Compiled by Robert Fieldhouse
Nevirapine/AZT single dose cuts drug resistance
in babies
Giving
babies a single dose of nevirapine (Viramune) plus AZT (Retrovir) after birth
minimises nevirapine resistance rates, a new report has found. The use of
both HIV drugs together cuts transmission of the virus from mother to child.
Treatment of HIV positive pregnant women and their babies with single-dose
nevirapine is associated with the development of nevirapine resistance in
some women and infants who become HIV positive despite prophylaxis.
Researchers investigated nevirapine resistance rates in babies who received
either
single-dose nevirapine alone or a regimen of single-dose nevirapine plus AZT.
Additionally, another group of mums received single-dose nevirapine during
delivery, while another did not. The researchers used data from two clinical
trials to prevent mother-to-child HIV transmission in Malawi.
Genotypic HIV drug resistance testing was conducted on 78 of 95 samples from
babies who became HIV positive despite receiving antiretroviral drugs.
Eighty-seven per cent of the babies who received single-dose nevirapine alone
and whose mothers also received single-dose nevirapine, developed nevirapine-resistance.
Fewer babies harboured nevirapine-resistant virus if their mothers did not
receive single-dose nevirapine (57 per cent).
The proportion of babies with nevirapine-resistant virus was lowest if they
had received single-dose nevirapine plus AZT and whose mothers had not received
single-dose nevirapine (27 per cent).
Mother-to-child transmission of HIV did not differ significantly by treatment
group, and AZT resistance did not develop in any infant.
“These preliminary results are encouraging but need to be confirmed
in larger studies,” the authors concluded.
Journal Infectious Diseases 2006; 193:
479-481
Neutropenia common in women with advanced
HIV
Women are more likely to develop the blood disorder neutropenia as their HIV
progresses, according to a new report. Neutropenia occurs when the level of
neutrophils, a type of immune cell, falls below normal levels. People affected
are more vulnerable to infections.
Researchers found 80 per cent of women with HIV followed up over seven and
half years had developed neutropenia. Taking HAART was associated with protecting
against its development.
When neutropenia was defined as a neutrophil count less than 2,000/ml, 44
per cent of HIV positive women were deemed neutropenic at the start of the
study. A third had a neutrophil count less than 1,000/ml.
Low CD4 (below 200) and high viral load (above 100,000) increased the risk
of neutropenia by 83 per cent and 47 per cent respectively.
Combination therapy not containing AZT significantly decreased the risk of
developing neutropenia but combinations including AZT failed to protect against
it. Developing neutropenia was not associated with poorer survival in women
with HIV. This prompted researchers to conclude that women should not avoid
AZT just because of neutropenia.
Arch Intern Med 2006; 166: 405-410
Opportunistic infections remain the biggest
killers
Opportunistic infections are still the leading cause of death in people living
with HIV, even in the HAART era.
A new analysis of 22 groups of people living with HIV found overall death
rates had declined significantly since wide introduction of HAART. In the
CASCADE study, 1,938 out of 7,680 people with a known HIV seroconversion date
had died. Researchers found the cumulative risk of death from Aids-related
cancers, non-Aids defining cancers, and opportunistic infections fell significantly
among gay men after the wider availability of HAART. There was also a non-significant
drop in death from hepatitis and liver-related complications.
However, these improvements were not experienced by all people living with
HIV. People who injected drugs experienced a significant increase in death
from unintentional causes.
AIDS 2006; 20: 741-749
Higher death rates seen in HIV positive drug
users
People
living with HIV who regularly use cocaine and heroin are at greater risk of
opportunistic infections, disease progression and death than those who don’t,
according to a new study.
These risks are similar, regardless of whether people are regular or intermittent
drug takers. The risk is only reduced when people abstain from the drugs completely.
Researchers at Johns Hopkins University School of Medicine used confidential
computer-based interviews to survey patients every six months, starting in
1998.
Of the 1,851 participants, 1,028 people did not use any drugs, 588 used intermittently
and 235 were persistent users. An intermittent user was defined as using drugs
an average of 14 days in the previous six months. Persistent users had taken
drugs an average of 27 days in the previous six months.
After three years, non-drug users were estimated to have survival rates of
87 per cent while intermittent users had
survival rates of 80 per cent. The rate was 68 per cent for persistent users.
The researchers speculated that effects of drug use on disease progression
might be mediated by biological effects, such as increased HIV replication
and impaired immune cell function, or by reducing access to care and adherence
to therapy.The researchers called for greater emphasis on psychiatric care
and substance abuse treatment when treating HIV positive people using cocaine
or heroin.
American Journal of Epidemiology, 2006; 63: 412-419
New compound kills HIV in test tube trials
Scientists have identified a drug that hunts and kills HIV in a new way. Ceragenix
Pharmacueticals say CSA-54, a Ceragenin, works by targeting the membrane of
the virus to stop it locking on to cells.
It mimics disease-fighting characteristics of anti-microbial and anti-viral
agents produced by healthy immune systems. Preliminary test tube studies carried
out at two US universities are exciting.As well as HIV, CSA-54 may eventually
find a role fighting bird flu, smallpox and herpes. But animal and human trials
are likely to take three to seven years to complete.
Chemo plus HAART proves safe and effective
for HIV-related lymphoma
People with the HIV-related cancer lymphoma fair better if treated with chemotherapy
and highly active antiretroviral therapy (HAART).
Researchers concluded that chemotherapy comprising of cyclophosphamide, doxorubicin,
vincristine and prednisone (CHOP) plus HAART was safe and effective. This
is good news as some clinicians have been concerned about combining the two
therapies, fearing excessive side-effects.
Seventy-two people with HIV-related lymphoma were divided into two groups:
one contained 48 patients deemed ‘standard risk’ because they
only had one of three risk factors: CD4 counts less than 50, symptoms of HIV
illness,
or a previous Aids-defining opportunistic infection. Twenty-four people in
the high risk group had two or three of these risk factors. All received six
cycles of CHOP, and HAART was continued or started in all but six patients.
In the standard risk group, 79 per cent achieved a complete response while
66 per cent were still alive after three years and 33 per cent after five.
In the high-risk group, 29 per cent achieved complete response. The average
survival period was seven months. Four weeks after the chemo cycle, patients
in the standard risk group had CD4 and CD8 cell counts similar to pre-chemo
levels and lowered viral loads.
Progressive disease accounted for 10 out of 17 deaths in the standard risk
group and 17 out 21 in the high risk group.
Cancer 2006; 106
HAART in late-stage HIV infection reduces
Aids
Sticking with highly active antiretroviral therapy (HAART) during late-stage
HIV infection is beneficial, even if your CD4 and viral load responses are
poor.
US researchers looked at more than 300 HIV positive people with sub-200 CD4
counts before starting therapy.
These people were divided into two groups. Group one comprised 88 people treated
between 1990 and 1995,
during the pre-HAART era.
Group two was made up of 214 patients treated between 1996 and 2004 with HAART.
Researchers found that even with a low increase in CD4 cell counts, the rate
of Aids was lower in people treated with HAART compared with those treated
in the pre-HAART era. This was despite the patients in each group having similar
CD4 cell counts and viral loads.
This data complements similar findings from drug interruption studies that
provide
indirect evidence that it may be clinically beneficial to continue HAART in
spite of virologic failure. It also shows that new antiretrovirals effective
against drug-resistant strains of HIV need to be developed.
Clinical Infectious Diseases 2006; 42: 878-884
Young people less likely to stick to meds
Young people, those living alone or those who are treatment experienced are
more likely to struggle to take antiretrovirals as prescribed, a large study
has found. Taking
a ritonavir-boosted PI was another fact that increased the risk of poor adherence.
The Swiss HIV cohort study looked at 3,607 people on antiretrovirals for at
least six months and their current combo for at least one month.
Almost one in three participants reported missing one or more doses in the
previous four weeks while around 15 per cent missed two or more doses, and
around seven per cent reported taking fewer than 95 per cent of doses in the
preceding four weeks. Overall, around six per cent reported taking a drug
holiday.
The authors concluded that investment in behavioral dimensions of HIV was
crucial to improve adherence in ARV recipients.
JAIDS 2006; 41: 385-392
Cancer cases fail to halt drug study
Drug manufacturer Schering-Plough has revealed that five people taking its
investigational CCR5 inhibitor, vicriviroc, have developed cancer during a
mid-stage clinical trial.
In a statement, the company said a causal relationship between the drug and
cancer had not been established and that all five had very advanced HIV.
The company said the trial, involving 118 US patients with advanced HIV and
limited treatment options, will continue, despite four cases of lymphoma and
one case of stomach cancer.
First proof that protease inhibitors boost
corticosteroid levels
The HIV protease inhibitor ritonavir significantly increases blood levels
of the corticosteroid prednisolone, new research suggests.
Scientists have previously suggested that corticosteroid exposure and side
effects might increase in people on antiretrovirals, and this new study supports
this theory.
Corticosteroid medications have been associated with a variety of side effects
such as osteonecrosis (bone death) and Cushing’s syndrome in people
living with HIV on protease inhibitor-containing regimens.
It’s thought these complications are caused by protease inhibitors blocking
the elimination of
corticosteroids leading to higher concentrations in the blood.
Ten HIV negative volunteers got a single oral dose of prednisone before, on
day four and day 14 of a two-week ritonavir regimen. After each prednisone
dose, researchers measured prednisolone blood levels.
Researchers noticed increases in the prednisolone levels by day four and this
was sustained until day 14. The study offers proof that corticosteroid levels
increase significantly when taken alongside a protease inhibitor. The next
step will be to assess the interaction in people living with HIV.
“But these findings already suggest if a physician has to administer
a corticosteroid treatment to an HIV patient, he should start with a low dose,
then increase only depending on how the patient is responding,” the
researchers concluded.
Journal of Acquired Immune Deficiency Syndrome 2005; 40: 573-580
New target to block HIV discovered
US scientists have discovered how a cellular protein can control the way HIV
integrates into human cells.
The protein, LEDGF, binds to the HIV enzyme integrase and cellular DNA, reducing
integration of viral DNA into the cell nucleus.
When researchers manufactured cells depleted of LEDGF, they found integration
of viral DNA into cell DNA was much less frequent, reducing HIV’s ability
to hijack CD4 cells.
Nature Rev Microbiology 3, 848-859 (2005)
Antacids fail to weaken new protease inhibitor
tablet
Researchers have investigated the effect of over-the-counter acid reducing
drugs on protease inhibitors (PIs).
PIs need an acid environment to ensure appropriate levels of drug absorption.
Acid-reducing drugs include proton pump inhibitors like omeprazole and H2
antagonists like ranitidine. Using them decreases the levels of some PIs.
Many people living with HIV use over-the-counter acid reducing drugs to deal
with stomach problems.
Researchers at Abbott Laboratories evaluated the effect of omeprazole and
ranitidine and how decreased stomach acidity affected levels of the new, soon-to-be
licensed lopinavir/ritonavir (Kaletra). This tablet is taken once or twice
daily. They also looked at their effects on once-daily PI atazanavir (Reyataz).
Omeprazole (40mg, once-daily) was given an hour before breakfast on study
days 11 to 15 or 150mg ranitidine was given an hour before breakfast on study
day 11.
Blood samples were collected during a dosing interval (for 12 or 24 hours
after dosing) on study days 10, 11, and 15. Blood levels of lopinavir, ritonavir,
and atazanavir were compared with and without omeprazole or ranitidine. Researchers
found that if atazanavir was taken without ritonavir, levels of atazanavir
decreased significantly when
combined with omeprazole and ranitidine.
But ritonavir-boosting atazanavir was sufficient to keep atazanavir levels
high enough to inhibit HIV if omeprazole and ranitidine were also present.
Levels of the new lopinavir/ritonavir tablet were unaffected by omeprazole
or ranitidine, regardless of whether taken once- or twice-daily.
Abstract 578, 13th CROI
New drug class offers strong hope
Scientists have been trying to develop a new class of HIV drugs called integrase
inhibitors for over a decade and it finally looks like efforts are paying
off.
Integrase inhibitors stop HIV splicing its genetic information into our own;
the central event in the virus’s life cycle.
Furthest along the pipeline is Merck’s MK-0518. Almost nine out of 10
patients taking it achieved a viral load under 400 after 16 weeks. This was
compared with a quarter of patients on a placebo.
Two-thirds achieved a viral load under 50, compared with eight per cent on
placebo.
These results are impressive because participants had resistance to all three
commonly-used drug classes, and almost a third showed resistance to every
licensed HIV drug. Each had spent an average of eight years on therapy.
Merck are rapidly progressing toward large-scale effectiveness studies and
are talking about getting the drug to patients who need it as early as next
year.
Not far behind is an integrase inhibitor made by Gilead called GS9137. This
achieved a 100-fold viral load drop in patients taking the drug for ten days.
However, unlike MK-0518, GS9137 will probably have to be taken with ritonavir
to boost its levels.
Doctors are excited about integrase inhibitors because it appears that HIV
only develops resistance to them very slowly. Gus Cairns. Abstract 159LB,
160LB, 13th CROI
Interaction warning on new drugs
New research has shown an interaction between the investigational non-nuke
TMC-125 and the recently licensed ritonavir- boosted protease inhibitor tipranavir
(Aptivus).
When TMC-125 and tipranavir are taken at the same time there is a significant
and clinically relevant decrease in the levels of TMC 125 and combining these
drugs is not currently recommended.
Abstract 583, 13th CROI
