Colliding epidemics: HIV, TB and other diseases
Lessons learned during the global scale-up of HIV treatment can be used to address epidemics of tuberculosis (TB) and non-communicable diseases (NCDs), which have become leading causes of death for HIV-positive people in low- and middle-income countries. Unless additional measures are taken, experts explained on Friday, July 27, at the XIX International AIDS Conference (AIDS) in Washington, DC, there may be some erosion in antiretroviral therapy’s ability to prolong the lifespan of an aging global population of HIV-positive people.
A Global View: HIV Care as a Model For Treating Other
Illnesses
Two researchers operating mainly in sub-Saharan Africa, Yogan
Pillay, PhD, the deputy director general for health in South
Africa, and Anthony Harries, MD, senior advisor at the
International Union Against Tuberculosis and Lung Disease in
Paris, shared the view that with the right adjustments lessons
learned during the scale-up of HIV treatment can cross over to
reduce the global death rates from HIV/AIDS and a number of
other illnesses.
Even though AIDS deaths are still a regular occurrence in many
countries and approximately 28 million people living with HIV
worldwide are currently not on treatment, over the last decade
there has been a significant global reduction in opportunistic
infections and deaths attributed to AIDS. To give a sense of
this unprecedented global scale-up in HIV treatment, Pillay
explained that 20 million South Africans have been tested for
HIV in the past 20 months, and the country has put 1.7 million
people on antiretroviral treatment since 2004.
In this context, Pillay encouraged low- and middle-income
countries to promote the sustainable development of their health
infrastructure and interventions. Pillay said that countries can
translate lessons learned from the HIV treatment scale-up into
prolonged life expectancy for the people living in these
countries—with significant benefits for HIV-positive
people. He recommended integrating different types of
health-related services, promoting country ownership, and
committing more funding while improving efficiencies, such as
technical and structural efficiencies. Pillay also emphasized
the need to increase spending on high-impact interventions.
The Limits of a Non-Integrated Approach
While researchers have tracked the life-expectancy benefits of
antiretroviral treatment and concluded that people who go on
treatment early gain the greatest life-expectancy benefit, they
are also beginning to outline the challenges of continuing to
increase the lifespan of an aging population of people living
with HIV, particularly in low- and middle-income settings.
New research suggest that the current scale-up of HIV treatment
may see diminished results in its ability to continue reduce
deaths and prolong life expectancy— especially if the
impact of other illness is not factored into national and global
strategies. For example, between 8 percent and 26 percent of
patients starting antiretroviral treatment in Africa still die
in the first year of therapy, and both diagnosed and undiagnosed
TB are major causes of this mortality, doctor Harries explained.
TB is still the number-one cause of death globally for
HIV-positive people. Internationally, approximately 350,000
people with HIV-associated tuberculosis died 2010, which is
especially tragic since both conditions are treatable.
In Europe and North America, more than half of all HIV-positive
people on treatment are now dying prematurely from
non-communicable diseases (NCDs), such as cardiovascular
disease, non-AIDS cancers, diabetes, chronic respiratory disease
and other illnesses not directly related to AIDS, according to a
1996-2006 Antiretroviral Therapy Cohort Collaboration (ART-CC)
study. The numbers are also rising in middle- and low-income
settings.
To demonstrate the need for an integrated approach to HIV care,
Harries explained the three underlying reasons for
HIV-associated TB deaths. First, among people with HIV/AIDS,
tuberculosis was not diagnosed and not treated. Second, patients
with TB were not tested for HIV and co-infection was not
diagnosed or treated. Lastly, neither HIV nor TB was diagnosed
or treated—or diagnosis and treatment came too late.
To stop or greatly reduce these deaths, Harries proposed that
tuberculosis deaths need to be approached just as aggressively
and strategically as AIDS deaths. To greatly reduce TB deaths
among people living with HIV, Harries proposes early
antiretroviral therapy, the introduction of isonazid preventive
therapy for TB, and better, cheaper and expanded diagnostic
testing for TB. Harries also recommended locating HIV and TB
treatment within the same facilities (with mandatory infection
control standards so that TB is not passed from one person to
another). Harries added that it’s important that patients
do not have to walk miles from one service to another, because
this may disrupt their care. Although Harries’s research
is TB-focused, the type of integrated approach he proposed is
also gaining popularity among researchers focused on HIV/AIDS in
the United States.
Other Illnesses Associated With Aging With HIV
Judith Currier, MD, MPH, the co-director of the Center For AIDS
Research at University of California, Los Angeles (UCLA),
offered a global epidemiological picture of epidemics of HIV and
NCD colliding. First, she showed that the demographic trend of
people living with HIV in many countries is shifting (or has
already shifted) to people over 50, now that HIV-positive people
are living longer because of access to antiretroviral treatment.
Second, Currier showed evidence of a rising global epidemic of
NCDs, which appears to be most acute in regions with high HIV
infection rates.
The World Health Organization estimates that 36 million people
died globally of NCDs in 2008; 80 percent of these deaths
occurred in low- and middle-income countries. Currier explained
that NCD epidemics are often fueled by poor nutrition, high
levels of tobacco and alcohol use and low levels of physical
activity, particularly in urban areas. NCD deaths are projected
to increase to 57 million by the year 2030.
Since geographic proximity isn’t enough to demonstrate
that these epidemics will affect one another, Currier cited
several studies that show that patients being treated for HIV
are at higher risk for several NCDs, including cardiovascular
disease, chronic obstructive pulmonary disease, non-AIDS
cancers, diabetes—as well as illnesses that aren’t
considered traditional NCDs, such as osteoporosis, frailty,
cognitive disorders, chronic liver disease and chronic renal
disease.
There is also mounting evidence that aging with HIV increases
the risk of comorbidities—and in many cases the
comorbidity is an NCD. Currier presented a graph that tracked
comorbidity in relation to older age among two separate groups,
HIV-negative people and HIV-positive people. The graph
illustrated that over the age of 50, HIV-positive people were
more likely to have one or multiple comorbidities when compared
to same-age HIV-negative people. This disparity became more
pronounced at older ages. For example, HIV-positive people aged
60 to 65 were approximately twice as likely to have three or
more comorbidities.
Why is old age liked to greater risk for comorbidities for
HIV-positive people? Currier explained that normal and abnormal
aging is already associated with progressive changes to the
immune system, and in aging HIV-negative people there is a
reduction in number of naïve t-cells and a decline in their
proliferative potential. Seniors also generally experience an
expansion of senescent t-cells and an increased production of
cytokines like IL-6, which can also have negative health
effects. Currier proposed that aging with HIV—even on
treatment—may deal a “double hit to the immune
system,” which may underlie the increased risk for other
non-communicable chronic diseases.
How to Lower NCD Risk Among People Aging With HIV
When it comes to reducing HIV-positive patients’ risk for
NCDs, Currier highlighted the central importance of early HIV
diagnosis and treatment. “We need to remember that early
diagnosis of HIV and prompt entry to care is going to be an
important component of reducing the long-term risk for
NCDs,” Currier said.
Putting opportunistic infections aside, she further explained
the biological process by which untreated HIV can do lasting
damage to the body through inflammation and immune activation,
which in turn may pose an increased risk of various cancers,
coronary disease, stroke, coagulation disorders; untreated HIV
may also increase the risk for atherosclerosis and osteoporosis.
Drawing this medical lesson into an intervention strategy,
Currier focused on the need expand HIV testing, to start people
on antiretroviral treatment between the CD4 count of 350 and
550, and to monitor and screen HIV-positive patients and
identify those who may be at the highest risk for NCDs.
Changing lifestyle factors was another significant way
HIV-positive people may be able to reduce the risk of developing
NCDs, according to Currier. She showed that tobacco use is
prevalent in many HIV-positive populations and has been linked
to increased risk for cancer, cardiovascular disease, bone loss
and impaired neurocognitive function. In one study,
approximately 40 percent of one U.S. cohort of HIV-positive
people were smokers, which is twice the rate of the general
population. A second study showed that smokers had a reduced
response to antiretroviral treatment compared to non-smokers.
Currier’s conclusion: If you’re an HIV-positive
smoker, you may reap additional health benefits from quitting as
soon as possible.
Interventions to help people living with HIV reduce saturated
fat and salt intake and get regular aerobic and resistance
exercise should also be encouraged as ways to promote overall
health and protect against NCDs, Currier said. There have
already been recommendations made for people living with HIV
over the age of 50 to get aerobic exercise three days per week
for 20 to 40 minutes, including stretching and resistance
training—all of which can be done without a gym
membership.
Currier voiced the need to continue to track how the side
effects of different anti-viral medications are affecting
patients’ long-term health so care providers can promote
the safest drugs globally. She also discussed the need for
researchers to evaluate the treatment for NCDs in the setting of
HIV, since there is much that can still be learned about the
long-term interactions of different treatments and drugs.
“The NCD and HIV worlds are often competing against each
other,” Currier added. “I think the secret is to
gang up on the problem rather than each other.” On this
last point, all three researchers seemed to be in agreement.
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