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February 5, 2012)
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February 2, 2012
A drug regimen containing
Isentress (raltegravir), Intelence (etravirine) and Norvir (ritonavir)–boosted
Prezista (darunavir) has been shown to be “highly potent and durable in terms
of efficacy and safety” in a French clinical trial involving heavily
treatment-experienced people living with HIV. According to the research paper
published ahead of print by the Journal of Acquired Immune Deficiency Syndromes
(JAIDS), 88 percent of those using this regimen had undetectable viral loads
after nearly two years of treatment.
The arrivals of Isentress, Intelence and Prezista—approved by the U.S. Food
and Drug Administration in 2007, 2008 and 2006, respectively—were considerable
milestones in our ability to treat people living with HIV resistant to many of
the longstanding antiretroviral (ARV) options. Isentress was the first of the
new class of integrase inhibitors, whereas Intelence, a non-nucleoside reverse
transcriptase inhibitor (NNRTI) and Prezista, a protease inhibitor (PI),
showed early promise against HIV with mutations conferring resistance to other
members of their respective drug classes.
Because these compounds were being evaluated in clinical trials around the same
time, studies evaluating the use of all three agents together were not possible.
However, because these drugs each demonstrated effectiveness against HIV
resistant to older ARVs, they were expected to perform well when used together.
Early results from a French study were highly encouraging. Preliminary 48-week
data from the Agence Nationale de Recherches sur le Sida et les Hépatites
Virales (ANRS) 139 TRIO study, testing all three drugs in combination with other
ARVs as needed, found that 86 percent of heavily treatment-experienced people
using the regimen had undetectable viral loads—a degree of success similar to
that expected in first-time treatment takers receiving standard ARV drug
combinations.
The final 96-week follow-up data from TRIO have now been published by Catherine
Fagard, MD, and her colleagues by JAIDS. The results are similar to those
reported in 2011 at the 18th Conference on Retroviruses and Opportunistic
Infections in
The study enrolled 103 HIV-positive patients to take Isentress, Intelence and
Norvir-boosted Prezista with an optional background regimen of nucleoside
reverse transcriptase inhibitors (NRTIs) with or without Fuzeon (enfuvirtide).
Researchers continued to follow 100 study volunteers for 96 weeks.
Eighty-eight percent of the participants were male, and the average age was 45.
The average viral load upon entering the study was 16,000 copies, and the
average CD4 cell count was 258. Volunteers had been on ARV treatment for an
average of 13 years, and about 40 percent had a CD4 count below 200 upon
entering the trial.
As for pre-treatment resistance profiles, patients in TRIO had an average of
four major PI mutations, five major NRTI mutations and one major NNRTI mutation
in their HIV, which was evidence of significant drug resistance. In addition, 96
percent and 65 percent of participants had between one and three HIV mutations
conferring at least partial resistance to Prezista and Intelence, respectively.
The authors also reported that 59 percent of the patients were using a
background regimen that didn’t contain any ARVs that were fully active against
their HIV.
Yet the results after nearly two years are remarkable. According to Fagard and
her colleagues, 88 percent of the 100 patients enrolled in the study had viral
loads below 50 copies per milliliter (ml) at the 96-week time point.
Though 19 people in the study had two repeated episodes of detectable viral
load—changes to the background drugs used with the TRIO regimen were made in
five cases—14 of these patients had undetectable viral loads at 96 weeks.
Fagard and her colleagues also observed an average CD4 count increase of 110
cells after 96 weeks. What’s more, the proportion of patients with CD4 counts
below 200 decreased from 40 percent at study entry to 16 percent at the 96-week
mark.
The regimens containing Isentress, Intelence and Norvir-boosted Prezista were
generally well tolerated. Moderate-to-severe abnormalities in lab results were
reported in 25 people, usually during the first 48 weeks of treatment, none of
which required discontinuing treatment.
Fagard’s group reported that lipid levels, notably triglyceride and
cholesterol levels, remained largely unchanged over the entire study period.
Clinical side effects were reported in 93 percent of the study participants,
mostly during the first year of the study. Twenty-six patients experienced
moderate-to-severe side effects, but only four of these were believed to be
related to the treatment regimen. One patient with a rash and fever discontinued
treatment.
“This study confirms that in treatment-experienced patients, an antiretroviral
regimen containing raltegravir, etravirine and darunavir/ritonavir showed high
efficacy, with a good safety profile,” Fagard’s team concludes. “Long-term
efficacy in this population appeared to be as high as that reported for
treatment-naive patients receiving either PI-containing regimens associated with
NRTIs or combinations containing new antiretroviral drugs, such as
raltegravir.”
Michael Carter
31 January 2012
Raltegravir could have a
“useful” role in HIV post-exposure prophylaxis, according to investigators
from the
Doctors in
None of the patients who
returned for follow-up monitoring was infected with HIV. Side-effects were
generally mild and were significantly less common, compared to PEP combinations
based on a ritonavir-boosted protease inhibitor.
“The current study is
the first to evaluate an integrase inhibitor, raltegravir, as the third active
agent in a PEP regimen,” write the authors. “The rationale was based on
findings that this drug has been shown to be extremely well tolerated, with
potent antiretroviral activity.”
The use of PEP is
recommended after some unprotected sexual encounters that could have involved
exposure to HIV.
Generally, a three-drug
regimen is prescribed consisting of two nucleoside reverse transcriptase
inhibitors (NRTIs) and a ritonavir-boosted protease inhibitor. Treatment lasts
for 28 days. Very few people have gone on to seroconvert for HIV after
completing a course of PEP.
However, the side-effect
profile of current PEP regimens could explain poor rates of adherence and
treatment completion. A simple and well-tolerated regimen could therefore
improve compliance, boosting the efficacy of therapy.
Truvada forms of the
backbone of many HIV treatment combinations and has a generally mild side-effect
profile. Raltegravir is less widely used, but has been shown to have a powerful
anti-HIV effect with few side-effects.
Investigators from Fenway
Health, a community clinic in
Between 2008 and 2010 a
total of 100 people were prescribed the regimen after possible sexual exposure
to HIV. Almost all (98%) were men, with the majority identifying as gay or
bisexual. All the participants tested HIV-negative at baseline.
A little over a third of
people (37%) accessed PEP after unprotected sex with a partner known to be
HIV-positive.
The participants received
a three-week course of standard-dose raltegravir (400 mg twice daily) and
Truvada (one daily tablet combining 300mg tenofovir with 200 mg FTC). Adherence
was measured using pill counts. People were asked to keep a diary recording
side-effects.
A total of 85 people
returned after 28 days for a follow-up HIV antibody test. None were positive.
The most commonly reported
side-effects were nausea and vomiting (27%), diarrhoea (21%), headache (15%),
fatigue (14%), and abdominal discomfort including bloating and flatulence (16%).
In most cases, these side-effects were mild, and they resolved once therapy was
completed.
The profile and prevalence
of side-effects was similar to that observed at the clinic when a two-drug
Truvada PEP regimen was prescribed.
Moreover, comparison with
historic controls showed that the raltegravir/Truvada regimen was significantly
better tolerated than triple-drug regimens based on a ritonavir-boosted protease
inhibitor.
In total, 67% of people
who completed their therapy took 100% of their doses. However, approximately a
quarter of patients consistently missed their second a dose of raltegravir. All
these patients reported adherence to their daily dose of Truvada, as well
as the dose of raltegravir taken at the same time.
“Clinicians prescribing
PEP might want to emphasise the importance of the second daily raltegravir dose
as part of their initial counselling, and might use the conversation with their
patients to think of strategies to enhance adherence to the second dose,”
suggest the investigators.
They conclude, “This
study was the first in humans to demonstrate that an integrase inhibitor can be
well-tolerated as part of an HIV chemoprophylactic regimen...the lack of
incident HIV infections and high level of tolerability was reassuring.”
(AFP) – 5 Feb., 2012
Other changes as part of
an annual update to US immunization schedules included a recommended hepatitis B
vaccine to the protect the livers of adults up to age 60 who have diabetes and a
vaccine against whooping cough for pregnant women.
The updates, agreed upon
by the Centers for Disease Control and Prevention's Advisory Committee on
Immunization Practices (ACIP), were published in the CDC's Morbidity and
Mortality Weekly report of February 3.
The HPV vaccine has been
approved for girls since 2006 but the CDC had not expressly urged it for boys,
though boys were included among those who could receive it to prevent certain
cancers and genital warts.
Health experts have
expressed hope that if pre-teen boys and girls are both encouraged to get the
vaccine, the rate of infection will decrease in the general population.
About half of all sexually
active adults will get HPV in their lifetime. There are more than 100 types of
HPV, and most clear the body on their own, but some strains can linger and lead
to cervical, anal or oral cancer.
Only about 20 percent of
women aged 19-27 reported having received the HPV vaccine in 2010, up slightly
from 17.6 percent in 2009, the CDC said.
The vaccine, currently
recommended for girls age 11-26, has faced resistance from some parents over
fears that immunizing young girls would encourage them to be promiscuous.
The new guidelines, which
were first urged by ACIP in October, call for all males aged 11-12 to get the
vaccine too, with a catch up vaccination for those between the ages of 13 and 21
if they missed it.
HPV vaccine also is
recommended for males 22-26 years old who have not been vaccinated before and
who have weakened immune defenses, who test positive for human immunodeficiency
virus (HIV), or who have sex with men.
The hepatitis B shot is
now being recommended for all adults up to 60 who have diabetes as soon as
possible after they are diagnosed, and for those older based on the need for
assisted blood glucose monitoring.
The combination Tdap
vaccine against tetanus, diphtheria, and acellular pertussis (or whooping cough)
had been urged for adults with close contact to children and for women after
they gave birth if they had not previously been vaccinated as adults.
The new recommendation
calls for pregnant women to get the Tdap vaccine at 20 weeks gestation or later
so they can pass the antibodies on to the fetus.
All people age six months
and older can get the annual flu vaccine, the update added. Patients with an egg
allergy should get the inactivated flu shot.
Copyright © 2012 AFP. All
rights reserved.
FOR six years, Roche
In the
The hospital’s H4 BL
Pavilion is the country’s premier institution on HIV/AIDS under the Department
of Health, particularly serving indigent Filipino patients. With its holistic
approach to HIV/AIDS including treatment, financial and moral support, research
and advocacy, San Lazaro’s H4 BL Pavilion has become the refuge for treatment
and place of hope for many of our countrymen infected with HIV/AIDS.