Compiled by Robert Fieldhouse
Women with HIV more likely to need hysterectomies
New
research shows women living with HIV are more likely to need their uterus
removed than HIV negative women.
Reports of hysterectomy were collected from 3,752 women in the Women’s
Interagency HIV Study.
This is a prospective cohort study of women with HIV who are compared with
at-risk HIV negative women.
Over time, 106 out of 2361 HIV positive women (4.5 per cent) underwent hysterectomies,
compared with 24 out of 837 HIV negative women (2.9 per cent).
The most common reason for hysterectomy was cervical neoplasia, a precursor
to cervical cancer associated with human papillomavirus (HPV) infection.
These finding coupled with those from other studies that showing HIV positive
women are more likely to be infected with HPV and to develop cervical neoplasia
underline the importance of regular Pap smear test for women living with HIV.
Pap smears detect abnormal cervical cell changes at an early stage when they
are more easily treated.
• JAIDS. 25/01/07 [Epub ahead of print]
Biojector linked to nerve pain
The drug information sheet for T-20 (Fuzeon) has been updated to caution against
people with blood disorders like haemophilia using the Biojector applicator.
Biojector 2000 is a product that propels T-20 through the skin using gas.
The updated info sheet describes nerve pain and haemotoma (an accumulation
of blood under the skin leading to swelling) after using Biojector.
T-20’s recommended dose is 90mg (1ml) twice-daily injected subcutaneously
into the upper arm, thigh, or abdomen.
To reduce the likelihood of injection site reactions, you should never inject
T-20 in the same area as the previous injection.
And you should never inject T-20 near the elbow, knee, groin, the lower or
inner buttocks, directly over a blood vessel, around the navel (belly button),
scar tissue, a bruise, a mole, a surgical scar, tattoo, or burn site, or where
there is an injection site reaction.
Biojector is a trademark of Bioject Medical Technologies Inc and not a product
of Roche, the manufacturer of T-20.
Alarm raised over multi-drug resistant HIV
strain in US
Public health officials have reported four cases of multi-drug resistant HIV
in newly diagnosed gay men in Seattle, USA.
The strain of HIV is resistant to at least two classes of antiretroviral drugs,
with partial resistance to a third. It was found in all four men diagnosed
within 15 months of each other.
None had taken treatment for HIV, all reported crystal meth use and multiple
sexual partners, but none had had sex with any of the others.
King County health agency is distributing fliers warning about the new strain
at gay bars and saunas, and has asked doctors to test all newly diagnosed
people for drug resistance.
It is unknown whether the Seattle men will progress more rapidly to Aids,
but the presence of a multidrug-resistant viral strain means their HIV will
probably be harder to treat.
These recent cases highlight the importance of drug resistance testing for
all newly diagnosed people.
“Men who have sex with men need to know that drug-resistant strains
can and are being transmitted and may be much less treatable,” said
King County HIV/Aids programme director Dr Bob Wood.
• Seattle Post-Intelligencer. 2/02/07
Fast-track approval sought for new type of HIV drug
US and European regulators are poised to consider fast-track licensing of
a new class of HIV drug that blocks the virus entering uninfected cells.
All currently available HIV drugs (except the fusion inhbitor T-20) interfere
with HIV replication inside cells already infected.
Pfizer has applied for accelerated approval for their CCR5 antagonist maraviroc
to the US Food and Drug Administration and the European Agency.
The application is based on data from two late stage clinical trials, Motivate
1 and 2, which followed 1,000 highly treatment- experienced patients with
virus that uses only the CCR5 receptor to gain access to CD4 cells.
More than half of the highly treatment-experienced patients given maraviroc
and background HIV therapy (selected by resistance testing) achieved a viral
load below 400 copies over 24 weeks of therapy.
All trial participants had HIV viral loads above 5,000 copies on their previous
treatment and resistance to at least one drug from the nuke and non-nuke (NNRTI)
classes and at least two protease inhibitors.
Some took placebo, others maraviroc (300mg once-daily) and some took 150mg
maraviroc twice-daily. Patients on a ritonavir-boosted protease inhibitor
other than tipranavir (Aptivus) or the non-nuke (NNRTI) delavirdine (never
licensed in the UK) took the 150mg dose. Up to 75 per cent of patients were
taking two or fewer active drugs along side maraviroc.
After 24 weeks, 31 per cent of those who received placebo plus other HIV meds
in Motivate 1, and 23 per cent of patients receiving placebo plus other meds
in the Motivate 2 trial, had a viral load below 400 copies.
Adding maraviroc almost doubled their chances of achieving an undetectable
viral load below 400 copies; 55 per cent in both studies achieved this. Those
taking twice-daily maraviroc were slightly more likely to achieve an undetectable
viral load (60 per cent in Motivate 1 and 61 per cent in Motivate 2).
CD4 cell gains were significantly different between the placebo and treatment
groups. In Motivate 1, CD4 cell count increased by on average 52 cells in
placebo patients compared with gain of 107 cells among those taking maraviroc
once-daily and 111 in those taking maraviroc twice a day.
Similar results were found in Motivate 2, where CD4 counts increased by an
average of 64 in patients on placebo, but by 112 and 102 in those treated
with once and twice-daily maraviroc respectively.
• Abstracts 104aLB, 104bLB, 14th CROI, Los Angeles, USA. Press Release.
13/02/07, Pfizer Inc.
‘Erb eases pain of HIV-related nerve
damage
People
with peripheral neuropathy (nerve damage in feet and hands) get as much or
more pain relief from marijuana than prescription painkillers, a study has
found.
The five-day study of 50 people with neuropathy, which is related to HIV drugs
as well as HIV infection, also found those who smoked marijuana experienced
fewer side effects than people taking painkillers.
Study participants rated the pain they felt on a scale of one to 100 after
a small hot iron was held against their skin and after capsaicin (a topical
cream derived from chili peppers) was applied.
Participants smoked three joints a day in an enclosed room at 8am, 2pm and
8pm.
They were asked to inhale for five seconds, exhale after 10, and inhale the
marijuana cigarette again after 45 seconds.
More than half of the patients who smoked marijuana reported significant reductions
in pain, compared with less than a quarter who smoked placebo joints.
The control group smoked marijuana altered to remove the component which produces
a psychoactive effect and leaving it with one-quarter of the potency of commercially
available cannabis.
Opioids and other painkillers typically reduce pain by 20-30 per cent but
frequently cause drowsiness and confusion.
Half those who smoked real marijuana reported a greater than 30 percent reduction
in pain from neuropathy compared with the 17 per cent reduction reported by
those smoking placebo.
• Neurology (2007;68(7)515-521).
High rates of drug resistance found in untreated
in US
An increasing number of people with HIV in the US who have never taken antiretrovirals
have been found to have types of virus resistant to certain medication.
Researchers used genotypic drug resistance testing to look for changes in
HIV’s genes that make it less susceptible to HIV drugs.
This enabled them to measure resistance in a group of 103 people who had not
yet started HIV treatment in the US. They found that a quarter had resistance
to at least one class of antiretroviral drugs.
Six per cent had resistance to two drug classes, while one per cent had resistance
to three protease inhibitors, non-nukes (NNRTIs) and nukes.
The most common resistance mutation detected in 12 patients was K103N, which
signals resistance to NNRTIs nevirapine (Viramune) and efavirenz (Sustiva).
The M184V mutation, which signals resistance to certain nukes (NRTIs), particularly
3TC and FTC, was detected in six patients. Only two patients had PI-resistance
mutations.
The resistance rate observed in 2005 was higher than the rates seen in previous
studies, ranging from eight to 20 per cent. This suggests the prevalence of
transmitted drug resistance may be increasing over time.
Currently in the UK, we are not seeing such high rates of transmitted NNRTI
resistance.
• Clinical Infectious Diseases 44(3): 456-458. 1/02/07
New non-nuke is safe with first integrase
inhibitor
The investigational non-nuke TMC 125 from Tibotec can be safely used with
Merck’s investigational integrase inhibitor MK-0518.
Results from an interaction study confirmed there were no clinically significant
interactions between them.
Microbicide trial cancelled over increased
HIV risk fears
A trial to see if a microbicide gel can prevent HIV transmission has been
halted amid fears it may make women more likely to get HIV.
CONRAD, the reproductive health research organisation, stopped the phase 3
clinical trial of Ushercell, a gel that was being tested on 1,300 women in
South Africa, Uganda, Benin and India.
It was halted after early results indicated the main ingredient, cellulose
sulfate, increased women’s risk of catching HIV. A similar trial in
Nigeria was also halted as a precautionary measure.
UNAIDS said it was a “disappointing and unexpected setback” but
added there were three other microbicides, Carraguard, PRO 2000 and BufferGel,
currently in testing.
PIs may thicken key artery in women
Protease
inhibitors may lead to increases in the thickness of the lining of the carotid
artery, which supplies blood to the head.
Thickening of this artery is a marker of early heart disease. US researchers
found women treated with protease inhibitors had significantly thicker carotid
arteries, compared with women not treated with PIs.
Forty five percent of the women treated with PIs had elevated blood fats,
compared with only four per cent of HIV negative women.
Antiretroviral drugs save lives, but PIs, which increase blood fats, may increase
risk of heart disease.
Everyone on treatment should have careful monitoring for the development of
coronary artery disease. If you don’t know whether your blood fats are
normal ask at your next clinic visit.
• J Clin Endocrinol Metab 2006;
91:4916-4924.
Europe approves new PI for treatment experienced
Europe has licensed a new protease inhibitor that targets resistant virus
in highly-treatment experienced people.
Darunavir (Prezista 600mg) is taken twice daily in combination with 100mg
ritonavir and food.
Professor Margaret Johnson, chair of the British HIV Association (BHIVA),
welcomed the manufacturer’s decision to price the drug lower than other
currently available options for highly treatment-experienced patients.
“Darunavir will provide a vital new option for patients in the UK. It
has been shown to reduce viral load to undetectable levels and this is one
of the key aims of antiretroviral therapy.”
Recent trials have shown the drug is very potent even if you already have
high levels of resistance to PIs, and it is also very lipid friendly.
Europe approves new PI for treatment experienced
British drug giant GlaxoSmithKline has cited problems in creating an oral
dosage of brecanavir as the reason why it halted work on its investigational
protease inhibitor.
Brecanavir had reached phase II testing and early results in treatment-naïve
and treatment-experienced patients were promising. The drug had appeared active
against some PI resistant virus.
People currently receiving brecanavir in clinical trials will be switched
to other therapies.
GSK said: “This decision has been taken as we have been unable to develop
a viable oral dosage formulation capable of delivering the desired drug levels
in patients with multi-drug-resistant HIV.”
Poz people have average 35 year life span
after diagnosis
Young people recently diagnosed with HIV could live an average of 35 years,
a study suggests.
Danish researchers studied data on 3,990 people with HIV treated in Denmark
between 1995 and 2005.
Each was matched with up to 99 controls from the general population.
The highest HIV death rate was seen in 1995/96 before highly active anti-retroviral
therapy (HAART) became widely available.
From the age of 25, the average life expectancy was 19.9 years in people with
HIV compared with 51.1 years in the general population.
Survival rose to 32.5 years in people diagnosed with HIV between 2000 and
2005, the early HAART era.
Survival rates rose again to 38.9 years when people with hepatitis C coinfection
were excluded from the calculation.
The researchers said their findings depended on the continued success of HAART.
So, plan for your future because you have one.
• Ann Intern Med 2007; 146:87-95.
Protein may protect CD4 in immune-suppressed
people
A
naturally occurring protein called interleukin-7 (IL-7) is a good candidate
for immunotherapy in people with HIV, say researchers.
The role of this protein is to send out messages to the immune system.
US investigators at the National Institute of Allergy and Infectious Diseases
showed IL-7 could be most effective in people with the greatest degree of
immune system damage.
They isolated a certain kind of blood cell from 24 people at different stages
of HIV infection.
When they treated the cells with IL-7 cell death declined up to 28.4 per cent
over a period of six days.
People with the greatest immune damage saw the greatest improvements. Reassuringly,
researchers found no increase in HIV replication.
IL-7 should now be studied further alongside antiretroviral therapy.
• Proc Natl Acad Sci USA 2007.
Crystal meth linked to non-nuke resistance
transmission
Studies have found use of the drug crystal meth, which causes increased sexual
appetite and a loss of inhibitions, is associated with higher rates of unprotected
sex.
Experts fear this in turn may lead to an increase in HIV transmission and
make HIV progress faster.
In a recent study, researchers in San Francisco looked at whether people who
used meth were more likely to become infected with strains of HIV that were
already resistant to antiretrovirals.
This is termed ‘primary resistance’, as opposed to resistance
that evolves over time due to taking HIV drugs.
The study involved 300 men who have sex with men between 1996 and 2005. All
had become HIV positive within the previous year. Thirteen men reported taking
HIV drugs within six months of their exposure to HIV, including post-exposure
prophylaxis (PEP).
Twenty-eight per cent reported meth use during the previous 30 days while
12 per cent reported weekly or more frequent use.
Twenty-six per cent had resistance to at least one antiretroviral drug. Thirty-four
per cent of frequent meth users were resistant to at least one drug class,
compared with 21 per cent of infrequent users and 25 per cent of non-users.
Frequent (defined as weekly or more often) meth use was strongly associated
with primary resistance to non-nukes (NNRTIs, efavirenz or nevirapine), but
not with protease inhibitors or nukes (NRTIs).
“Our results, and such high prevalence rates of methamphetamine use
among MSM, suggest methamphetamine may be an important co-factor in the transmission
of NNRTI resistance in this population,” the authors concluded.
The association may be due to gay men with HIV taking treatment breaks while
taking meth. They also suggested HIV negative meth users were likely to be
having unprotected sex with HIV positive users with drug resistance due to
suboptimal adherence to their meds.
“The convergence of treatment interruptions and high-risk behavior could
be responsible for the high rates of drug resistance we report here,”
they added.
• AIDS 21(2): 239-241. 11/01/07
