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May 3, 2010)
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Apr 30, 2010
Researchers in
According to the World
Health Organization, HIV is one of the world's biggest health challenges,
infecting almost three million people and killing some two million people every
year. When a person is infected, HIV enters into the immune system's crucial T
lymphocytes – or T cells – and replicates itself by integrating with the
DNA. As a result the cells die and the immune system slowly weakens until it can
no longer fight off opportunistic infections, a status classified as AIDS.
The scale of the AIDS
epidemic has prompted many scientists to search for an HIV vaccine, but this has
proved difficult. HIV is different from other viruses in that it can mutate very
quickly, thereby evading the normal immune-system defences. Some scientists
think that a vaccine will only become available once there is a leap in the
theoretical understanding of the virus.
'Detailed and realistic'
Physicist Jianwei Shuai
and chemical biologist Hai Lin of
In the model, single HIV
particles, known as virions, sit on lattice sites alongside two types of T cell:
CD4+ T cells, which direct other immune-system cells, and CD8+ T cells, which
kill infected cells. The virions and cells take a "random walk" around
the lattice sites until two meet each other, at which point they interact in one
of several ways. At the same time, the model takes into account the virions'
mutations and the responses of the T cells.
One of the results of the
researchers' model concerns the so-called asymptomatic phase in HIV-positive
patients – the period from which they are infected with HIV to when they begin
to develop AIDS. Although for the majority of people this phase is 5–10 years,
it can be 15 years or longer. Physicians had thought the discrepancy was due to
the abilities of different patients' immune systems, but Shuai and Lin think the
reason could simply be a product of the immune system's random response.
Decisive role
A potentially more
important result, however, comes in the way that the two types of T cell react
to HIV. In their model, Shuai and Lin found that it is the CD8+ T cells that
play a decisive role in suppressing the virus. "This observation implies
that CD8+ T-cell response might be an important goal in the development of an
effective vaccine against AIDS," explains Shuai.
Yet some researchers claim
that this result is nothing new. "The model makes a large number of
assumptions, none of which are examined by comparison to [clinical] data,"
says Alan Perelson, a theoretical immunologist at Los Alamos National
Mathematical exercise?
David Ho, an AIDS
scientist at the
Still, Shuai and Lin are
planning to take their model further. By modelling the effects of different
drugs, they hope to find an optimal therapy to fight HIV.
The research is available
to read free in the New Journal of Physics.
About the author
Jon Cartwright is a
freelance journalist based in
May 3, 2010
WASHINGTON (Reuters) -
Regulators are investigating potential risks from Abbott Laboratories Inc's HIV
drug Kaletra, GlaxoSmithKline Plc's prostate drug Avodart and other medicines.
The Food and Drug
Administration said on Monday it was probing reports of liver toxicity with
patients who used Kaletra to prevent HIV infection after exposure to the AIDS
virus.
The agency also said it
was investigating cases of male breast cancer in patients treated with Avodart
as well as Merck & Co's prostate drug Proscar and baldness treatment
Propecia.
The FDA releases a
quarterly list of safety probes to inform the public about early investigations
of potential side effects that have been reported. The list released on Monday
covered issues identified between October and December 2009.
Being on the list does not
mean the FDA has concluded the drug causes the specific risk, the agency said.
Michael Carter, Wednesday,
April 28, 2010
Lifestyle and social
factors need to be addressed if the full potential of HIV treatment to lower
mortality is to be realised, according to results from a large cohort study
published in the May 15th edition of Clinical Infectious Diseases.
Diseases associated with ageing but nevertheless influenced by HIV infection,
and risk behaviours associated with HIV infection, such as cardiovascular
disease, non-AIDS-defining cancers, kidney disease and liver disease, are the
causes of death in a growing proportion of people with HIV, while deaths from
AIDS-defining causes such as opportunistic infections and AIDS-defining cancers
have fallen over the past ten years.
Investigators from the international Antiretroviral Therapy Cohort Collaboration
examined recorded causes of death amongst patients taking HIV treatment in
Europe and
Their retrospective analysis included 13 studies, which included a total of
39,272 patients.
These individuals contributed a total of 154,667 person-years of follow-up, the
median duration of follow-up for each patients being a little under four years.
At the time HIV treatment was started, the patients had a median age of 37
years. The median calendar month when antiretroviral therapy was initiated was
December 2000. The majority of patients (62%) took a combination that included a
protease inhibitor.
There were a total of 1876 deaths (5%). The overall mortality rate was 12 deaths
per 1000 person-years. Those who died had a lower median CD4 cell count at
baseline (110 cells/mm3) than those who survived (217 cells/mm3).
A cause of death was recorded for 1597 patients. Almost half (49.6%) were due to
AIDS. When the investigators looked at the AIDS-related mortality in further
detail, they noted that 23% of all deaths were due to AIDS-defining infections
and 15% to AIDS-defining cancers.
Non-AIDS-defining cancers were the next most common cause of death (12%). Over a
third (37%) of non-AIDS-defining cancer deaths were caused by lung cancer.
Infections not considered AIDS-defining caused 8% of all deaths, and 8% of
deaths were also attributed to cardiovascular death. Violence accounted for 8%
of deaths, liver disease for 7%, respiratory diseases for 2% and renal failure
for 2% of mortality.
The cause of death changed over time. The proportion of AIDS-related deaths fell
from 58% in 1996-99 to 44% in the period 2003 to 2006. The percentage of deaths
due to AIDS-defining cancers fell from 21% in the earlier period to 13% after
2003.
However, at the same time non-AIDS-defining cancers became an increasingly
important cause of death. The proportion of deaths attributed to such
malignancies more than doubled from 7% before 1999 to 15% in the period between
2003 and 2006.
A low CD4 cell count was associated with an increased risk of death from
non-AIDS-related cancers (HR per 100 cell/mm3 fall = 1.43; 95% CI, 1.34 to
1.53)and renal cancers (HR per 100 cell/mm3 fall = 1.73; 95% CI, 1.18 to 2.55).
“The strong inverse association of rates of death due to AIDS with CD4 cell
counts at the time of starting antiretroviral therapy supports arguments for
earlier initiation of antiretroviral therapy,” comment the investigators.
A baseline viral load above 5 log10/copies/ml was significantly associated with
an increased risk of death due to AIDS (HR = 1.31; 95% CI, 1.12 to 1.53),
infections (HR = 1.85; 95% CI, 1.25 to 2.73), cardiovascular disease (HR = 1.54;
95% CI, 1.05 to 2.27), and respiratory disorders (HR = 3.63; 95% CI, 1.30 to
10.09).
“Systematic immune activation secondary to high viral replication, rather than
additional or additional to immunodeficiency, may promote death from infections
and cardiovascular disease,” write the study’s authors.
Mortality rates for all causes with the exception of renal disease were higher
for injecting drug users than other risk groups. Especially strong associations
between injecting drug use and death due to liver disease, respiratory
illnesses, violence and infections were observed.
Older age was strongly associated with an increased risk of death from
non-AIDS-related cancers (HR per 10 years = 2.32; 95% CI, 2.04 to 2.63), and
cardiovascular disease (HR per 10 years = 2.05; 95% CI, 1.76 to 2.39). The rate
of kidney-related death was especially high amongst patients aged over 60.
The investigators believe that these results “imply that the process of aging
will become a dominant factor in HIV mortality in the next decade.”
Overall, mortality rates were 16% were lower in women in men. In addition, women
were 50% less likely than men to die of non-AIDS-related cancers.
As the duration of antiretroviral therapy increased, the risk of death from
AIDS, non-AIDS-related infections, and kidney disease decreased (p < 0.001).
Starting HIV therapy after 2000 was associated with a significant reduction in
the risk of death due to AIDS (p < 0.001).
“Antiretroviral therapy continues to dramatically reduce rates of mortality
attributable to HIV infection in high-income countries,” conclude the
investigators.
However, they express concern about the high mortality rates due to conditions
“associated with social and lifestyle factors…the importance of lifestyle is
reinforced by the observation that the most common non-AIDS malignancy was lung
cancer, likely caused by smoking.”
The investigators believe that these findings have implications for the care of
patients with HIV. They suggest: “interventions to address risk factors for
lifestyle-related causes of death, as well as monitoring for and care of
diseases associated with old age, will be necessary if the full benefit of
antiretroviral therapy in decreasing mortality is to continue n the second
decade of antiretroviral treatment.”
Reference
The Antiretroviral Therapy Cohort Collaboration. Causes of death in
HIV-1-infected patients treated with antiretroviral therapy, 1996-2006:
collaborative analysis of 13 HIV cohort studies. Clin Infect Dis 50: 1387-96,
2010.
Roger Pebody, Friday,
April 30, 2010
In the
Ruth Smith of the Health Protection Agency announced these findings at the joint
conference of the British HIV Association (BHIVA) and the British Association
for Sexual Health and HIV (BASHH) last week. Also at the conference, other
studies highlighted issues involved in the treatment and care of older people
with HIV.
During the period 2000 to 2008, one in twelve (8.5%) new adult HIV diagnoses
were in a person over the age of 50. The numbers increased year on year, from
304 in 2000 to 787 in 2008.
The profile of people diagnosed over 50 is somewhat different to those diagnosed
at a younger age. They are more likely to be male, homosexual and white than
other groups. The HPA have noted a number of diagnoses in older heterosexual men
who acquired their infection in southeast Asia.
By looking at the CD4 count at the time of diagnosis, the researchers were able
to estimate how long each person had had HIV when diagnosed. Just under half
(48%) of infections were thought to have been acquired when the person was over
50, suggesting that prevention work cannot ignore older adults.
Nonetheless, late diagnosis is more of a problem in older adults than in younger
groups. A total of 48% are diagnosed with a CD4 count below 200 cells/mm3,
compared to 33% of people under 50. In gay and bisexual men, double the number
of over-50s are diagnosed late compared to younger men (40% and 21%
respectively).
Moreover, these late diagnoses make a substantial contribution to short-term
mortality. Amongst people diagnosed over the age of 50, 14% of those diagnosed
late died within a year, compared to 1% of people not diagnosed late.
Whereas people over the age of 50 represented 11% of the individuals accessing
HIV care in 2000, they now make up 17% of those doing so.
Other studies at the conference looked at the treatment and care needs of these
older adults. A poster profiled 257 patients aged 50 or over attending HIV
services in
85% of patients had at least one co-morbidity, with 43% having three or more. As
a result, in addition to anti-HIV drugs, two-thirds of patients were taking
medication for other conditions (12% reported five or more other drugs) and 79%
of patients were under the care of other medical specialists (dermatology, ENT,
cardiology, gastroenterology, etc,). The authors recommended that HIV clinicians
should work in close co-operation with these other specialists.
Another poster highlighted the importance of carrying out additional tests and
assessments, for example for prostate cancer and other malignancies. Moreover
regular review of all medication is required to monitor possible drug-drug
interactions.
Finally, the
Some of the key themes were:
Health: concerns about the
unknown effects of HIV and antiretroviral treatment over time; the number of
co-morbidities; a desire to have continuity of medical care and more
psychosocial support. “Obviously the antiretrovirals are keeping me alive but
there must be some long-term damage,” said one interviewee.
Survival: stories of
outliving peers and of not having prepared for the future because none was
expected. “They’re all dead and I’m the only one left alive and I’ve got
no pension.”
Self-esteem and rejection,
linked to a youth-orientated gay scene, changes in physical appearance and
sexual dysfunction. “Who wants an old faggot like me?” was one comment from
the interviews.
References
Smith R et al. Refocusing our efforts – transmission and late diagnosis of HIV
among adults aged 50 and over. HIV Medicine 11 (supplement 1), O3, 2010.
Patel R et al. Greying with HIV: an observational study of healthcare needs of
HIV-infected patients aged 50 years or over. HIV Medicine 11 (supplement 1),
P68, 2010.
Ward B et al. Ageing and HIV/AIDS: evaluation of a dedicated clinical service
for HIV-infected individuals over 50 years of age. HIV Medicine 11 (supplement
1), P66, 2010.
Perry N et al. i>Growing older and living longer with HIV-1 – a qualitative
study. HIV Medicine 11 (supplement 1), P79, 2010.
By Andrew Jack
Published: April 29 2010
03:00 |
Strong sales in emerging
markets and from pandemic flu vaccines helped GlaxoSmithKline cut its
traditional reliance on pills sold in western markets to a quarter of turnover,
as it reported results for the first three months of 2010.
The UK-based
pharmaceutical group reported earnings per share up 18 per cent to 26.4p on the
first quarter last year on sales up 9 per cent to £7.4bn - an increase of 13
per cent at constant exchange rates.
Andrew Witty, chief
executive, said: "These results reinforce the fact that GSK is delivering a
sustained performance . . . [showing] that our strategy is delivering." He
played down the impact of
Flu vaccine sales
accoun-ted for much of the rise in overall sales, without which turnover rose 4
per cent to £6.6bn, with the company indicating that it expected full-year
sales to be in line with last year in spite of a slump in demand as the swine
flu outbreak proved more mild than feared.
GSK also revealed more
detailed financial performance for each business unit for the first time,
highlighting operating margins of 68 per cent for its
In the quarter, GSK's
vaccines arm generated margins of 54 per cent, consumer healthcare 16 per cent
and dermatology 48 per cent, while GSK's ViiV Healthcare joint venture for HIV
drugs with Pfizer had margins of 57 per cent.
While
Gbola Amusa, a
pharmaceuticals analyst with UBS, said: "GSK is heading in the right
direction, but we model products by geographies, so what AstraZeneca does will
be pivotal. I hope it won't be too long before GSK follows."