|
March News Briefs
FDA Reports: Clinical Trial Data Suggest the Combination of Invirase (Saquinavir)
and Norvir (Ritonavir) May Affect the Electrical Activity of the Heart
AIDSinfo At-A-Glance Volume 6 Issue 8 (2.26.10)
“The U.S. Food and Drug Administration (FDA) is reviewing clinical trial data
about a potentially serious effect on the heart from the use of Invirase (saquinavir)
in combination with Norvir (ritonavir). The data suggest that together the two
drugs may affect the electrical activity of the heart.
“The changes to the electrical activity of the heart possibly associated with
these drugs, known as prolonged QT or PR intervals, can be seen on an
electrocardiogram (EKG). A prolonged QT interval can increase the risk for
abnormal heart rhythms, including a serious abnormal rhythm called torsades de
pointes. …
“FDA's analysis of these data is ongoing. However, healthcare professionals
should be aware of this potential risk for changes to the electrical activity of
the heart. Invirase and Norvir should not be used in patients already taking
medications known to cause QT interval prolongation such as Class IA (such as
quinidine,) or Class III (such as amiodarone) antiarrhythmic drugs; or in
patients with a history of QT interval prolongation. …
“This communication is in keeping with FDA's commitment to inform the public
about its ongoing safety review of drugs. The agency will update the public as
soon as this review is complete.”
More information is available:
Reported at CROI: Early Development of Gene Therapy for HIV Promising
“Existing AIDS drugs allow many patients to live fairly normal lives despite
being infected with HIV. But they can cause a variety of side effects, and some
patients become immune to them over time. …
“In [a] new study, the [University of] Pennsylvania [research] team tested a
gene therapy approach in which scientists first remove immune cells from
patients, tinker with their genes and then put them back into the bodies of the
patients.
“Eight HIV-infected people took part in the study. After the genetically
modified cells were placed back into the patients, ‘we stopped HIV treatment and
tried to see what happened,’ [Dr. Pablo] Tebas said. …
“The levels of HIV fell below the expected levels in seven of the eight
patients, the team found. …
“It's still early in the development of the treatment: the current research
is in phase 2 of the customary three phases of research that new medical
treatments go through.
“If gene therapy does become a treatment for HIV patients, it may be best for
those who aren't doing well on existing antiretroviral drugs, said John Rossi,
chairman of the molecular and cellular biology department at the Beckman
Research Institute of City of Hope Medical Center near Los Angeles. …
“And it's not clear how long the treatment would last, he said, since the
immune cells aren't permanent.”
More information is available:
Study Suggests Overall Treatment Outcomes Similar in
Once-Daily versus Twice-Daily Combination Antiretroviral Therapy Despite
Adherence Differences
AIDSinfo At-A-Glance Volume 6 Issue 9 (3.5.10)
“Dosing frequency is an important determinant of regimen effectiveness. ...To
compare efficacy of once-daily (QD) versus twice-daily (BID) antiretroviral
therapy, we randomized human immunodeficiency virus (HIV)-positive,
treatment-naive patients to lopinavir-ritonavir (LPV/r) administered at a dosage
of 400 mg of lopinavir and 100 mg of ritonavir BID … or 800 mg of lopinavir and
200 mg of ritonavir QD …, plus either emtricitabine 200 mg QD and
extended-release stavudine at a dosage of 100 mg QD or tenofovir at a dosage of
300 mg QD. Randomization was stratified by screening HIV RNA level <100,000
copies/mL versus 100,000 copies/mL. The primary efficacy end point was sustained
virologic response (SVR; defined as reaching and maintaining an HIV RNA level
<200 copies/mL) through week 48. ...Subjects were 78% male, 33% Hispanic, and
34% black. A total of 82% of subjects completed the study, and 71% continued to
receive the initially assigned dosage schedule. The probability of SVR did not
differ significantly for the BID versus QD comparison, with an absolute
proportional difference of 0.03 (95% confidence interval [CI], -0.07 to 0.12).
The comparison depended on the screening RNA stratum…; in the higher RNA
stratum, the probability of SVR was significantly better in the BID arm than in
the QD arm: 0.89 (95% CI, 0.79-0.94) versus 0.76 (95% CI, 0.64-0.84), a
difference of 0.13 (95% CI, 0.01-0.25). Lopinavir trough plasma concentrations
were higher with BID dosing. Adherence to prescribed doses of LPV/r was 90.6% in
the QD arm versus 79.9% in the BID arm …. Although subjects assigned to QD
regimens had better adherence, overall treatment outcomes were similar in the QD
and BID arms. Subjects with HIV RNA levels 100,000 copies/mL had better SVR with
BID regimens at 48 weeks, which suggests a possible advantage in this setting
for more frequent dosing.”
More information is available:
Study Suggests Elvitegravir Produces Rapid Virologic
Suppression in Treatment-Experienced People on Active Background Therapy
AIDSinfo At-A-Glance Volume 6 Issue 9
(3.5.10)
“This phase 2, randomized, active-controlled, 48-week study assessed the
noninferiority of the human immunodeficiency virus (HIV) integrase inhibitor
elvitegravir to comparator ritonavir-boosted protease inhibitor (CPI/r) in
treatment-experienced subjects. … Subjects had HIV RNA levels 1000 copies/mL and
1 protease resistance mutation. Subjects received nucleoside or nucleotide
reverse-transcriptase inhibitors (NRTIs) with or without T-20 and either CPI/r
or once-daily elvitegravir at a dose of 20 mg, 50 mg, or 125 mg (blinded to
dose) with ritonavir. After week 8, the independent data monitoring committee
stopped the elvitegravir 20 mg arm and allowed subjects in the elvitegravir 50
mg and 125 mg arms to add protease inhibitors. The primary end point was the
time-weighted average change from baseline in HIV RNA level through week 24
(DAVG(24)). … A total of 278 subjects with a median of 11 protease and 3
thymidine analog mutations were randomized and treated. One-half of subjects
received NRTIs without expected antiviral activity. Compared with the DAVG(24)
for the CPI/r arm (-1.19 log(10) copies/mL), the elvitegravir 50 mg arm was
noninferior (-1.44 log(10) copies/mL), and the elvitegravir 125 mg arm was
superior (-1.66 log(10) copies/mL; …). Efficacy was impacted by activity of
background agents. There was no relationship between elvitegravir dosage and
adverse events. … Elvitegravir was well-tolerated and produced rapid virologic
suppression that was durable with active background therapy.”
More information is available:
ClinicalTrials.gov:
Study summary
FDA Reports: Clinical Trial Data Suggest the Combination of Invirase (Saquinavir)
and Norvir (Ritonavir) May Affect the Electrical Activity of the Heart
AIDSinfo At-A-Glance Volume 6 Issue 8 (2.26.10)
“The U.S. Food and Drug Administration (FDA) is reviewing clinical trial data
about a potentially serious effect on the heart from the use of Invirase (saquinavir)
in combination with Norvir (ritonavir). The data suggest that together the two
drugs may affect the electrical activity of the heart.
“The changes to the electrical activity of the heart possibly associated with
these drugs, known as prolonged QT or PR intervals, can be seen on an
electrocardiogram (EKG). A prolonged QT interval can increase the risk for
abnormal heart rhythms, including a serious abnormal rhythm called torsades de
pointes. …
“FDA's analysis of these data is ongoing. However, healthcare professionals
should be aware of this potential risk for changes to the electrical activity of
the heart. Invirase and Norvir should not be used in patients already taking
medications known to cause QT interval prolongation such as Class IA (such as
quinidine,) or Class III (such as amiodarone) antiarrhythmic drugs; or in
patients with a history of QT interval prolongation. …
“This communication is in keeping with FDA's commitment to inform the public
about its ongoing safety review of drugs. The agency will update the public as
soon as this review is complete.”
More information is available:
Reported at CROI: Early Development of Gene Therapy for HIV Promising
AIDSinfo At-A-Glance Volume 6 Issue 8 (2.26.10)
“Existing AIDS drugs allow many patients to live fairly normal lives despite
being infected with HIV. But they can cause a variety of side effects, and some
patients become immune to them over time. …
“In [a] new study, the [University of] Pennsylvania [research] team tested a
gene therapy approach in which scientists first remove immune cells from
patients, tinker with their genes and then put them back into the bodies of the
patients.
“Eight HIV-infected people took part in the study. After the genetically
modified cells were placed back into the patients, ‘we stopped HIV treatment and
tried to see what happened,’ [Dr. Pablo] Tebas said. …
“The levels of HIV fell below the expected levels in seven of the eight
patients, the team found. …
“It's still early in the development of the treatment: the current research
is in phase 2 of the customary three phases of research that new medical
treatments go through.
“If gene therapy does become a treatment for HIV patients, it may be best for
those who aren't doing well on existing antiretroviral drugs, said John Rossi,
chairman of the molecular and cellular biology department at the Beckman
Research Institute of City of Hope Medical Center near Los Angeles. …
“And it's not clear how long the treatment would last, he said, since the
immune cells aren't permanent.”
More information is available:
AUSTRALIA:
"Smoking Cessation Reduces CVD Risk in HIV"
MedPage Today , (02.19.2010) Michael Smith
CDC NPIN Summary
The risk of cardiac events drops sharply when HIV-positive smokers quit,
mirroring what is seen in people not infected with the virus, according to
preliminary data presented at the recent 17th Conference on Retroviruses and
Opportunistic Infections.
The finding comes from the Data Collection on Adverse Events of Anti-HIV Drugs
(DAD) study, which was designed to investigate cardiovascular risks associated
with various HIV treatments. Kathy Petoumenos, PhD, of the University of New
South Wales, and colleagues assessed risk of myocardial infarction; coronary
heart disease, including MI; cardiovascular disease (CVD), including CHD and
stroke; and all-cause mortality. The international cohort of 27,000 participants
included 8,920 who had never smoked and served as a control.
Compared to the control group, previous smokers had a 73 percent increase in MI
risk, a 60 percent increase in CHD risk and a 38 percent increase in CVD.
Current smokers had a 3.4-fold elevated risk for MI, 2.5-fold for CHD, and
2.2-fold for CVD, respectively, compared to the control group. Current but not
previous smokers had an increased risk for all-cause mortality.
According to the team, the key finding was that quitting smoking during the
study reduced the risk of an adverse cardiac outcome. For MI, smoking cessation
for less than a year still was associated with a 3.73-fold elevated risk, but
this dropped to 2.07-fold after three years. For CHD, elevated risk fell from
2.93-fold to 1.83-fold. For CVD, elevated risk fell from 2.32-fold to 1.49-fold
- the latter not being significantly different from that seen among
never-smokers. However, quitting smoking had no significant effect on all-cause
mortality, said Petoumenos.
A lack of data on smoking start and stop dates and the number of pack-years
smoked limits the study’s findings, Petoumenos said. Due to the nature of the
study, she added, it is not possible to make inferences about cause and effect.
Even so, “These are the data you can use to persuade a patient to stop smoking,”
said Andrew Carr, MD, a member of the conference program committee and a staffer
at St. Vincent’s Hospital, Sydney.
See February
Archived News
|
CROI Reports
See February
HIV/AIDS Clinical Care for March 8, 2010
SUMMARY AND COMMENT
Understanding Tenofovir-Associated Renal
Toxicity
March 8, 2010 | Lynda Szczech, MD, MSCE
Such toxicity does not appear to be
completely reversible with withdrawal of the medication.
Reviewing: Wever K et al. J Acquir Immune
Defic Syndr 2010 Feb 19;
SUMMARY AND COMMENT
Does Circumcision Reduce HIV Acquisition in
Men Who Have Sex with Men?
March 8, 2010 | Raphael J. Landovitz, MD
The jury's still out.
Reviewing: Gust DA et al. AIDS 2010
Feb 17;
SUMMARY AND COMMENT
Acyclovir Slows HIV Disease Progression
March 8, 2010 |
Abigail Zuger, MD
Another study confirms this association. The
question now: What to do about it?
Reviewing: Lingappa JR et al. Lancet
2010 Mar 6; 375:824
Buvé A and Lynen L. Lancet 2010
Mar 6; 375:782
SUMMARY AND COMMENT
Minority Variants — Major or Minor Impact?
March 8, 2010 |
Helmut Albrecht, MD
Two studies demonstrate that even very low
levels of certain nonnucleoside reverse transcriptase inhibitor (NNRTI)
mutations increase the risk for failure of NNRTI-based regimens. The
clinical relevance of this finding remains unclear.
Reviewing: Halvas EK et al. J Infect Dis
2010 Mar 1; 201:672
Paredes R et al. J Infect Dis
2010 Mar 1; 201:662
Heneine W. J Infect Dis 2010 Mar
1; 201:647
SUMMARY AND COMMENT
FTC vs. 3TC — Is There a Difference?
March 8, 2010 | Jonathan Z. Li, MD, and
Paul E. Sax, MD
In a retrospective analysis of patients with
virologic failure, tenofovir + 3TC was associated with higher rates of
drug resistance than tenofovir/FTC.
Reviewing: Maserati R et al. AIDS
2010 Jan 30;
SUMMARY AND COMMENT
Lack of Care for HIV-Infected Crack Cocaine
Users
March 8, 2010 | Ingrid V. Bassett, MD, MPH
Twenty percent of the HIV-infected crack
cocaine users hospitalized at two U.S. sites reported that they had
never received outpatient HIV care.
Reviewing: Bell C et al. J Acquir Immune
Defic Syndr 2010 Feb 18;
CLINICAL PRACTICE GUIDELINE WATCH
Management of Healthcare Workers Who Are
Infected with Bloodborne Pathogens
March 3, 2010 |
Richard T. Ellison III, MD
This updated document provides guidance on
restricting the patient-care activities of such workers.
Reviewing: Henderson DK et al. Infect
Control Hosp Epidemiol 2010 Mar 31:203
Editor's Pick from across Journal Watch:
SUMMARY AND COMMENT
Pneumococcal Conjugate Vaccine: Not Just for
Kids Anymore
Free!
March 3, 2010 |
Larry M. Baddour, MD |
Infectious Diseases
A 7-valent pneumococcal conjugate vaccine
proved efficacious in preventing invasive pneumococcal disease among
HIV-infected adolescents and adults.
Reviewing: French N et al. N Engl J Med 2010 Mar 4; 362:812
Journal Watch
HIV/AIDS Clinical Care for March 1, 2010
SUMMARY AND COMMENT
Pregabalin Is Similar to Placebo for
HIV-Related Neuropathy
February 25, 2010 |
Abigail Zuger, MD
Neuropathic pain improved substantially with
both pregabalin and placebo.
Reviewing: Simpson DM et al. Neurology
2010 Feb 2; 74:413
SUMMARY AND COMMENT
A Better Approach for Tuberculosis Screening
and Diagnosis
Free!
February 24, 2010 |
Rajesh T. Gandhi, MD
Almost all HIV-infected patients with TB have
cough, fever, or night sweats; however, culture is required for
diagnosis in most patients with these symptoms.
Reviewing: Cain KP et al. N Engl J Med
2010 Feb 25; 362:707
MEDICAL NEWS
FDA Says HIV Drug Combo Might Carry Cardiac
Risks
Free!
February 24, 2010
SUMMARY AND COMMENT
When to Start Antiretroviral Therapy in
HIV-Infected Patients with Tuberculosis?
Free!
February 24, 2010 |
Carlos del Rio, MD
Trial results from South Africa demonstrate
unequivocally that coinfected patients should start antiretroviral
therapy no more than 4 weeks after completing the intensive phase of
tuberculosis therapy. Whether earlier initiation leads to better
outcomes remains to be determined.
Reviewing: Abdool Karim SS et al. N Engl
J Med 2010 Feb 25; 362:697
SUMMARY AND COMMENT
Body/Brain Discordance in HIV Control
February 24, 2010 |
Abigail Zuger, MD
In this case series, breakthrough
drug-resistant HIV in the central nervous system was associated with
clinical disease.
Reviewing: Canestri A et al. Clin Infect
Dis 2010 Mar 1; 50:773
|
Special
Offers from Journal Watch