Compiled by Compiled by Robert Fieldhouse from the Toronto International
Aids Conference
Growth hormone boosts CD4 levels
People with HIV who have incomplete immune reconstitution after a year or
more of HAART may benefit from recombinant human growth hormone (r-hGH).
Adding r-hGH appears to improve production of CD4 cells in the thymus.
Researchers stress it is unlikely that r-hGH can be used alone to increase
CD4 cells but may be incorporated into a therapeutic vaccine to enhance immune
response.
In a previous study, where people received r-hGH to treat HIV-related body
fat changes, investigators reported people had increases in thymic mass, as
well as an increased CD4 percentage and total number of CD4 cells.
US researchers studied 60 people living with HIV whose CD4 cell counts had
failed to rise above 350 cells on HAART, but whose virus had declined to under
400 copies. Participants either got HAART plus r-hGH at 1.5mg subcutaneously
every day for 48 weeks, or stayed on HAART alone for 24 weeks and then took
r-hGH at 3mg daily for 24 weeks.
A CT scan was used to measure the thymus in 20 participants at the start of
the study and again after 24 weeks of treatment.
Eighty per cent of the people were aged over 40 and the majority were white
men with average CD4 counts of about 220 cells.
After 48 weeks, both treatment groups saw increases in CD4 cell counts. The
continual treatment group saw increases in the number and percentage of naive
CD4 cells (68 per cent and 42 per cent respectively).
For patients who started r-hGH later, the corresponding increases were 47
per cent and 18 per cent.
Researchers hope to expand the study using a higher dose of r-hGH. They reiterated
that their current work did not show that CD4 count increase had any clinical
effect. MoAx0403
‘On-off’ therapy proves bad
for your health
All HIV patients do worse on intermittent therapy, according to further analysis
of the largest ever HIV clinical trial.
Results of the SMART study, that looked at 5,000 people with HIV, found people
who took episodic antiretroviral therapy, sometimes referred to as structured
treatment interruptions, were 2.5 times more likely to experience disease
progression or death.
The researchers told the Toronto conference that their analysis showed continual
therapy to be safer for all groups of patients, regardless of age, sex, HIV
risk category, prior Aids, lowest ever CD4 count, baseline CD4 and CD4 percentage.
Black people were shown to be more at risk of of disease progression or death,
but researchers were unable to explain this finding.
WEAB0202
Anti-HIV vaginal ring looks promising
A
number of drugs are being studied as potential candidates for microbicides
to enable women to protect themselves from HIV infection.
Microbicides are expected to make a big
difference to women in poorer, high HIV prevalence countries who are unable
to make their partners wear a condom.
Microbicides are generally administered through gels or creams, but other
methods, such as vaginal rings, are also in development.
A vaginal ring that provides sustained release of the antimicrobial TMC120
(dapivirine) for more than 30 days has just completed a phase I/II trial.
The US-based International Partnership for Microbicides wanted to know if
the rings caused side-effects and assess the concentrations of the new drug
in the women’s vaginal fluid and tissues.
It found the rings were well tolerated with only mild side-effects unrelated
to the drug. It also found the drug was delivered throughout the genital tract
at good concentrations while levels in their blood were low.
The seven-day trial involved 13 sexually active women aged 18-26 who were
randomised to receive a ring containing 25mg of dapivirine or placebo.
There were no serious events or deaths and none of the women stopped the trial.
A few cases of unexplained vaginal bleeding occurred in both groups. Larger
studies in Africa are planned.
Other microbicide candidates in mid- and late-stage clinical trials include
HIV entry inhibitors (Carr guard, PRO 2000); surfactants (C31G); acid buffers
(Buffer Gel); and other antiretrovirals (tenofovir).
Selenium improves Africans’ response
to HAART
A
new research study suggests a significant role for selenium alongside antiretroviral
therapy. People using HAART in Nigeria who took daily selenium supplements
saw their CD4 cell counts rise more significantly than people who took HAART
alone.
Selenium is a trace metal found in cereals, fish meat and eggs, and in high
levels in liver and Brazil nuts. It is vital for good health, although toxic
in high doses. Low levels in the body can lead to immune suppression, HIV
disease progression and increases mortality rates in people living with HIV.
Equally, ongoing HIV replication diminishes selenium levels.
Researchers looked at group of 170 people with advanced HIV disease and studied
the effect of giving people a 200mg dose of selenium every day alongside d4T,
3TC and nevirapine for 72 weeks. This was then compared to antiretroviral
therapy alone.
They measured HIV viral load, CD4 counts, and other blood and chemical levels
at the start of the study and then every three months after. Participants
were also given advice on sticking to their medications and how to eat healthily.
People started the study with an average CD4 count of less than 50 cells.
Those just on HAART alone gained an average of 50 CD4 cells over 72 weeks,
while those who took selenium gained an average of 120 cells.
People taking selenium plus HAART
developed fewer opportunistic infections, experienced greater haemoglobinisation,
spent less time in hospital and gained more weight.
Presenting the research to the Toronto conference, Dr Odunukwe warned against
people or doctors replacing HIV treatments with selenium supplementation.
Selenium has not been shown to have any effect on reducing viral load.
MoAb0403
Dairy-free advice flawed
Eating moderate quantities of dairy foods does not make HIV-related diarrhoea
worse, a new study has found.
Chronic diarrhoea is common among people with HIV in the HAART era and people
are often urged to avoid products containing lactose. But there is little
evidence to support this dietary strategy.
In a study of 49 HIV positive people with diarrhoea, researchers compared
stool weight in the eight hours following drinking low-fat milk (12g of lactose)
or lactose-free milk. Lactose was considered not to have had a harmful effect
if the stool weight did not differ by more than 167g in those that drank the
low fat milk. All but one participant was male and the average age was 42.
The average CD4 count was 390 and average viral load was 112 copies. Thirty-nine
were taking HAART.
Use of the lactose-containing milk was associated with a slight decrease in
stool weight from 167.6g to 126.3g. There was also a slight increase in stool
weight among those drinking the lactose-free milk.
“Given the risks of malnutrition and osteopenia in this population,
practitioners may wish to encourage their HIV patients with diarrhoea to include
moderate quantities of dairy products in their diets,” the authors concluded.
Arch Intern Med 2006; 166: 1178-1183
KLEAN price cuts
The KLEAN study, a head-to-head open label comparison between ritonavir boosted
protease inhibitors fosamprenevir (Telzir), and lopinavir/ritonavir (Kaletra)
showed remarkable similarities in treatment benefits and tolerability. The
results, published in the Lancet in August and announced at Toronto, showed
both regimes produced a 73 per cent and 71 per cent reduction in viral load
below 400 copies within their sample groups.
GlaxoSmithKline (GSK), who produce fosamprenevir, want the drug treated as
a preferred choice in therapy, in the same way as Kaletra. As part of its
marketing drive, GSK have reduced the prices of fosamprenevir (Telzir) in
the UK by 33 per cent; from £274 to £184 for a 30-day pack.
CO’C
Four drugs no better than three
Adding a fourth drug to a triple combination regimen that includes
efavirenz (Sustiva) or a ritonavir-boosted protease inhibitor gives no additional
benefit to people starting HIV therapy.
Researchers recruited 765 people new to HIV treatment. Average viral load
was around 59,000 copies and the average CD4 count was 240 cells.
People either received the coformulated nucleoside analogue Combivir (AZT/3TC)
plus the NNRTI efavirenz (Sustiva) or Trizivir (AZT/3TC/abacavir) plus efavirenz.
After an average of three years, 26 per cent of people on Combivir/efavirenz
(three drugs) experienced treatment failure. This compared with 25 per cent
receiving Trizivir/efavirenz (four drugs) the Toronto conference heard.
Treatment failure was defined as two successive viral loads above 200 copies.
Black participants who struggled to stick to taking their meds as prescribed
were at the highest risk of treatment failure.
Of those left on the study who had not failed treatment three years later,
viral load was below 200 copies in 90 per cent of those still taking Combivir/efavirenz
and 92 per cent of those taking Trizivir/efavirenz. Gains in CD4 cell count
did not differ significantly between the two groups.
The researchers said the findings supported current guidelines that recommend
two nucleosides plus efavirenz for initial treatment for HIV-1 infection.
“Adding abacavir as a fourth drug provided no additional benefit,"
they added.
THLB0211
Super-bug hits positive people outside of
hospital
Rates
of the super-bug MRSA (methicillin resistant Staphylococcus aureus) infection
caught outside hospital are rapidly increasing among people living with HIV.
HIV positive people now have an 18-fold higher risk compared to the general
population. This study included all the cases of community-acquired MRSA seen
between 1993 and 2005 at a large Californian HIV clinic. Patients with positive
MRSA cultures and not hospitalised during the previous year were considered
to have community-acquired MRSA.
Community-acquired MRSA was confirmed in 25 out of 425 people. All cases occurred
after 2002, and between 2003 and 2005 the incidence increased 17-fold. More
than half of those who developed community-acquired MRSA were taking HAART.
Risk factors included the recent use of beta-lactam antibiotics and a history
of syphilis, indicating high-risk sexual activity. Other factors were low
current CD4 counts and high viral load.
As most of the patients were in the army, researchers could not consider the
effect of sexual preference or practices, or the role of drug use, due to
military policies. MRSA most commonly presents as an abscess on the scrotum
or buttocks. MoAb0304
Nuke-sparing combo works for first line HIV
therapy
New research suggests people starting therapy with efavirenz (Sustiva) are
more likely to be virologically undetectable after two years than those starting
with the ritonavir-boosted protease inhibitor lopinavir (Kaletra).
A nuke-sparing combo combining efavirenz with lopinavir/ritonavir was almost
as effective as the current ‘gold standard’ efavirenz-based triple
therapy, the study found. Until now there has been no large
randomised clinical trial comparing the two combinations.
A total of 753 people living with HIV in the US starting HAART for the first
time received one of three different treatment approaches: 250 people got
efavirenz plus two nukes; 253 received the old soft-gel formulation of lopinavir
twice-daily with two nukes, while 250 received one NNRTI efavirenz plus lopinavir.
The nukes included: 3TC, AZT, d4T, or tenofovir. At the begining of the study,
the average viral load was 100,000 and the average CD4 was 180.
CD4 cell counts rose higher among people receiving lopinavir over 96 weeks;
up by 285 cells in those receiving lopinavir-based triple therapy, and by
268 cells in those receiving lopinavir plus efavirenz.
This compares to a rise of 241 cells among those receiving efavirenz-based
triple therapy.
Fewer on lopinavir plus two nukes achieved an undetectable viral load below
50 copies at 96 weeks, 77 per cent, compared with 89 per cent of those on
efavirenz plus two nukes. Researchers were uncertain why. Lopinavir/efavirenz
led to more lab toxicities, mainly increases in triglycerides and
LDL cholesterol. Dr Sharon Riddler told a press conference at Toronto: “As
we found that the NRTI-sparing two drug combination of efavirenz and lopinavir
had a similar level of effectiveness to the efavirenz plus two NRTI regimen,
there should be little doubt that patients can benefit from this ‘nuke-sparing’
treatment regimen when NRTI [nuke] side-effects are a problem." But there
was a note of caution.People on lopinavir plus efavirenz were more likely
to develop resistance to efavirenz following the failure of that combination
than those experiencing treatment failure with efavirenz plus two nukes. Respectively
69 per cent compared to 48 per cent who underwent gentypic resistance testing.
ThLB0204
Anal cancer rates up
Doctors are reporting a dramatic increase in new cases of anal cancer
in people with HIV.
They say the incidence rate is now almost four times higher in the recent
HAART era (1999-2003) than the
pre-HAART period.
Research in France shows rates of anal cell abnormalities and cancer, caused
by strains of the human papilloma virus (HPV), have not declined, despite
people taking HAART.
Researchers used data from 81,752 patients’ records in the French Database
on HIV. During the follow-up period, there were 97 new cases of anal cancer:
9.3 per cent in women; 23.7 per cent in heterosexual men and 67 per cent in
men who have sex with men.
People who developed anal cancer were typically in their early forties; more
than 40 per cent had received a prior Aids diagnosis and a quarter had never
used HAART before their anal cancer diagnosis.
In total, 37 people with anal cancer died. The three-year survival rate was
74 per cent. Researchers reiterated that there was an “urgent need"
to develop anal cancer screening programmes for people living with HIV. TUAB0305
Double PI therapy offers hope
People with few viable nuke options may be able to get a decent treatment
response from combining two protease inhibitors (PI) and boosting them with
a low dose of ritonavir.
The LOPSAQ study looked at 128 heavily pre-treated patients experiencing therapy
failure on their current regimen due to resistance or side effects. These
were switched to twice-daily saquinavir plus lopinavir/ritonavir (LPV/r).
HIV viral load at the start of the trial averaged 116,000 copies, while CD4
cell counts averaged 172.
Seventy-six participants with PI resistance mutations or nuke side effects
took a structured treatment interruption (STI) until their virus reverted
to being drug susceptible or their side effects resolved.
Treatment response was classed as having a viral load below 400 copies at
week 48. Around two thirds experienced a virologic response to therapy. By
week 48, CD4 cell counts rose to an average of 280 and the average viral load
declined to 144 copies. Seventy-eight people stayed on therapy at week 48.
While the STI failed to have a significant effect on therapy outcome, it enabled
a greater virologic response for a subgroup of patients with extensive PI
mutations (more than four).
The authors commented: “The combination of LPV/r and SQV without reverse
transcript inhibitors is a potential option as salvage therapy for patients
experiencing therapy failure due to resistance or RTI-toxicity."
They added that the regimen might be unsuitable for patients who start with
very low CD4 cell counts, very broad antiretroviral therapy experience or
with extensive PI-resistance mutations.
TUPE0135
Global hunt launched for ‘elite viral
controllers’
An
international search has been launched to find ‘elite controllers’;
HIV positive people who have controlled their virus at very low levels without
HIV drugs.
The aim is to study whether genetic factors can explain how a very small minority
of
people are able to control the virus without treatment for many years after
HIV infection.
Professor Bruce Walker, of Harvard University Medical School, estimated the
study would need to recruit around 800 people.
Professor Walker said: “If we could discover how these individual coexist
with this virus without damage to their immune system and could find a way
to replicate that ability in others, we would have a recipe for halting the
HIV epidemic." The researchers want to find a group of people diagnosed
with HIV for at least one year who have maintained a viral load below 50 copies
and never received treatment.
They also want to recruit a second group of ‘viral controllers’;
people living with HIV for at least one year who’ve had a viral load
below 2,000 copies without treatment. If you wish to participate in the Elite
Controller Collaborative Study, you just need to give one blood sample, drawn
by your doctor, which is then sent to the US for analysis. For further information
email:
rrosenberg2@partners.org
