"HIV Infection or Medications Age Brain"
United Press International , (01.27.2010) CDC NPIN Summary
Researchers theorize that HIV infection itself and/or the treatments used to fight it might explain their finding that HIV patients had brain function similar to those of persons 15-20 years older.
Dr. Beau Ances, of Washington University School of Medicine in St. Louis, and colleagues used functional magnetic resonance imaging (fMRI) and “arterial spin labeling” to examine 26 HIV-positive patients and 25-negative patients, with both groups comparable in mean age and education.
HIV serostatus and age independently affected fMRI measures, though they did not interact, the authors wrote. The brains of those HIV-infected needed to work harder to complete particular assignments. Reduced brain blood flow was observed even among young, recently infected patients.
“Brain blood flow levels decline naturally as we age, but HIV, the medications we use to control it or some combination of the two appear to be accelerating this process independently of aging,” Ances said.
In the future, fMRI might be used as a noninvasive biomarker for HIV infection in the brain, the team suggested.
The full report, “HIV Infection and Aging Independently Affect Brain Function as Measured by Functional Magnetic Resonance Imaging,” was published in the Journal of Infectious Diseases (2010;201:336-340).
New Longer Lasting NNRTI Could Also Be
Microbicide
Currently, there are eight clinically approved
NRTIs, but they can protect cells for only short
periods of time. A University of Missouri
researcher is developing a compound that is more
potent and longer-lasting than current HIV
therapies. With the new EFdA, patients could be
protected for two days instead of few hours and
would not need to take the drug as often. Dr.
Sarafianos hopes EFdA also can
double as a preventative agent
in the form of a vaginal gel or
cream. This would provide
additional protection to women
whose partners refuse to use
condoms. Theresearch was published in
The Journal of Biological
Chemistry. See
the report in
ScienceDaily.com
"Increased Presence, Severity of
Coronary Artery Plaques in HIV-Infected Men"
Science Daily , (01.08.2010) DC NPIN Summary
Young to middle-aged men with longstanding HIV infection were
significantly more likely to have coronary atherosclerotic
plaques than uninfected men in a new study. One hundred and ten
men (78 HIV-positive, 32 HIV–negative) ages 18-55 with few
traditional cardiovascular risk factors were examined for the
study with CT scans and CT angiography by Massachusetts General
Hospital (MGH) researchers. All were asymptomatic for
cardiovascular disease. The vast majority of HIV-positive
subjects were receiving antiretroviral therapy.
"We were particularly surprised to find that several of the HIV
patients - none of whom had symptoms of heart disease - had
obstructive coronary artery disease, which was found in none of
the controls," said Janet Lo, MD, of MGH's Department of
Medicine. "It appears that both traditional and nontraditional
risk factors are contributing to atherosclerotic disease in
HIV-infected patients."
While the CT scan can identify calcium deposits in coronary
arteries, CT angiography can also detect non-calcified arterial
plaques. Among those with HIV, the scans showed coronary calcium
that might be expected, based on past studies, in men who were
six years older. Angiography found atherosclerosis in 59 percent
of HIV patients, compared with 34 percent among HIV–negative
men. Five of the men with HIV had critical coronary stenosis, or
a 70 percent or greater restriction, while none of the
uninfected men did.
"Our findings highlight the need to address reduction of cardiac
risk factors early in the course of HIV disease and for
caregivers to consider that even asymptomatic patients with
longstanding HIV disease and minimal cardiac risk factors may
have significant coronary artery disease," Lo said. "We also
found interesting associations between atherosclerosis levels
and how long participants had been infected with HIV and with
several inflammatory and immune factors. Future studies are
needed to clarify the role of these nontraditional risk factors
and find the best prevention and treatment strategies for these
patients."
The full report, "Increased Prevalence of Subclinical Coronary
Atherosclerosis Detected by Coronary Computed Tomography
Angiography in HIV-Infected Men," was published in the journal
AIDS (2010;24(2):243-253).
PROMISE Study to
Begin Enrolling Women and Their Infants to Examine Best Ways to
Prevent HIV Transmission During Pregnancy and Breastfeeding
AIDSinfo At-A-Glance Volume 6 Issue 3 (1.22.10)
"On January 15, a large, multinational clinical trial began
to determine how best to reduce the risk of HIV transmission
from infected pregnant women to their babies during pregnancy
and breastfeeding while preserving the health of these children
and their mothers.
The PROMISE ('Promoting Maternal-Infant Survival Everywhere')
study addresses four distinct research questions. Most
volunteers will participate in multiple components of the study
to answer these questions. The components will first examine
which of two proven strategies is safer and more effective at
preventing mother-to-child HIV transmission (MTCT) before and during
delivery. The second will compare the
safety and efficacy of two methods of preventing MTCT during breastfeeding.
The third component will examine the
effects of short-term use of a three-antiretroviral-drug regimen
during pregnancy and breastfeeding to prevent MTCT on the health
of HIV-infected mothers who do not yet need treatment. The
fourth the last component of the study involves protecting the
health of HIV-exposed but uninfected infants through age 18
months. More information is available: NIAID:
Press release; ClinicalTrials.gov: Study
summary
AIDSinfo At-A-Glance Volume 6 Issue 3 (1.22.10)
“Participants were randomized to receive once nightly didanosine plus lamivudine, or twice-daily combivir (zidovudine plus lamivudine) both in combination with efavirenz. Medication Event Monitoring Systems were used to compile drug-dosing histories. Beliefs about HAART (necessity and concerns) were measured at baseline using validated questionnaires. Perceptions of HAART intrusiveness were assessed after 4 weeks. … Eighty-seven patients were randomized (44 once-nightly and 43 twice-daily). Overall adherence was higher among the once-nightly arm (P = 0.0327). Eighty-one percent once-nightly and 62% twice-daily patients persisted with treatment for 48 weeks (P = 0.0559). Regimen execution was similar between both arms. Participants were significantly less likely to persist with HAART if their initial concerns about HAART were high relative to their perceived need for treatment (P = 0.025). … The difference in adherence observed between once-nightly and twice-daily dosing was driven by a difference in persistence with treatment. Psychological preparation for starting HAART should address patients' perceptions of necessity for HAART and concerns about adverse effects to maximize persistence with treatment.”
More information is available: PubMed: Study abstract
Study Suggests New Wave of
Antiretroviral-Resistant HIV Could Emerge
AIDSinfo At-A-Glance Volume 6 Issue 3 (1.22.10)
“Over the past two decades, HIV resistance to antiretrovirals
(ARVs) has risen to high levels in the wealthier countries of
the world able to afford widespread treatment. We have gained
insights into the evolution and transmission dynamics of ARV
resistance by designing a biologically complex multistrain
network model. Using this model, we traced the evolutionary
history of ARV resistance in San Francisco and predict the
future dynamics. Using classification and regression trees, we
have identified the key immunologic, virologic, and treatment
factors that increase ARV resistance. Our modeling shows that
60% of the currently circulating ARV-resistant strains in San
Francisco are capable of causing self-sustaining epidemics, as
each individual infected with one of these strains can cause on
average more than one new resistant infection. It is possible
that a new wave of ARV-resistant strains that pose a significant
threat to global public health is emerging.”More information is available: PubMed:
Study abstract; MedlinePlus:
News article
"Fewer HIV Patients Becoming Drug-Resistant: B.C. Study"
Vancouver Sun , (01.10.2010) Denise Ryan
“This is good news with big implications,” said Dr. Richard Harrigan, lead author. Patients are on treatments that work, stopping the progress of the disease, he said.
“You can’t imagine what it’s like to be given your life back,” said Tiko Kerr, who has had HIV for 25 years and was one of five B.C. patients who had to fight to receive then-experimental treatments. On one of the newer treatments he began in 2006, Kerr’s viral load was cut by 90 percent.
“In the early days, people would have to take 30 pills a day,” Harrigan said. “Now it’s often just one pill a day.”
“The main thing that we saw is that the [highly active antiretroviral therapies] are becoming more successful every year in keeping the level of virus in patients down below the level we can even detect,” Harrigan said. “That prevents the virus from replicating, from making copies of itself and the disease doesn’t progress,” and it ensures fewer transmissions of resistant HIV, he said.
“Our results suggest an increasing effectiveness of highly active antiretroviral therapy at the population level,” the authors concluded. “The vast majority of treated patients in British Columbia now have either suppressed plasma viral load or drug-susceptible HIV-1, according to their most recent study results.”
The full study, “Improved Virological Outcomes in British Columbia Concomitant with Decreasing Incidence of HIV Type 1 Drug Resistance Detection,” was published in Clinical Infectious Diseases (2010;50(1):98-105).
Participatory medicine model may lead
to better outcomes
AJMPlus (1.21.10) summary
Atripla (Efavirenz/Emtricitabine/Tenofovir
disoproxil fumarate) Product Label Updated
“On January 7, 2010, FDA approved an updated Atripla label including new efficacy, safety and resistance data in treatment experienced patients from a trial (Study 073: A Phase IV, Open-Label, Randomized, Multicenter Study Evaluating Efficacy and Tolerability of single Tablet Regimen of Efavirenz/Emtricitabine/Tenofovir DF Compared to Unmodified HAART in HIV-1 Infected Subjects Who Have Achieved Virological Suppression on their HAART Regimen) in which HIV-1 infected adults on a stable antiretroviral regimen were either switched to Atripla or remained on their background regimen to compare the effectiveness (efficacy, safety, and tolerability) of Atripla to that of subjects continuing unmodified HAART as measured by the proportion of subjects who maintain HIV-1 RNA <200 copies/mL on their original assigned regimen at Week 48 based on the time-to-loss of virologic response (TLOVR) analysis.
“Other revisions were made to the label for consistency between Sustiva, Viread, Truvada and Emtriva labels.”
T
he complete revised labeling will be available at the FDA Web site.More information is available:
- FDA: Press release
- AIDSinfo: Efavirenz/Emtricitabine/Tenofovir disoproxil fumarate (Atripla) fact sheet
New Study Results Available for Women and Infants
Transmission Study (WITS)AIDSinfo At-A-Glance Volume 6 Issue 2 (1.15.10)
“Detectable HIV-1 RNA at delivery is the strongest predictor of mother-to-child transmission. The risk factors for detectable HIV, including type of regimen, are unknown. We evaluated factors, including highly active antiretroviral (HAART) regimen, associated with detectable HIV-1 RNA at delivery in the Women and Infants Transmission Study (WITS).... Data from 630 HIV-1-infected women who enrolled from 1998 to 2005 and received HAART during pregnancy were analyzed. Multivariable analyses examined associations between regimens, demographic factors, and detectable HIV-1 RNA (>400 copies/milliliter) at delivery.... Overall, 32% of the women in the cohort had detectable HIV-1 RNA at delivery. Among the subset of 364 HAART-experienced women, a lower CD4 cell count at enrollment [adjusted odds ratio (AOR) = 1.20 per 100 cells/muL, confidence interval (CI) 1.04 to 1.37] and higher HIV-1 RNA at enrollment (AOR = 1.52 per log10 copies/milliliter, CI 1.32 to 1.75) were significantly associated with detectable HIV-1 RNA levels at delivery. For the 266 HAART-naive women, both lower CD4 cell count at enrollment (AOR = 1.24 per 100 cells/muL, CI 1.05 to 1.48) and higher HIV-1 RNA at enrollment (AOR = 1.35 per log10 copies/milliliter, CI 1.12 to 1.63) were associated with detectable HIV-1 RNA at delivery.… Lack of viral suppression at delivery was common in the WITS cohort, but differences by antiretroviral regimen were not identified. Despite a transmission rate below 1% in the last 5 years of the WITS cohort, improved measures to maximize HIV-1 RNA suppression at term among high-risk women are warranted.”
More information is available:
- PubMed: Study abstract
- NICHD: Information about WITS
DHHS Panel on Antiretroviral Guidelines for Adult and Adolescents Announces New Panel Members
The DHHS Panel on Antiretroviral Guidelines for Adults and Adolescents (a Working Group of the Office of AIDS Research Advisory Council) is pleased to welcome five new members to the Panel. See People on the Move.
Study Suggests Combined
Antiretroviral Therapy (cART) Decreased the Average Mortality
Rate in HIV-Infected Individuals
AIDSinfo At-A-Glance Volume 6 Issue 1 (1.8.10)
“A collaboration of 12 prospective cohort studies from Europe and the United States (the HIV-CAUSAL Collaboration) that includes 62[,]760 HIV-infected, therapy-naive individuals [were] followed for an average of 3.3 years. …Two thousand and thirty-nine individuals died during the follow-up. The mortality hazard ratio was 0.48 (95% confidence interval 0.41-0.57) for cART initiation versus no initiation. In analyses stratified by CD4 cell count at baseline, the corresponding hazard ratios were 0.29 (0.22-0.37) for less than 100 cells/microl, 0.33 (0.25-0.44) for 100 to less than 200 cells/microl, 0.38 (0.28-0.52) for 200 to less than 350 cells/microl, 0.55 (0.41-0.74) for 350 to less than 500 cells/microl, and 0.77 (0.58-1.01) for 500 cells/microl or more. The estimated hazard ratio varied with years since initiation of cART from 0.57 (0.49-0.67) for less than 1 year since initiation to 0.21 (0.14-0.31) for 5 years or more (P value for trend <0.001). …We estimated that cART halved the average mortality rate in HIV-infected individuals. The mortality reduction was greater in those with worse prognosis at the start of follow-up."
More information is available:
- Read the study abstract
- Read the MedlinePlus article
Study Suggests Genotypic Scoring
Algorithm Optimizes Resistance Interpretations for Etravirine
AIDSinfo At-A-Glance Volume 6 Issue 1
(1.8.10)
“A multivariate analysis was performed to refine the initial etravirine [resistance-associated mutation] RAM list and improve the predictive value of genotypic resistance testing with regard to virologic response and relationship to phenotypic data. ...Week 24 data were pooled from the phase III studies with TMC125 to Demonstrate Undetectable viral load in patients Experienced with ARV Therapy (DUET). The effect of baseline resistance to etravirine on virologic response (<50 HIV-1 RNA copies/ml) was studied in patients not using de-novo enfuvirtide and excluding discontinuations for reasons other than virologic failure (n = 406). ...Clinical cutoffs for etravirine were established by analysis of covariance models and sliding fold change in 50% effective concentration (EC50) windows. ...Etravirine RAMs were identified as those associated with decreased virologic response/increased etravirine fold change in EC50. Relative weight factors were assigned to the etravirine RAMs using random forest and linear modeling techniques. ...Baseline etravirine fold change in EC50 predicted virologic response at week 24, with lower and preliminary upper clinical cutoffs of 3.0 and 13.0, respectively. A fold change in EC50 value above which etravirine provided little or no additional efficacy benefit could not be established. Seventeen etravirine RAMs were identified and attributed a relative weight factor accounting for the differential impact on etravirine fold change in EC50. Virologic response was a function of etravirine-weighted genotypic score. ...The weighted genotypic scoring algorithm optimizes resistance interpretations for etravirine and guides treatment decisions regarding its use in treatment-experienced patients.”
More information is available:
- Read the study abstract
- Read the AIDSinfo etravirine (Intelence) fact sheet
HIV-Infected Women May
Experience a Higher Risk of Bone Fractures
By
Donna Parker • Jan 11th, 2010
Better Health Research