cause mortality after adjustment for age and sex.

Results:  A total of 1696 HIV+ patients (1046 men) were analyzed.
Median observation follow-up period was 3.5 years (IQR 2 to 5); 96% of
patients were on ART, and during the follow-up period 37 died. BMI
change and FFMI change appeared stable over time (ß = 0.001, p = 0.111;
ß = 0.001, p = 0.070, respectively). In men, the prevalence of low
muscle mass using t- and z-scores was 0.2% and 8.5%, respectively
. In
women, the prevalence of low muscle mass using t- and z-scores was 0%
and 1.5%, respectively. The highest prevalence of low muscle mass was
detected in the 41- to 50-year age group strata (t-score 0.5% and
z-score 16%). Predictors of FFMi change were:  age (ß = –0.01, p =
0.002), change of leg fat percentage (as a surrogate for lipoatrophy
recovery) (ß = –0.05, p <0.001), and time between DXA scans (ß = 0.17,
p = 0.013). FFMi was associated with all-cause mortality (HR 0.87,
95%CI 0.78 to 0.98) after adjustment for age and sex.

Conclusions:  Prevalence of low muscle mass increases with age. The
highest prevalence was found in the 41- to 50-year age group.
Predictors of FFMi change appear to be associated with age, lipoatrophy
recovery, and time
. FFMi is associated with all-cause mortality in HIV+
patients, suggesting that this biological entity can provide prognostic
information, in HIV+ patients.
---------------------

Frailty Predicts Mortality in a Cohort of HIV+ and At-risk IDU

Damani Piggott*, A Muzaale, S Mehta, T Brown, S Leng, and G Kirk

Johns Hopkins Univ, Baltimore, MD, US

Background:  Frailty, a syndrome of diminished physiologic reserve with
increased stressor vulnerability, predicts hospitalization, disability,
and mortality in older HIV– adults. We have previously observed a
significant association between frailty and HIV+, particularly advanced
HIV infection, among injection drug users (IDU). In this study, we
evaluated the impact of frailty on mortality in a cohort of aging HIV+
and at-risk IDU.

Methods:  Frailty was assessed biannually from 2005 to 2008 among
current and former IDU in the ALIVE cohorts and was defined by the
presence of ≥3 of 5 standard criteria:  weakness (grip strength), slow
gait speed, weight loss, low physical activity, and exhaustion. Cox
proportional hazards models with time-varying co-variates were used to
estimate the risk (hazard ratios with 95% confidence intervals) for
all-cause mortality among frail persons relative to their robust
counterparts (defined by the absence of any criteria) and to non-frail
persons.

Results:  For 1230 subjects at baseline, the median age was 48 years,
89% were African American, 418 (34%) were female, and 351 (29%) were
HIV+. The prevalence of frailty was 9%, while 31% met no frailty
criteria. In Cox multivariable analysis of 3365 person-visits,
increasing age and HIV status were associated with increased mortality
risk.
 Adjusting for age, race/ethnicity, gender, educational level, and
HIV status, frail persons had a 3.4-fold increased risk of death
relative to robust persons
 (HR 3.42, 95%CI 1.66 to 7.03). In stratified
analysis, increased mortality risk with frailty was observed among both
HIV– persons (HR 2.91, 95%CI 1.06 to 7.96) and HIV+ persons (HR 4.05,
95%CI 1.39 to 11.8). Controlling for advanced HIV infection (CD4 <350,
HIV RNA+), frailty remained a significant predictor of mortality (HR
3.13, 95%CI 1.25 to 7.82). In comparison to non-frail persons, similar
associations of frailty with mortality were observed.

Conclusions:  Frailty is a significant predictor of mortality among
both HIV+ and at-risk IDU
. Frailty provides prognostic information even
when accounting for advanced HIV disease suggesting that standardized
assessment may inform prediction of significant clinical endpoints.
Further exploration of the biological mechanisms and clinical utility
of frailty may aid management of aging HIV+ persons.
------------------------

Mitochondrial Function in vivo in Aging HIV+ Patients

Brendan Payne*1,2, M Trenell2, K Hollingsworth2, J Baxter3, V Lee4, E
Wilkins3, A Price1, and P Chinnery2

1Royal Victoria Infirmary, Newcastle upon Tyne, UK; 2Newcastle Univ,
Newcastle upon Tyne, UK; 3Northern Manchester Gen Hosp, UK; and
4Manchester Royal Infirmary, UK

Background:  We have recently demonstrated that patients with prior
exposure to nucleoside analog ARV, which inhibit DNA polymerase-γ,
accumulate acquired mitochondrial DNA (mtDNA) mutations in skeletal
muscle, in an apparent acceleration of the process seen in normal
aging. Here we explore an in vivo functional correlate in aging HIV+
patients.

Methods:  We recruited older HIV+ patients in clinical care (n = 24;
age 48 to 74 years) and age-matched controls (HIV–). Phosphorus
magnetic resonance spectroscopy (31P-MRS) was performed using a 3-T
scanner. Spectra were obtained from gastrocnemius/soleus at rest and
during recovery from brief exercise. Key measures were:  adenosine
triphosphate (ATP) production during recovery (as Qmax (ADP), maximal
rate of adenosine diphosphate (ADP) clearance; τ1/2 (PCr), half-life of
phosphocreatine); and pH handling. In HIV+ subjects, comparison was
made with cellular mitochondrial function by COX (cytochrome c oxidase)
histochemistry of lower-limb muscle biopsy.

Results:  Basal parameters of ATP metabolism differed between subjects
groups:  ADP (mean ±SD) HIV+ 10.2±0.7 mM, HIV– 9.5±0.5 mM (p = 0.001);
PCr HIV+ 41.0±15.2 mM, HIV– 30.7±2.1 mM (p = 0.003). Furthermore, basal
ADP levels in HIV+ subjects correlated with biopsy COX defect (r =
0.45, p = 0.032). In contrast, dynamic measures of ATP production
during exercise recovery were similar in HIV+ and control subjects:
Qmax (ADP) (mean±SD) HIV+ 26.6±18.6 mM/min, HIV– 23.0±10.2 mM/min; Ï„1/2
(PCr) HIV+ 29.9±13.4 s, HIV– 27.5±8.3 s. There was more variance seen
in the HIV+ than the HIV– group, however no disease or treatment
variable was significantly correlated with ATP production rate, nor was
cellular COX defect. HIV+ subjects showed disordered pH handling
compared with HIV– controls as evidenced by higher basal pH (mean±SD,
7.07±0.03 vs 7.04±0.02, p = 0.001) and post-recovery pH (7.09±0.03 vs
7.06±0.02, p = 0.008) but similar exertional minimum pH (6.98±0.13 vs
7.00±0.03, ns). Resting pH correlated with COX defect (r = 0.42, p =
0.044).

Conclusions:  The altered basal ATP metabolite levels in HIV+ subjects
coupled with preserved dynamic function, despite cellular mitochondrial
defects on biopsy, suggests functional compensation to an acquired
mtDNA defect, once therapy has been switched to a cleaner agent.
Abnormalities of resting muscle pH handling have been associated with
fatigue and may contribute to functional decline in this patient group.
-----------------------

Functional Impairment Is Associated with Low Bone and Muscle Mass in
Middle-aged HIV-1+ Persons


Kristine Erlandson*, A Allshouse, C Jankowski, S MaWhinney, W Kohrt,
and T Campbell
Univ of Colorado Denver, Aurora, US

Background:  Physical function impairment may be accelerated in the
presence of osteoporosis, obesity, or sarcopenia. HIV+ persons have
early physical impairment, but little is known about the contributions
of bone or body composition changes to impairment in persons aging with
HIV-1.

Methods:  We conducted a prospective study of 45- to 65-year-old HIV-1+
subjects who had been on ART >6 months and whose plasma HIV-1 RNA <48
copies/mL. Low functioning (LF) and high functioning (HF) subjects were
identified by deficits on both Fried’s frailty criteria and the Short
Physical Performance Battery and were matched by age, gender, and time
since HIV diagnosis. Bone, fat, and muscle were assessed by
densitometry. Osteoporosis was defined as T-score ≤–2.5, osteopenia as
T-score <–1 but >–2.5, sarcopenia as appendicular skeletal muscle index
(ASMI) <5.45 kg/m2 (female) and <7.26 kg/m2 (male). Insulin-like growth
factor (IGF)-1 and IGF-binding protein (BP)-3 were measured. Stratified
logistic regression for categorical variables and linear mixed effects
regression for continuous variables were estimated to account for
correlation within matched pairs. Body mass index (BMI), tobacco, and
nadir CD4+ T cells were adjusted in models of bone loss.

Results:  We identified 30 LF and matched them to 48 HF subjects; mean
age 52.7 years, CD4 T cell 598, 96% HIV-1 viral load <48 copies/mL, 18%
female, 77% white, 17% Hispanic. LF and HF were similar in age,
duration of ART, tenofovir use, and CD4 T- cells (all p >0.2). LF
subjects had significantly lower BMD and T scores at the hip and spine;
differences remained significant in multivariate analyses.
 Although all
persons with BMI <18.5 kg/m2 were LF, LF trended toward higher relative
body fat content. LF subjects had a greater prevalence of sarcopenia
(50% vs 25%, p = 0.04), lower lean mass, and lower IGF-1/IGFBP3.


Conclusions:  Impaired functional capacity is strongly associated with
lower bone density and lower muscle mass in middle-aged HIV-1+ persons. 

Whether bone or muscle loss is the result of disuse due to impairment,
or if low muscle or bone mass, mediated through effects of IGF-1, leads
to impairment by progressive weakness or inflammatory pathways remains
to be established. Further studies should investigate the role of
increased muscle/bone mass and increased IGF-1 on preserving functional
independence as persons with HIV age.
--------------------------

Co-morbidity Is Predictive of Muscle Strength in HIV+ Veterans: Results
from the VACS Index


Krisann Oursler*1, J Tate2, T Gill2, K Crothers3, T Brown4, S Crystal5,
J Womack2, D Leaf6, J Sorkin1, A Justice2, and Veterans Aging Cohort
Study Project Team

1Univ of Maryland Sch of Med and Publ Hlth and VA Maryland Hlthcare
System, Baltimore, US; 2Yale Univ Sch of Med and Publ Hlth and VA
Connecticut Hlthcare System, New Haven, US; 3Univ of Washington,
Seattle, US; 4Johns Hopkins Univ, Baltimore, MD, US; 5Rutgers Univ, New
Brunswick, NJ, US; and 6Univ of California, Los Angeles Sch of Med and
Greater Los Angeles VA Hlthcare System, US

Background:  Despite improved survival, HIV+ adults have increased risk
for physical disability due to muscle weakness, poor ambulatory
function, and low cardiorespiratory fitness. The objective of this
study was to determine whether the VACS Index, a comprehensive index of
generalized organ injury based on routine clinical laboratory data, is
associated with hand-grip and leg-strength, 6-minute walk distance, and
cardiorespiratory fitness (peak oxygen consumption, VO2 peak).

Methods:  HIV+ patients enrolled in the Veterans Aging Cohort Study
(VACS) participated in this cross-sectional study at the Baltimore VA
Medical Center from 2004 to 2007. The VACS Index was calculated
incorporating hemoglobin, FIB-4, eGFR, hepatitis C infection, CD4
count, HIV-1 viral load, and age; higher score reflected greater
co-morbidity. Analyses included nonparametric correlation (Spearman’s
rank) and linear regression models.

Results:  We included 2 women and 53 men:  91% African American race,
mean age of 52 (SD 7) years. The VACS Index was inversely correlated
with hand-grip strength (r = –0.36, p = 0.01) and lower extremity
strength (quadriceps, r = –0.45, p <0.01), but was not significantly
associated with 6-minute walk distance (r = –0.26, p = 0.07) or VO2
peak (r = –0.13, p = 0.3). A 20-point higher VACS Index score was
associated with a 10% lower leg strength (mean 76 newtons; 95%CI –124
to –29; p <0.001; see the figure), which remained significant after
adjustment for muscle cross-sectional area (p = 0.04). The VACS Index
explained 34% of the variance in specific leg strength. In contrast, an
index restricted to CD4 count, viral load, and age did not correlate
with any of these measures (p >0.08).

Conclusions:  In this sample of predominantly African American men
ranging in age from 31 to 72 years, the VACS Index was significantly
associated with upper and lower extremity strength
. The VACS Index may
be valuable for identification of patients at high risk for disability
due to muscle weakness. Association of Leg Strength with the VACS Index.

Fw: Breaking, Clinically Relevant HIV/AIDS Research From CROI 2012



From: "The Body PRO" <news@thebodypro.com>
Date: 08 Mar 2012 14:38:17 -0500
To: <powertx@aol.com>
ReplyTo: "The Body PRO" <news@thebodypro.com>
Subject: Breaking, Clinically Relevant HIV/AIDS Research From CROI 2012

Welcome to The Body PRO Newsletter, a bi-weekly review of the latest breaking news and research in HIV medicine, aimed specifically at informing health care professionals.
TheBodyPRO.com covers CROI 2012

STUDY SUMMARIES AND ANALYSES FROM CROI 2012

The 19th Conference on Retroviruses and Opportunistic Infections (CROI 2012) is wrapping up in Seattle, Wash., but TheBodyPRO.com's coverage of this critical meeting is just heating up!

Visit our CROI 2012 home page for a growing selection of articles in which our team recaps and analyzes the clinical significance of a wide array of presented studies. Currently available conference coverage includes:


Much more will be added over the next several days, including the latest on antiretroviral clinical trials, immune-based therapies and a range of HIV-related comorbidities. Be sure to check back often for the latest summaries, analyses and discussions on clinically relevant CROI 2012 research -- and follow @MylesatTheBody on Twitter for bite-sized, real-time updates directly from the conference.


IN OTHER NEWS

Although CROI 2012 is capturing headlines on the research front this week, the world keeps on turning, and there are other developments to report that are of importance to HIV frontline professionals. Here is a sampling of stories recently published on TheBodyPRO.com:

  • New HIV Care Guidelines Focus on Entry Into and Retention in Care
    In this week's Annals of Internal Medicine, an expert panel convened by the International Association of Physicians in AIDS Care (IAPAC) published guidelines on entry into care, patient retention and adherence to HIV medications. Ben Young, M.D., Ph.D., examines why we these new guidelines are worth paying attention to.


  • Interactions Between Protease Inhibitors and Statins Can Increase the Risk of Muscle Injury
    A new U.S. Food and Drug Administration warning cautions against drug-drug interactions between statins and protease inhibitors used in the treatment of HIV and hepatitis C. The warning states that the interaction can cause an increase in statin levels that may increase myopathy risk.


  • Tenofovir Linked With Risk of Kidney Damage
    A recent study offers the most conclusive evidence to date that tenofovir (Viread), one of the fundamental backbones of antiretroviral therapy in the U.S., can increase an HIV-infected patient's risk of kidney damage and chronic renal disease. Despite the findings, the clinical ramifications of the data are unclear.


  • HIV/AIDS Organization Spotlight: Mujeres Unidas
    HIV stigma still runs deep in San Antonio, Texas, where many HIV-infected patients are Latinos. "We've got people in doctors' offices -- front offices, back offices -- where we've had clients that appear for an appointment, and they're told, 'Oh, the doctors won't see patients like you,'" says Tina Sigler, the executive director of Mujeres Unidas.


  • Mapping the Virus With Geographic Information Systems
    A new type of technology may allow frontline HIV professionals and public health officials across the U.S. to develop a more complete understanding for the drivers of HIV in their communities than ever before. It does so by tying basic info about the area (such as education, income levels or even the presence of mass transportation options) into HIV-specific data such as incidence and prevalence.



Advertisement

About This E-Mail

This e-mail newsletter was sent to powertx@aol.com. It is provided free of charge to our registered members of The Body PRO.

Want to change your subscription? Click here to modify your subscription information online.

Missed a newsletter? Our archive of past newsletters will keep you up-to-date.

Have any other questions or comments? Feel free to e-mail us at news@thebodypro.com or snail-mail us at:

The Body PRO Newsletter
Remedy Health Media, LLC
250 West 57 Street
New York, NY 10107

Support PoWeR

Program For Wellness Restoration

Health News

Blog Archive

The Cure of HIV is Possible in Our Lifetime